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Q fever epidemic among employees in a factory in the suburb of Zadar, Croatia. To examine the role of wind in the spread of Q fever (Coxiella burnetii) from the source of infection (sheep on the pastures) to the factory where there was an outbreak of Q fever among the employees. We performed clinical (fever, coughing, myalgias, arthralgias), laboratory (complete blood test, aminotransferases, antibodies to Coxiella burnetii), radiographic (chest X-ray), and epidemiological (questionnaire) analysis on 47 of 110 employees of the plant in a suburb of Zadar. Sera of 182 sheep were tested for antibody to C. burnetii by complement fixation reaction. During the first half of March 2004, 14 of 110 employees of a factory in a suburb of Zadar were diagnosed with Q fever on the basis of clinical and laboratory findings. In three sections of the plant, directly exposed to the north wind, a diagnosis of Q fever was confirmed in 14 of 110 employees by clinical, laboratory, and X-ray analysis, whereas there were no sick employees in the other four sections. North of the plant there were pastures where many flocks of sheep grazed. Antibodies to C. burnetii were found in 20 out of 182 sheep sera. Employees who were exposed to the north wind, had a significantly higher possibility of acquiring Q fever than did those working in sections protected from the wind. North wind (bura) containing the aerosolized C. burnetii likely influenced the Q fever outbreak in persons far from the source of the infection.

YouTube as a source of information on dialysis: a content analysis. End-stage renal disease is a prevalent and growing health problem worldwide. With increasing Internet use, video-sharing websites could potentially serve as a powerful platform for dissemination of information on dialysis. We conducted a cross-sectional study to assess the accuracy, content and viewership of YouTube videos on dialysis. YouTube videos identified using the search term 'dialysis' were classified independently by two physicians as 'useful,' 'misleading' and 'patient's personal experiences'. Five-point ordinal scales were used to grade reliability and quality. Information regarding source of upload, content in seven pre-defined domains and various viewer interaction metrics was collected. Of the 115 videos with cumulative duration of 16.2 h and viewership of approximately 2.7 million, 67 (58.3%) were useful, 19 (16.5%) were misleading and 29 (25.2%) represented patient's personal experiences; kappa statistic for inter-observer agreement was 0.985. Useful videos were the most comprehensive and had the highest reliability and quality scores. However, viewership per day was the lowest for useful videos at a median of 3 (interquartile range (IQR) 1-17), as compared with 11 (IQR 4-43) for misleading videos and 14 (IQR 5-30) for patient experiences (P = 0.013). All misleading videos were uploaded by individual users with unknown credentials. Of these, 68.4% promoted alternative therapies such as herbs and osmotherapy; 47.4% included advertisements for related services. Viewers favoured misleading videos and patient narratives over scientifically accurate information. Authoritative sources should use popular social media websites to provide relevant and easy-to-understand information on dialysis; including patient stories can make this material more engaging.

[Study of diffusion weighted magnetic resonance imaging in Wilson's disease]. We analyzed diffusion weighted magnetic resonance images (diffusion MRI) of the basal ganglia, which were obtained from four patients with Wilson's disease, and compared them with the images from ten age-matched normal individuals. In all patients, T2-MRI of the basal ganglia disclosed low or iso-signals, but diffusion MRI revealed abnormal high signals in some areas of the basal ganglia in each case. Pathological changes except for copper and/or iron deposits are difficult to estimate by T2-MRI because the low signal on T2-MRI emphatically reflects the deposits, while the abnormal high signal on diffusion MRI is thought to reflect parenchymal lesions such as cell loss, demyelination and/or increase of the extracellular fluid. From our results, we confirmed that diffusion MRI was very useful for estimating parenchymal lesions with metal deposits.

[Typical changes of lymphocyte surface architectonics in chronic viral infection]. With the use of scanning electron microscopy, lymphocyte surface architectonics has been described in cases of chronic viral persistence at tick-borne (vernal) encephalitis, hepatitis types A and B, and Herpes simplex. In lymphocytic population smooth and plicate cells in addition to cells with vesicles and outgrowths on the surface prevailed. The appearance of lymphocytes with a combined type of superficial microrelief was registered. It is supposed that despite the variety of types of lymphocyte surface architectonics and possible causes promoting their polymorphism, changes in superficial ultrastructure of immunocompetent cells for chronic viral infection have a nonspecific character.

TPA inhibits the tyrosine kinase activity of the neu protein in vivo and in vitro. P185 is a receptor-like protein encoded by the neu/erbB-2 proto-oncogene. A point mutation in the transmembrane domain renders this protein oncogenic. We report here that incubation of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulates the phosphorylation of the normal neu protein (p185) and the oncogenic neu protein (p185*). The increased phosphorylation occurs mainly on serine and threonine residues. Phosphate labeling experiments showed that TPA causes a reduction of basal phosphotyrosine in p185 but not p185*. Immunoblotting with antiphosphotyrosine antibody yielded similar results. TPA also inhibited tyrosine phosphorylation of p185* in an in vitro immune complex kinase assay. These data suggest that protein kinase C, the receptor for TPA, regulates p185 function through serine or threonine phosphorylation.

The complementary contribution of the rhinologist and the neurologist at the clinical study and treatment of the cluster headache. New neurophysiological techniques and pluridisciplinary approach contribute to progress in the diagnosis and medico-surgical treatment of headaches.

Acute admissions to a community hospital: experiences from Hallingdal sjukestugu. Acute admissions to anywhere other than general hospitals are uncommon in Norway, but at Hallingdal sjukestugu, a community hospital in a rural district, this has been practiced for years. This article presents experiences from this practice. Materials and Hallingdal sjukestugu is a decentralized, specialist healthcare service, under the administration and funding of Ringerike sykehus, the nearest general hospital, which is 170 km away. General practitioners under telephone supervision of the hospital specialists run the inpatient department. Six municipalities with 20,000 inhabitants make use of the community hospital. Statistics were obtained from the patient administration systems and from manual statistics continuously registered in 2009-10. In 2009-10 the inpatient department, an intermediate care unit with 14 beds, had an average of 605 admissions a year, with a mean length of stay of 6.3 days. There were 455 acute admissions to Hallingdal sjukestugu. Forty per cent of these patients were younger than 67 and 36% were older than 80 years of age. Half were admitted for observation and half for treatment. The main diagnostic groups were infections, injuries and palliative care. Seventeen per cent of the acute admitted patients were later transferred to the general hospital for further work-up or treatment; 70% were discharged to their homes. The experiences from Hallingdal sjukestugu indicate that it is feasible to give a selected group of patients an alternative to acute admissions to a general hospital.

A platform for high-throughput molecular characterization of recombinant monoclonal antibodies. We describe quantitative characterization of a sample preparation platform for rapid and high-throughput analysis of recombinant monoclonal antibodies (MAbs) and their post-translational modifications. MAb capture, desalting and in situ reduction/alkylation were accomplished by sequential adsorption of analyte to solid phase beads (protein A, reverse-phase) suspended in microtiter plate wells. Following elution and rapid tryptic digestion in the presence of acid-labile surfactant (RapiGest), peptides were fractionated by stepwise elution from reverse-phase pipet tips and the fraction containing Fc N-glycopeptides isolated. Direct quantitative analysis of the relative abundance of peptide glycoforms by MALDI-TOF MS in linear mode closely correlated with normal phase HPLC analysis of fluorophore labeled N-glycans released by PNGaseF.

Laparoscopic transperitoneal nephrectomy is feasible in the first year of life and is not affected by kidney size. We analyzed the feasibility of laparoscopic nephroureterectomy in children younger than 1 year, with regard to size of impaired kidney. A total of 40 consecutive children underwent transperitoneal laparoscopic nephrectomy during a 4-year period. Of the patients 19 (48%) were younger than 1 year and were analyzed in detail. Nine of these patients (47.4%) had a multicystic dysplastic kidney, 9 (47.4%) had reflux nephropathy and 1 (5.3%) had obstructive nephropathy. The duration of operation, reasons for conversion, and intraoperative and postoperative complications were prospectively documented. Mean operative time was 133 minutes (range 60 to 240), and did not differ significantly between patients up to age 12 months compared to children 1 year and older (126 vs 148 minutes, NS). Nephroureterectomy was completed laparoscopically in 17 of 19 children (89%) up to age 12 months vs 20 of 21 (95%) 1 year and older (NS). In 1 child younger than 1 year suture dislocation at the renal artery required laparoscopic resuturing. No further complications were seen. In children younger than 1 year the mean operating time was not significantly different for resection of multicystic dysplastic kidney (8 patients, 113 minutes) compared to reflux nephropathy (9, 134 minutes, NS). Mean operating time did not differ significantly for kidney volumes less than 10 cc (8 patients, 119 minutes) compared to kidney volumes greater than 10 cc (9, 129 minutes, NS). The feasibility of transperitoneal laparoscopic nephroureterectomy in children younger than 1 year is excellent. The duration of operation is not affected by patient age, underlying disease or kidney size.

Total and intrasynovial work of flexion of human cadaver flexor digitorum profundus tendons after modified Kessler and MGH repair techniques. The purpose of this study was to compare directly the total work of flexion (TWOF) and the intrasynovial work of flexion (IWOF) of human flexor digitorum profundus tendons and to analyze the ratio of the IWOF to the TWOF of human flexor digitorum profundus tendons. These factors may be important clinically in understanding the role of different methods of postoperative tendon rehabilitation for different types of tendon repairs, especially at the early stage after tendon repair. Two different tendon repairs, the modified Kessler and the Massachusetts General Hospital, were used in 18 digits from 6 freshly frozen human cadaver hands. The TWOF and the IWOF were tested by using a digit-resistance testing device. After tendon repair the TWOF increased 11.2% and 26.9% for the modified Kessler and MGH groups, respectively. The differences in increase between the 2 groups were significant. The IWOF increased 126.8% and 308.8% for the modified Kessler and Massachusetts General Hospital groups, respectively. The IWOF accounted for 16.4% of the TWOF for the intact tendon; this percentage was 28.6% and 45.0% for the modified Kessler and Massachusetts General Hospital groups, respectively. The IWOF accounts for 16% of the TWOF of normal human cadaver digits but it accounts for a much higher fraction after tendon repair. The ratio of the work of flexion within the synovial sheath to the TWOF varies depending on the type of repair chosen.

Structural and functional changes in nerve roots due to tension at various strains and strain rates: an in-vivo study. This study investigates the functional and structural responses of spinal nerve roots in vivo to various strains and strain rates. Seventy-two L5 dorsal nerve roots from male Sprague-Dawley rats were each subjected to a predetermined strain (<10%, 10-20%, and >20%; n = 8) and rate (0.01 mm/sec, 1 mm/sec, or 15 mm/sec; n = 24). Neurophysiologic recordings were performed before and after stretch to determine changes in conduction velocity (CV), amplitude, and area of the compound action potential (CAP). Morphological injury as evident by primary and secondary axotomy as well as impaired axoplasmic transport (IAT) was determined using the palmgren silver impregnation technique and betaAPP immunostaining, respectively. The results from neurophysiologic recordings indicate that as strain and rate increased, there was a decrease in CV, amplitude, and area of the CAP. Further, high strains led to a complete conduction block that appeared to be rate dependent. Strains of 16%, 10%, and 9%, at 0.01 mm/sec, 1 mm/sec, and 15 mm/sec, respectively, led to 50% probability of complete conduction block in the nerve roots. Results from histological assessment indicate an increase in periaxonal spacing (secondary axotomy) and torn fibers (primary axotomy), as well as impaired IAT, with increasing strain and rate. Overall, the results from the current study indicate that (1) functional nerve root injuries as evident by changes in the CV, amplitude, and area of the CAP are strain- and rate-dependent; (2) high strains at low rates cause complete conduction block in the roots, while a similar block was observed at lower strains at the high rate; (3) the extent of IAT and primary and secondary axotomy occurred concomitant with functional injury and were strain- and rate-dependent.

Autoantibodies against TIF-1-γ and CADM-140 in Spanish patients with clinically amyopathic dermatomyositis (CADM): clinical significance and diagnostic utility. Patients with clinically amyopathic dermatomyositis (CADM) appear to be at risk for developing cancer and interstitial lung diseases, but population data to confirm this hypothesis are limited. Moreover, CADM presents cutaneous and histological findings that may overlap with subacute cutaneous lupus erythematosus (SCLE). To determine the association between myositis-specific autoantibodies, myositis-associated autoantibodies and CADM in Spanish patients. In addition, to study the usefulness of these autoantibodies in the differential diagnosis between CADM and SCLE. Serum samples were tested for myositis-specific autoantibodies and myositis-associated autoantibodies through immunoprecipitation and other standardized methods. Anti-CADM-p140 and anti-p155 antibodies were the only myositis-specific autoantibodies found and were associated with interstitial lung diseases and cancer respectively. No myositis-associated autoantibodies were found in CADM. Moreover, clinical subsets and proportions seemed to differ from Asian cohorts, where anti-CADM-p140 is considered a CADM hallmark antibody and a risk factor for the development of interstitial lung disease. Interestingly, anti-SSA was highly associated with SCLE, whereas no myositis-specific autoantibodies were found in this entity. Association between CADM and myositis-specific autoantibodies and differences between CADM and SCLE were tested on a relatively small cohort of patients. There is an association between cancer-associated myositis and interstitial lung diseases and their hallmark autoantibodies in our cohort. In addition, the combined determination of myositis-specific autoantibodies and SSA autoantibodies may help to accurately discriminate SCLE from CADM.

