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Enhancement by somatostatin of experimental gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. The effects of somatostatin on the incidence, number, and histological type of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats. Rats received alternate-day s.c. injections of 100 or 200 micrograms/kg body weight of somatostatin in depot form after 25 weeks of p.o. treatment with the carcinogen. Prolonged administration of somatostatin at both dosages significantly increased the incidence and number of gastric cancers of the glandular stomach in Week 52. Furthermore, somatostatin at 200 micrograms/kg caused a significant increase in the incidence of gastric cancers penetrating the muscle layer or deeper layers. However, somatostatin at both dosages did not influence their histological appearance. Histologically, somatostatin at both dosages significantly elevated the labeling index of gastric cancers but not of the antral mucosa and significantly reduced the gastrin levels. These findings indicate that somatostatin enhances gastric carcinogenesis after N-methyl-N'-nitro-N-nitrosoguanidine treatment and that this effect may be related to its effect in increasing proliferation of gastric cancers and decreasing serum gastrin level.

Selected elements of Poison Pax Paxillus involutus. Concentrations of Ag, Al, Ba, Ca, Cd, Co, Cu, Cr, Cs, Fe, Ga, Hg, K, Mg, Mn, Mo, Na, Ni, Pb, Rb, Se, Sb, Sr, V, Tl and Zn have been determined in the whole fruiting bodies as well as separately in caps and stalks of Poison Pax collected from three geographically distant sites across Poland. The elements were determined using ICP-MS, ICP-OES, HG-AAS and CV-AAS, respectively. Based on arithmetic mean and median values for Poison Pax specimens from the Lezno site the elements such as Ag, Co, Cr, Cs, Mn, Mo, K, Pb, Rb, Sb, Se, V and Tl occur at similar concentration both in the caps and stalks, while for Cd, Cu, Hg, Mg and Zn around two-fold greater concentrations were noted in caps than stalks (cap/stalk concentration quotient > 1). Cs, Cd, Ni and Rb occurred at much greater concentration in specimens collected from the Kłodzka Hollow in the Sudety Mountains when compared to the lowland site (Mann-Whitney U-test), and slightly greater values were noted also for Cr, Mo and Rb, while for Ca, Co, Mg and Mn were smaller The results provide useful environmental and biological baseline level of information for metallic elements of Poison Pax.

Peripherally inserted central venous lines versus central lines in surgical newborns--a comparison. To compare the insertion characteristics, utilization profile, life span and the complication rates of Central lines (CL) and Peripherally inserted central lines (PICL). A prospective study of all CL or PICL insertions during January 2007 to September 2007 in the Neonatal Surgical Intensive Care Unit of a tertiary care center was done. The number of attempts, procedure time, duration of catheter stay, number of dressing done, complication during insertion and maintenance and cause of removal were noted and the differences analyzed statistically using Pearson chi square / t test. P value. 0.05 was considered significant. Ninety two neonates were included in the present study of whom 60 were PICL insertions and 32 CL insertions. The two groups were comparable in terms of age, weight and the use of total perental nutrition (TPN) through the catheters. On comparing the PICL and CL groups, the number of attempts for successful insertion (p=0.003), the time taken (p=0.005), the number of dressing changes required during the indwelling period (p=0.005) and the overall complication rates (p=0.002) were significantly less in the PICL group. The PICL could be maintained for longer periods of time (p= 0.005) and only in 11.5% of the patients it had to be removed before completion of therapy as compared to 37.5% early removals for CL (p=0.02) PICL is a safe, effective and reliable method of providing prolonged IV access in newborns. It also has the least incidence of complications during insertion and maintenance over prolonged period of time when compared to CL and should be recommended for routine use in neonatal surgical patients.

Meta-analysis of Specific Music Therapy Measures and Their Implications for the Health Care System. The purpose of the activity reported in this article was to conduct an exhaustive search of the Journal of Music Therapy, filter the articles on the desired parameters, and organize data for analysis and interpretation. Specifically, the researcher studied whether (a) there was a significant difference in physiological measures, (b) there was a significant difference in quality of life, (c) there was a significant difference in satisfaction levels, (d) there was a significant difference in pain reduction, (e) there was a significant difference in procedural length, (f) there was a significant difference in length of stay, and (g) whether the overall effect size and 95% confidence level support the recommendation of music therapy in the health care setting. Twenty-four studies met criteria for inclusion in the systematic review. Results revealed an overall effect size of d = 0.61. However, results of the 95% confidence interval included 0, which suggests that there may not be a statistically significant difference in the health care setting on desired measures. Further results and implications are discussed within the article.

The relationship between busyness and research utilization: it is about time. To explore the concept of busyness in nursing and to understand the relationship between busyness and nurses' research utilization better. Lack of time and busyness are consistently reported as barriers to research utilization. Current literature fails to identify the dimensions of busyness and offers little insight into the relationship between busyness and nurses' research utilization. We performed a secondary analysis of qualitative data and created a conceptual map of busyness in nursing. Our results suggested that busyness consists of physical and psychological dimensions. Interpersonal and environmental factors influenced both dimensions. Cultural and intrapersonal factors contributed to psychological elements. The effects of busyness reported included missed opportunities, compromised safety, emotional and physical strain, sacrifice of personal time, incomplete nursing care and the inability to find or use resources. Our beginning description of busyness contributes to a greater understanding of the relationship between busyness and research utilization. Our findings suggest that lack of time as a barrier to research utilization is more complex than depicted in the literature. Instead, the mental time and energy required to navigate complex environments and a culture of busyness more accurately reflect what may be meant by 'lack of time' as a barrier to research utilization. Future interventions aimed at increasing research utilization may be more effective if they focus on factors that contribute to a culture of busyness in nursing and address the mental time and energy required for nurses to use research in practice.

Circadian and senescence-enhanced expression of a tobacco cysteine protease gene. A cDNA clone encoding a cysteine protease was isolated from a tobacco cDNA library, utilizing as a probe a PCR fragment obtained from degenerated primers based on the conserved sequences of plant cysteine protease genes. A putative protein encoded by the clone NTCP-23 had an amino acid sequence with significant similarities to those of plant senescence-associated cysteine proteases and mammalian cathepsin H. Northern blot analysis showed that NTCP-23 mRNA is expressed in all organs and the mRNA and protein expression is enhanced during natural senescence. We propose that NTCP-23 is responsible for amino acid remobilization especially in senescencing leaves. Furthermore, it was found that the mRNA expression follows a circadian rhythm and is reduced by continuous darkness, wounding and hypersensitive reaction (HR). NTCP-23 is the first cysteine protease whose mRNA expression has been shown to be temporarily reduced by wounding.

Protoporphyrin-IX conjugated cellulose nanofibers that exhibit high antibacterial photodynamic inactivation efficacy. Towards the development of anti-infective nanoscale materials employing a photodynamic mechanism of action, we report the synthesis, physical properties (SEM, mechanical strength, water contact angle), spectroscopic characterization (infrared, Raman, DRUV), and evaluation of antibacterial efficacy of porphyrin-conjugated regenerated cellulose nanofibers, termed RC-TETA-PPIX-Zn. Cellulose acetate was electrospun to produce nanofibers, thermally treated to enhance mechanical strength, and finally hydrolyzed to produce regenerated cellulose (RC) nanofibers that possessed a high surface area and nanofibrous structure. Covalent grafting of a protoporphyrin IX (PPIX) photosensitizer using epichlorohydrin/triethylenetetramine (TETA), followed by zinc chelation, afforded RC-TETA-PPIX-Zn. The high surface area afforded by the nanofibers and efficient photosensitizer conjugation led to a very high loading of 412 nmol PPIX/mg material, corresponding to a degree of substitution of 0.1. Antibacterial efficacy was evaluated against Staphylococcus aureus (ATCC-6538) and Escherichia coli (ATCC-8099), with our best results achieving detection limit inactivation (99.999+%) of both bacteria after only 20 min illumination (Xe lamp, λ ≥ 420 nm). No statistically significant loss in antibacterial activity was observed when using nanofibers that had been 'photo-aged' with 5 h of pre-illumination to simulate the effects of photobleaching. Post aPDI, scanning electron microscopy revealed that the bacteria had undergone cell membrane leakage, consistent with oxidative damage caused by photo-generated reactive oxygen species. Taken together, the conjugation strategy employed here provides a scalable, facile and efficient route to creating nanofibrous materials from natural polymers with a high photosensitizer loading, enabling the use of commercially-available neutral porphyrin photosensitizers, such as PPIX, in the design and synthesis of potent anti-infective nanomaterials.

Antiatherosclerotic actions of isradipine. Isradipine, a calcium antagonist of the dihydropyridine type, shows antiatherosclerotic actions that interfere with all three main mechanisms of atherosclerosis. These actions are mediated by the release of prostaglandin I2 and endothelium-derived relaxing factor, and the subsequent elevation of intracellular adenosine-3',5'-cyclic phosphate and 3',5'-guanosine monophosphate, respectively. These mechanisms have been proven in vitro and in animal models. Preliminary data in humans suggest that these mechanisms have clinical relevance in the long-term treatment of patients as well.

Purine levels and metabolism in human follicular fluid. Adenosine (ADO) in low micromolar levels and hypoxanthine (HYP) in millimolar levels have been shown to inhibit maturation of cumulus-enclosed oocytes. To determine the effect of ovarian stimulation with gonadotrophins on follicular purine metabolism, we measured ADO, HYP, inosine (INO), adenine (ADE) and cyclic AMP (cAMP) levels in follicular fluid (FF) from natural (n = 7) or human menopausal gonadotrophin/human chorionic gonadotrophin (HMG/HCG)-stimulated (n = 35) cycles. Purines were extracted immediately (natural cycles) or within 30 min of recovery (HMG/HCG cycles) and analysed by high pressure liquid chromatography (HPLC). The concentration of all ADE purines in FF was in the low micromolar range (1-20 microM); cAMP levels were markedly increased (greater than 100 microM) in FF of HMG/HCG-treated patients. While ADO levels were within the range effective for inhibition of oocyte maturation, those of HYP were not. No correlation was found between purine levels in FF and ovum maturation. Purine levels in FF of natural cycles were uniformly lower than those of stimulated cycles. Significant conversion of 5'-AMP into ADO, ADO into INO and INO into HYP occurred within 1 h when FF was incubated at 25 but not at 4 degrees C. These purine levels in human FF confirm our previous findings with bovine FF and suggest a possible role of ADO, but not of HYP, in the inhibition of oocyte maturation in the human.

Para-aminosalicylic acid (PAS) desensitization review in a case of multidrug-resistant pulmonary tuberculosis. Tertiary care hospital in the Upper Midwest, United States. Rapid desensitization to para-aminosalicylic acid (PAS) in a patient with previous hypersensitivity reaction and a review of published PAS desensitization protocols. Composition and implementation of a short-course PAS desensitization protocol for a 34-year-old woman with multidrug-resistant (MDR) pulmonary tuberculosis, incorporating published experiences of PAS desensitization over the past 50 years. We composed a protocol and successfully desensitized our patient to PAS (Paser granules). By starting with a low dose (50 mg), then doubling the PAS dose on each successive day, our patient was able to tolerate full dose in 1 week. No steroids were required and no adverse reactions were encountered. Previous published PAS desensitization protocols used starting doses of 10-500 mg, desensitization time ranges from 7 to 54 days and commonly used steroids or corticotropin. Rapid desensitization to PAS can be successfully conducted within 1 week without the use of steroids or corticotropin. Given the limited number of drugs available for many patients with MDR-TB, desensitization to PAS is a valid alternative to drug discontinuation for patients with hypersensitivity reactions.

Inertial extended-Lagrangian scheme for solving charge equilibration models. The inertial extended Lagrangian/self-consistent field scheme (iEL-SCF) has been adopted for solving charge equilibration in LAMMPS as part of the reactive force field ReaxFF, which due to the charge conservation constraint requires solving two sets of linear system of equations for the new charges at each molecular dynamics time-step. Therefore, the extended Lagrangian for charge equilibration is comprised of two auxiliary variables for the intermediate charges which serve as an initial guess for the real charges. We show that the iEL-SCF is able to reduce the number of SCF cycles by 50-80% of the original conjugate gradient self-consistent field solver as tested across diverse systems including water, ferric hydroxide, nitramine RDX, and hexanitrostilbene.

[cAMP response-element binding protein participates in the phosphorylated extracellular signal-regulate kinase mediated neuropathic pain]. It has been reported that extracellular signal-regulate kinase (ERK) is involved in the modulation of nociceptive information and central sensitization produced by intense noxious stimuli and/or peripheral tissue inflammation. Few studies have explored the relationship between ERK and cAMP response-element binding protein (CREB) in neuropathic pain after nerve injury, such as chronic constriction injury (CCI) of the sciatic nerve. In the present study, CCI model was employed to investigate the activation of ERK on the expression of phosphorylated CREB (pCREB) in chronic neuropathic pain. Lumbar intrathecal catheters were chronically implanted in male Sprague-Dawley rats. The left sciatic nerve was loosely ligated proximal to the sciatica's trifurcation at around 1.0- mm intervals with 4-0 silk suture. Mitogen-activated protein kinase kinase (MEK) inhibitor U0126 and phosphorothioate-modified antisense oligonucleotides (ODN) were intrathecally administered one day before and three consecutive days after CCI. Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal lantency (PWL) to radiant heat and von Frey filaments respectively. The expression of pCREB and Fos were assessed by both Western blot and immunohistochemical analysis. The results showed that intrathecal injection of U0126 or ERK antisense ODN attenuated significantly CCI-induced mechanical and thermal hyperalgesia. Correlating with behavior results, the injection also markedly suppressed the increase of CCI-induced pCREB and c-Fos expression. The results obtained suggest that CREB participates in the pERK-mediated neuropathic pain.

Strategies used by families to simplify tasks for individuals with Alzheimer's disease and related disorders: psychometric analysis of the Task Management Strategy Index (TMSI). Little is known about the specific behavioral strategies used by families to manage the physical dependency of persons with Alzheimer's disease and related disorders (ADRD). This study reports the psychometric properties of the Task Management Strategy Index (TMSI), a measure designed to identify actions taken by caregivers to simplify everyday self-care tasks for persons with ADRD. Relationships between use of these strategies and caregiver and care-recipient characteristics were also examined. A pool of 20 items was developed and initially tested with 202 family caregivers (Sample 1) recruited for a dementia-management intervention study. Principal axis factor analysis was performed to determine scale structure. Convergent and discriminant evidence was examined using Pearson cor-relation and multiple regression analyses with a separate sample of 255 family caregivers (Sample 2) recruited for the Philadelphia site of the National Institutes of Health multisite initiative, Resources for Enhancing Alzheimer's Caregiver Health. Exploratory principal axis factoring yielded one general factor accounting for 60.2% of variance in the first sample. Nineteen items, loading at.3 or above, constituted the final scale (Cronbach's alpha =.81 in Sample 1 and.74 in Sample 2). In Sample 2, TMSI scores were significantly associated with greater functional dependency of ADRD patients, high self-efficacy, and greater use of positive coping strategies. As expected, caregiver upset with disruptive behaviors and caregiver use of criticism-based strategies were not associated with TMSI scores. Higher caregiver education was significantly associated with greater use of task strategies. Results provide preliminary evidence that the TMSI is an easily administered, reliable, valid scale. Caregivers with lower education may benefit from instruction in the use of these strategies.