Intranuclear dynamics of corticosteroid receptors and effects of proteasomal activity in cultured hippocampal neural cells. Adrenal corticosteroids readily enter the brain and exert markedly diverse effects, such as stress responses in the target neural cells. These effects are regulated by two receptor systems via the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), which are both ligand-dependent transcription factors. Several steroid hormone receptors including GR, estrogen receptor, and androgen receptor, have been shown to move rapidly in the nucleus even after ligand treatment, supposedly corresponding to transcriptional "fine-tuning". We applied fluorescence recovery after photobleaching (FRAP) to assess the mobility of green fluorescent protein (GFP)-tagged GR and -MR in the nucleus of transiently transfected cultured hippocampal neurons. FRAP results showed high mobility of GR and MR in the nucleus. Half-recovery time of GR was longer than that of MR in the presence of 10(-6)M corticosterone (CORT), but shorter in the presence of 10(-9)M CORT. Proteasome inhibition reduced the subnuclear mobility of GR and MR, and increased the transcriptional activity at both concentrations of CORT. We also investigated the differential effects of CORT concentration and proteasome inhibition on the nuclear retention level of these receptors. Our findings may provide intriguing new insights into the dynamics of corticosteroid receptors in neural cells and the molecular basis of stress regulation by these receptors in the hippocampus.

Controlled release, blind tests of DNAPL characterization using partitioning tracers. The partitioning tracer technique for dense nonaqueous phase liquid (DNAPL) characterization was evaluated in an isolated test cell, in which controlled releases of perchloroethylene (PCE) had occurred. Four partitioning tracer tests were conducted, two using an inverted, double five-spot pumping pattern, and two using vertical circulation wells. Two of the four tests were conducted prior to remedial activities, and two were conducted after. Each test was conducted as a "blind test" where researchers conducting the partitioning tracer tests had no knowledge of the volume, method of release, nor resulting spatial distribution of DNAPL. Multiple partitioning tracers were used in each test, and the DNAPL volume estimates varied significantly within each test based on the different partitioning tracers. The tracers with large partitioning coefficients generally predicted a smaller volume of PCE than that expected based on the actual release volume. However, these predictions were made for low DNAPL saturations (average saturation was approximately 0.003), under conditions near the limits of the method's application. Furthermore, there were several factors that may have hindered prediction accuracy, including tracer degradation and remedial fluid interference.

Hydra effects in stable communities and their implications for system dynamics. A hydra effect occurs when the mean density of a species increases in response to greater mortality. We show that, in a stable multispecies system, a species exhibits a hydra effect only if maintaining that species at its equilibrium density destabilizes the system. The stability of the original system is due to the responses of the hydra-effect species to changes in the other species' densities. If that dynamical feedback is removed by fixing the density of the hydra-effect species, large changes in the community make-up (including the possibility of species extinction) can occur. This general result has several implications: (1) Hydra effects occur in a much wider variety of species and interaction webs than has previously been described, and may occur for multiple species, even in small webs; (2) conditions for hydra effects caused by predators (or diseases) often differ from those caused by other mortality factors; (3) introducing a specialist or a switching predator of a hydra-effect species often causes large changes in the community, which frequently involve extinction of other species; (4) harvest policies that attempt to maintain a constant density of a hydra-effect species may be difficult to implement, and, if successful, are likely to cause large changes in the densities of other species; and (5) trophic cascades and other indirect effects caused by predators of hydra-effect species can exhibit amplification of effects or unexpected directions of change. Although we concentrate on systems that are originally stable and models with no stage-structure or trait variation, the generality of our result suggests that similar responses to mortality will occur in many systems without these simplifying assumptions. In addition, while hydra effects are defined as responses to altered mortality, they also imply counterintuitive responses to changes in immigration and other parameters affecting population growth.

Determination of CYP4A11-catalyzed lauric acid 12-hydroxylation by high-performance liquid chromatography with radiometric detection. Lauric acid serves as an endogenous substrate for the cytochrome P450 enzyme CYP4A11. A reverse-phase, high-performance liquid chromatography method is described for the quantification of 12-hydroxylauric acid formed enzymatically by incubation of 14C-labeled lauric acid with cDNA-expressed CYP4A11 or human liver microsomes. Analytical separation is achieved using a C18 column and a gradient of 30% acetonitrile and 2 mM perchloric acid to 100% methanol, using a detection scintillation counter. This method is applicable to enzymatic studies for determination of lauric acid 12-hydroxylation activity.

Cytochrome P450 2C19 loss-of-function polymorphism is associated with an increased treatment-related mortality in patients undergoing allogeneic transplantation. The polymorphic gene expression of CYP2C19 causes individual variability in drug metabolism and thereby in pharmacologic and toxicologic responses. We genotyped 286 patients and their donors for the CYP2C19 gene who underwent allogeneic transplantation for various diseases and analyzed their outcome. Patients were classified as: poor metabolizers (PMs; 3.1%), intermediate metabolizers (IMs; 24.5%) and extensive metabolizers (EMs; 72.5%). Patients genotyped as PMs had significant higher hepato- and nephrotoxicities compared to IMs or EMs. Maximum bilirubin and serum creatinine levels measured after transplant were approximately twofold higher than those of EMs or IMs. The increased toxicity resulted in an increased 4-year estimate for transplant-related mortality (TRM) with 50+/-18.6% for PMs compared to 25.1+/-3.7% for EMs (P<0.018) and 22.7 +/-5.6% for IMs (P<0.042), whereas no significant influence for relapse rate, overall survival or incidence of acute graft-versus-host disease grade 2-4 were found between the groups. Multivariate analysis including all potential factors that might influence TRM confirmed that the genotype of CYP2C19 is an independent factor, which influenced TRM significantly. These results suggest that genotyping for CYP450 2C19 can help to identify patients with higher risk for TRM.

Type 2 diabetes mellitus and heart failure. Diabetes mellitus and heart failure are common comorbidities, and their prevalence has increased significantly over the past decade. We examined the relationships between diabetes and heart failure, the effect of commonly prescribed antidiabetic drugs on the development of heart failure, and the benefits and risks of recommended heart failure therapies in patients with diabetes. Compared with patients with heart failure who do not have diabetes, patients with both diabetes and heart failure have a poorer prognosis, including a 1.5-2-fold higher risk of mortality. Based on the results of randomized controlled trials, insulin and sulfonylureas do not appear to protect against or contribute to the development of new-onset heart failure, whereas metformin may modestly reduce the risk. The use of metformin in patients with established heart failure is controversial; retrospective analyses have shown that metformin may have a beneficial effect on outcomes, but there are no prospective, randomized clinical trials to support its use in this population. The thiazolidinediones, however, contribute to the development of heart failure and increase the risk of heart failure exacerbations particularly when used in combination with insulin. Recommendations for the treatment of symptomatic heart failure in patients with diabetes have been largely derived from post hoc analyses or preplanned subgroup analyses in landmark clinical trials. The data clearly support the use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for both the prevention and treatment of symptomatic heart failure in patients with diabetes. Despite concerns regarding the potential risks of beta-blockers in patients with diabetes, these drugs have a clear mortality benefit in patients with stages B and C heart failure. Therefore, patients with diabetes should not be denied beta-blocker therapy unless there is a clear contraindication. Likewise, aldosterone receptor antagonists should be added to standard therapies in patients with stages C and D heart failure. Future heart failure studies should include a sufficiently large diabetes cohort to conduct meaningful preplanned subgroup analyses that examine the effect of proposed treatments on both heart failure-related and diabetes-related outcomes.

The Regulation of Wearable Medical Devices. This article provides a guideline for the design, manufacture, regulatory approval, and post-market surveillance (PMS) of wearable medical devices (WMDs). The integration of regulatory considerations can accelerate wearable device (WD) development from laboratory to market while mitigating device failure risks. The implementation of stringent clinical evaluations will transcend WDs beyond consumer products.

Phosphate solubility and the cyanate-mediated synthesis of pyrophosphate. The justification for a less alkaline primordial ocean (than present) is briefly reviewed, along with constraints on aqueous phosphate under such conditions. Based on the assumption that CaHPO(4) dihydrate determined the availability of phosphorus species, we have carried out laboratory simulations to determine equilibrium concentrations as a function of pH (in PIPES buffer) with added NaCl and CaCl(2). Consistent with expectations, solubility declines with higher pH and [CaCl(2)], but increases only slightly with [NaCl]. Significantly, PIPES shows no specific effect on the dissolution beyond its influence on pH and ionic strength. Data are also presented on the synthesis of pyrophosphate from the NaOCN/CaHPO(4).2H(2)O system, which could have provided a source of this phosphate anhydride on the early Earth.

A pilot study of telephone cognitive-behavioural therapy for obsessive-compulsive disorder in young people. Cognitive-behaviour therapy (CBT) is the recommended psychological treatment for obsessive compulsive disorder (OCD) in young people. Access to CBT may be limited by a number of factors, including lack of trained therapists, and geographic or financial factors preventing access to a specialized service. Telephone delivery of CBT represents one way of overcoming some of these accessibility issues. This pilot study describes outcomes for a telephone-based cognitive-behavioural treatment for obsessive-compulsive disorder (OCD) in young people. Ten participants, aged 13 to 17 years, and their parents received up to 16 sessions of telephone CBT (TCBT). Measures of OCD symptoms were obtained using multiple informants and a repeated measures design. Assessments were conducted at pre-treatment, post-treatment, and at 6- and 12-month follow-up. Improvements were found for OCD symptoms across all informants. Family satisfaction with treatment over the telephone was high. The findings suggest that TCBT is a clinically effective, feasible and acceptable means of service delivery that offers the potential to make CBT a more accessible treatment for young people. TCBT requires further evaluation in randomized, controlled trials to compare effectiveness with face-to-face CBT, which currently represents the usual care model.

Neuronal control of mammalian vocalization, with special reference to the squirrel monkey. Squirrel monkey vocalization can be considered as a suitable model for the study in humans of the neurobiological basis of nonverbal emotional vocal utterances, such as laughing, crying, and groaning. Evaluation of electrical and chemical brain stimulation data, lesioning studies, single-neurone recordings, and neuroanatomical tracing work leads to the following conclusions: The periaqueductal gray and laterally bordering tegmentum of the midbrain represent a crucial area for the production of vocalization. This area collects the various vocalization-triggering stimuli, such as auditory, visual, and somatosensory input from diverse sensory-processing structures, motivation-controlling input from some limbic structures, and volitional impulses from the anterior cingulate cortex. Destruction of this area causes mutism. It is still under dispute whether the periaqueductal region harbors the vocal pattern generator or merely couples vocalization-triggering information to motor-coordinating structures further downward in the brainstem. The periaqueductal region is connected with the phonatory motoneuron pools indirectly via one or several interneurons. The nucleus retroambiguus represents a crucial relay station for the laryngeal and expiratory component of vocalization. The articulatory component reaches the orofacial motoneuron pools via the parvocellular reticular formation. Essential proprioceptive feedback from the larynx and lungs enter the vocal-controlling network via the solitary tract nucleus.

[Effect of an alternating magnetic field on the development of spontaneous hypertension in rats]. The effect of varying magnetic field on the development of spontaneous hypertension was studied in experiments on Okamoto rats. The influence of magnetic field during antenatal development caused persistent changes in lymphocyte and organ metabolism and accelerated the appearance of spontaneous hypertension in rats. Based on enzymatic activity of lymphocytes it is possible to predict the development of spontaneous arterial hypertension.

Decontamination of biological agents from drinking water infrastructure: a literature review and summary. This report summarizes the current state of knowledge on the persistence of biological agents on drinking water infrastructure (such as pipes) along with information on decontamination should persistence occur. Decontamination options for drinking water infrastructure have been explored for some biological agents, but data gaps remain. Data on bacterial spore persistence on common water infrastructure materials such as iron and cement-mortar lined iron show that spores can be persistent for weeks after contamination. Decontamination data show that common disinfectants such as free chlorine have limited effectiveness. Decontamination results with germinant and alternate disinfectants such as chlorine dioxide are more promising. Persistence and decontamination data were collected on vegetative bacteria, such as coliforms, Legionella and Salmonella. Vegetative bacteria are less persistent than spores and more susceptible to disinfection, but the surfaces and water quality conditions in many studies were only marginally related to drinking water systems. However, results of real-world case studies on accidental contamination of water systems with E. coli and Salmonella contamination show that flushing and chlorination can help return a water system to service. Some viral persistence data were found, but decontamination data were lacking. Future research suggestions focus on expanding the available biological persistence data to other common infrastructure materials. Further exploration of non-traditional drinking water disinfectants is recommended for future studies.

Systematic Review of Measurement Property Evidence for 8 Financial Management Instruments in Populations With Acquired Cognitive Impairment. To critically appraise the measurement property evidence (ie, psychometric) for 8 observation-based financial management assessment instruments. Seven databases were searched in May 2015. Two reviewers used an independent decision-agreement process to select studies of measurement property evidence relevant to populations with adulthood acquired cognitive impairment, appraise the quality of the evidence, and extract data. Twenty-one articles were selected. This review used the COnsensus-based Standards for the selection of health Measurement Instruments review guidelines and 4-point tool to appraise evidence. After appraising the methodologic quality, the adequacy of results and volume of evidence per instrument were synthesized. Measurement property evidence with high risk of bias was excluded from the synthesis. The volume of measurement property evidence per instrument is low; most instruments had 1 to 3 included studies. Many included studies had poor methodologic quality per measurement property evidence area examined. Six of the 8 instruments reviewed had supporting construct validity/hypothesis-testing evidence of fair methodologic quality. There is a dearth of acceptable quality content validity, reliability, and responsiveness evidence for all 8 instruments. Rehabilitation practitioners assess financial management functions in adults with acquired cognitive impairments. However, there is limited published evidence to support using any of the reviewed instruments. Practitioners should exercise caution when interpreting the results of these instruments. This review highlights the importance of appraising the quality of measurement property evidence before examining the adequacy of the results and synthesizing the evidence.

Activation of MAPK signaling pathway and NF-kappaB activation in pterygium and ipsilateral pterygium-free conjunctival specimens. To evaluate mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) signaling pathways in pterygium and pterygium-free conjunctivas. Primary pterygia (n = 21), ipsilateral superior-temporal bulbar conjunctivas (n = 8), and healthy conjunctival (n = 5) biopsy specimens were analyzed. Total and phosphorylated (phospho) levels of extracellular-regulated 1/2 (ERK1/2), p38, and c-jun N-terminal (JNK) MAPKs and NF-κB inhibitor-alpha (IκΒ-α) were analyzed by immunobead-based assay. Tissue phospho-, total protein, and activation values determined by phospho/total ratios were compared. Correlation among those values and clinical parameters were determined. Average-linkage hierarchical cluster analysis identified patients with similar protein activation values. The k-nearest neighbor classifier predicted the origin of specimens based on protein levels. Pterygium samples had significantly lower total JNK and IκΒ-α levels than did healthy conjunctivas. Decreased total JNK and IκΒ-α and increased phospho-IκΒ-α levels and phospho/total ratio of JNK and IκΒ-α were present in ipsilateral conjunctivas compared with healthy conjunctivas. Protein levels were correlated among them in pterygium, ipsilateral, and healthy conjunctivas and with sun exposure, pterygium grade, and pterygium measurements. Cluster analysis of activation values and ratios in pterygium and ipsilateral-conjunctiva revealed different groups of patients with similar values. Prediction accuracy was 70% to 80% for the classifiers phospho- and total protein levels and phospho/total ratio. Pterygium and pterygium-free ipsilateral conjunctivas had alterations in MAPK and NF-κB pathways not present in healthy conjunctivas. The high prediction accuracy based on phospho- and total protein levels and phospho/total ratio of ERK1/2, p38, JNK, and IκB-α suggests these molecules as potential biomarkers of inflammation in pterygia.

Smoking habits among physicians in Istanbul and their attitudes regarding anti-smoking legislation. The purpose of this study was to analyze smoking related beliefs, attitudes and knowledge on anti-smoking legislation among physicians practicing in Istanbul, Turkey. Questionnaires were sent to 18.000 physicians who were also members of Istanbul Chamber of Medicine. Three hundred-seventy and four physicians responded. Two hundred-fifty of the respondents were males (66.8%) and 124 were females (33.2%). Sixty out of 374 physicians were smokers. Eighteen of them (30%) were females, 42 of them (70%) were males. 91.5% of physicians who smoked tobacco and 98.4% of non-smoker physicians agreed that smoking is a serious health issue. 91.1% of nonsmoker physicians and 70.7% of smokers asked their patients about their smoking habits. The difference between smokers and non-smokers was statistically significant in both comparisons (p= 0.012 and p= 0.00, respectively). 25% of smoking physicians and 34.5% of non-smokers referred their patients to smoking cessation centers. 21.7% of smoking physicians and 28.8% of non-smokers believed in the success of pharmacological therapy. The difference between smokers and non-smokers was statistically non significant (p= 0.167 and p= 0.262, respectively). This results suggests that physicians have insufficient knowledge on smoking cessation therapies and the law regarding the use of tobacco and that smoking cessation techniques should be incorporated in the curriculum of the faculties and post graduation training programs.

Plasma pancreatic polypeptide concentrations in acute pancreatitis. Plasma human pancreatic polypeptide (hPP) concentrations were measured in 17 patients with acute pancreatitis. On admission the mean plasma hPP concentration was 33 +/ 6,9 pmol/l (range 11-92 pmol/l), which was similar to the mean hPP concentration of 43 +/- 4 pmol/l (range 11-92 pmol/l) in age-matched healthy subjects. The plasma immunoreactive glucagon (IRG) concentration was elevated 5-fold. Nine patients were managed conventionally and received prolonged glucagon infusion, and 8 were managed conventionally and received saline infusion. Treatment was carried out in a double-blind manner. Glucagon infusion caused a further 5-fold rise in circulating IRG concentrations and an increase in the blood glucose concentration from 7,5 to 9,7 mmol/l. This was associated with a fall in hPP concentrations and a significant reduction in variability. It is suggested that plasma hPP levels are not elevated in patients with acute pancreatitis and, therefore, do not reflect acute pancreatic damage.

Lysophosphatidylcholine increases the secretion of matrix metalloproteinase 2 through the activation of NADH/NADPH oxidase in cultured aortic endothelial cells. Matrix metalloproteinases (MMPs) play a pivotal role in angiogenesis, atherogenesis, vascular remodeling after vascular injury, and instability of atherosclerotic plaque. The present study was undertaken to investigate the effect of lysophosphatidylcholine, a major component of oxidized low density lipoprotein (LDL), on the regulation of MMPs in cultured bovine aortic endothelial cells (BAECs). Furthermore, we explored the potential role of oxidative stress in the regulation of MMP. LPC increased the secretion of gelatinolytic activity, as well as, protein of MMP-2 from BAECs. The stimulation of BAEC with superoxide increased the production of MMP-2 and it also induced its activation. Electron spin resonance (ESR) with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as spin trap agent demonstrated that lysophosphatidycholine (LPC) induced generation of reactive oxygen (ROS) species from BAECs. The inhibition of NADH/NADPH oxidase, one of the potential sources of superoxide in endothelial cells, attenuated the effect of LPC. Our findings suggest that LPC might activate the endothelial NADH/NADPH oxidase to enhance superoxide production, and it might, in turn, enhance MMP-2 induction.

[Simple renal cysts]. With the widespread use of non-invasive diagnostic tools, such as abodminal ultrasound and computerized tomography, renal cysts are diagnosed with increasing frequency. In patients 50 years or older, simple renal cysts of various size may be found in nearly one third. Increasing frequency with age is clearly demonstrated. Two thirds of simple renal cysts are 2 cm or less in diameter. The average renal cyst needs about 10 years to reach 2 cm in size. Simple renal cysts (category I according to Bosniak classification) usually are asymptomatic, produce no harm to the kidney and require no treatment once diagnosed. However, an occasional eypanding cyst causes progressive obstruction to caliceal and pelvic outflow. There is a possible association between renal cysts and arterial hypertension. Renal cysts may produce segmental renal ischemia, and in turn activate the renin angiotensin system. Percutaneous cyst aspiration or surgical cyst removal could cause a fall in blood pressure. Bosniak suggested a classification in an attempt to sort out the different cases into nonsurgical (category I and II), and surgical ones (category III and IV). Borderline between cystic lesions type II and III is not clear-cut, but Bosniak type IV lesions are clearly cystic renal cell carcinoma.

Patient Perspectives on Nurse-led Consultations Within a Pilot Structured Transition Program for Young Adults Moving From an Academic Tertiary Setting to Community-based Type 1 Diabetes Care. We aimed to evaluate patient self-management activities, patient perceptions of the therapeutic relationship and satisfaction with nurse-led consultations as part of a structured, pilot program transitioning young adults with type 1 diabetes (T1DM) to adult-oriented community-based practices. A descriptive, cross-sectional study of patients receiving nurse-led consultations. Patients provided sociodemographic/health information, glycated hemoglobin (HbA1c) measures and completed questionnaires assessing self-management (Revised Self-Care Inventory) and the therapeutic relationship (Caring Nurse-Patient Interaction - short scale). HbA1c values were compared to guideline recommendations. Twenty patients participated. HbA1c was ≤7.5% in 3/14 (21%) and 5/14 (36%) exhibited poor glycemic control (≥9.5%). The greatest concordance for self-care was in relation to insulin therapy (4.5±0.5) while patients reported the lowest adherence to diet recommendations (2.9±0.8). Overall satisfaction with nurse-led consultations was high (4±0.5 out of 5). Patients considered diabetes knowledge and technical competence as very important and were most pleased with the humanistic aspects of nursing care. Respect for privacy was deemed the most important (and most frequently observed) nursing attitude/behavior during consultations. Young adults found the nurse-led consultations with therapeutic education to develop T1DM self-care skills are an important complement to medical management during transition. Patient autonomy and privacy should be respected during this developmental period. Nurses taking a humanistic approach towards accompanying and supporting the patient can enhance the therapeutic relationship during transition and promote continuity of care. Transition nurses can use technical competence and therapeutic education to empower patients for self-management.

Synthesis and biological evaluation of fluoropyrazolesulfonylurea and thiourea derivatives as possible antidiabetic agents. Fluorinated pyrazoles, benzenesulfonylurea and thiourea and their cyclic sulfonylthiourea derivatives were prepared as hypoglycemic agents. The chemistry involves the condensation of 4-hydrazino benzenesulfonamide hydrochloride with fluorochalcones to give pyrazoline derivatives which upon oxidation with bromine water afforded corresponding pyrazoles. Reaction of pyrazolines with isocyanates and isothiocyanates give the corresponding ureas and thioureas. Subsequent cyclization of these thiourea derivatives with ethyl bromoacetate and α-bromoacetophenone yielded the 4-oxothiazolidines and thiazolines, respectively. Preliminary biological screening of the prepared compounds revealed significant antidiabetic activity. Molecular and biological properties calculations revealed favorable drug-like profiles of six compounds. The structure-activity relationship (SAR) and in silico drug relevant properties calculations (HBD, HBA, tPSA, miLogP, molecular weight, % ABS, drug-likeness and drug score) endorse that these compounds are potential leads for future drug discovery study.

Validating assessment of neonatal jaundice with transcutaneous bilirubin measurement. In response to current trends in maternity care, nurses are assuming a major role in providing quality care for new mothers and their babies postdischarge through follow-up home care. Jaundice has been identified as the most commonly encountered cause of morbidity among healthy infants during the first week of life, and nurses must possess accurate neonatal assessment skills. Unlike nurses who work in hospital settings, those who provide home care do not have ready access to colleagues for consultation and validation of assessments. The result of unrefined assessment skills of nurses may be requests for unnecessary invasive procedures for infants and, consequently, monetary charges to patients for unnecessary lab work. A quasi-experimental design was used to determine whether the use of a jaundice meter to validate nurses' visual assessments would help them develop more accurate assessments of neonatal jaundice. Findings revealed high correlations between visual scale rankings of jaundice and jaundice meter readings (RS = .85, p < .01). The results of this pilot study indicate that the use of a jaundice meter may be a noninvasive as well as a cost-effective way to validate nurses' visual assessments of neonatal jaundice in the home.

[Study on the water-soluble composition release of compound Danshen sustained-release tablet]. To study on the release of compound Danshen sustained-release tablet and the evaluate method of Chinese material medica compound sustained-release preparation. Rotating basket method and HPLC were employed. Through the determination of 6 time-point samples, the water-soluble compositions of compound Danshen sustained-release tablet had a Well-balanced release behavior with a zero-grade release model or Higuchi release model. Compound Danshen sustained-release tablet had a zero-grade release model. The method was rapid and stable and could be applied to evaluate the water-soluble composition release of compound Danshen sustained-release Tablet.