Relative cervical incompetence in twin pregnancy. Assessment and efficacy of cervical suture. A total of 88 women with a twin pregnancy who had elective cervical suture were compared with 76 women with a twin pregnancy who had cervical assessment between the 13th and the 28th weeks of gestation but received no active treatment. The incidence of spontaneous onset of labour before 36 weeks was higher in the cervical suture group, and 53.4% of them sustained cervical damage.

Investigating water interactions with collagen using 2H multiple quantum filtered NMR spectroscopy to provide insights into the source of double quantum filtered signal in tissue. In an effort to provide insight into the molecular origins of the (2)H double quantum filtered (DQF) NMR signal observed in connective tissue, specifically spinal disc tissue, (2)H multiple quantum filtered (MQF) NMR spectroscopy is used to study the structure and dynamics of D2O in collagen as a function of hydration. Residual quadrupolar coupling constants are measured and decrease from 3500 to 20 Hz while T2 relaxation times increase from 0.65 to 20 ms as hydration increases. Analysis of the data indicates that the quadrupolar coupling and T2 relaxation arises when water molecules spend time in restricted environments. The residual quadrupolar coupling is influenced almost exclusively by the most restricted water sites, the clefts of the triple helices not exposed on the surface of the fibrils, while the T2 relaxation has secondary contributions from less restricted water environments. The magnitudes of the measured values are consistent with results from DQF NMR studies of spinal disc tissue, supporting the assertion that water binding to collagen is a major contributor to the DQF NMR signal observed in spinal disc tissue.

Age differences in deactivation: a link to cognitive control? The network of regions shown by functional imaging studies to be deactivated by experimental tasks relative to nominally more passive baselines (task < baseline) may reflect processes engaged during the resting state or "default mode." Deactivation may result when attention and resources are diverted from default-mode processes toward task processes. Aging is associated with altered patterns of deactivation which may be related to declining resources, difficulties with resource allocation, or both. These possibilities predict that greater task demand, which increases deactivation levels in younger adults, should exacerbate age-related declines in allocating resources away from the default mode. The present study investigated the magnitude and temporal properties of deactivations in young and older adults during tasks that varied in their demand for cognitive control. Two versions of a verb generation task that varied in their demand for selection among competing alternatives were compared to word reading and a fixation baseline condition. Consistent with our hypothesis, greater deactivations were found with increasing demand. Young and older adults showed equivalent deactivations in the minimal selection condition. By contrast, age differences in both the magnitude and time course of deactivation increased with selection demand: Compared to young adults', older adults' deactivation response showed less sensitivity to demand. Demand-related changes in deactivation magnitude correlated with performance changes, suggesting that individual and group differences in deactivation have functional significance.

Changes in apolipoprotein A-I mRNA level in the liver of rats with experimental nephrotic syndrome. In previous studies we had shown that: one of the most specific feature of hyperlipoproteinemia found in rats with experimental nephrotic syndrome is the accumulation of apolipoprotein A-I-rich HDL in plasma and this disorder is associated with an overproduction of apolipoprotein A-I by the liver. The present study was designed to investigate whether the increased hepatic synthesis of apolipoprotein A-I was due to an accumulation of functionally active apolipoprotein A-I mRNA in liver of nephrotic rats. Hepatic mRNA was translated in vitro by rabbit reticulocyte lysate in the presence of [35S]methionine and in vitro synthesized apolipoprotein A-I, albumin and apolipoprotein E were immunoprecipitated by specific rabbit IgG. In nephrotic rats the amount of in vitro synthesized apolipoprotein A-I was almost twice that found in the controls, suggesting that functionally active apolipoprotein A-I mRNA was increased in liver of nephrotic rats. To confirm that this difference in apolipoprotein A-I mRNA activity was due to an actual increase of hepatic apolipoprotein A-I mRNA sequences, we performed nucleic acid hybridization experiments (northern blot) using several cloned cDNA probes (rat and human apolipoprotein A-I, rat apolipoprotein E and apolipoprotein A-II). The results indicate that in nephrotic rats the amount of hybridizable apolipoprotein A-I mRNA sequences was about 3-fold higher than that in controls. In contrast, there was no difference in the amount of hybridizable apolipoprotein A-II and apolipoprotein E mRNA sequences, indicating that the change in apolipoprotein A-I mRNA induced by the nephrotic state was specific for this mRNA.

Effects of varying argon ion laser intensity and exposure time on the ablation of atherosclerotic plaque. Using continuous wave (CW) argon ion laser light, a total of 253 laser exposures of varying power (1.5, 3, 5, 8 or 10 W) and duration (20-1,333 ms) were delivered to four segments of human atheromatous aorta obtained at autopsy. Exposure conditions were controlled by using an optically shielded laser catheter that provided a 500 micron spot of light of known power. Two thresholds for consistently reproducible ablation could be defined-an intensity threshold at 25.5 W/mm2 and a fluence threshold at 3.2 J/mm2. Above threshold, a fluence of 5.1 J/mm2 was found to produce the most efficient ablation, ie, removed the greatest volume (mm3) per energy delivered (J) compared to other fluence levels employed (p less than 0.0001). Between aortic segments, however, considerable variability in efficiency (mm3/J) was observed, possibly owing to different optical properties and/or plaque composition. Low-intensity laser radiation produced inconsistent ablation and extensive coagulation effects to surrounding tissue. When a fluence of 5.1 J/mm2 was constructed with a high-intensity laser beam and a short exposure time, consistent and efficient tissue removal resulted without histologic evidence of coagulation necrosis.

Effect of platelet-rich plasma on sinus lifting: a randomized-controlled clinical trial. The combination of anorganic bovine bone (ABB) with platelet-rich plasma (PRP) has been widely used in bone regeneration procedures although its benefits are still unclear. The purpose of this study was to evaluate whether or not PRP improves the efficacy of ABB in sinus floor augmentation. In addition, we have investigated the effect of residual bone height and tobacco on implant survival in sinus augmentation procedures. Eighty-seven patients recruited for this study underwent 144 sinus floor augmentation procedures using ABB alone or ABB plus PRP (ABB+PRP) in a randomized clinical trial. A total of 286 implants were placed in the augmented bone, and their evolution was followed up for a period of 24 months. In order to investigate on a histological level and any adjunctive effects, we performed an ancillary study in five edentulous patients with a symmetrical severely resorbed maxilla. In these patients, a bilateral sinus augmentation was randomly performed using ABB or ABB+PRP in a split-mouth design, and after 6 months, bone biopsies were taken from the implant sites for histological and histomorphometric analysis. Overall, 96.2% of ABB and 98.6% of ABB+PRP implant success were obtained during the monitoring period and differences were not found between sites grafted with and without PRP in the 87 patients studied. Densitometry assessments and graft resorption were similar in both experimental groups. However, the histological and histomorphometrical analysis in the five edentulous patients revealed that bone augmentation was significantly higher in sites treated with ABB+PRP (p <or= 0.05). Another outcome from our study is that the lack of initial bone support (p <or= 0.05) and smoking (p=0.05) appeared to have a negative effect on the treatment success, which was accentuated when both circumstances coincided. PRP is not a determining factor for implant survival in sinus lifting procedures. However, this study revealed that PRP can improve the osteoconductive properties of ABB by increasing the volume of new bone formed. Moreover, in sinus augmentation procedures the implant's survival rate appears to be more influenced by the residual bone height or by tobacco than by the type of bone graft.

Canola Nutrition and Variety Affect Oviposition and Offspring Performance in the Generalist Herbivore, Mamestra configurata (Lepidoptera: Noctuidae). Bertha armyworm Mamestra configurata Walker (Lepidoptera: Noctuidae) is a generalist herbivore that feeds on several crops in different plant families. Canola Brassica napus L. (Capparales: Brassicaceae) is one of the most favored host plants making the bertha armyworm a significant insect pest in the Canadian Prairie Provinces. The performance of the bertha armyworm on canola may vary with the quality of the canola plant. We tested the impact of plant nutrition and canola variety on oviposition and subsequent larval development of the bertha armyworm. A range of fertilization levels (0.0, 1.0, 3.0, and 5.0 g/pot) were applied to three different canola varieties: Clearfield 5535 CL, Roundup Ready hybrid 6060RR, and Q2. The total number of eggs laid on plants in a no-choice experiment increased with fertilizer level but a similar number of eggs were laid on plants that received moderate and high fertilizer treatments. Larvae reared on plants that received the moderate fertilizer application yielded heavier pupae than those reared on plants with low and high fertilizer treatments. Most eggs were laid on the Q2 variety when compared to Clearfield 5535 CL and Roundup Ready 6060 RR. Bertha armyworm females preferred to lay eggs on plants that received moderate or high fertilization over plants with the low fertilizer treatment. Plant leaf tissue nutrient content and plant growth were highest in plants that received moderate and high fertilizer treatment. We conclude that bertha armyworm oviposition behavior and larval performance are influenced by fertilizer treatment and canola variety.

Effect of dibutyryl cyclic AMP and dexamethasone on glutamine synthetase gene expression in rat astrocytes in culture. Astrocytes are the primary site of glutamate conversion to glutamine in the brain. We examined the effects of treatment with either dibutyryl cyclic AMP and/or the synthetic glucocorticoid dexamethasone on glutamine synthetase enzyme activity and steady-state mRNA levels in cultured neonatal rat astrocytes. Treatment of cultures with dibutyryl cyclic AMP alone (0.25 mM-1.0 mM) increased glutamine synthetase activity and steady state mRNA levels in a dose-dependent manner. Similarly, treatment with dexamethasone alone (10(-7)-10(-5) M) increased glutamine synthetase mRNA levels and enzyme activity. When astrocytes were treated with both effectors, additive increases in glutamine synthetase activity and mRNA were obtained. However, the additive effects were observed only when the effect of dibutyryl cyclic AMP alone was not maximal. These findings suggest that the actions of these effectors are mediated at the level of mRNA accumulation. The induction of glutamine synthetase mRNA by dibutyryl cyclic AMP was dependent on protein synthesis while the dexamethasone effect was not. Glucocorticoids and cyclic AMP are known to exert their effects on gene expression by different molecular mechanisms. Possible crosstalk between these effector pathways may occur in regulation of astrocyte glutamine synthetase expression.

Modulation of pro-inflammatory mediators in LPS-stimulated human periodontal ligament cells by chitosan and quaternized chitosan. The aim of this study was to evaluate the effects of chitosan and quaternized chitosan (HTCC) modulate IL-1β and TNF-α in LPS-stimulated human periodontal ligament cells (HPDLCs). MTT assay revealed that chitosan stimulated the proliferation of HPDLCs. However, HTCC inhibited the proliferation of HPDLCs at concentrations of 1000 and 100 μg/mL more than the control, especially after 5d (P<0.001). ELISA assay exhibited that chitosan inhibited the production of IL-1β and TNF-α at 24, 48 and 72 h. IL-1β and TNF-α secreted by HPDLCs with LPS and treated with 1000 μg/mL of HTCC significantly increased compared to both the control and the chitosan group (P<0.001). The bioactive role for bFGF in modulating the responses of HPDLCs cells to LPS via inhibiting IL-1β and TNF-α production was demonstrated. All results were necessary to enhance our understanding of the biomedical properties of chitosan and HTCC for modulation of pro-inflammatory mediators.

Disagreement between self-reported and clinician-ascertained suicidal ideation and its correlation with depression and anxiety severity in patients with major depressive disorder or bipolar disorder. To study the disagreement between self-reported suicidal ideation (SR-SI) and clinician-ascertained suicidal ideation (CA-SI) and its correlation with depression and anxiety severity in patients with major depressive disorder (MDD) or bipolar disorder (BPD). Routine clinical outpatients were diagnosed with the MINI-STEP-BD version. SR-SI was extracted from the 16 Item Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR-16) item 12. CA-SI was extracted from a modified Suicide Assessment module of the MINI. Depression and anxiety severity were measured with the QIDS-SR-16 and Zung Self-Rating Anxiety Scale. Chi-square, Fisher exact, and bivariate linear logistic regression were used for analyses. Of 103 patients with MDD, 5.8% endorsed any CA-SI and 22.4% endorsed any SR-SI. Of the 147 patients with BPD, 18.4% endorsed any CA-SI and 35.9% endorsed any SR-SI. The agreement between any SR-SI and any CA-SI was 83.5% for MDD and 83.1% for BPD, with weighted Kappa of 0.30 and 0.43, respectively. QIDS-SR-16 score, female gender, and ≥4 year college education were associated with increased risk for disagreement, 15.44 ± 4.52 versus 18.39 ± 3.49 points (p = 0.0026), 67% versus 46% (p = 0.0783), and 61% versus 29% (p = 0.0096). The disagreement was positively correlated to depression severity in both MDD and BPD with a correlation coefficient R(2) = 0.40 and 0.79, respectively, but was only positively correlated to anxiety severity in BPD with a R(2) = 0.46. Self-reported questionnaire was more likely to reveal higher frequency and severity of SI than clinician-ascertained, suggesting that a combination of self-reported and clinical-ascertained suicidal risk assessment with measuring depression and anxiety severity may be necessary for suicide prevention.

Sensitivity of category cued recall to very mild dementia of the Alzheimer type. We sought to replicate Buschke, Sliwinski, Kulansky, and Lipton's (1997) finding that the Category Cued Recall portion of the Double Memory Test can discriminate individuals with mild dementia of the Alzheimer type (DAT) and healthy older controls. We then attempted to extend this finding to those with very mild DAT. Finally, we compared these results with those of other tests that discriminate DAT from normal aging. Although we replicated Buschke et al.'s finding that the Category Cued Recall portion of the Double Memory Test discriminates effectively between mildly demented people and controls, it was little more effective in detecting very mild DAT than the WMS Logical Memory subtest nor did it add substantially to the discriminative ability of a brief battery of psychometric tests identified previously.

Synthesis and biochemical characterization of tricyclothymidine triphosphate (tc-TTP). Tricyclo-DNA (tc-DNA) is a conformationally restricted oligonucleotide analogue that exhibits promising properties as a robust antisense agent. Here we report on the synthesis and biochemical characterization of tc-TTP, the triphosphate of a tc-DNA nucleoside containing the base thymine. Tc-TTP turned out to be a substrate for the Vent (exo(-) ) DNA polymerase, a polymerase that allows for multiple incorporations of tc-T nucleotides under primer extension reaction conditions. However, the substrate acceptance is rather low, as also observed for other sugar-modified analogues. Tc-TTP and tc-nucleotide-containing templates do not sustain enzymatic polymerization under physiological conditions; this indicates that tc-DNA-based antisense agents will not enter natural metabolic pathways that lead to long-term toxicity.