The canonical network of autotrophic intermediary metabolism: minimal metabolome of a reductive chemoautotroph. Chemoautorophs that fix carbon by the reductive tricarboxylic acid cycle represent one of the dominant bacterial life forms that make a major contribution to biomass production. From the viewpoint of biogenesis, construction of a canonical chart of intermediary metabolism for this class of organisms may help us to understand early cellular evolution and point us to the last universal common ancestor. Data-mining the KEGG Pathways database enabled us to integrate required biosynthetic pathways and derive a chart that represents the complete anabolic network of a reductive chemoautotroph. Compounds of this metabolic network together constitute a representative minimal metabolome that comprises 287 metabolites. These compounds have been classified into different groups including those compounds that form nodes in the network. It can be seen that a relatively sparse set of organic chemical reactions dominate the anabolic synthesis in the assembly of the minimal autotrophic metabolome. Empirical generalizations that result from analyzing this metabolic network may aid in elucidating selection rules that govern its emergence and further evolution and may also help in delineating attributes that impart the observed robustness to these metabolites.

Arterial protocol including prophylactic distal perfusion catheter decreases limb ischemia complications in patients undergoing extracorporeal membrane oxygenation. Venoarterial extracorporeal membrane oxygenation (ECMO) is a salvage therapy in patients with severe cardiopulmonary failure. Owing to the large size of the cannulas inserted via the femoral vessels (≤24-F) required for adequate oxygenation, this procedure could result in significant limb ischemic complications (10%-70%). This study evaluates the results of a distal limb perfusion arterial protocol designed to reduce associated complications. We conducted a retrospective institutional review board-approved review of consecutive patients requiring ECMO via femoral cannulation (July 2010-January 2015). To prevent arterial ischemia, a distal perfusion catheter (DPC) was placed antegrade into the superficial femoral artery and connected to the ECMO circuit. Limb perfusion was monitored via near-infrared spectroscopy (NIRS) placed on both calves. Decannulation involved open repair, patch angioplasty, and femoral thrombectomy as needed. A total of 91 patients were placed on ECMO via femoral arterial cannula (16-F to 24-F) for a mean duration of 9 days (range, 1-40 days). A percutaneous DPC was inserted prophylactically at the time of cannulation in 55 of 91 patients, without subsequent ischemia. Of the remaining 36 patients without initial DPC placement, 12 (33% without DPC) developed ipsilateral limb ischemia related to arterial insufficiency, as detected by NIRS and clinical findings. In these patients, the placement of a DPC (n = 7) with or without a fasciotomy, or with a fasciotomy alone (n = 4), resulted in limb salvage; only one patient required subsequent amputation. After decannulation (n = 7), no patients had further evidence of limb ischemia. Risk factors for the development of limb ischemia identified by categorical analysis included lack of DPC at time of cannulation and ECMO cannula size of less than 20-Fr. There was a trend toward younger patient age. Overall ECMO survival rate was 42%, whereas survival in patients with limb ischemia was only 25%. Limb ischemia complications from ECMO may be decreased by prophylactic placement of an antegrade DPC. Without DPC, continuous monitoring using NIRS may identify limb ischemia, which can be treated subsequently with DPC and or fasciotomy.

Withholding medical treatment from the severely demented patient. Decisional processes and cost implications. We performed an observational study to determine the prevalence of severe dementia in a general medicine unit, the categories of acute medical care provided to these patients, the process by which treatment decisions are made, and their cost implications. The prevalence of severe dementia was 4.4%. The patients from whom some form of acute medical care was withheld (26 [45.6%] of 57) were more severely ill at admission and had a mortality rate five times higher than those who received full care. Physicians cited family wishes in 75.9% of the decisions to limit care but in only 10.9% of the decisions to give full care. The only differences in charges incurred were due to differential mortality rates in individuals from whom care was withheld. We recommend that hospitals develop and implement protocols for decision making in the care of the severely demented to promote open discussions among providers and families and to increase family contributions to decision making. We believe that the extension of this consultative approach to decisions involving severely demented patients may have the virtue of combining more humane care with more cost-effective care.

Analysis of Mitochondrial Markers of Programmed Cell Death. Mitochondria play a crucial role in programmed cell death (PCD) in plants. In most cases of mitochondria-dependent PCD, cytochrome c (Cyt c) released from mitochondria due to the opening of mitochondrial permeability transition pore (MPTP) and the activation of caspase-like proteases. Here we describe the analytic methods of mitochondrial markers of PCD including mitochondria isolation, mitochondrial membrane permeability, mitochondrial inner membrane potential, Cytc release, ATP, and mitochondrial reactive oxygen species (ROS).

Isolation and characterisation of the pyruvate dehydrogenase complex of anaerobically grown Enterococcus faecalis NCTC 775. In this contribution the isolation and some of the structural and kinetic properties of the pyruvate dehydrogenase complex (PDC) of anaerobically grown Enterococcus faecalis are described. The complex closely resembles the PDC of other Gram-positive bacteria and eukaryotes. It consists of four polypeptide chains with apparent molecular masses on SDS/PAGE of 97, 55, 42 and 36 kDa, and these polypeptides could be assigned to dihydrolipoyl transacetylase (E2), lipoamide dehydrogenase (E3) and the two subunits of pyruvate dehydrogenase (E1 alpha and E1 beta), respectively. The E2 core has an icosahedral symmetry. The apparent molecular mass on SDS/PAGE of 97 kDa of the E2 chain is extremely high in comparison with other Gram-positive organisms (and eukaryotes) and probably due to several lipoyl domains associated with the E2 chain. NADH inhibition is mediated via E3. The mechanism of inhibition is discussed in view of the high PDC activities in vivo that are found in E. faecalis, grown under anaerobic conditions.

Rapid protein extraction from Saccharomyces cerevisiae. We have developed and evaluated an easy and rapid method for extraction of proteins from yeast cells for sodium dodecyl sulphate (SDS)-gel electrophoresis and Western blotting. The procedure comprises a centrifugation step to harvest the cells, addition of a sample buffer and heating, then another centrifugation step before applying the extracted proteins found in the supernatant to an SDS gel. It is applicable to the study of large numbers of samples in 1 day. This procedure is easier, quicker, and as efficient as procedures using base and 2-mercaptoethanol, but somewhat less efficient than lysis with glass beads under certain conditions.

Prognostic value of collagen turnover biomarkers in cardiac resynchronization therapy: A subanalysis of the TRUST CRT randomized trial population. A substantial proportion of patients do not respond to cardiac resynchronization therapy (CRT). Various echocardiographic and biochemical markers including collagen turnover biomarkers were suggested to predict CRT results. However, pathological significance of collagen turnover biomarkers in CRT remains controversial. The aim of the present study was to evaluate the relationship between levels of collagen turnover biomarkers (amino-terminal propeptide of procollagen type I and amino-terminal propeptide of procollagen type III [PIIINP]), N-terminal of the prohormone brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein, and matrix metalloproteinases (metalloproteinase-2 and metalloproteinase-9) and echocardiographic response to CRT and clinical outcomes. The study population consisted of patients enrolled in the Triple Site Versus Standard Cardiac Resynchronization Therapy trial. Blood samples were obtained before implantation of a CRT with defibrillator. The levels of PIIINP, amino-terminal propeptide of procollagen type I, metalloproteinase-2, and metalloproteinase-9 were determined using commercially available ELISA kits. High-sensitivity C-reactive protein and NT-proBNP levels were determined in a standard way. Samples were collected from 74 of 100 enrolled patients. The multivariate logistic regression analysis demonstrated that low PIIINP levels (odds ratio [OR] 3.56; 95% confidence interval [CI] 1.23-10.24; P = .017) and baseline ejection fraction (OR 2.14; 95% CI 1.11-4.11; P = .02) were favorably associated with echocardiographic response. PIIINP and NT-proBNP levels appeared to be independent predictors of all-cause mortality (PIIINP: OR 3.11; 95% CI 1.21-7.89; P = .033; NT-proBNP: OR 2.05; 95% CI 1.11-4.96; P = .039) and risk of major cardiac adverse event (PIIINP: OR 3.56; 95% CI 1.53-9.15; P = .007; NT-proBNP: OR 4.51; 95% CI 1.75-11.6; P = .001). PIIINP levels showed significant additive value in predicting mortality as compared with NT-proBNP levels, but they were not superior to ejection fraction in predicting response. Survival analysis with cutoff values identified by receiver operating characteristic analysis confirmed a significant benefit associated with low baseline PIIINP levels. Low PIIINP levels are associated with favorable echocardiographic response and long-term survival in CRT recipients.

A novel assay for the evaluation of the prooxidant-antioxidant balance, before and after antioxidant vitamin administration in type II diabetes patients. The application of a novel assay for the direct measurement of prooxidant-antioxidant balance (PAB) in type II diabetes and the evaluation of antioxidant therapy. The assay is based on 3,3',5,5'-tetramethylbenzidine and its cation, used as a redox indicator participating in two simultaneous reactions. PAB was determined in the sera of healthy volunteers and type II diabetes patients. The results were compared with clinical and biological parameters, protein oxidation markers, as well as the results of antioxidant and prooxidant assays. PAB, after administration of vitamins C and E for 1 day, 1 month and 2 months was also determined. Increased PAB was found in the patients' group and correlated with parameters involved in diabetic complications, protein oxidation markers, antioxidant and prooxidant assays. One day after vitamin administration, a significant shift of PAB towards antioxidants was observed. PAB remained unchanged after 1 month and changed marginally in favor of prooxidants in the second month of the therapy. These results indicate that the measurement of PAB may be useful to identify and follow-up patients who need antioxidant therapy.

Motivating donors to genetic research? Anthropological reasons to rethink the role of informed consent. In this article we explore the contribution from social anthropology to the medical ethical debates about the use of informed consent in research, based on blood samples and other forms of tissue. The article springs from a project exploring donors' motivation for providing blood and healthcare data for genetic research to be executed by a Swedish start-up genomics company. This article is not confined to empirical findings, however, as we suggest that anthropology provides reason to reassess the theoretical understanding of autonomy as generally defined by Beauchamp and Childress. Careful consideration of the trust expressed by donors through the act of donation, furthermore, suggests that there is reason to redirect the ethical scrutiny from informed consent to issues concerning institutional arrangements and social responsibility. In particular, we suggest that an anthropological approach could facilitate a reconsideration of the political implications of using informed consent as a regulatory practice in tissue-based research.

Novel mutations in sarcomeric protein genes in dilated cardiomyopathy. Mutations in sarcomeric protein genes have been reported to cause dilated cardiomyopathy (DCM). In order to detect novel mutations we screened the sarcomeric protein genes beta-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), troponin T (TNNT2), and alpha-tropomyosin (TPM1) in 46 young patients with DCM. Mutation screening was done using single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The mutations in MYH7 were projected onto the protein data bank-structure (pdb) of myosin of striated muscle. In MYH7 two mutations (Ala223Thr and Ser642Leu) were found in two patients. Ser642Leu is part of the actin-myosin interface. Ala223Thr affects a buried residue near the ATP binding site. In MYBPC3 we found one missense mutation (Asn948Thr) in a male patient. None of the mutations were found in 88 healthy controls and in 136 patients with hypertrophic cardiomyopathy (HCM). Thus mutations in HCM causing genes are not rare in DCM and have potential for functional relevance.

Anti-Caries Effect of Arginine-Containing Formulations in vivo: A Systematic Review and Meta-Analysis. To assess the anti-caries effect of arginine-containing formulations in vivo on caries lesions compared with fluorides or placebo. Randomized or quasi-randomized human clinical trials wherein arginine was delivered by any method were considered. The MEDLINE, Web of Science, EMBASE, Cochrane Library, and CBM databases were searched to identify relevant articles published up to December 2014. Grey literature was also searched. Two authors performed data extraction independently and in duplicate using data collection forms. Each included study was assessed using the Cochrane risk of bias assessment tool. Of the 470 studies screened, 31 full articles were scrutinized and assessed for eligibility. Ten studies (n = 15,546 participants) were selected for final inclusion. The meta-analysis results (n = 7 studies) demonstrated a synergistic effect of arginine when used in conjunction with fluoride on early coronal and root caries compared with placebo or fluoride alone. No specific side effects related to arginine usage were identified. When used in combination with a calcium compound and fluoride, arginine potentially provides a superior anti-caries effect compared with matched formulations of fluoride alone. However, the level of evidence was downgraded because of risks of bias and potential publication bias. In the future, more high quality, non-industry-supported clinical studies in this research area are required before any definitive recommendations can be made.

[Effects of sexual abuse experiences on therapeutic outcome: study of eating disordered patients 2 years after inpatient psychotherapy]. The incidence of CSA in the general female population is supposed to range between 10 and 40 percent. There has not yet been done much research on how CSA victims differ in comparison to non-CSA patients in regard to psychotherapy outcome. This paper presents the results of a study concerning this problem. 670 female patients suffering from anorexia or bulimia nervosa, who had undergone an inpatient treatment were asked to fill out a questionnaire on their body image two years later. Moreover the patients were asked if their symptomatology persisted, if they had been satisfied with the therapy, how often they were ill (and unable to work) before and after the therapy and if they attempted suicide before or after the therapy. The questionnaires of 393 patients could be evaluated. 21.1% (n = 83) of them had a history of CSA. There were only few statistically significant differences: 1. CSA patients more often improved their attitude towards their head and their genitals in comparison to non-CSA patients. 2. They more often attempted suicide before therapy. 3. After the therapy only among the anorexic CSA patients suicidal attempts happened more often than among anorexics without CSA. These results suggest that CSA patients benefit from an inpatient therapy at least as well as non-CSA patients do. On the other hand further qualitative research is needed to understand more about the individual coping strategies of CSA victims.

Moebius syndrome: the new finding of hypertrophy of the coronoid process. The first detailed description of congenital facial paralysis was reported by Moebius in 1888. It is characterized by either unilateral or bilateral paralysis of the facial muscles and an associated abducens palsy. The present report is of two patients with Moebius syndrome, who were also diagnosed with trismus at birth. Each patient also demonstrated bilateral hypertrophy of the coronoid process of the mandible. In effect, the zygoma obstructed the excursion of the mandible because of a "coronoid block." A three-dimensional computed tomography scan demonstrated normal temporomandibular joints but bilateral hypertrophy of the coronoid processes and micrognathia. Both patients demonstrated less than 10 mm of oral excursion. Bilateral coronoidectomies were performed through an intraoral approach. The oral excursions after surgery increased to at least 20 mm. In each of these patients, the coronoid process was enlarged relative to the zygoma, which was of normal size and configuration. The trismus was associated with blocking of the coronoid by the anterior zygoma, preventing open or full excursion of the hypoplastic mandibles. Moebius syndrome can have a variable presentation at birth. In two patients, the authors describe a new finding of hypertrophy of the coronoid process and trismus secondary to obstruction of the coronoid by the hypertrophic zygomas during oral excursions. Each patient is described, and a review of the literature is discussed.

Cytoarchitecture of the fetal murine soleus muscle. The organogenesis of the soleus muscle of the 129 ReJ mouse (a mixed muscle, which in the adult contains approximately equal numbers of slow-twitch oxidative and fast-twitch oxidative-glycolytic myofibers) was studied in spaced, serial transverse, and longitudinal sections of muscles of 14-, 16-, and 18-day in utero and 1- and 5-day postnatal mice. A discrete soleus muscle was distinguished by 14 days in utero. It consisted of groups of closely apposed primary myotubes displaying junctional complexes and a pleomorphic population of mononucleated cells. Between 14 and 16 days in utero there was little de novo myotube formation. At 16 days in utero, basal lamina surrounded groups of primary myotubes; and primitive motor endplates were found on these myotubes. At 18 days in utero, the basal-lamina-enclosed groups of primary myotubes were no longer present. At this stage, basal lamina surrounded clusters (consisting of one primary myotube and one or more secondary myotubes) or independent myotubes (single myotubes surrounded by their own basal lamina). Cluster formation and cluster dispersal occurred concurrently, beginning at 18 days in utero and extending until birth. At birth, there was still a substantial population of immature, secondary myotubes that interdigitated with larger, more mature primary myofibers. At this stage, intermuscular axons had begun to myelinate, and postsynaptic specialization of the motor endplates had begun. Cluster dispersal and myonuclear migration was completed during the first 5 days postnatally with the muscle taking on adult characteristics. Beginning at 16 days in utero and extending into the neonatal period, there was evidence of myotube death in the soleus muscle.

A new surgical method of dynamic nasal valve collapse. To describe a technique for internal nasal valve collapse using radiofrequency-induced thermotherapy (RFITT). Prospective study. Academic research center. A total of 28 patients with nasal obstruction due to inspiratory nasal valve collapse were included in this study. Radiofrequency-induced thermotherapy. Visual analog scale score. Severity of obstruction scores improved in all patients, with the mean score improving at the left nostril from 8.2 before treatment to 3.4 after treatment and at the right nostril from 8.9 before treatment to 4.1 after treatment. The outcomes were measured using visual analog scale score before treatment and at 16 weeks after treatment. Improvement was shown in severity of obstruction (P < .001). This new method appears to be safe, quick, bloodless, and painless. These good, encouraging preliminary results must be confirmed by further study and long-term follow-up.

Identification of an equilibrium intermediate in the unfolding process of galectin-1, which retains its carbohydrate-binding specificity. The unfolding process of galectin-1 (Gal-1) in the presence of a denaturing agent was examined using fluorescence and far-UV circular dichroism (CD) spectroscopy determinations, and was found to be completely reversible. The data showed that the transitions of guanidine hydrochloride (GdnHCl)-induced lectin unfolding, in the absence of ligand, were biphasic in nature, clearly showing the existence of at least one stable intermediate. On the other hand, the unfolding in the presence of disaccharide yielded data that could fit very well to a two-state model, indicating a stabilizing effect of the ligand. The folding intermediate was further characterized by size exclusion chromatography, near-UV CD and anilinonaphtalene sulfonate binding, and shown to belong to the molten globule type. Strikingly, this intermediate retained its carbohydrate-binding specificity, as evidenced by the tryptophan fluorescence changes detected upon its interaction with lactose.

Long-term systemic exposure of orlistat, a lipase inhibitor, and its metabolites in obese patients. Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract; its systemic exposure is not required for its efficacy. However, knowledge of the extent of its systemic exposure is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening in obese patients was carried out by monitoring plasma concentrations of unchanged orlistat and its metabolites in five key double-blind, placebo-controlled phase II/III studies. Results of these studies involving the monitoring of plasma samples indicate that detection of intact orlistat in plasma was sporadic, and measurable concentrations were low (< 10 ng/mL or 0.02 microM) without evidence of accumulation, which is consistent with minimal absorption. It is concluded that systemic exposure of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition.

Study on drug interactions. Studies on the interactions of the drugs used in combination therapy of leprosy were attempted at this Institute. INH supplementation with clofazimine, therapy appeared to lower the skin levels of clofazimine, raising the plasma and urinary content of clofazimine. Concurrent administration of clofazimine with DDS does not appear to exert any influence on the excretion of DDS. The plasma DDS lowering effect of Rifampicin does not vary between fast and slow acetylators for DDS.

Helminths of saiga antelope in Kazakhstan: implications for conservation and livestock production. Saiga antelope (Saiga tatarica) graze extensively on livestock pasture, potentially enabling transmission of a wide range of parasitic helminths between saigas and domestic ruminants. Thirty-six of the 38 species of helminth that have been found in saigas in Kazakhstan in the past have been found also in domestic livestock. We examined 133 saigas culled for meat in autumn 1997, and found three species of cestode and 12 nematodes (nine in the abomasum), but no trematodes or lungworms. The most abundant species were Marshallagia marshalli, Marshallagia mongolica, and Nematodirus gazellae in the abomasum, Nematodirus gazellae in the small intestine, and Skrjabinema ovis in the large intestine. There was no clear relationship between intensities of abomasal nematodes and body condition. Age-intensity patterns differed between species: N. gazellae intensities were highest in saigas around 2-3 yr old, and declined in older animals, whereas the intensity of Marshallagia spp. rose asymptotically with age. Fecal egg density was directly proportional to adult worm intensity across ages for Marshallagia spp., but only in young animals for N. gazellae. There was no evidence that helminths, at the intensities observed, adversely affect saiga populations. The host range of many of the parasites found is broad, and transmission between saigas and livestock in both directions might become important to agriculture and conservation as livestock numbers recover. Simplified sampling techniques used in this study, and statistical analysis based on bootstrapping, could prove useful in other parasitologic surveys of wildlife in remote areas.

Influence of fungal elicitors on biosynthesis of natamycin by Streptomyces natalensis HW-2. To investigate the effect of fungal elicitors on biosynthesis of natamycin in the cultures of Streptomyces natalensis HW-2, the biomass and filtrate of the broth from Aspergillus niger AS 3.6472, Penicillium chrysogenum AS 3.5163, A. oryzae AS 3.2068, and Saccharomyces cerevisiae AS 2.2081 were used to induce natamycin production in S. natalensis HW-2. The results showed that the biomass of P. chrysogenum AS 3.5163 could enhance the yield of natamycin from 0.639 to 0.875 g l(-1). The elicitor from the fermentation broth of P. chrysogenum AS 3.5163 showed the highest inducing efficiency with the yield of natamycin enhanced from 0.632 to 1.84 g l(-1). The elicitor that was cultured for 2 days showed the strongest inducing activity during the fermentation of S. natalensis HW-2 for 24 h, and the yield of natamycin was enhanced from 0.637 to 2.12 g l(-1). The biochemical parameters were examined at the end of fermentation and the results demonstrated that both the growth of cells and the concentration of residual sugar could be influenced. The residual sugar decreased from 5.03 to 4.27 g l(-1), and the biomass decreased from 10.26 to 6.87 g l(-1). Finally, the elicitor was identified as a low molecular weight substance with a similar polarity to that of butyl alcohol by primary qualitative analysis.

Identification of glioma-specific RFX4-E and -F isoforms and humoral immune response in patients. For regulatory factor X4 (RFX4), two alternatively spliced variants, RFX4-A and -B, were reported in the testis. In this study, we identified transcript variants RFX4-C, -D, -E, and -F, and demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) that RFX4-A, -B and -C mRNAs were expressed only in the testis, and RFX4-D mRNA was expressed only in normal brain tissues. In tumors, RFX4-E and -F in addition to RFX4-D mRNA were expressed in gliomas by rapid amplification of cDNA ends and RT-PCR analyses. Expression of RFX4 mRNA was not observed in other tumors, such as lung, esophageal, stomach, colon or liver cancers. Quantitative real-time RT-PCR using common primer pairs detecting all of the variant transcripts showed high expression in normal testis, low expression in the brain (1% compared to the expression in testis), and overexpression in 17 of 61 gliomas (28%). Western blot analysis using DC28 monoclonal antibody (mAb) produced against recombinant RFX4-D C-terminus protein showed expression of RFX4-A and -C proteins, but not RFX4-B protein, in the testis, and expression of RFX4-D protein in the brain. Moreover, expression of RFX4-E and -F proteins, but not RFX4-D protein, was observed in gliomas. Immunohistochemistry analysis using DC28 mAb showed positive staining in the nuclei of spermatocytes in the testis and glioma cells. Antibody against RFX4 was detected in the sera of 3 of 58 (5%) glioma patients by enzyme-linked immunosorbent assay, suggesting the immunogenicity of RFX4-E and -F proteins in glioma patients.

Hierarchically porous bio-inspired films prepared by combining "breath figure" templating and selectively degradable block copolymer directed self-assembly. Polymer films with hierarchical micro- and nano-porosities were prepared by combining the fast solvent evaporation "Breath Figure" (BF) method, exhibiting a highly regular honeycomb micro-porous texture, with the additional nanoscale self-assembly of polylactide-block-polystyrene (PLA-b-PS) diblock copolymers, PLA being used thereafter as a sacrificial component for nano-porosity.

Ultrasound scanning for recalcitrant plantar fasciopathy. Basis of a new classification. The treatment of recalcitrant plantar fasciopathy is often empirical. Imaging is usually in the form of radiographs, if undertaken at all. The aim of this study is to characterise the disease pattern in recalcitrant cases of plantar fasciopathy. This allows classification of the pathology, which in turn allows meaningful evaluation of current and future treatments. One hundred and twenty-five consecutive feet with symptoms of 'plantar fasciitis' lasting longer than 6 months (all of which had failed to improve with a stepwise conservative management protocol) had confirmed plantar fasciopathy on ultrasound scanning. The disease characteristics were evaluated based on the scan findings. Of the patients evaluated, 66 % had typical insertional disease. The remaining 34 % had atypical distal fascia disease; 22 % had mixed insertional and distal disease, and 12 % had pure distal disease. Patients with pure distal disease were found to have either distal thickening or discrete fibromata. In this cohort of recalcitrant cases, ultrasound scans detected a high proportion of atypical non-insertional plantar fascia disease. This would not be detected without imaging studies, and therefore we recommend the use of ultrasound scanning in cases of recalcitrant plantar heel pain that have failed proper first-line management, in order to confirm the clinical diagnosis and to classify the disease as either insertional or non-insertional plantar fasciopathy (or mixed disease). Only in this way can treatments for this group of patients be systematically evaluated against different disease patterns to determine their effectiveness.