Hypergravity effects on normal and avulsed developing avian radii. Rhode Island Red female chicks were subjected to complete closed fracture of the right radius at 2 weeks post-hatching. The animals were allowed to heal for 1 week at either earth gravity or 2 G hypergravity state with control and estrogen-injected groups. Intact and fractured radial length, weight, average epiphysial-diaphysial diameters, and length, width, and weight of healing fracture callus were measured. Daily 2000 IU estrogen administration for 7 d increased intact radial length. Estrogen augments the effects of the 2-G state by inhibiting growth and depleting the mass of both intact and fractured radii and by decreasing the average distal epiphysial diameter of fractured bones. Animals exposed to the hypergravity state without hormonal treatment showed decreased fractured radial length, weight, and smaller proximal epiphysial diameters. The measurable parameters of the fracture callus (width, length, and weight) were depressed by the hypergravity state regardless of whether the animal was untreated or supplemented with estrogen.

Activity-based diary for Parkinson's disease. The objective of this study was to develop a Parkinson's disease diary that evaluates a patient's difficulties in performing activities as a substitute for the amount of "on"- and "off"-time and to assess its clinimetric qualities. In this study, 84 patients with Parkinson's disease kept a diary for 2 or 3 periods of 5 days. Daily, five items were recorded across 11 time periods. Patients simultaneously recorded "on-off" in the traditional way. The diary was easily understood, and median recording time was 5-10 minutes a day. Clinimetric analysis showed that the diary could be reduced successfully to 3 days, in which five items (walking, transfers, manual activities, dyskinesias, and sleep) with four response options (no, slight, moderate, and severe difficulty) were assessed seven times daily. Sumscores of the first three items accurately predicted being "on" or "off" in 93% of the cases, making separate scoring of "on" and "off" unnecessary. The diary was internally consistent and showed good reproducibility. Construct validity with external measures was adequate, and comparisons between patients grouped by disease severity and by degree of fluctuations revealed significant differences in the expected directions. Taken together, this Parkinson's disease diary has a sound clinimetric basis, provides information on the extent of perceived disability, and thereby accurately reflects the severity of "off"-periods and the variability of motor fluctuations.

Safety evaluation of irradiated foods in China: a condensed report. Eight trials, with 439 human volunteers who consumed irradiated foods including rice, potatoes, mushrooms, peanuts, and Chinese sausages, as well as diets composed of multiple irradiated foods (irradiated at dosages of 0.2 to 8 kGy) that accounted for 60-66% of the entire diet, were carried out for 2-3 months according to a unified protocol. No adverse effects on body weight, blood pressure, ECG, hematology, blood enzyme activities, serum lipids or blood or urine 17-hydroxycortisol contents and no chromosomal aberration of peripheral blood lymphocytes were found. It is especially worthwhile to note that there was no change in the polyploidy after consumption of irradiated diets. On the basis of these results and a comprehensive analysis of the physical and chemical characteristics of irradiated foods, temporary hygienic standards for irradiated rice, potatoes, onions, garlic, Chinese sausages, peanuts, and mushrooms were promulgated by the Chinese Ministry of Public Health.

[Prophylaxis of varicella in pediatric staff.]. Varicella is an ubiquitous, highly contagious viral disease of childhood which may be severe in non immune adults and pregnant women. Pediatric staff is particularly at risk of nosocomial varicella and susceptible staff should be prospectively idenfitifed by serologic tests. A number of different approaches may be used to prevent disease depending on the at risk population and the preexposure or postexposure status. This article reviews and evaluates the different approaches to the prevention of varicella in pediatric staff.

First place winner of the Conrad Jobst Award in the gold medal paper competition. Nitric oxide synthase inhibitors N-monomethylarginine and aminoguanidine prevent the progressive and severe hypotension associated with a rat model of pancreatitis. The objective of this study was to determine whether the observed vascular collapse and other pathologic features of severe pancreatitis may be related to the induction of nitric oxide synthase (NOS). The rat model of pancreatitis reported by Schmidt et al. was employed. Rats in the experimental groups received pretreatment with known NOS inhibitors, N-Monomethylarginine (NMMA) or Aminoguanidine (AG). Controls included sham-operated rats without pancreatic insult and a diseased control group which received pretreatment with normal saline (NS). Arterial blood pressure was continuously recorded with a femoral arterial catheter connected to a transducer and monitor. Fluid resuscitation for hypotension followed a strict protocol with the administration of 5.0 cc NS for sustained decreases in systolic blood pressure (SBP) below 90 mm Hg at 5-minute intervals. Laboratory parameters and histopathology confirmed the induction of pancreatitis, with 6 to 15-fold increases in serum amylase levels and an average of approximately 20% decrease in serum ionized Ca++ levels. Immunohistochemical studies of the pancreas revealed that pancreatic insult resulted in the induction of NOS. Rats in the saline control group (n = 5) became hypotensive (SBP less than 90 mm Hg) between 3 and 4 hours post pancreatic insult and required an average of 110.0 cc (3-4 x blood volume) of NS fluid resuscitation. Rats which were not resuscitated (n = 5) did not survive.(ABSTRACT TRUNCATED AT 250 WORDS)

Test for linear trend in 2 x K ordered tables with open-ended categories. A method of evaluating trend (positive or negative) in 2 x K ordered tables is suggested for cases in which the scores for the first (K-1) categories are known a priori but the score for the last category is not known. Such a category is termed as open-ended category in this paper. Ordered tables with an open-ended category are often encountered while evaluating the Cochran-Armitage-Mantel (CAM) trend. In the present paper, the distribution of the test statistic is presented and simulations are carried out to check the asymptotics. The method is then exemplified by an existing data set.

Protective effect of nicotinamide against poly(ADP-ribose) polymerase-1-mediated astrocyte death depends on its transporter-mediated uptake. Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA repair enzyme, and its excessive activation, following ischemia, trauma, etc., depletes cellular nicotinamide adenine dinucleotide (NAD(+)) as a substrate and eventually leads to brain cell death. Nicotinamide, an NAD(+) precursor and a PARP-1 inhibitor, is known to prevent PARP-1-triggered cell death, but there is no available information on the mechanisms involved in its transport. Here we clarified the transport characteristics of nicotinamide in primary cultured mouse astrocytes. Uptake characteristics of [(14)C]nicotinamide were assessed by a conventional method with primary cultured mouse astrocytes. Cell viability and PARP-1 activity were determined with intracellular LDH activity and immunocytochemical detection of PAR accumulation, respectively. PARP-1 activation was induced by treatment of astrocytes with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), an alkylating agent. MNNG-triggered astrocyte death and PAR accumulation were completely inhibited by treatment with nicotinamide as with DPQ (3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone), a second generation PARP inhibitor. The uptake of [(14)C]nicotinamide was time-, temperature-, concentration- and pH-dependent, and was inhibited and stimulated by co- and pre-treatment with N-methylnicotinamide, a representative substrate of an organic cation transport system, respectively. Co-treatment of astrocytes with nicotinamide and N-methylnicotinamide resulted in a decrease in PAR accumulation and absolute prevention of cell death. These findings suggest that nicotinamide has a protective effect against PARP-1-induced astrocyte death and that its transporter-mediated uptake, which is extracellular pH-sensitive and common to N-methylnicotinamide, is critical for prevention of PARP-1-triggered cell death.

From the big bang to the brain. Current research on the capacities of the infant has lead to a better understanding of developmental processes underlying cognition and motor skill acquisition. ASHA's Eighth Annual Research Symposium on Infant-Toddler Development, in November 1998, included a presentation on developmental cognitive science by Dr. Andrew Meltzoff and a presentation on motor skill acquisition by Dr. Esther Thelen. The theoretical constructs and data presented served to broaden our current perspectives on infant abilities. The data reported by Meltzoff and Thelen challenged several long-standing theories of infant cognition and motor development. Alternative theoretical models were used to describe skill acquisition during the first several years of life. Our response will include a brief summary of each investigator's presentation, discuss their findings with respect to research in the area of infant speech physiology and production, and provide possible future directions and challenges for individuals conducting developmental research.

[Is the intravenous cholangiogram of value in the preoperative period?]. The need for a routine preoperative intravenous cholangiogram (IVC) has been controversially discussed. We decided to assess if preoperative criteria such as history, clinical examination or laboratory findings could be used for selective indication for preoperative IVC. In a series of 146 patients with a preoperative IVC before undergoing laparoscopic cholecystectomy, history, clinical findings and laboratory results (bilirubin, transaminases, alkaline phosphatase, amylase) have been correlated with the radiological findings. ERCP was taken as the standard to assess the value of IVC. A normal IVC was quite reliable in excluding any pathology of the bile ducts or common bile duct stones. Thus specificity reached 96% and the negative predictive value was 97%. On the other hand a pathological IVC proved not to be a valid predictor of true pathological alterations. Sensitivity was only 60% and the positive predictive value just 55%. Over all accuracy was quite satisfactory (94%). We could not find a correlation between history, clinical or laboratory findings and the final result as assessed by ERCP. Therefore we could not find any useful parameters to define a selective policy for indication of preoperative IVC. On the other hand the IVC still proved useful to exclude relevant pathological findings. At the time being there is no strong argument for abandoning routine preoperative IVC.

Aneurysms of the gastroduodenal artery: a case report. Aneurysms of the gastroduodenal artery are the rarest of all splanchnic artery aneurysms. A case of gastroduodenal artery aneurysm diagnosed preoperatively and successfully managed surgically is described. A 68-year-old woman was admitted to our institution as a result of recurrent epigastric pain. Arteriography of the coeliac trunk and of the upper mesenteric artery showed a coeliac axis occluded at the origin and a voluminous round aneurysmatic formation of the gastroduodenal artery measuring approx. 3 cm. Such lesions may be asymptomatic and initially pass unnoticed or may appear only on rupturing with a profile of haemoperitoneum. The preoperative diagnosis is difficult: in many cases only non-specific signs such as pain, jaundice or upper digestive tract haemorrhage are present. Selective arteriography, in this case, permitted the definitive diagnosis of a gastroduodenal aneurysm, as well as establishing its size and morphology and the vascular pattern of the lesions, all of which was of great assistance in selecting the surgical strategies to be adopted. The operation consisted in the proximal and distal ligation of the gastroduodenal artery and in resection of the aneurysm after preparation of the portal vein, the common hepatic artery and the VBP. We maintain that, because of the risk of rupture of the aneurysm, which so often has a fatal profile, an aggressive surgical approach is both justifiable and advisable.

Impact of left atrial size on isolation area in the acute phase of pulmonary vein isolation using 28 mm cryoballoon. The impact of left atrial (LA) size on isolation area (ISA) using a 28-mm second-generation cryoballoon (CB) in the acute phase after pulmonary vein isolation (PVI) and the differences of CB from contact force-guided radiofrequency (RF) ablation have not been fully investigated. We examined 85 consecutive patients (CB group, 35; RF group, 50) with drug-refractory paroxysmal atrial fibrillation who underwent their first PVI procedure at two institutions. We evaluated ISA after PVI using 3D-Merge computed tomography images (GE Healthcare, Little Chalfont, UK) and high-resolution electroanatomical mapping. Total ISA was significantly smaller in the CB group (20.6 ± 6.0 cm2 ) than in the RF group (29.0 ± 7.1 cm2 ; P < 0.0001). In the CB group, ISA of the left pulmonary vein (LPV), right pulmonary vein (RPV), and total ISA were not correlated with the left atrial surface area (LASA). The ratios of ISA to LASA (%ISA) of LPV and total ISA negatively correlated with LASA in the CB group (LPV: r = -0.4001, P = 0.0173; total ISA: r = -0.4733, P = 0.0041). In contrast, in the RF group, ISA of LPV, RPV, and total ISA positively correlated with LASA; (LPV: r = 0.5155, P = 0.001; RPV: r = 0.6398, P < 0.0001; total ISA: r = 0.7299, P < 0.0001). ISA created using CB was significantly smaller than that using RF and did not change regardless of LASA increment. Differences in ISA between the two groups became more prominent in the large atrium.

Therapeutic effect of oral levofloxacin, ciprofloxacin, and ampicillin on experimental murine pneumonia caused by penicillin intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations of the quinolones are similar. The therapeutic efficacy of oral treatment with levofloxacin, ciprofloxacin, and ampicillin on an experimental pneumonia caused by the penicillin-intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations (MICs) of the quinolones are similar was assessed in immunocompetent CBA/J mice. Levofloxacin exhibited a dose-dependent therapeutic effect, and achieved complete eradication of S. pneumoniae from the lungs at 120 mg/kg/day, whereas ciprofloxacin and ampicillin were hardly effective at all. A pharmacokinetic study in infected mice revealed good oral absorption and lung tissue penetration of levofloxacin (peak lung concentration: 5.95 microg/g of lung), low oral absorption of ciprofloxacin in spite of a good penetration into lung tissue (1.10 microg/g of lung), and low lung tissue penetration of ampicillin despite rather good oral absorption (1.71 microg/g of lung). In an in vitro time-kill study that simulated the peak concentration of drugs in the lungs of infected animals, the killing activity of levofloxacin was found to be greater than that of ciprofloxacin and ampicillin. These data suggest that the therapeutic efficacy of levofloxacin in this model is attributable to both its potent bactericidal activity and excellent pharmacokinetic profile.

The rsmA-like gene rsmA(Xcc) of Xanthomonas campestris pv. campestris is involved in the control of various cellular processes, including pathogenesis. RsmA is an RNA-binding protein functioning as a global post-transcriptional regulator of various cellular processes in bacteria and has been demonstrated to be an important virulence regulator in many animal bacterial pathogens. However, its function in other phytopathogenic bacteria is unclear, except for the Erwinia carotovora RsmA, which acts as a negative virulence regulator. In this work, we investigated the function of the rsmA-like gene, named rsmA(Xcc), of the phytopathogen Xanthomonas campestris pv. campestris. Deletion of rsmA(Xcc) resulted in complete loss of virulence on the host plant Chinese radish, hypersensitive response on the nonhost plant pepper ECW-10R, and motility on the surface of an agar plate. The rsmA(Xcc) mutant displayed a significant reduction in the production of extracellular amylase, endoglucanase, and polysaccharide, but a significant increase in intracellular glycogen accumulation and an enhanced bacterial aggregation and cell adhesion. Microarray hybridization and semiquantitative reverse-transcription polymerase chain reaction analysis showed that deletion of rsmA(Xcc) led to significantly reduced expression of genes encoding the type III secretion system (T3SS), T3SS-effectors, and the bacterial aggregate dispersing enzyme endo-beta-1,4-mannanase. These results suggest that rsmA(Xcc) is involved in the control of various cellular processes, including pathogenesis of X. campestris pv. campestris.