A study of the informatics literacy of clinical nurses in Taiwan. The purpose of this study is to identify the essential components for informatics literacy for clinical nurses working in Taiwanese hospitals. We developed a framework to explore the critical informatics literacy factors that clinical nurses should understand to be proficient in performing their professional duties. Survey methodology was used and the participants were senior administrators of nursing and other personnel in charge of implementing nursing information systems for 84 regional hospitals and medical centers. A total of 50 valid questionnaires was returned, with a 59.5% response rate. In summary, the results of the Taiwanese study are divided into three factors: informatics knowledge, informatics skills, and computer attitudes. A total of 58 questions was used for the measurement of initial nursing informatics literacy, and 49 items were considered to be the most required informatics literacy skills specifically for clinical nurses.

Shape diagram of vesicles in Poiseuille flow. Soft bodies flowing in a channel often exhibit parachutelike shapes usually attributed to an increase of hydrodynamic constraint (viscous stress and/or confinement). We show that the presence of a fluid membrane leads to the reverse phenomenon and build a phase diagram of shapes-which are classified as bullet, croissant, and parachute-in channels of varying aspect ratio. Unexpectedly, shapes are relatively wider in the narrowest direction of the channel. We highlight the role of flow patterns on the membrane in this response to the asymmetry of stress distribution.

Review: Epidemiology of Helicobacter pylori infection. This review summarizes recent publications on the epidemiology of Helicobacter pylori. Two major systemic analyses, from Malaysia and Ethiopia, were published. The Brazilian Consensus Conference has stated that H pylori infection is an infectious disease with an indication for antimicrobial therapy. A continuous decrease in H pylori prevalence was reported from many regions worldwide, including Korea, China, Iran, and Austria. A cross-sectional H pylori prevalence study conducted in the United Arab Emirates found 41% prevalence in a group of healthy children and adults. Several studies from Asia addressed H pylori prevalence in adults undergoing regular checkup. The largest of such studies, performed in Korea, involved 24 471 subjects and reported 41.5% seroprevalence. A relatively smaller study from East China on 3252 subjects reported 27.5% prevalence. In contrast, a study from Spain reported 87.2% seroprevalence. A report on the association between smoking and H pylori seropositivity was published on behalf of the Stomach Cancer Pooling (StoP) Project-a consortium of epidemiological studies of gastric cancer. Also, other potential risk factors, including occupational risk factors, water supply, and food were analyzed. Gastroesophageal reflux and sexual partners has been associated with a higher risk for H pylori acquisition, and gut microbiota was suggested to play a role in intrafamilial transmission of H pylori. Finally, in a few studies (from Mexico and Japan), the catalytic model for predicting the potential risk of acquiring H pylori infection in the future was used. As anticipated, a further decline in H pylori-related disease was demonstrated by applying the modeling.

[Experience of the ENT clinic--rehabilitation hospital of Iaşi in the diagnosis of hearing loss in children between 1 and 5 years of age]. The aim of this study is to asses the average age of diagnosis of congenital hearing loss in children up to 5 years old. A group of 48 children aged between 1-5 years old were admitted in our clinic in 2005 because of hearing impairment, noticed in most cases by their parents. All cases were investigated in our clinic by transient evoked oto-acoustic emission test, threshold auditory brainstem response, impedance-metry and, whenever possible, audiometry. Sensori-neural hearing loss of variable gravity was diagnosed in 30 cases, most of them in the 2-3 yrs group of age (9 cases). The etiology of hearing loss could be established in 9 cases only. 19 patients (63%) were hearing aided, but follow-up was not possible. The average age of congenital hearing loss diagnosis may be reduced by applying universal neonatal hearing screening and a well established modality of confirmation of deafness in infants identified by the universal screening.

Nuclear factor kappa B-dependent Zif268 expression in hippocampus is required for recognition memory in mice. Long-term memory formation requires gene expression after acquisition of new information. The first step in the regulation of gene expression is the participation of transcription factors (TFs) such as nuclear factor kappa B (NF-кB), which are present before the neuronal activity induced by training. It was proposed that the activation of these types of TFs allows a second step in gene regulation by induction of immediate-early genes (IEGs) whose protein products are, in turn, TFs. Between these IEGs, zif268 has been found to play a critical role in long-term memory formation and reprocessing after retrieval. Here we found in mice hippocampus that, on one hand, NF-кB was activated 45 min after training in a novel object recognition (NOR) task and that inhibiting NF-кB immediately after training by intrahippocampal administration of NF-кB Decoy DNA impaired NOR memory consolidation. On the other hand, Zif268 protein expression was induced 45 min after NOR training and the administration of DNA antisense to its mRNA post-training impaired recognition memory. Finally, we found that the inhibition of NF-кB by NF-кB Decoy DNA reduced significantly the training-induced Zif268 increment, indicating that NF-кB is involved in the regulation of Zif268 expression. Thus, the present results support the involvement of NF-кB activity-dependent Zif268 expression in the hippocampus during recognition memory consolidation.

KH-type splicing regulatory protein is regulated by nuclear factor-κB signaling to mediate innate immunity in Caco-2 cells infected by Salmonella enteritidis. Salmonella enteritidis infection occurs in enterogenous diseases, such as gastroenteritis and parenteral focal infection, which often involve inflammation of intestinal epithelial cells. The nuclear factor kappa B (NF-κB) pathway participates in the innate immune response to many gram-negative pathogenic bacteria and initiates inflammation in epithelial cells. KH-type splicing regulatory protein (KSRP) is a multi-domain RNA-binding protein that recruits the exosome-containing mRNA degradation complex to mRNAs coding for inflammatory response factors. However, it remains unclear whether KSRP is regulated by NF-κB signaling pathway in response to S. enteritidis infection and affects the development of inflammation. Accordingly, in this study, we investigated the role of KSRP in mediating the response to S. enteritidis in Caco-2 cells. The data revealed that S. enteritidis infection decreased KSRP expression, which was suppressed by blocking the NF-κB pathway. Additionally, S. enteritidis infection significantly increased the expression of inducible nitric oxide synthase and cyclooxygenase-2. Overexpression of KSRP reduced the expression levels of inflammatory factors in Caco-2 cells. KSRP was regulated by the NF-κB signaling pathway and participated in mediating the innate immune response to S. enteritidis infection in Caco-2 cells, and KSRP acted as a negative regulator of inflammatory gene expression.

[Risk evaluation on H7N9 avian influenza in Guangzhou, China]. We conducted both quick surveillance and evaluation programs within one week after the novel H7N9 influenza cases had been released by the Ministry of Health (MOH), to get the basic information on H7N9 virus in Guangzhou. We sampled live birds from food markets and the natural habitat of birds to detect H7N9, H5 and H9 viruses. We interviewed workers from both markets and natural habitats. We also reviewed records on pneumonia patients with unknown causes from the surveillance system, to find clues related to the identification of severe pneumonia. We sampled 300 specimens from 49 stalls in 13 food markets and a natural habitat but none showed H7N9 positive result. A chopping block was detected positive of carrying H5 avian influenza virus, while another 4 specimens including a chicken cage, a duck cage, a chopping block and a pigeon cage were detected positive of carrying H9 avian influenza virus. In the past month, no sick, dead birds or ILI cases among the workers were discovered. 21.2% (7/33) of the stalls did not follow the set regulations for prevention. 10.3% (4/39) of the stalls had the cages cleaned, 4 days after the inspection. 3.7% (2/54) of the workers wore masks and 40.7% (22/54) of them wore gloves during the slaughtering process. 102 bird feces specimens were tested negative on H7N9 virus. No pneumonia cases with unknown reason were identified. From April 3(rd) to 17(th), we found 26 severe pneumonia cases but with negative results on influenza A (H7N9). According to the data and information from 1) lab tests, 2) pneumonia cases with unknown reasons under the surveillance system, 3) the identification of severe pneumonia cases, and 4) preventive measures and actions taken by the workers, we inferred that no H7N9 virus or related cases were found prior to April in Guangzhou. However, the risk of H7N9 epidemic does exist because of the following reasons:1) improper market management process, 2) negligent behavior of the workers and 3) potential trend of the national situation, suggesting strategies related to poultry markets management, health education and preventive measures against the avian influenza need to be strengthened.

Collagenolytic enzymes assayed by spectrophotometry with suspensions of reconstituted collagen fibrils. Collagenolytic enzymes were quantitated by a method based on spectrophotometry of suspended reconstituted collagen fibrils. To obtain optically stable suspensions it was necessary to perform a short sonication of the aggregated fibrils at 10 degrees C. When fibrils were cleaved with mammalian fibroblast collagenase at 35 degrees C the triple helical collagen fragments (TCA and TCB) would uncoil spontaneously and the decreasing turbidity was used as an estimate of enzyme activity. The method is a specific collagenase assay since a possible cleavage in the non-helical parts of the collagen molecule with contaminating proteinases is without effect on the turbidity of the suspension and the collagen substrate is not converted to gelatin at 35 degrees C. After 1 h of incubation 0.2 U (equivalent to 0.2 micrograms) of fibroblast collagenase could be detected. In purification procedures with microbial collagenases many fractions were tested by overnight incubations in disposable cuvettes. Sealing of cuvettes with square silicone stoppers allowed rotation of enzyme-substrate mixtures directly in the cuvettes. Only standard laboratory equipment is required for this assay, which is not dependent on radiolabeling or preparation of specific immunologic reagents.

A proteomic study of the arabidopsis nuclear matrix. The eukaryotic nucleus has been proposed to be organized by two interdependent nucleoprotein structures, the DNA-based chromatin and the RNA-dependent nuclear matrix. The functional composition and molecular organization of the second component have not yet been resolved. Here, we describe the isolation of the nuclear matrix from the model plant Arabidopsis, its initial characterization by confocal and electron microscopy, and the identification of 36 proteins by mass spectrometry. Electron microscopy of resinless samples confirmed a structure very similar to that described for the animal nuclear matrix. Two-dimensional gel electrophoresis resolved approximately 300 protein spots. Proteins were identified in batches by ESI tandem mass spectrometry after resolution by 1D SDS-PAGE. Among the identified proteins were a number of demonstrated or predicted Arabidopsis homologs of nucleolar proteins such as IMP4, Nop56, Nop58, fibrillarins, nucleolin, as well as ribosomal components and a putative histone deacetylase. Others included homologs of eEF-1, HSP/HSC70, and DnaJ, which have also been identified in the nucleolus or nuclear matrix of human cells, as well as a number of novel proteins with unknown function. This study is the first proteomic approach towards the characterization of a higher plant nuclear matrix. It demonstrates the striking similarities both in structure and protein composition of the operationally defined nuclear matrix across kingdoms whose unicellular ancestors have separated more than one billion years ago.

Explaining the relationship between race/ethnicity and pharmacy purchased syringes among injection drug users in New York City. Pharmacy syringe sales without a prescription became legal in New York State on January 1, 2001 through the Expanded Syringe Access Demonstration Program (ESAP). At the same time, Pharmacy use among Black and Hispanic injection drug users was found to be significantly lower when compared to Whites. The purpose of this study was to assess the factors that could explain the relationship between race/ethnicity and pharmacy use. Data were combined from 2 on-going injection drug user (IDU) studies in 2 New York City neighborhoods. Social and behavioral factors independently associated with ever purchasing a nonprescription syringe in the past 6 months and examined using cross-sectional logistic regression. Of 337 IDUs, the majority were male (79%), Hispanic (73%) and had a mean age of 35 years. In bivariate analysis, IDUs who reported pharmacy use were less likely to be Black or Hispanic, older, and to have reported recent syringe exchange program (SEP) attendance compared to non-pharmacy users. Additionally, pharmacy users were more likely to have knowledge of ESAP, and report discrimination by police in the past year compared to non-users. After adjustment for recent SEP attendance (adjusted odds ratio [AOR]=0.27; 95% confidence interval [CI]=0.14-0.55), ESAP knowledge (AOR=13.11; 95% CI=6.54-26.31), discrimination by police (AOR=3.56; 95% CI=1.73-7.35), and discrimination due to race (AOR=0.25, 95% CI=0.11-0.58), race/ethnicity was not a significant predictor of pharmacy use. Race/ethnicity may not be an important determinant of ESAP when more salient social circumstances, such as past discrimination, are considered. Educational efforts should be enhanced to reach those who continue to perceive barriers to ESAP.