Antinephrolithiatic and antioxidative efficacy of Dolichos biflorus seeds in a lithiasic rat model. Dolichos biflorus sensu auct non L. (Fabaceae) is widely used for the treatment of kidney stones, leucorrhoea, urinary disorders, and menstrual troubles, and is known for its antioxidant activity. To evaluate the preventive effect of hydro-alcoholic extract of Dolichos biflorus seeds (DBE) in ethylene glycol induced nephrolithiasis. In vitro antioxidative capacity of DBE was estimated in terms of reducing power, superoxide radical, 2,2- diphenyl-1-picrylhydrazyl radical, and nitric oxide scavenging activity. A validated HPLC method was used for standardization using quercetin as a marker. Adult female Wistar rats were administered with DBE (150 and 300 mg/kg body weight/day) along with ethylene glycol (0.75%, v/v) for 28 d. The various biochemical parameters were measured in urine, serum, and kidney followed by histochemistry. Ethylene glycol caused a significant increase in calcium, oxalate, phosphate, and total protein in urine as well as in kidney whereas decrease in calcium, sodium, and magnesium in serum was observed (p < 0.001). Ethylene glycol also caused a significant increase in lipid peroxidation and concurrent decrease in activities of antioxidant enzymes in kidney (p < 0.001). However, the seed extract of D. biflorus caused significant restoration of all these parameters (p < 0.001). Histopathological and histochemical studies also showed the reduced calcifications in kidney of seed extract treated rats. These results indicated that seeds of D. biflorus have significant prophylactic effect in preventing the nephrolithiasis, which might be due to the antioxidant activity of the active compounds of the plant.

[Determination of the anti-infective action of an immunomodulator. Biostim as an example]. In order to evaluate the antiinfectious action of an immunomodulator, either in vitro or in vivo, in both animal and man, we have to answer three questions: What the targets are? Which models best allow the study of the mode of action? Which method should be used to evaluate clinical improvement? The targets of RU 41740 (Biostim), a purified Immunomodulator of biological origin, are the pool of immunocompetent cells with an enhancement of two major mediators: IL1 and CSF. As there are numerous interactions between antiinfectious, antiinflammatory, antiallergic responses and mediators pleiotropism, no reliable predictions exist. Moreover concerning the "in vivo" activity experimentally induced infections represent a preferential pharmacologic model in order to study the antiinfectious activity of an immunomodulating compound. Under such conditions, RU 41740 testing administered either orally, intraperitoneally or by aerosol is effective, whatever the responsible infectious agents are: extra or intracellular development bacteria, virus or yeasts. In regard to the differences of the local defenses (pulmonary and cutaneous), the targeted organ has to be identified during the mode of action studies. RU 41740 enhances alveolar macrophage metabolic functions in the respiratory tract. From a pharmacoclinical point of view, this stimulation of immune components has been investigated under different doses and treatment schedule of RU 41740 with a double blind versus placebo studies. The targeted pathology involves the risk of infections and immune deficiency. In chronic bronchitis infections often occur and are responsible for acute respiratory failures and this contributes to the obstructive syndrome. The clinical efficiency on prophylaxis must be evaluated by double blind versus placebo, randomized studies with a long follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of wavelet transform voltammetric analyzer. An on-line wavelet transform algorithm and development of voltammetric analyzer with the on-line wavelet transform (WT-voltammetric analyzer) are described. Because the on-line wavelet transform decomposes the sampled signal simultaneously with the progress of sampling, the WT-voltammetric analyzer gives all the components contained in the sampled voltammogram. Applications of the WT-voltammetric analyzer in linear sweep voltammetric analysis of mixtures of Pb(II) and Tl(I) and in square wave voltammetric analysis of mixture of Cd(II) and In(III) were investigated. Results showed that the overlapping peaks of Pb(II) and Tl(I) can be separated easily, and the peak position after the on-line wavelet transform does not change. The linearity of the calibration curves for Cd(II) and In(III) in the overlapping square wave voltammetric curves were kept after the on-line wavelet transform. Quantitative determination of Cd(II) and In(III) in mixture samples were investigated. The recoveries are between 92.5 and 107.1%.

Serodiagnosis of tuberculosis: specific detection of free and complex-dissociated antibodies anti-mycobacterium tuberculosis recombinant antigens. The diagnostic test characteristics of detecting free and complex-dissociated IgG to three recombinant antigens of Mycobacterium tuberculosis (38-kDa, Ag16 and Ag85B), singly and in combination, were evaluated in sera from 161 tuberculous patients [smear-positive pulmonary TB (50), smear-negative pulmonary TB (pTBsm-) (60) and extrapulmonary TB (51)) and 214 control patients (mycobacteriosis (14), mycoses(14), leprosy(4), other underlying diseases (82) and healthy people (100)]. The individual antigens ranged from 25% to 42% in sensitivity and from 93% to 96% in specificity, while considering free IgG response. Addition of complex-dissociated antibodies against each individual antigen improved the sensitivity up to 55%. The number and levels of specific antibodies varied greatly from individual to individual. Combination of individual results for free and complex-dissociated IgG to 38-kDa, Ag16 and Ag85B offered 76% sensitivity and 83% specificity. When the three antigens were placed in the same well, the sensitivity was lower than that expected on the basis of single antigen (63%) but with a good specificity (95%), even in the group of mycobacteriosis or mycoses. The highest contribution of complex-dissociated IgG results to free IgG results was seen for the diagnosis of pTBsm- patients. In conclusion, although neither single recombinant antigen was reactive with most sera from TB patients even after the measurement of both free and complex-dissociated antibodies, the use of multi-antigen cocktails improved the diagnostic utility of the ELISA assay, allowing the identification of almost 70% of pTBsm-, with a high level of specificity; the use of additional, well selected antigens should lead to the detection of almost all patients with TB.

Structural organization of the multienzyme complex of mammalian aminoacyl-tRNA synthetases. The multienzyme complexes of mammalian aminoacyl-tRNA synthetases were purified from rat liver, rabbit liver, and rabbit reticulocytes according to the procedure slightly modified from Kellermann et al. [Kellermann, O., Brevet, A., Tonetti, H., & Waller, J.-P. (1979) Eur. J. Biochem. 99, 541-550]. Three forms of the synthetase complex with slightly different protein compositions were identified, suggesting a microheterogeneity of the synthetase complex. The hydrodynamic properties and the protein composition of the purified complexes were determined. The electron micrographs of the complex showed mostly amorphous particles and some hollow rings with an outer diameter of 164 A and an inner diameter of 42 A. The predicted hydrodynamic properties of several models of the complex were calculated. The properties of a ring model appear to best fit with those of the synthetase complex.

Variability and cardiovascular homeostasis. The inability to maintain the upright posture due to a failure in the arterial blood pressure regulatory mechanisms on return from space travel or after a period of head down tilt bed rest (HDBR) is the ultimate sign of cardiovascular deconditioning. Yet, the final response of syncope is potentially heralded by a series of precursor events that can be quantified and analyzed in new, more insightful ways to attempt to understand the integrative nature of autonomic control of the cardiovascular system.

Transcriptional regulation of autocrine IL-6 expression in multiple myeloma cells. Multiple myeloma (MM) is an as to date incurable hematopoietic malignancy. The importance of Interleukin-6 (IL-6) as an autocrine growth factor for MM cells is widely accepted, yet very little is known about the mechanisms at the basis of deregulated IL-6 expression in MM cells. Here we show that the in vivo chromatin organization of the IL-6 gene is different in MM cells, that constitutively express IL-6 (U266), as compared to MM cells, in which the IL-6 promoter is inactive (L363). We observed enhanced nuclease accessibility of the AP-1- and, especially, the Sp1-responsive elements in the IL-6 promoter in U266 cells. Interestingly, we found that Sp1 was eliminated from the IL-6 promoter after treatment with the ERK inhibitor U0126. The importance of ERK and Sp1 in regulating IL-6 transcription was, furthermore, supported by the observation that treatment of U266 cells with U0126 or mithramycin, an antibiotic that prevents Sp1-DNA binding, abrogated constitutive IL-6 transcription. Importantly, the finding that both U0126 and mithramycin were more potent inhibitors of U266 cell viability than the synthetic glucocorticoid drug, dexamethasone, indicates that targeting the Sp1 transcription factor might have therapeutic value in treatment of autocrine MM.

Ocular globe topography in radiotherapy. Ocular lens, retina, and olfactory bulb exposure are common concerns in contemporary radiotherapy practice. Methods to clinically localize soft tissue structures (i.e., lens and retina) are varied and often imprecise. We hypothesized that eyelid markers constituted a better reference point than the commonly used lateral canthus marker for lateral beam simulations, unless diagnostic computed tomography or ultrasound examinations were available and/or used. Sixty-six pre-Magnetic Resonance Image, normal, orbital computed tomography scans from adult patients were used to measure (a) sagittal distances from eyelid to posterior lens surface, from lateral canthus to posterior lens surface and to the globe's posterior pole, (b) supero-inferior distances in the lateral projection from the lens to the cribriform plate, and (c) common dimensions to establish internal validity of the measurements. The eyelid to lens and retina topography is individually more constant than that from the canthus. There is little if any supero-inferior separation between the lens and the cribriform plate lateral projections. The lateral canthus does not specify lens or retina locations. Eyelid markers of known size provide more accurate anatomical information. Lateral beam ocular globe shielding has to be individualized. Lens shielding is questionable if the olfactory bulb needs to be irradiated by a lateral beam.

DNA-binding studies of fluoxetine antidepressant. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant that is widely prescribed. The DNA-binding behavior of fluoxetine antidepressant and calf thymus DNA was investigated in Tris-HCl buffer at physiological pH 7.4 with a series of techniques, including UV-Vis and circular dichroism spectroscopies, competitive study with Hoechst 33258, viscometry, and cyclic voltammetry. Fluoxetine molecules bind to DNA via groove mode as illustrated by hypochromism with no red shift in the UV absorption band of fluoxetine, decrease in Hoechst-DNA solution fluorescence, and no significant changes in viscosity of DNA. The CD spectra of DNA molecules show a little change in stacking mode of base pair but no modification changes in DNA conformation, for example, from B-DNA to A or C-DNA. The binding constant (K(b)) of DNA with fluoxetine was calculated to be 6.7 × 10(4) M(-1), which is in the range of reported and known groove binders, such as distamycin. All results showed the groove-binding mode of interaction of fluoxetine with DNA.

Clinical evaluation of a surface pre-reacted glass (S-PRG) filler-containing dental sealant placed with a self-etching primer/adhesive. To clinically evaluate the retention rates and caries-prevention effect of a resin-based, non-etch and rinse, self-etch primed pit and fissure sealant containing Sealant Pre-reacted Glass Ionomer Cement (S-PRG) fillers, in comparison to a conventional resin-based sealant over an 18-month period. There were 81 children, aged 6-12 years old, who were randomly assigned to one of two sealant-groups, either the self-etch primed sealant (Beautisealant, Shofu) or the conventional etch and rinse sealant (Seal it, Spident). A total of 218 sealants of both groups were placed on first permanent molars with either sound surfaces (The International Caries Detection and Assessment System [ICDAS], code 0) or incipient enamel caries lesions (ICDAS code 1) according to the manufacturers' instructions. Each sealant restoration was independently evaluated in terms of retention and caries status at 6, 12 and 18 months. The data were statistically analysed with the Chi-squared test and z-test and the level of significance was preset at α = 0.05. The differences between the complete retention rates of the two sealant groups were statistically significant in all periods of evaluation (p < 0.01). Survival rates of each sealant-group were comparable on sound (ICDAS 0) and enamel caries lesions (ICDAS1). Caries prevention effect of the two sealant groups was similar at the end of the evaluation period. The clinical performance of the S-PRG filler-containing dental sealant placed with a self-etching primer was poor regarding its retention. Its significantly higher loss did not lead to more carious occlusal surfaces at the 18-month recall.

Purinoceptors in microglia and neuropathic pain. Emerging evidence indicates that microglia play a critical role in the pathogenesis of neuropathic pain, a debilitating chronic pain condition that can occur after peripheral nerve damage caused by disease, infection, or physical injury. Microglia are immunocompetent cells of the central nervous system and express various ionotropic P2X and metabotropic P2Y purinoceptors. After injury to a peripheral nerve, microglia in the spinal cord become activated and upregulate expression of the P2X4 receptor. Recent findings suggest that activation of P2X4 receptors evokes release of brain-derived neurotrophic factor from microglia and that this mediates microglia-neuron signaling leading to pain hypersensitivity. Thus, P2X4 receptors and the intracellular signaling mediators in microglia are promising therapeutic targets for the development of novel pharmacological agents in the management of neuropathic pain.

Decreasing temporal lobe dose with five-field intensity-modulated radiotherapy for treatment of pituitary macroadenomas. To compare temporal lobe dose delivered by three pituitary macroadenoma irradiation techniques: three-field three-dimensional conformal radiotherapy (3D-CRT), three-field intensity-modulated radiotherapy (3F IMRT), and a proposed novel alternative of five-field IMRT (5F IMRT). Computed tomography-based external beam radiotherapy planning was performed for 15 pituitary macroadenoma patients treated at New York University between 2002 and 2007 using: 3D-CRT (two lateral, one midline superior anterior oblique [SAO] beams), 3F IMRT (same beam angles), and 5F IMRT (same beam angles with additional right SAO and left SAO beams). Prescription dose was 45 Gy. Target volumes were: gross tumor volume (GTV) = macroadenoma, clinical target volume (CTV) = GTV, and planning target volume = CTV + 0.5 cm. Structure contouring was performed by two radiation oncologists guided by an expert neuroradiologist. Five-field IMRT yielded significantly decreased temporal lobe dose delivery compared with 3D-CRT and 3F IMRT. Temporal lobe sparing with 5F IMRT was most pronounced at intermediate doses: mean V25Gy (% of total temporal lobe volume receiving ≥25 Gy) of 13% vs. 28% vs. 29% for right temporal lobe and 14% vs. 29% vs. 30% for left temporal lobe for 5F IMRT, 3D-CRT, and 3F IMRT, respectively (p < 10(-7) for 5F IMRT vs. 3D-CRT and 5F IMRT vs. 3F IMRT). Five-field IMRT plans did not compromise target coverage, exceed normal tissue dose constraints, or increase estimated brain integral dose. Five-field IMRT irradiation technique results in a statistically significant decrease in the dose to the temporal lobes and may thus help prevent neurocognitive sequelae in irradiated pituitary macroadenoma patients.

Specific inhibition of hair follicle formation by epidermal growth factor in an organ culture of developing mouse skin. Embryonic mouse skin undergoes a drastic morphological change from 13 to 16 gestational days, i.e., formation of rudiments of hair follicles and stratification and cornification of interfollicular epidermis. To investigate underlying molecular mechanisms of the morphogenesis, we established an organ culture system that allows skin tissues isolated from 12.5- or 13.5-days postcoitus embryos to develop in a manner that is histologically and temporally similar to the process in vivo. Expression of differentiation markers of epidermal keratinocytes including cholesterol sulfotransferase and cytokeratin K1 was induced in culture, as it occurs also in vivo. The morphogenic process was observed by time-lapse videomicrography. In this culture system, epidermal growth factor (EGF) and transforming growth factor alpha specifically and completely inhibited the hair follicle formation with marginal effects on interfollicular epidermis. The inhibitory action by EGF was reversible and stage specific, i.e., at an early stage of the development of hair rudiments. Among known ligands to the EGF receptor, Schwannoma-derived growth factor and heparin-binding EGF were expressed in in vivo epidermis during the period of the initial formation of hair follicles. EGF receptor is expressed in epidermis throughout the developing period examined. Using an adenovirus vector, we demonstrated that the lacZ gene was transduced into the epidermal and dermal cell layers without appreciable toxicity. These results indicate that the present culture system provides a unique opportunity to investigate molecular mechanisms of skin morphogenesis including the role of EGF signaling under defined experimental conditions.

Protein constituents of the eggshell: eggshell-specific matrix proteins. In this article, we review the results of recent proteomic and genomic analyses of eggshell matrix proteins and draw attention to the impact of these data on current understanding of eggshell formation and function. Eggshell-specific matrix proteins from avian (ovocleidins and ovocalyxins) and non-avian (paleovaterin) shells are discussed. Two possible roles for eggshell-specific matrix proteins have been proposed; both reflect the protective function of the eggshell in avian reproduction: regulation of eggshell mineralization and antimicrobial defense. An emerging concept is the dual role (mineralization/antimicrobial protection) that certain eggshell matrix proteins can play.

Involvement of IGF-II receptors in the antioxidant and neuroprotective effects of IGF-II on adult cortical neuronal cultures. Insulin-like growth factor-II (IGF-II) is a naturally occurring peptide that exerts known pleiotropic effects ranging from metabolic modulation to cellular development, growth and survival. IGF-II triggers its actions by binding to and activating IGF (IGF-I and IGF-II) receptors. In this study, we assessed the neuroprotective effect of IGF-II on corticosterone-induced oxidative damage in adult cortical neuronal cultures and the role of IGF-II receptors in this effect. We provide evidence that treatment with IGF-II alleviates the glucocorticoid-induced toxicity to neuronal cultures, and this neuroprotective effect occurred due to a decrease in reactive oxygen species (ROS) production and a return of the antioxidant status to normal levels. IGF-II acts via not only the regulation of synthesis and/or activity of antioxidant enzymes, especially manganese superoxide dismutase, but also the restoration of mitochondrial cytochrome c oxidase activity and mitochondrial membrane potential. Although the antioxidant effect of IGF-I receptor activation has been widely reported, the involvement of the IGF-II receptor in these processes has not been clearly defined. The present report is the first evidence describing the involvement of IGF-II receptors in redox homeostasis. IGF-II may therefore contribute to the mechanisms of neuroprotection by acting as an antioxidant, reducing the neurodegeneration induced by oxidative insults. These results open the field to new pharmacological approaches to the treatment of diseases involving imbalanced redox homeostasis. In this study, we demonstrated that the antioxidant effect of IGF-II is at least partially mediated by IGF-II receptors.

Binding of dyes to hydroxyapatite treated with cetylpyridinium chloride or cetrimonium bromide. The effect of cetylpyridinium chloride (CPC) and cetrimonium bromide (CTAB) on the adsorption of some acidic food dyes to hydroxyapatite was studied. The dyes investigated were brilliant blue (FD&C Blue No. 1), tartrazine (FD&C Yellow No. 5), sunset yellow (FD&C Yellow No. 6) and amaranth (FD&C Red No. 2). The apatite had adsorbed 9.2 mumol CPC per g dry weight. The adsorbed CPC was in equilibrium with a free concentration of 20 microgram/ml (58 micrometer). The adsorption of CPC and CTAB to the apatite was followed by an increased ability of the crystals to bind the dyes. The dyes were very firmly adsorbed and were not released during a series of washings. Untreated apatite showed only a minor affinity for the dyes. The adsorbed dyes were easily washed out. CPC and CTAB showed the smae specific ability to increase the binding capacity of the apatite. The results are discussed and related to the formation of stains on the teeth in persons using quaternary ammonium compounds for mouthrinsing. A mechanism explaining the production of stains is proposed.

Understanding treatment decisions from the perspective of people with relapsing remitting multiple Sclerosis: A critical interpretive synthesis. Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system that mainly affects young adults. While there is no cure for MS, disease modifying treatments (DMTs) reduce the relapse rate and partial accrual of disability. More effective DMTs may have higher risks including life-threatening infections or secondary autoimmunity. The complexity and novelty of available treatments cause challenges for clinicians when prescribing treatments and for people with MS (PwMS) when deciding what trade-offs they are willing and ready to make. To explore the experience of people with relapsing remitting MS (PwRRMS) and their perspectives in choosing treatments. Critical interpretive synthesis was employed to review and synthesis the published literature. Eighty-three publications were selected in a multi-step systematic process. Findings are presented in four interrelated areas: the influence of the clinical evidence-base in decision making; the meaning of DMT efficacy for PwRRMS; the influence of models of decision-making and information acquisition practices in PwRRMS; and the importance of psychosocial dimensions in DMT decision making. Synthesis of the findings revealed that alongside medical and individual reasoning, contextual circumstances play an important role in making treatment decisions. This review identifies and explains the importance of diverse contextual circumstances (clinical, social, psychological) that are important for PwRRMS when making treatment decisions. The findings demonstrate the importance of eliciting, understanding and addressing such contextual factors.

Efficacy and safety of bosentan treatment for portopulmonary hypertension associated with syncope. Pulmonary arterial hypertension (PAH) in patients with portal hypertension is also referred to as portopulmonary hypertension (PPHTN). Here, we report a case of PPHTN caused by alcoholic liver cirrhosis in a 43-year-old male who experienced repetitive syncope on exertion. The continuous monitoring of pulmonary artery pressure and radial artery pressure revealed that his PAH was aggravated with a drop in systemic arterial pressure during an exercise test. Bosentan, an endothelin A/B receptor antagonist, improved the patient's hemodynamic parameters and abolished his syncope without adverse effects. This is the first report that bosentan may be effective and safe for PPHTN associated with syncope.

Cyanobacteria growing on tree barks possess high amount of sunscreen compound mycosporine-like amino acids (MAAs). The present study describes cyanobacterial species composition and their dominance in biological crusts from barks of different trees, roof top of building and soil of agricultural field. An attempt was also made to explore the presence of photoprotective compounds such as mycosporine-like amino acids (MAAs) in the crust samples. Microscopic examination and growth studies revealed the presence of Oscillatoria species in all the crust samples excluding the crust of roof top of a building. Study on the abundance of dominant genera showed marked differences among various crust samples but Hapalosiphon, Lyngbya, Oscillatoria and Scytonema sp. were the most dominant genera, Oscillatoria being dominant in three crust samples. Screening for the presence of photoprotective compounds showed the presence of major peaks in the range of 308-334 nm thereby pointing to the presence of MAAs in all the crust samples. The highest amount of MAAs was found in the crust of Borassus flabellifer (15,729 nmol g dry wt-1 of bark) followed by crust of roof top (14,543 nmol g dry wt-1 of crust). MAAs were separated and partially purified employing HPLC, the most common MAA present in all the crusts was identified as mycosporine-glycine. Presence of mycosporine-glycine (M-Gly) was further confirmed by FTIR and NMR. Test of in vitro colonization on the bark of Mangifera indica and Azadirachta indica by three isolates namely Hapalosiphon, Oscillatoria and Scytonema sp. showed sign of active colonization. It is felt that identification of all the MAAs other than M-Gly may prove useful in future studies especially for assessing their significance in the protection mechanism of cyanobacteria/algae against various types of abiotic stresses.

Is laparoscopic appendectomy an effective procedure? To compare the results of open and laparoscopic appendectomy and to determine if the laparoscopic approach might be more effective for some subgroups of patients. We retrospectively analysed the computerised data of 326 consecutive adult patients operated on for suspected appendicitis between 2001 and 2005. The series consisted of 166 men and 160 women with a mean age of 32 +/- 16 years and a mean Body Mass Index (BMI) of 24 +/- 4. There were 265 ASA I, 46 ASA II and 5 ASA III patients. According to the surgeon's preference, 176 patients had an open appendectomy (OA) and 150 a laparoscopic appendectomy (LA). The mean operative time and hospital stay were equivalent in the two groups : respectively 49 +/- 19 min. and 4.1 +/- 2.5 days in OA and 50 +/- 16 min. and 3.5 +/- 1.8 days in LA. However, subgroup analysis revealed that overweight (BMI > 25) patients (n = 102) and patients with ectopic appendices (n = 86) had an obvious benefit from LA. In cases of OA, operative time and hospital stay were longer in overweight patients than in normal weight patients: respectively 63 +/- 20 min. and 5.3 +/- 2.9 days versus 44 +/- 16 min. (p < 0.01) and 3.7 +/- 2.2 days (p < 0.01). On the contrary, no difference was observed in the LA group. Operative time and hospital stay were also longer in patients with ectopic appendices submitted to OA than in patients with an appendix in the normal position: respectively 60 +/- 18 min. and 4.7 +/- 2.7 days versus 45 +/- 18 min. (p < 0.01) and 3.9 +/- 2.4 days (p < 0.01). Again, such a difference was not observed in cases of LA. We noted no mortality, but 24 patients (7%) developed an abdominal complication : 18 wound infections and 6 intra-abdominal abscesses. Wound infections were more common in the OA than in the LA group : 7.3% (13/176) versus 3.3% (5/150) (p = 0.1). In the LA group, 4 wound infections were observed in our early experience, at a time where no endoscopic bag was used for the removal of the appendix. The rate of intra-abdominal abscesses was similar: 1.7% (3/176) in the OA group and 2% (3/150) in the LA group. LA is an effective procedure with a reduced risk of developing wound infection. The laparoscopic approach is particularly effective for overweight patients and/or patients with ectopic appendices as far as shortening the operative time and hospital stay is concerned.

Characterization of the 25-kilodalton subunit of the energy-transducing NADH-ubiquinone oxidoreductase of Paracoccus denitrificans: sequence similarity to the 24-kilodalton subunit of the flavoprotein fraction of mammalian complex I. The NADH dehydrogenase complex isolated from Paracoccus denitrificans is composed of approximately 10 unlike polypeptides [Yagi, T. (1986) Arch. Biochem. Biophys. 250, 302-311]. Structural genes encoding the subunits of this enzyme complex constitute at least one gene cluster [Xu, X., Matsuno-Yagi, A., & Yagi, T. (1991) Biochemistry 30, 6422-6428]. The 25-kDa subunit (NQO2), which has been isolated from sodium dodecyl sulfate-polyacrylamide gels, is a polypeptide of this enzyme complex. The partial N-terminal amino acid sequence and amino acid composition of the NQO2 subunit have been determined. On the basis of the amino acid sequence, the NQO2 gene was found to be located 1.7 kilobase pairs upstream of the gene for NADH-binding subunit (NQO1). The complete nucleotide sequence of the NQO2 gene was determined. It is composed of 717 base pairs and codes for 239 amino acid residues with a calculated molecular weight of 26,122. The NQO2 subunit is homologous to the Mr 24,000 subunit of the mammalian mitochondrial NADH-ubiquinone oxidoreductase which bears an electron paramagnetic resonance-visible binuclear iron-sulfur cluster (probably cluster N1b). Comparison of the predicted amino acid sequence of the Paracoccus NQO2 subunit with those of its mammalian counterparts suggests putative binding sites for the iron-sulfur cluster. In addition, nucleotide sequencing shows the presence of two unidentified reading frames between the NQO1 and NQO2 genes. These are designated URF1 and URF2 and are composed of 261 and 642 base pairs, respectively. The possible function of the protein coded for the URF2 is discussed.

[Assessment of some oxidative stress parameters in bronchial asthma patients beyond add-on selenium supplementation]. The goal of this study was to investigate the effect of selenium deficit replenishment in patients with bronchial asthma (BA) on manifestations of oxidative stress and conditions of the antioxidant system (AOS). The need of correction of selenium deficit in BA-patient is determined by the increased needs in antioxidants due to chronic inflammatory process responcible for pathogenesis of BA. Latvia and also Eastern Finland, Byelorussia, some regions of Ukraine, some regions of the NorthWestern Russia, New Zealand belong to endemic areas with marked selen deficit in soils and foodstuff. Twenty patients (7 men and 13 women) with selen deficit and verified diagnosis of BA have been examined. In addition to basic therapy all patients received organic selenium SelenoPRECISE, ("PharmaNord") 200 microg daily for 16 weeks. This caused statistically significant increase of plasma selenium from 50.94+/-7.58 microg/l to 63.59+/-10.87 microg/l (p<0.001), the increase of selenium-dependent glutathione peroxidase (from 38.64+/-10.72 U/g Hb to 58.57+/-14.64 U/g Hb, p<0.001). Treatment of patients with selenium also normalized parameters charecterizing oxidative stress (chemiluminescence). The use of selenium in addition to basic therapy allows to abolish or alternate manifestations of oxidative stress by correcting the antioxidant system.

Angiostrongylus costaricensis and the intermediate hosts: observations on elimination of L3 in the mucus and inoculation of L1 through the tegument of mollucs. Human accidental infection with Angiostrongylus costaricensis may result in abdominal disease of varied severity. Slugs from the Veronicellidae family are the main intermediate hosts for this parasitic nematode of rodents. Phyllocaulis variegatus, Phyllocaulis soleiformis and Phyllocaulis boraceiensis were experimentally infected to describe the kinetics of L3 elimination in the mucus secretions of those veronicelid species. A maximum of 2 L3/g/day was found in the mucus, while the number of L3 isolated from the fibromuscular tissues varied from 14 to 448. Productive infection was established by inoculations in the hyponotum or in the body cavity, through the tegument. Intra-cavity injection is a less complex procedure and permits a better control of inocula. A preliminary trial to titrate the infective dosis for P. variegatus indicated that inocula should range between 1000 and 5000 L1. The data also confirmed the importance of P. variegatus as an intermediate host of A. costaricensis.

Penfluridol: an open phase III study in acute newly admitted hospitalized schizophrenic patients. An open study was carried out in 17 acutely ill, newly admitted, floridly psychotic schizophrenic patients to a city hospital in New York. Penfluridol was given on a daily basis up to doses of 120 mg and patients were rated objectively by means of different psychometric evaluations; vital signs were monitored daily as were side effects. The drug was found to be a rapid acting, well-tolerated, and highly effective antipsychotic agent within the population of patients explored and within the dose range used. It was particularly effective in acutely agitated floridly paranoid schizophrenics; a statistically significant impact was achieved by 7 days and usually within 72 h after initiating treatment. The drug appears unique in that (1) its effects are realized without the untoward and usually troublesome effects of nonspecific sedation attendant upon the use of many other 'neuroleptic' medications, and (2) even within the relatively high doses used it produced no hypotensive effects. It is concluded that this appears to be a unique antipsychotic agent and a potentially important addition to the treatment armamentarium of both acute and chronic schizophrenic individuals.