Localization of the insulin receptor in caveolae of adipocyte plasma membrane. The insulin receptor is a transmembrane protein of the plasma membrane, where it recognizes extracellular insulin and transmits signals into the cellular signaling network. We report that insulin receptors are localized and signal in caveolae microdomains of adipocyte plasma membrane. Immunogold electron microscopy and immunofluorescence microscopy show that insulin receptors are restricted to caveolae and are colocalized with caveolin over the plasma membrane. Insulin receptor was enriched in a caveolae-enriched fraction of plasma membrane. By extraction with beta-cyclodextrin or destruction with cholesterol oxidase, cholesterol reduction attenuated insulin receptor signaling to protein phosphorylation or glucose transport. Insulin signaling was regained by spontaneous recovery or by exogenous replenishment of cholesterol. beta-Cyclodextrin treatment caused a nearly complete annihilation of caveolae invaginations as examined by electron microscopy. This suggests that the receptor is dependent on the caveolae environment for signaling. Insulin stimulation of cells prior to isolation of caveolae or insulin stimulation of the isolated caveolae fraction increased tyrosine phosphorylation of the insulin receptor in caveolae, demonstrating that insulin receptors in caveolae are functional. Our results indicate that insulin receptors are localized to caveolae in the plasma membrane of adipocytes, are signaling in caveolae, and are dependent on caveolae for signaling.

Extensive gene duplication of acetylcholinesterase associated with organophosphate resistance in the two-spotted spider mite. Monocrotophos-resistant two-spotted spider mites (TSSMs), Tetranychus urticae, are known to possess three mutations on the acetylcholinesterase (AChE) gene (Tuace) that are involved in target site insensitivity. Cross-strain comparison of three strains (highly resistant AD, moderately resistant PyriF and susceptible UD strains) revealed that resistant strains have relatively more Tuace copies than the UD strain and that the levels of transcript were directly proportional to copy numbers. AChEs from the AD and PyriF strains had similar V(max) values to those of AChE from the UD strain but increased K(m) and reduced k(cat) constants, suggesting that the mutated, resistant form of AChE may carry a fitness cost. Relative copy numbers of Tuace in field populations varied from 2.4 to 6.1, correlating well with their levels of resistance (r(2)= 0.895). These results are suggestive of the involvement of Tuace gene duplication in resistance. Thus, monocrotophos resistance in TSSMs appears to have evolved through a combination of mutation accumulation and extensive gene duplication.

Comparative study of liposomes, transfersomes, ethosomes and cubosomes for transcutaneous immunisation: characterisation and in vitro skin penetration. Lipid colloidal vaccines, including liposomes, transfersomes, ethosomes and cubosomes, were formulated, characterised and investigated for their ability to enhance penetration of a peptide vaccine through stillborn piglet skin in vitro. Liposomes and transfersomes were formulated using a film-hydration method, ethosomes using a modified reverse phase method and cubosomes using a lipid precursor method. The size, zeta potential, peptide loading and interfacial behaviour of the formulations were characterised. Skin penetration studies were performed using Franz diffusion cells with piglet skin as the membrane. The localization of peptide in the skin was examined using confocal laser scanning microscopy. The various formulations contained negatively charged particles of similar size (range: 134-200 nm). Addition of the saponin adjuvant Quil A to the formulations destabilised the monolayers and reduced peptide loading. Cubosomes and ethosomes showed superior skin retention compared with the other systems. Confocal laser scanning microscopy showed greater peptide penetration and accumulation in the skin treated with cubosomes and ethosomes. With the other systems peptide was only located in the vicinity of the hair follicles and within the hair shaft. We conclude from the in-vitro studies that cubosomes and ethosomes are promising lipid carriers for transcutaneous immunisation.

Value of magnetic resonance imaging with an endovaginal receiver coil in the pre-operative assessment of Stage I and IIa cervical neoplasia. To assess the value of high resolution endovaginal magnetic resonance images (MRI) of the uterine cervix in planning management of early cervical cancer. Prospective cross-sectional study. Specialist gynaecological oncology unit of a postgraduate teaching hospital. Thirty nine women aged 25-76 years old (mean 42.5 years) with invasive carcinoma Stage I or IIa of the cervix. A ring coil was positioned endovaginally around the cervix. Imaging was performed on a 1.0 T HPQ Vista or 0.5 T Asset (Picker, Highland Heights, Ohio, USA) using T1 weighted and T2 weighted sequences in transverse and sagittal planes with thin slices (2.5 mm) and small fields of view (12 cm). Tumour volumes were measured and any extension into adjacent organs and parametrium was noted. The patients were followed up after treatment and the outcome related to the MRI findings. There was one false positive and one false negative result among five Stage Ia patients being assessed for residual disease after cone biopsy or LLETZ. The MRI assessment of the size and distribution of the tumour was confirmed histologically in all 31 patients with Stage Ib or IIa disease who were treated surgically. One of these patients in whom no endocervical tumour was visible on MRI underwent radical trachelectomy. Three patients had radiotherapy as primary treatment. Patients with Stage Ib or IIa disease who had tumour volumes > 10 cm3 with early parametrial extension on MRI had a substantially worse prognosis at 24 months (disease-free survival 58.3% vs 95.5%, P = 0.003). High resolution MRI with an endovaginal coil allows precise measurement of tumour volume and identifies patients with small volume disease who might be considered for more conservative therapy. This technique also reveals early parametrial invasion that cannot be identified reliably by any other method. Early parametrial invasion in women with large tumours appears to have a very much worse prognosis.

Evolution of fat oxidation during exercise in obese pubertal boys: clinical implications. In this study, we examined fat oxidation rates during exercise in obese pubescent boys. Three groups of pubescent boys (16 pre-pubescent, Tanner's stage I; 16 pubescent, Tanner's stage III; and 14 post-pubescent, Tanner's stage V) performed a graded test on a leg cycle ergometer. The first step of the test was fixed at 30 W and power was gradually increased by 20 W every 3.5 min. Oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) were determined as the means of measurements during the last 30 s of each step, which allowed us to calculate fat oxidation rates versus exercise intensity. Between 20 and 50% of peak oxygen consumption (VO(2peak)), fat oxidation rate in relative values (mg . min(-1) . kg FFM(-1)) decreased continuously with pubertal development. In the same way, the maximum rate of fat oxidation occurred at a lower percentage of VO(2peak) (pre-pubescent: 49.47 +/- 1.62%; pubescent: 47.43 +/- 1.26%; post-pubescent: 45.00 +/- 0.97%). Our results confirm that puberty is responsible for a decrease in fat free mass capacities to use fat during exercise. The results suggest that post-pubescent obese boys need to practise physical activity at a lower intensity than pre-pubescent boys to enhance lipolysis and diminish adipose tissue and the consequences of obesity.

Psychiatrists' and internists' knowledge and attitudes about delivery of clinical preventive medical services. Changes in the health care environment have placed a greater responsibility on psychiatrists to deliver basic primary care services. The study assessed baseline knowledge and attitudes about clinical preventive medical services among psychiatric faculty and psychiatric residents at a tertiary care medical center. Residents and faculty in psychiatry and general internal medicine completed a structured questionnaire, including 20 case scenarios, that assessed their baseline knowledge of clinical preventive medical services, their attitudes concerning delivery of those services, and their beliefs about the effectiveness of those services in changing patients' behavior. The case scenarios and knowledge questions were based on the clinical preventive medical services recommendations outlined by the U. S. Preventive Services Task Force. Psychiatrists reported more frequent assessment of and counseling about the use of illicit drugs and weapons, and internists were more likely to query about measures related to physical health such as cancer screening and immunizations. The two groups reported similar attitudes toward the need for and the efficacy of preventive medical services. Commonly cited barriers to the delivery of preventive care included lack of time and education. Psychiatrists scored reasonably well on baseline knowledge about guidelines for preventive medical services, particularly given their recent lack of specific education in these matters. Psychiatrists believe clinical preventive services are important and express interest in their delivery. Additional educational interventions are needed to train psychiatrists in clinical preventive services to avoid missed clinical opportunities for intervention in psychiatric populations that may have poor access to other medical care.

Residues affecting the catalysis and inhibition of rat lens aldose reductase. Aldose reductase (AR), the first enzyme of the polyol pathway, has been implicated in diabetic complications. Results of recent clinical studies have shown that compounds that inhibit aldose reductase (ARIs) and block the flux of glucose through the polyol pathway have provided benefit to diabetic neuropathic patients. Since many ARIs show broad substrate specificity, emphasis on the structure-function properties of the AR enzyme will help in the refinement and design of future inhibitors. To this end, catalysis and inhibition of rat lens aldose reductase was examined following site-directed mutagenesis. Replacement of tyrosine 48 with phenylalanine (Y48F) resulted in an enzyme form with less than 0.25% activity with DL-glyceraldehyde and no detectable activity with p-nitrobenzaldehyde or xylose, although circular dichroism spectra and NADPH binding affinity were similar to wild-type AR. Mutation of histidine 110 to glutamine (H110Q) also resulted in a less active protein with an approximate 3-fold decrease in kcat for the reduction of DL-glyceraldehyde; slight or no activity was measured with other substrates and an increase of 195-fold over wild type was observed in the Km for glyceraldehyde. H110Q was less sensitive to inhibition by aldose reductase inhibitors. The most dramatic change was seen with imeristat, which showed an 1800-fold increase in IC50. Mutation of cysteine 298 to serine (C298S) affected enzyme function by increasing kcat 2- to 4-fold and increasing Km 15- to 48-fold, with DL-glyceraldehyde, p-nitrobenzaldehyde or xylose as substrates. As a result kcat/Km, catalytic efficiency, dropped to approx. 10% of control. Inhibition of C298S was not noticeably different from wild type. Substitution of histidine 187 or 200 with glutamine (H187Q, H200Q) had little effect on AR catalysis or inhibition. Based on structural and mutagenesis studies of human AR and the conservation of amino acids between human and rat, these data would indicate that Y48, H110, and C298 are important residues in the active site of rat AR and that Y48 is most likely the proton donor during substrate reduction by rat lens aldose reductase. In addition, these studies indicate that mutagenesis of H110 also affects aldose reductase inhibition.

Economic crisis and access to care: Cuba's health care system since the collapse of the Soviet Union. This article explores the effects on access to health care in Cuba of the severe economic crisis that followed the collapse of the Soviet Union and the monetary and market reforms adopted to confront it. Economic crises undermine health and well-being. Widespread scarcities and self-seeking attitudes fostered by monetary and market relations could result in differential access to health services and resources, but the authors found no evidence of such differential access in Cuba. While Cubans generally complain about many shortages, including shortages of health services and resources before the economic recovery began in 1995, no interviewees reported systemic shortages or unequal access to health care services or resources; interviewees were particularly happy with their primary care services. These findings are consistent with official health care statistics, which show that, while secondary and tertiary care suffered in the early years of the crisis because of interruptions in access to medical technologies, primary care services expanded unabated, resulting in improved health outcomes. The combined effects of the well-functioning universal and equitable health care system in place before the crisis, the government's steadfast support for the system, and the network of social solidarity based on grassroots organizations mitigated the corrosive effects of monetary and market relations in the context of severe scarcities and an intensified U.S. embargo against the Cuban people.

The proton transfer step catalyzed by yeast pyruvate kinase. The nature of the proton donor to the C-3 of the enolate of pyruvate, the intermediate in the reaction catalyzed by yeast pyruvate kinase, was investigated by site-directed mutagenesis and physical and kinetic analyses. Thr-298 is correctly located to function as the proton donor. T298S and T298A were constructed and purified. Both mutants are catalytically active with a decrease in k(cat) and k(cat)/K(m)(,PEP). Mn(2+)-activated T298S and T298A do not exhibit homotropic kinetic cooperativity with phosphoenolpyruvate (PEP) in the absence of fructose 1,6-bisphosphate, although PEP binding to enzyme-Mn(2+) is cooperative. The pH dependence of k(cat) for T298A indicates the loss of pK(a)(,2) = 6.4-6.9. Thr-298 affects the ionization (pK(a) approximately 6.5) responsible for modulation of k(cat). Fluorescence studies show altered dissociation constants of ligands to each enzyme complex upon Thr-298 mutations. The rates of the phosphoryl transfer and proton transfer steps in the pyruvate kinase-catalyzed reaction are altered; pyruvate enolization is affected to a greater extent. Proton inventory studies demonstrate solvent isotope effects on k(cat) and k(cat)/K(m)(,PEP). Fractionation factors are metal-dependent and significantly <1. The data suggest that a water molecule in a water channel is the direct proton donor to enolpyruvate and that Thr-298 affects a late step in catalysis.