Entamoeba histolytica contains a beta 1 integrin-like molecule similar to fibronectin receptors from eukaryotic cells. Entamoeba histolytica trophozoites do interact with extracellular matrix components in order to invade and finally destroy tissue. An important step in this interaction involves the binding of a 140-kDa membrane protein that binds to fibronectin. The similarity of this amoebic receptor to fibronectin receptors from higher eukaryotic cells was defined by indirect immunofluorescence, western blot and immunohistochemistry, using polyclonal monospecific antibodies raised against the amoebic protein. These results suggest that lower eukaryotic cells have and use a beta 1 integrin-like molecule as well as mechanisms similar to those present in higher eukaryotic cells during interaction with extracellular matrix components.

Fear of falling and associated activity curtailment among middle aged and older adults with multiple sclerosis. The purpose of this study was to identify factors associated with increased likelihood of reporting fear of falling (FoF) among people with multiple sclerosis (MS) and factors associated with activity curtailment among the subset of individuals reporting FoF. Cross-sectional data from telephone interviews with 1064 individuals with MS, aged 45-90 years living in the Midwestern United States were used. Logistic regression models examined factors associated with FoF and with activity curtailment among individuals reporting FoF. Of the participants, 63.5% reported FoF. Increased likelihood of reporting FoF was associated with being female, experiencing greater MS symptom interference during everyday activities, history of a fall in the past 6 months, and using a walking aid. Among participants reporting FoF, 82.6% reported curtailing activity. Increased likelihood of activity curtailment among people reporting FoF was associated with using a walking aid, needing moderate or maximum assistance with instrumental activities of daily living, and having less than excellent self-reported mental health. We concluded that FoF and associated activity curtailment are common among people aged 45-90 with MS. While FoF and associated activity curtailment may be appropriate responses to fall risk, the findings suggest that factors beyond realistic appraisal of fall risk may be operating.

[Determination of amoxicillin in human plasma by high performance liquid chromatography and its pharmacokinetics]. A rapid and sensitive assay for amoxicillin in human plasma has been developed using reversed phase high performance liquid chromatography. Plasma samples were prepared for analysis by addition of internal standard (tinidazole) followed by protein precipitation with HClO4. A YWG C18H37 column as stationary phase and a 0.033 mol.L-1 phosphate buffer (pH 7.2)--methanol mixture (85:15) as mobile phase were used with the UV detector set at 229 nm. The calibration curve was linear in the range from 0.2 microgram.ml-1 to 20.0 micrograms.ml-1 with gamma > 0.999. The analytical recovery of amoxicillin from plasma was > 86.7%. The relative standard deviations for within-day and between-day were < 5.48% and < 8.29%, respectively. Following oral administration of 500 mg in human volunteers, the peak levels of amoxicillin in plasma averaged 6.88 +/- 2.25 micrograms.ml-1 at 84.4 +/- 21.1 min. The mean half life time for amoxicillin was 62.8 +/- 14.6 min.

Morphometric parameters of cardiac implantable electronic device (CIED) pocket walls observed on device replacement. The final stage of a conventional de-novo cardiac implantable electronic device (CIED) implantation procedure with transvenous lead insertion involves the formation of a pocket by tissue separation superficial to the pectoralis major muscle in the right or left infraclavicular region, where the device is subsequently placed. Over time, a scar "capsule" forms around the CIED as a result of normal biological remodeling. The purpose of this study was to analyze the structure and present the variations of CIED capsules observed during device replacement. The nature and extent of this local tissue remodeling, which had occurred from the time of device implantation to its replacement in 2016 (10 ±3.1 years), was analyzed in 100 patients (mean age 77.1±14.5 years), including 45 women and 55 men. The largest type of "capsules" (70% of cases) were those with similar thickness of both walls or a slightly thicker posterior (<1.0mm) than anterior wall (<0.5mm). The second most common capsule type (23% of cases) was characterized by a significantly thicker posterior wall of scar tissue (˃1.0mm). The third group of capsules was characterized by various degrees of wall calcification (7% of cases). The extent and nature of scar tissue structure in the CIED pocket walls seems to correlate with the relative position of cardiac lead loops with respect to the device itself; where the more extensive scarring likely resulting from pocket wall irritation in the capsule formation phase due to lead movements underneath the device. The group of cases with calcified capsules was characterized by "old" device pockets (˃ 13 years) and the oldest population (patients in their 80s and 90s).

Effectiveness of Scene-Based Psychodramatic Family Therapy (SB-PFT) in adolescents with behavioural problems. Scene-Based Psychodramatic Family Therapy (SB-PFT) is a multiple-family intervention for adolescents with behavioural problems implemented by Child Welfare Services in Spain. This intervention is aimed at promoting adolescent well-being. The aim of this study was to evaluate the effectiveness of SB-PFT in 17 trials, measuring its impact on the emotional intelligence, parental attachment, peer attachment and antisocial behaviour of 216 adolescents (109 participating in the intervention and 107 in the control group). Repeated measures ANOVAs for pretest/posttest differences and long-term growth models were estimated. In the short term, the intervention had a positive impact on emotional intelligence and had a stabilising effect on parental attachment, whereas the long-term results showed significant logarithmic growth in emotional intelligence and exponential growth in parental attachment and a decrease in antisocial behaviour. However, no changes in peer attachment were shown. This study demonstrates SB-PFT to be a potentially effective intervention for adolescents with behavioural problems and emphasises the importance of fostering emotional intelligence.

Digestive flexibility during fasting in the characid fish Hyphessobrycon luetkenii. Digestive flexibility is a widespread phenomenon among animals, and the congruence between empirical data and optimal digestion models strongly supports the idea that it has evolved by natural selection. However, current understanding of the evolution of this amazing flexibility is far from being comprehensive. Evidence from vertebrate tetrapods suggests that there are two major mechanisms for intestinal down-regulation during fasting periods: a decrease in the number of enterocytes in the mucosal epithelium in endothermic species, and a transitional epithelium in concert with a marked hypotrophy of enterocytes in ectothermic species. Here, we analyze the intestinal changes, at the morphological and histological levels, occurring after 9 and 16 days of fasting in a small characid fish species (Hyphessobrycon luetkenii). We found that short-term fasting was correlated with a marked down-regulation of gut size (i.e., caeca and intestine dry mass fall to a 42.3%, while intestinal length was reduced to a 73.9% of the feeding values) and that these changes were accompanied by a shift in intestinal epithelial organization from a simple columnar to pseudostratified one. This result, in conjunction with data on changes in enterocyte turnover rates during fasting in other fish species, suggests that gut regulation at both levels, cell renewal rate and epithelia configuration, is the basal condition to all tetrapods. More data, especially in some key taxonomic groups (e.g., fish that follow an endothermic strategy), will be needed in order to reach a clear understanding of digestive flexibility evolution.

Hospital Factors Associated With Care Discontinuity Following Emergency General Surgery. Although there is evidence that changes in clinicians during the continuum of care (care discontinuity) are associated with higher mortality and complications among surgical patients, little is known regarding the drivers of care discontinuity among emergency general surgery (EGS) patients. To identify hospital factors associated with care discontinuity among EGS patients. We performed a retrospective analysis of the 100% Medicare inpatient claims file, from January 1, 2008, to November 30, 2011, and matched patient details to hospital information in the 2011 American Hospital Association Annual Survey database. We selected patients aged 65 years and older who had the most common procedures associated with the previously defined American Association for the Surgery of Trauma EGS diagnosis categories and survived to hospital discharge across the United States. The current analysis was conducted from February 1, 2016, to March 24, 2016. Care discontinuity defined as readmission within 30 days to nonindex hospitals. There were 109 443 EGS patients readmitted within 30 days of discharge and 20 396 (18.6%) were readmitted to nonindex hospitals. Of the readmitted patients, 61 340 (56%) were female. Care discontinuity was higher among patients who were male (19.5% vs 18.0%), those younger than 85 years old (19.0% vs 16.6%), and those who lived 12.8 km (8 miles) or more away from the index hospitals (23.7% vs 14.8%) (all P < .001). Care discontinuity was independently associated with mortality (adjusted odds ratio [aOR], 1.16; 95% CI, 1.08-1.25). Hospital factors associated with care discontinuity included bed size of 200 or more (aOR, 1.45; 95% CI, 1.36-1.54), safety-net status (aOR, 1.35; 95% CI, 1.27-1.43), and teaching status (aOR, 1.18; 95% CI, 1.09-1.28). Care discontinuity was significantly lower among designated trauma centers (aOR, 0.89; 95% CI, 0.83-0.94) and highest among hospitals in the Midwest (aOR, 1.15; 95% CI, 1.05-1.26). Nearly 1 in 5 older EGS patients is readmitted to a hospital other than where their original procedure was performed. This care discontinuity is independently associated with mortality and is highest among EGS patients who are treated at large, teaching, safety-net hospitals. These data underscore the need for sustained efforts in increasing continuity of care among these hospitals and highlight the importance of accounting for these factors in risk-adjusted hospital comparisons.

Antigen and epitope specificity of anti-glomerular basement membrane antibodies in patients with goodpasture disease with or without anti-neutrophil cytoplasmic antibodies. Goodpasture disease (GP) is defined by the presence of anti-glomerular basement membrane (anti-GBM) antibodies and rapidly progressive glomerulonephritis. Besides anti-GBM, many patients with GP produce anti-neutrophil cytoplasmic antibodies (ANCA). For elucidation of the pathophysiologic significance of ANCA in this setting, epitope and antigen specificity of the anti-GBM antibodies and antigen specificity of ANCA were studied. Bovine testis alpha(IV)NC1 (tNC1); recombinant human alpha1, alpha3, alpha4, and alpha5(IV)NC1 (ralpha1 through ralpha5); and three chimeric proteins that contain previously defined epitope regions designated E(A), E(B), and S2 were used to examine the anti-GBM antibodies by ELISA in 205 Chinese patients with GP with or without ANCA. In the 205 anti-GBM antibody-positive sera, 63 (30.7%) were also ANCA positive (61 myeloperoxidase-ANCA and six proteinase 3-ANCA, four being triple positive). All 205 sera recognized tNC1 and ralpha3(IV)NC1. In the double-positive group, 54.0, 66.7, 71.4% of the sera could recognize ralpha1, ralpha4, and ralpha5, respectively, compared with 49.3, 60.6, and 55.6% for patients with anti-GBM antibodies alone. The levels of the antibodies to ralpha3, tNC1, and the alpha3/alpha1 ratio were lower in the double-positive group than that in patients with anti-GBM antibody alone (P < 0.05). Most of the sera could recognize the epitope regions E(A), E(B), and S2, but the absorbance values to E(A), E(B), and S2 were lower in double-positive group (P < 0.05). Double-positive patients had a broader spectrum of anti-GBM antibodies and lower levels of antibodies against alpha3(IV)NC1 compared with that of patients with anti-GBM antibodies alone.

Full-spectrum volumetric solar thermal conversion via photonic nanofluids. Volumetric solar thermal conversion is an emerging technique for a plethora of applications such as solar thermal power generation, desalination, and solar water splitting. However, achieving broadband solar thermal absorption via dilute nanofluids is still a daunting challenge. In this work, full-spectrum volumetric solar thermal conversion is demonstrated over a thin layer of the proposed 'photonic nanofluids'. The underlying mechanism is found to be the photonic superposition of core resonances, shell plasmons, and core-shell resonances at different wavelengths, whose coexistence is enabled by the broken symmetry of specially designed composite nanoparticles, i.e., Janus nanoparticles. The solar thermal conversion efficiency can be improved by 10.8% compared with core-shell nanofluids. The extinction coefficient of Janus dimers with various configurations is also investigated to unveil the effects of particle couplings. This work provides the possibility to achieve full-spectrum volumetric solar thermal conversion, and may have potential applications in efficient solar energy harvesting and utilization.

A Superhydrophobic Smart Coating for Flexible and Wearable Sensing Electronics. Superhydrophobic surfaces have shown versatile applications in waterproofing, self-cleaning, drag reduction, selective absorption, etc. The most convenient and universally applicable approach to forming superhydrophobic surfaces is by coating; however, currently, superhydrophobic, smart coatings with flexibility and multiple functions for wearable sensing electronics are not yet reported. Here, a highly flexible multifunctional smart coating is fabricated by spray-coating multiwalled carbon nanotubes dispersed in a thermoplastic elastomer solution, followed by treatment with ethanol. The coatings not only endow various substrate materials with superhydrophobic surfaces, but can also respond to stretching, bending, and torsion-a property useful for flexible sensor applications. The coatings show superior sensitivity (gauge factor of 5.4-80), high resolution (1° of bending), a fast response time (<8 ms), a stable response over 5000 stretching-relaxing cycles, and wide sensing ranges (stretching: over 76%, bending: 0°-140°, torsion: 0-350 rad m-1 ). Moreover, multifunctional coatings with thicknesses of only 1 µm can be directly applied to clothing for full-range and real-time detection of human motions, which also show extreme repellency to water, acid, and alkali, which helps the sensors to work under wet and corrosive conditions.

Application of morphological and physiological parameters representative of a Brazilian population sample in the respiratory tract model. The human respiratory tract model (HRTM) adopted by ICRP in its Publication 66 accounts for the morphology and physiology of the respiratory tract. The characteristics of air drawn into the lungs and exhaled are greatly influenced by the morphology of the respiratory tract, which causes numerous changes in pressure, flow rate, direction and humidity as air moves into and out of the lungs. These characteristics are important to determine the fractional deposition. It is known that the morphology and physiology are influenced by environmental, occupational and economic conditions. The ICRP recommends, for a reliable evaluation of the regional deposition, the use of parameters from a local population wherever such information is available. The main purpose of this study is to verify the influence of using the morphology and physiology parameters representative of a sample of the Brazilian population on the deposition model of the ICRP Publication 66 model.

Oxytocin excites neurones in the bed nucleus of the stria terminalis of the lactating rat in vitro. Unit recordings were made in the bed nucleus of the stria terminalis in brain slices obtained from lactating rats. Addition of 10(-8) to 10(-6) M oxytocin to the perfusate caused a reversible and repeatable excitation in 28/53 (53%) of neurones. The excitatory effect of oxytocin was completely blocked in the presence of the antagonist [d(CH2)5,D-Tyr(OEt)2,Val4,Cit8]vasopressin (5 x 10(-7) M) and a smaller excitation was achieved with equimolar concentration of arginine vasopressin, implicating the involvement of an oxytocin receptor. This effect is discussed in relation to the actions of centrally administered oxytocin in the lactating rat.

Leptospirosis. Equine clinical leptospirosis has been primarily related to uveitis and the often recurrent sequelae of ocular changes. Reports of equine hepatic and renal involvement are sporadic. More recently, serovar bratislava has been identified as a host-adapted serovar in the horse. More significantly, reports of equine abortion and stillbirth have become more frequent in the literature. This is more than likely a result of improved diagnostic techniques, not of increased prevalence of disease. In addition to abortion, equine neonatal disease is becoming more frequently recognized in association with leptospira infection. Whether leptospiral infection results in abortion or diseased foals may depend upon the stage of gestation when the mare is exposed and host immune status. Antibiotic of choice for treatment of equine leptospirosis remains speculative, as specific equine studies have not been performed. Extrapolation from other species suggests that the use of streptomycin remains a good choice of therapy for the chronic shedding state and may be used in combination with other antimicrobials for treatment of acute disease. Penicillin or potentiated penicillins and tetracycline at appropriate to high end dosages are logical choices for the treatment of acute leptospirosis.

Laboratory evaluations of the thermal degradation properties of toxic organic materials in sewage sludge. Laboratory thermal decomposition studies were performed to evaluate potential emissions from sewage sludge incinerators. Precisely controlled thermal decomposition experiments were conducted on sludge spiked with mixtures of hazardous organic compounds, on mixtures of pure compounds without sludge, and on unspiked sludge. Experiments were conducted in nitrogen and air atmospheres with gas phase reaction times of 2.0 seconds over the temperature range 300 degrees C-1000 degrees C. It was found that sludge inhibited the decomposition of moderately stable spiked contaminants but accelerated the decomposition of the most stable components. This effect was attributed to radical scavengers produced by the sludge matrix at lower temperatures which then decomposed at higher temperatures. A multiple hearth simulation study suggested that most of the organic material present in the sludge matrix is vaporized within the upper hearths that are held at lower temperatures and may consequently escape from such incinerators undestroyed. A number of stable byproducts resulted from the sludge decomposition that may be of environmental concern.

[Feasibility of apoptosis-imaging agent 99mTc-HYNIC-annexin V in early assessment of chemotherapeutic effect on tumor models]. To evaluate if 99mTc-HYNIC-annexin V may be used to detect the early chemotherapeutic effect and to determine the best timing for detecting apoptosis in vivo. Annexin V was labeled with 99mTc using HYNIC as a bifunctional agent. Normal Kunming mice received inoculation of Ehrlich ascites cells into the right upper limb. After the tumor reached 1 cm in diameter, the mice were randomly divided into saline treatment group as control and cyclophosphamide (150 mg/kg injected intraperitoneally) treatment group. 99mTc-HYNIC-annexin V was injected intravenously at 1 h and 24 h after treatment. Region of interest technique (ROI) from the SPECT images taken at different time was used to get the ratio of tumor/limb in each group. TUNEL staining was used to detect apoptotic cells and the rates of positive stained cells were calculated. After treatment with saline, only little amount of the radiolabeled tracer could be seen in the tumor and showed weak image of the tumor. But after 24 h of treatment with cyclophosphamide, clear image on the tumor could be seen. 24 h after the treatment of cyclophosphamide, the ratio of tumor/limb was (6.27 +/- 0.24) which was much higher than that at 24 h after treatment with saline (2.36 +/- 0.18) and that at 1 h after cyclophosphamide treatment (4.00 +/- 0.38). At 24 h after cyclophosphamide treatment, TUNEL staining showed a significantly higher rate of apoptotic cells in the mice. 99mTc-HYNIC-annexin V can be used as an apoptosis-imaging agent to detect and evaluate the early curative effect after chemotherapy. The effective detection of apoptotic response in tumor with 99mTc-HYNIC-annexin V requires a 24 h interval after chemotherapy. SPECT images can be obtained at 60 min after injection of the imaging agent. It suggests that 99mTc-HYNIC-annexin V may become a promising agent for apoptosis-imaging in clinical application.

Study of bacteriophage T4-encoded Dam DNA (adenine-N6)-methyltransferase binding with substrates by rapid laser UV cross-linking. DNA methyltransferases of the Dam family (including bacteriophage T4-encoded Dam DNA (adenine-N(6))-methyltransferase (T4Dam)) catalyze methyl group transfer from S-adenosyl-L-methionine (AdoMet), producing S-adenosyl-L-homocysteine (AdoHcy) and methylated adenine residues in palindromic GATC sequences. In this study, we describe the application of direct (i.e. no exogenous cross-linking reagents) laser UV cross-linking as a universal non-perturbing approach for studying the characteristics of T4Dam binding with substrates in the equilibrium and transient modes of interaction. UV irradiation of the enzyme.substrate complexes using an Nd(3+):yttrium aluminum garnet laser at 266 nm resulted in up to 3 and >15% yields of direct T4Dam cross-linking to DNA and AdoMet, respectively. Consequently, we were able to measure equilibrium constants and dissociation rates for enzyme.substrate complexes. In particular, we demonstrate that both reaction substrates, specific DNA and AdoMet (or product AdoHcy), stabilized the ternary complex. The improved substrate affinity for the enzyme in the ternary complex significantly reduced dissociation rates (up to 2 orders of magnitude). Several of the parameters obtained (such as dissociation rate constants for the binary T4Dam.AdoMet complex and for enzyme complexes with a nonfluorescent hemimethylated DNA duplex) were previously inaccessible by other means. However, where possible, the results of laser UV cross-linking were compared with those of fluorescence analysis. Our study suggests that rapid laser UV cross-linking efficiently complements standard DNA methyltransferase-related tools and is a method of choice to probe enzyme-substrate interactions in cases in which data cannot be acquired by other means.

Removal of Cr(VI) by thermally activated weed Salvinia cucullata in a fixed-bed column. The present study evaluates the feasibility of using a thermally activated fresh water weed in removing Cr(VI) from wastewater through column studies. The effect of flow rate, bed height and Cr(VI) concentration of the feed solution on the adsorption capacity of the activated weed was investigated. The adsorption capacity increased with decrease in both flow rate and bed height but increased with an increase in initial adsorbate concentration. Four different kinetic models, such as. Adams-Bohart, Bed Depth Service Time (BDST), Thomas and Yoon-Nelson models were first applied to the experimental data to predict the breakthrough curve and to determine the characteristic parameters of the column useful for designing large-scale column studies. Different statistical methods such as Sum of the Square of the Error (SSE), Sum of the Absolute Error (SAE), Average Relative Error (ARE), Average Relative Standard Error (ARS) and regression coefficient, were applied to evaluate the prominent and unique characteristic features of the experimental and predicted parameters under the respective models to find out the best fit. The performance stability of the adsorbent was tested by continuous adsorption-desorption studies.

Comparison of evaporation techniques for the preparation of salivary cortisol for analysis by liquid chromatography-electrospray tandem mass spectrometry. Compare evaporation techniques in the work-up procedure of saliva samples for cortisol analysis by a previously validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Samples were evaporated using freeze drying, centrifugal concentration, and nitrogen flow and analyzed by LC-MS/MS. Cortisol concentrations detected using each technique did not significantly differ. Factors other than the recovery of cortisol were evaluated. Evaporation using freeze drying/centrifugal concentration is an automated process, reducing overall processing time for analysis of numerous samples.

Role of [18F]-FDG-PET/MDCT in evaluating early response in patients with Hodgkin's lymphoma. The authors evaluated the prognostic role of 18-fluoro-fluorodeoxyglucose positron emission tomography/multidetector computed tomography ([(18)F]-FDG PET/MDCT) in treating patients with Hodgkin's lymphoma (HL). We retrospectively evaluated 132 patients with HL studied with PET/MDCT before the start of chemotherapy (CTX) for staging purposes and again after two CTX cycles with [doxorubicin (Adriblastin), bleomycin, vinblastine, dacarbazine (ABVD_] (interim PET/MDCT), at least 30 days after the end of the last CTX cycle and/or 3 months after the end of radiotherapy, if delivered (final PET-MDCT). Interim PET-MDCT was negative in 104/132 patients (79%), and their final PET-MDCT showed complete remission in 102/104 (98%) of cases, with disease recurrence/persistence in two (2%). In the remaining 28 (21%) patients, interim PET-MDCT revealed an early response in 68% of cases and chemoresistance with disease progression in 32% of cases; in these 28 patients, final PET-MDCT showed a lack of response to treatment in 43% of cases (43%) and complete remission in 57% of cases. Statistical analysis of these data showed that interim PET-MDCT had a negative predictive value of 98% and a positive predictive value of 42%, with values of sensitivity, specificity and diagnostic accuracy of 85.7%, 86.4% and 86.4%, respectively. Interim PET-MDCT has a reliable prognostic role in diagnosis and treatment of patients with HL, as it helps predict which patients are more likely to achieve a complete response at the end of treatment. PET/MDCT may also lead to a change in treatment, with reduced treatment-related toxic effects and significantly reduced total costs.

Injury Deaths Related to Hurricane Sandy, New York City, 2012. This project aimed to describe demographic patterns and circumstances surrounding injury deaths in New York City (NYC) related to Hurricane Sandy. Injury deaths related to Hurricane Sandy were classified by using data from multiple sources: NYC's Office of Vital Statistics death records, Office of Chief Medical Examiner case investigation files, and American Red Cross disaster mortality data. Injury deaths were classified as being related to Hurricane Sandy if they were caused directly by the storm's environmental forces or if they were indirectly caused by an interruption of services, displacement, or other lifestyle disruption. We identified 52 injury deaths in NYC related to Hurricane Sandy. Most decedents were male (75%); nearly half were aged 65 years and older (48%). Most (77%) deaths were caused by injuries directly related to Hurricane Sandy. Ninety percent of direct deaths were caused by drowning; most (73%) occurred within 3 days of landfall. Half (50%) of the 12 indirect deaths that occurred up to 30 days after the storm were caused by a fall. Nearly two-thirds (63%) were injured at home. Three-quarters (75%) of fatal injuries occurred in evacuation Zone A. Risk communication should focus on older adults, males, and those living in evacuation zones; more evacuation assistance is necessary. NYC's fatal injury profile can inform future coastal storm planning efforts. (Disaster Med Public Health Preparedness. 2016;10:378-385).

[Amiodarone-induced liver dysfunctions]. Amiodarone, a diiodinated benzofuran derivative, is widely used for treating ventricular and supraventricular tachyarrhythmias. Amiodarone is highly lipophilic and accumulation in the liver can be 500 times higher than serum amiodarone levels. Due to a long half-life and the lipophilic properties, the stored drug is capable of damaging the liver long after the drug has been stopped. Serious liver damage can lead to acute liver failure, cirrhosis and the need for liver transplantation. In this article we describe amiodarone-induced liver dysfunction and the diagnostic and therapeutic challenges in patients on amiodarone.

[Results of specific desensitization in allergic asthma]. Some recent works currently give some solid scientific basis to suppose that immunization with appropriate antigens might be beneficial for asthmatic patients. As numerous studies have now shown on the one hand that there was a relation between allergy, inflammation and bronchial hyper-reactivity and in the other that desensitization was able to modify the liberation of mediators to inflammation and the responses attributed to these mediators. The number of controlled studies performed up till now with the principal allergens are, for asthma, insufficient. However, no-one currently doubts the efficacy of specific desensitization to spasmodic pollen coryza. For pollen asthma, six studies conclude that there were superior results with desensitization than to placebo. Two studies showed no difference. Four controlled studies made for episodic house dust mite coryza ended with a favourable result. In allergic bronchial asthma to the dust mite, nine studies were favourable and five showed no benefit. It should be mentioned at this stage that all the studies on children have shown favourable results. There are few studies on the efficacy of desensitization to animal squamae (epithelial debris). Nevertheless, a very recently published study has shown, using cat squamae, clinical efficacy on bronchial, nasal and ocular symptoms. Desensitization with mould extracts cannot be judged at present, published controlled studies on the subject are almost nonexistent. On the other hand at the moment one can say that with microbial antigens non-standardised antigens, no clinical evidence has been shown to date. Incidents and accidents encountered during specific desensitization in respiratory allergy are extremely rare but may be serious.(ABSTRACT TRUNCATED AT 250 WORDS)

A transgenic zebrafish model for monitoring xbp1 splicing and endoplasmic reticulum stress in vivo. Accumulation of misfolded or unfolded proteins in the endoplasmic reticulum (ER) triggers ER stress that initiates unfolded protein response (UPR). XBP1 is a transcription factor that mediates one of the key signaling pathways of UPR to cope with ER stress through regulating gene expression. Activation of XBP1 involves an unconventional mRNA splicing catalyzed by IRE1 endonuclease that removes an internal 26 nucleotides from xbp1 mRNA transcripts in the cytoplasm. Researchers have taken advantage of this unique activation mechanism to monitor XBP1 activation, thereby UPR, in cell culture and transgenic models. Here we report a Tg(ef1α:xbp1δ-gfp) transgenic zebrafish line to monitor XBP1 activation using GFP as a reporter especially in zebrafish oocytes and developing embryos. The Tg(ef1α:xbp1δ-gfp) transgene was constructed using part of the zebrafish xbp1 cDNA containing the splicing element. ER stress induced splicing results in the cDNA encoding a GFP-tagged partial XBP1 without the transactivation activation domain (XBP1Δ-GFP). The results showed that xbp1 transcripts mainly exist as the spliced active isoform in unfertilized oocytes and zebrafish embryos prior to zygotic gene activation at 3 hours post fertilization. A strong GFP expression was observed in unfertilized oocytes, eyes, brain and skeletal muscle in addition to a weak expression in the hatching gland. Incubation of transgenic zebrafish embryos with (dithiothreitol) DTT significantly induced XBP1Δ-GFP expression. Collectively, these studies unveil the presence of maternal xbp1 splicing in zebrafish oocytes, fertilized eggs and early stage embryos. The Tg(ef1α:xbp1δ-gfp) transgenic zebrafish provides a useful model for in vivo monitoring xbp1 splicing during development and under ER stress conditions.

Driving change in rural workforce planning: the medical schools outcomes database. The Medical Schools Outcomes Database (MSOD) is an ongoing longitudinal tracking project ofmedical students from all medical schools in Australia and New Zealand. It was established in 2005 to track the career trajectories of medical students and will directly help develop models of workforce flow, particularly with respect to rural and remote shortages. This paper briefly outlines the MSOD project and reports on key methodological factors in tracking medical students. Finally, the potential impact of the MSOD on understanding changes in rural practice intentions is illustrated using data from the 2005 pilot cohort (n = 112). Rural placements were associated with a shift towards rural practice intentions, while those who intended to practice rurally at both the start and end of medical school tended to be older and interested in a generalist career. Continuing work will track these and future students as they progress through the workforce, as well as exploring issues such as the career trajectories of international fee-paying students, workforce succession planning, and the evaluation of medical education initiatives.

Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress. Trimethylamine-N-oxide (TMAO), gut microbiota-dependent metabolites, has been shown to be associated with cardiovascular diseases. However, little is known about the relationship between TMAO and vascular aging. Here, we observed a change in TMAO during the aging process and the effects of TMAO on vascular aging and endothelial cell (EC) senescence. We analyzed age-related plasma levels of TMAO in young adults (18-44 years old), older adults (≥ 65 years old), and 1-month-old, 3-month-old, 6-month-old and 10-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-accelerated mouse resistance 1 (SAMR1) models. We found that circulating TMAO increased with age both in humans and mice. Next, we observed that a TMAO treatment for 16 weeks induced vascular aging in SAMR1 mice and accelerated the process in SAMP8 mice, as measured by an upregulation of senescence markers including senescence-associated β-galactosidase (SA-β-gal), p53, and p21, vascular dysfunction and remodeling. In vitro, we demonstrated that prolonged TMAO treatment induced senescence in human umbilical vein endothelial cells (HUVECs), characterized by reduced cell proliferation, increased expressions of senescence markers, stagnate G0/G1, and impaired cell migration. Furthermore, TMAO suppressed sirtuin 1 (SIRT1) expression and increased oxidative stress both in vivo and in vitro and then activated the p53/p21/Rb pathway resulting in increased p53, acetylation of p53, p21, and decreased CDK2, cyclinE1, and phosphorylation of Rb. In summary, these data suggest that elevated circulating TMAO during the aging process may deteriorate EC senescence and vascular aging, which is probably associated with repression of SIRT1 expression and increased oxidative stress, and, thus, the activation of the p53/p21/Rb pathway.

Moving beyond attendance: lessons learned from assessing engagement in afterschool contexts. Youth engagement is the least researched, but potentially most important, aspect of participation in afterschool programs. The level of youth engagement can vary across programs, across youth within a program, and within individual youth over time. Engagement is important for both recruiting and retaining participants, and has been associated with more positive academic outcomes over time. This chapter integrates perspectives from practitioners, researchers, and the school engagement literature. Reasons why engagement is an important dimension of afterschool programming, different methods for assessing engagement, key features of engaging afterschool programs, and implications for practice are also outlined.

Regulation of intracellular pH and blood flow in rat duodenal epithelium in vivo. Duodenal mucosal defense was assessed by measuring blood flow and epithelial intracellular pH (pHi) of rat proximal duodenum in vivo. Fluorescence microscopy was used to measure epithelial pHi using the trapped, pHi-indicating dye 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein-AM. Blood flow was measured with laser-Doppler flowmetry. The mucosa was briefly superfused with NH4Cl, pH 2.2 buffer, the potent Na+/H+ exchange inhibitor 5-(N,N-dimethyl)-amiloride (DMA), or the anion exchange and Na+-HCO-3 cotransport inhibitor DIDS. Cryostat sections localized dye fluorescence to the villus tip. Steady-state pHi was 7. 02 +/- 0.01, which remained stable for 60 min. Interventions that load the cells with protons without affecting superfusate pH (NH4Cl prepulse, nigericin with low superfusate K+ concentration, DMA, and DIDS) all decreased pHi, supporting our contention that the dye was faithfully measuring pHi. An acid pulse decreased pHi, followed by a DIDS-inhibitable overshoot over baseline. Intracellular acidification increased duodenal blood flow independent of superfusate pH, which was inhibited by DMA, but not by DIDS. We conclude that we have established a novel in vivo microscopy system enabling simultaneous measurements of pHi and blood flow of duodenal epithelium. Na+/H+ exchange and Na+-HCO-3 cotransport regulate baseline duodenal epithelial pHi. Intracellular acidification enhances duodenal blood flow by a unique, amiloride-inhibitable, superfusate pH-independent mechanism.

Pharmacological, psychological, and patient education interventions for patients with neck pain: results of an international survey. Examination of practice patterns compared to existing evidence identifies knowledge to practice gaps. To describe the utilization of pharmacological, patient education, primary psychological interventions and relaxation therapies in patients with neck pain by clinicians. An international cross-sectional survey was conducted to determine the use of these interventions amongst 326 clinicians treating patients with neck pain. Nineteen countries participated. Results were analyzed by usage amongst physical therapists (39%) and chiropractors (35%), as they were the predominant respondents. Patient education (95%) and relaxation therapies (59%) were the most utilized interventions. Tests of subgroup differences determined that physical therapists used patient education significantly more than chiropractors. Use of medications and primary psychological interventions were reported by most to be outside of scope of practice. The high rate of patient education is consistent with supporting evidence. However, usage of relaxation therapies is contrary to evidence suggesting no benefit for improved pain or function for chronic neck pain. This survey indicates that patient education and relaxation therapies are common treatments provided by chiropractors and physical therapists for patients with neck pain. Future research should address gaps associated with variable practice patterns and knowledge translation to reduce usage of interventions shown to be ineffective.

Real-World Associations of Renin-Angiotensin-Aldosterone System Inhibitor Dose, Hyperkalemia, and Adverse Clinical Outcomes in a Cohort of Patients With New-Onset Chronic Kidney Disease or Heart Failure in the United Kingdom. Background Dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) may be modified to manage associated hyperkalemia risk; however, this approach could adversely affect cardiorenal outcomes. This study investigated real-world associations of RAASi dose, hyperkalemia, and adverse clinical outcomes in a large cohort of UK cardiorenal patients. Methods and Results This observational study included RAASi-prescribed patients with new-onset chronic kidney disease (n=100 572) or heart failure (n=13 113) first recorded between January 2006 and December 2015 in Clinical Practice Research Datalink and linked Hospital Episode Statistics databases. Odds ratios associating hyperkalemia and RAASi dose modification were estimated using logistic generalized estimating equations with normal (<5.0 mmol/L) serum potassium level as the reference category. Patients with serum potassium ≥5.0 mmol/L had higher risk of RAASi down-titration (adjusted odds ratios, chronic kidney disease: 1.79 [95% CI, 1.64-1.96]; heart failure: 1.33 [95% CI, 1.08-1.62]). Poisson models were used to estimate adjusted incident rate ratios of adverse outcomes based on total RAASi exposure (<50% and ≥50% of the guideline-recommended RAASi dose). Incidence of major adverse cardiac events and mortality was consistently higher in the lower dose group (adjusted incident rate ratios: chronic kidney disease: 5.60 [95% CI, 5.29-5.93] for mortality and 1.60 [95% CI, 1.55-1.66] for nonfatal major adverse cardiac events; heart failure: 7.34 [95% CI, 6.35-8.48] for mortality and 1.85 [95% CI, 1.71-1.99] for major adverse cardiac events). Conclusions The results of this real-world analysis highlight the potential negative impact of suboptimal RAASi dosing and the need for strategies that allow patients to be maintained on appropriate therapy, avoiding RAASi dose modification or discontinuation.

Effects of elevated CO(2) concentration on leaf characteristics and photosynthetic capacity of beech (Fagus sylvatica) during the growing season. Two-year-old beech (Fagus sylvatica L.) saplings were planted directly in the ground at high density (100 per m(2)), in an experimental design that realistically mimicked field conditions, and grown for two years in air containing CO(2) at either ambient or an elevated (ambient + 350 ppm) concentration. Plant dry mass and leaf area were increased by a two-year exposure to elevated CO(2). The saplings produced physiologically distinct types of sun leaves associated with the first and second growth flushes. Leaves of the second flush had a higher leaf mass per unit area and less chlorophyll per unit area, per unit dry mass and per unit nitrogen than leaves of the first flush. Chlorophyll content expressed per unit nitrogen decreased over time in plants grown in elevated CO(2), which suggests that, in elevated CO(2), less nitrogen was invested in machinery of the photosynthetic light reactions. In early summer, the photosynthetic capacity measured at saturating irradiance and CO(2) was slightly but not significantly higher in saplings grown in elevated CO(2) than in saplings grown in ambient CO(2). However, a decrease in photosynthetic capacity was observed after July in leaves of saplings grown in CO(2)-enriched air. The results demonstrate that photosynthetic acclimation to elevated CO(2) can occur in field-grown saplings in late summer, at the time of growth cessation.

Germline mutation analysis of STK11 gene using direct sequencing and multiplex ligation-dependent probe amplification assay in Korean children with Peutz-Jeghers syndrome. Background and Aims Peutz-Jeghers syndrome is an autosomal, dominantly inherited disease characterized by mucocutaneous hyperpigmentation and hamartomatous polyps of the gastrointestinal tract. In this study, mutation analysis of the STK11 gene was performed to establish the genetic background of Peutz-Jeghers syndrome in Korean children.Methods This study included 17 children who were diagnosed with Peutz-Jeghers syndrome based on clinical diagnostic criteria between July 2006 and December 2007.The clinical records of these children were reviewed retrospectively.Genomic DNA was extracted from the blood samples of each patient and used for direct sequencing and the MLPA (multiplex ligation-dependent probe amplification)assay.Results By direct sequencing, mutations in the STK11 gene were observed in five of 17 (29.4%) children with Peutz-Jeghers syndrome. Missense mutations were observed in four, and a frameshift mutation in one. All these mutations were present in the kinase domain of the STK11 gene. By MLPA analysis, mutations in the STK11 gene were observed in six (35.3%) children—exonic deletions were observed in five and exonic duplication in one. Conclusions The detection rate of STK11 gene mutations by direct sequencing is relatively low, even in children clinically diagnosed with Peutz-Jeghers syndrome. With the introduction of the MLPA assay as a new cytogenetic technique, large deletions and exonic duplications could also be detected in children with PJS. In the future, these results may be useful for the genetic diagnosis of Peutz-Jeghers syndrome in Korean children.

CNK2 couples NGF signal propagation to multiple regulatory cascades driving cell differentiation. Neuronal precursor cells have the capacity to engage the Raf-MEK-ERK signal module to drive either of two distinctly different regulatory programs, proliferation and differentiation. This is, at least in part, a consequence of stimulus-specific shaping of the kinase cascade response. For example, the mitogen EGF induces a transient ERK activation, whereas the neurotrophin NGF induces prolonged ERK activation. Here we define a novel component of the regulatory machinery contributing to the selective integration of MAP kinase signaling with discrete biological responses. We show that the scaffold/adaptor protein CNK2/MAGUIN-1 is required for NGF- but not EGF-induced ERK activation. In addition, CNK2 makes a separate, essential contribution to the coupling of NGF signaling to membrane/cytoskeletal remodeling. We propose that CNK2 integrates multiple regulatory pathways that must function in concert to drive an appropriate biological response to external stimuli.

Protein microarrays as an application for disease biomarkers. Protein microarrays are an increasingly powerful technology in the hunt for new and novel diagnostic and prognostic biomarkers. Lending credit to the highly established DNA microarray, protein microarrays are versatile tools that utilize a variety of formats to facilitate the discovery of new biomarkers and our understanding of disease pathways. The aims of this review are: to detail a variety of protein microarray technologies currently used, including forward-phase technologies and reverse-phase technologies useful in both the discovery and validation of candidate biomarkers; to explore the strengths and weaknesses of various proteomic microarray platforms; to explain how bioinformatics helps compare data between microarray data sets; and to discuss the downstream applications of such technologies as they relate to the development of a highly personalized approach to medicine.

Effects of methanethiol on the biological oxidation of sulfide at natron-alkaline conditions. The effects of methanethiol (MT) on biological sulfide oxidation were studied in a continuously operated bioreactor, in which chemolithoautotrophic bacteria belonging to the genus Thioalkalivibrio convert hydrogen sulfide (H2S) at natron-alkaline conditions. Previous bioreactor experiments have shown that always a fraction of the H2S is oxidized to sulfate and thiosulfate. This is unwanted, as it leads to caustic requirements for pH control and the formation of a bleed stream to discharge these compounds from the process. The current research shows that due to the addition of MT, sulfate formation is prevented. As a result, all supplied H2S is completely converted into elemental sulfur. Treatment of a continuous supply of 51.0 mM day(-1) H2S and 79 microM day(-1) MT was feasible for a prolonged period, with 99 mol% selectivity for sulfur formation. A part of the MT reacts with the freshly produced sulfur particles to form dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS). Results indicate that MT, DMDS, and DMTS partly adsorb onto the biosulfur particles. At concentrations above 10 microM, these volatile organic sulfur compounds induce biomass decay.

A sympathetic hypertensive reflex from the heart of conscious dogs. 1. The aim of the present experiment was to study in conscious animals the effect of chemical stimulation of cardiac sensory innervation by bradykinin, a physiological substance known to activate both vagal and sympathetic cardiac sensory nerve endings, at doses devoid of systemic haemodynamic effects. 2. In conscious dogs with implanted catheters bradykinin (100 ng/kg) injected into a cannulated branch of the left coronary artery induced significant (P less than 0.01, n = 5) reflex increases in mean arterial pressure and heart rate as well as increases in left ventricular pressure, left ventricular dP/dt max. and coronary blood flow. 3. These changes were obtained in the absence of pain reactions. 4. The concept, derived from experiments on anaesthetized animals, that chemical stimulation of the intact sensory supply of the heart always elicits a cardiovascular depressor reflex mediated by cardiac vagal afferents has to be modified, as pressor sympathetic reflexes may occur after an appropriate stimulus to the fully innervated heart of conscious dogs.

Linear rheological properties of low molecular weight polyethylene glycol solutions. This experimental study of the linear viscoelastic properties of PEG600 aqueous solutions at various concentrations and temperatures mainly aims at getting a better understanding, in concentrated regimes, of the role played on the structural and rheological properties by PEG assembly properties previously evidenced in the dilute regime. The results indicate a peculiar and unique viscoelastic behavior: the elastic modulus versus frequency curves are nearly the same for all concentrations and temperatures investigated. The key role played by hydrogen bonds in the rheological properties of PEG solutions is highlighted. The relaxation on long time scales is indicative of large scale complex associative polymeric structures. A schematic complete phase diagram of PEG600 in water is finally proposed.

Triage presenting complaint descriptions bias emergency department waiting times. The authors aimed to determine whether certain emergency department (ED) triage "presenting complaint" descriptions are associated with shorter or longer waiting times, when compared with matched controls. This was a retrospective, analytical study in three tertiary referral EDs. Data relating to adult patients with Australasian National Triage Scale (NTS) Category 3-5 complaints, who presented over 1 year, were accessed. A pilot study of 25 emergency physicians (EPs) identified five most liked and five most disliked presenting complaints. For each liked or disliked complaint, "cases" were identified using key words and phrases in the triage presentation description. For each case, the previous presentation at that institution with the same NTS category was used as a "control." Cases and controls were compared for waiting time and proportions seen within the Australasian College for Emergency Medicine (ACEM)-recommended waiting times. Data on 28,566 case-control pairs were examined. Compared to their controls, three of the five most liked complaints (dislocations, fractures, and palpitations) had significantly shorter waiting times, and significantly more were seen within the recommended waiting times (p < 0.05). In contrast, three of the five most disliked complaints (dizziness, constipation, and back pain) had significantly longer waiting times, and significantly fewer were seen within the recommended waiting times (p < 0.05). Other presenting complaints showed similar, although nonsignificant, trends. Waiting times for patients with certain presenting complaints are significantly associated with triage presenting complaint descriptions. It is likely that these descriptions allow EPs to selectively seek or avoid patients with liked or disliked complaints, respectively. The impact of this for patients and ED flow needs investigation.

Trichospirura leptostoma: a possible cause of wasting disease in the marmoset. An outbreak of wasting disease-like syndrome in a marmoset colony was found to have been caused by a nematode. After passing through several larval stages in an intermediate host, the cockroach, the parasite inhabited the pancreas of the marmoset. The cardinal symptoms were emaciation, anaemia, and elevated hepatic enzyme activities; the pancreas reacted with a fibrosing inflammation.