EPSPS Gene Amplification in Glyphosate-Resistant Italian Ryegrass (Lolium perenne ssp. multiflorum) Populations from Arkansas (United States). Glyphosate-resistant Italian ryegrass was detected in Arkansas (United States) in 2007. In 2014, 45 populations were confirmed resistant in eight counties across the state. The level of resistance and resistance mechanisms in six populations were studied to assess the severity of the problem and identify alternative management approaches. Dose-response bioassays, glyphosate absorption and translocation experiments, herbicide target (EPSPS) gene sequence analysis, and gene amplification assays were conducted. The dose causing 50% growth reduction (GR50) was 7-19 times higher for the resistant population than for the susceptible standard. Uptake and translocation of (14)C-glyphosate were similar in resistant and susceptible plants, and no mutation in the EPSPS gene known to be associated with resistance to glyphosate was detected. Resistant plants contained from 11- to >100-fold more copies of the EPSPS gene than the susceptible plants, whereas the susceptible plants had only one copy of EPSPS. Plants surviving the recommended dose of glyphosate contained at least 10 copies. The EPSPS copy number was positively related to glyphosate resistance level (r = 80). Therefore, resistance to glyphosate in these populations is due to multiplication of the target site. Resistance mechanisms could be location-specific. Suppressing the mechanism for gene amplification may overcome resistance.

Social support and sense of life in patients with anxiety disorders - preliminary report. Verification of the level of social support perception and sense of life in patients with anxiety disorder and healthy people; evaluation of the relationship between these variables. The Social Support Questionnaire short version (F-SozU K-22) by G. Sommer and T. Fydrich and the Life Attitude Profile (LAP-R) by G.T. Reker were used. Social support and its dimensions prove to be significantly lower in patients with anxiety disorders. Healthy individuals have a higher sense of purpose, greater internal coherence, control of life, personal sense and balance of life attitudes, and lower intensity of existential emptiness. Higher emotional support and older age increase the level of sense of life in people with anxiety disorders. For preventive and therapeutic purposes, it is important to develop and sustain the internal resources of the individual (sense of life and age-related experience). In patients with neurotic disorders, it also seems essential to use psychotherapy aimed at changing the patterns of personality that impede them from building social support networks. This is due to the fact that anxiety disorders are often characterized by lower confidence, avoidance of interpersonal relationships, falsified perception of social support, leading thus to distorted interpretation of supportive actions.

ChpA Controls Twitching Motility and Broadly Affects Gene Expression in the Biological Control Agent Lysobacter enzymogenes. Lysobacter enzymogenes (L. enzymogenes) is an agriculturally important Gram-negative bacterium that employs T4P (type IV pili)-driven twitching motility to exhibit its antifungal function. Yet, it is still unclear how this bacterium regulates its twitching motility. Here, by using strain OH11 as the working model organism, we showed that a hybrid two-component system ChpA acts as a positive regulator in controlling twitching motility in L. enzymogenes. ChpA is a hybrid TCS (two-component transduction system) contains 7 domains including those for auto-phosphorylation and phosphate group transfer, as well as a phosphate receiver (REC) domain. Mutation of chpA completely abolished the wild-type twitching motility, as evidenced by the absence of mobile cells at the margin of the mutant colonies. Further studies of domain-deletion and phenotypic characterization reveal that domains responsible for phosphorylation and phosphotransfer, but not the REC domain, were indispensable for ChpA in regulating twitching motility. Transcriptome analyses of the chpA knockout strain indicated that ChpA was extensively involved in controlling expression of a wide variety of genes (totaling 243). The products of these differentially expressed genes were involved in multiple physiological and biological functions in L. enzymogenes. Thus, we have not only identified a new regulator controlling twitching motility in L. enzymogenes, but also provided the first report demonstrating the broad impact of the conserved ChpA in gene regulation in Gram-negative bacteria.

Histone H1 binding does not inhibit transcription of nucleosomal Xenopus laevis somatic 5S rRNA templates. It has long been proposed that selective binding of histone H1 is, in part, responsible for the differential developmental regulation of the oocyte and somatic 5S rRNA genes in Xenopus laevis. In this study we show that histone H1 binds both oocyte and somatic genes equally after reconstitution into mononucleosomes or oligonucleosome arrays. Furthermore, we show that the binding of histone H1 selectively represses only oocyte gene transcription and that an RNA polymerase III transcription complex is able to initiate transcription of nucleosomal somatic templates regardless of whether histone H1 is present. These results support a model in which the differential regulation of the 5S rRNA genes is not simply due to the prevention of histone H1 binding by transcription complexes on the somatic genes, but rather to a difference in the histone H1 interaction with the somatic and oocyte genes.

Atomic-scale oxidation mechanisms of single-crystal magnesium. Understanding the oxidation process of active metals plays a crucial role in improving their mechanical/oxidation properties. Using in situ environmental transmission electron microscopy and density-functional theory, we firstly clarify the oxidation process of single-crystal Mg at the atomic scale by using a new double-hole technique. A unique incipient interval-layered oxidation mechanism of single-crystal Mg has been confirmed, in which O atoms intercalate through the clean (21[combining macron]1[combining macron]0) surface into the alternate-layered tetrahedral sites, forming a metastable HCP-type MgO0.5 structure. Upon the increased incorporation of oxygen at the neighboring interstitial sites, the HCP-type Mg-O tetrahedron structure sharply transforms into the FCC-type MgO oxide. In addition, a typical anisotropic growth mechanism of oxides has been identified, wherein it involves two routes: the epitaxial growth of the MgO layer and the inward migration of the MgO/Mg interface. The whole oxidation rate of single-crystal Mg is mostly determined by the inward migration rate of the MgO/Mg interface, which is about six times higher than that of the epitaxial growth rate of the MgO layer along the same orientation planes. Moreover, the inward migration rate of the (020)MgO‖(011[combining macron]0)Mg interface is about twice as large as that of the (200)MgO‖(0002)Mg interface. This continuous oxide growth is mainly related to the defects in the MgO layer, which builds effective channels for the diffusion of O and Mg atoms. The in situ double-hole observations together with theoretical calculations provide a potential trajectory to probe the oxidation fundamentals of other active metals.

Investigation into the interaction of the bacterial protease OmpT with outer membrane lipids and biological activity of OmpT:lipopolysaccharide complexes. Outer-membrane proteases T (OmpT) are important defence molecules of Gram-negative bacteria such as Escherichia coli found in particular in clinical isolates. We studied the interaction of OmpT with the membrane-forming lipids phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) from the inner leaflet and lipopolysaccharide (LPS) from the outer leaflet of the outer membrane. These investigations comprise functional aspects of the protein-lipid interaction mimicking the outer-membrane system as well as the bioactivity of LPS:OmpT complexes in the infected host after release from the bacterial surface. The molecular interaction of the lipids PE, PG, and LPS with OmpT was investigated by analysing molecular groups in the lipids originating from the apolar region (methylene groups), the interface region (ester), and the polar region (phosphates), and by analysing the acyl-chain melting-phase behaviour of the lipids. The activity of OmpT and LPS:OmpT complexes was investigated in biological test systems (human mononuclear cells and Limulus amoebocyte lysate assay) and with phospholipid model membranes. The results show a strong influence of OmpT on the mobility of the lipids leading to a considerable fluidization of the acyl chains of the phospholipids as well as LPS, and a rigidification of the phospholipid, but not LPS head groups. From this, a dominant role of the protein on the function of the outer membrane can be deduced. OmpT released from the outer membrane still contains slight contaminations of LPS, but its strong cytokine-inducing ability in mononuclear cells, which does not depend on the Toll-like receptors 2 and 4, indicates an LPS-independent mechanism of cell activation. This might be of general importance for infections induced by Gram-negative bacteria.

Superantigen can reactivate bacterial cell wall-induced arthritis. Intravenous injection of toxic shock syndrome toxin-1 (TSST-1) produced by Staphylococcus aureus, can reactivate arthritis in a rat ankle joint that has been previously inflamed by injection of peptidoglycanpolysaccharide polymers isolated from the cell walls of group A streptococci. The severity and chronicity of this renewed arthritis is dose dependent and at higher doses (125 micrograms/kg) a prolonged joint inflammation with pannus formation and marginal erosion of cartilage and bone is induced after a single injection of TSST-1. Only modest synovial hyperplasia is induced in control ankle joints by systemic injection of TSST-1. Another superantigen, streptococcal pyrogenic exotoxin induces a much weaker, acute reactivation of arthritis that resolves by 2 days. Repeated injections of TSST-1 at 7-day intervals give the same undiminished pattern of joint response, but the joint swelling persists at a higher level with each succeeding injection. Cyclosporin A suppresses all phases of the recurrent arthritis, indicating that TSST-1 could be functioning through its property of a superantigen activating T lymphocytes. II-1 receptor antagonist and anti-TNF-alpha neutralizing antibody, which reduce reactivation of arthritis by peptidoglycan-polysaccharide polymers, have no effect on reactivation by TSST-1. This experimental model provides a means to examine in vivo the possible role of superantigens in rheumatoid arthritis and related diseases, and to analyze the cellular and molecular pathways induced by this family of microbial products.

Spiritual Well-Being, Depression, and Stress Among Hemodialysis Patients in Jordan. The spiritual dimension of a patient's life is an important factor that may mediate detrimental impacts on mental health. The lack of research investigating spiritual well-being, religiosity, and mental health among Jordanian hemodialysis patients encouraged this research. This study explored levels of spiritual well-being and its associations with depression, anxiety, and stress. A quantitative, cross-sectional correlational study. A sample of 218 Jordanian Muslim hemodialysis patients completed a structured, self-administered questionnaire. The data were analyzed using descriptive statistics and linear multivariate regression models. The hemodialysis patients had, on average, relatively low levels of spiritual well-being, moderate depression, severe anxiety, and mild to moderate stress. The results of the regression models indicated that aspects of spiritual well-being were negatively associated with depression, anxiety, and stress, but only existential well-being consistently retained significant associations after controlling for religious well-being, religiosity, and sociodemographic variables. Greater spiritual and existential well-being of Jordanian hemodialysis patients were significantly associated with less depression, anxiety, and stress. It appears that these patients use religious and spiritual beliefs and practices as coping mechanisms to overcome their depression, anxiety, and stress. The implications for holistic clinical practice are explored.

Are Immunosuppressants Becoming Obsolete? Historically, in the 1950s, the introduction of simple, old-fashioned steroids resulted in a significant drop in mortality and hence offered for the first time a real therapeutic option for patients with inflammatory bowel disease. However, as we are all aware of, steroids are no option for maintenance of remission. This review will provide an overview of the available data on the current role of azathioprine in the therapy of Crohn's disease. Based on several controlled trials, the place of azathioprine for maintenance of remission is indisputable. Data from a pediatric cohort suggested that early introduction of azathioprine is beneficial for the disease course. Two recent studies aimed at reproducing these data in adult populations and failed. Hence indicating that azathioprine should only be introduced for maintenance of remission in a step-up-wise approach. An additional role for azathioprine in combo therapy with TNF antibodies has been indicated by several trials revealing a substantial benefit on response. This is partly attributed to the gain in the therapeutic effect by azathioprine itself and possibly through reduction of anti-drug antibody development. In summary, the current role of azathioprine in the therapy of Crohn's disease is manifold and still has an impact in times of targeted therapy.

On the use of SEM correlative tools for in situ mechanical tests. In situ SEM mechanical tests are key to study crystal plasticity. In particular, imaging and diffraction (EBSD) allow microstructure and surface kinematics to be monitored all along the test. However, to get a full benefit from different modalities, it is necessary to register all images and crystallographic orientation maps from EBSD into the same frame. Different correlative approaches tracking either Pt surface markings, crystal orientations or grain boundaries, allow such registrations to be performed and displacement as well as rotation fields to be measured, a primary information for crystal plasticity identification. However, the different contrasts that are captured in different modalities and unavoidable stage motions also give rise to artifacts that are to be corrected to register the different information onto the same material points. The same image correlation tools reveal very powerful to correct such artifacts. Illustrated by an in situ uniaxial tensile test performed on a bainitic-ferritic steel sample, recent advances in image correlation techniques are reviewed and shown to provide a comprehensive picture of local strain and rotation maps.

False aneurysm of the cavernous carotid artery: a complication of transsphenoidal surgery. Although excellent results currently are being achieved with transsphenoidal surgery, life-threatening complications may occasionally result from this approach. We present a patient with carotid injury sustained during transsphenoidal surgery, who presented 6 weeks postoperatively with a large false aneurysm in the cavernous part of the right internal carotid artery. This lesion was successfully treated by trapping. The pathogenesis of this complication is discussed and the relevant literature is reviewed.

Regulation of the oxidative phosphorylation rate in the intact cell. The mechanisms that underlie the balance between the consumption and oxidative generation of ATP in the intact cell are not well-defined. Cytosolic inorganic phosphate (Pi) and ADP levels, the cytosolic ATP/ADP ratio, and the cytosolic phosphorylation potential (PP) have all been proposed as major regulatory variables, the latter as a component of a "near-equilibrium" thermodynamic regulatory scheme. Therefore, the potential regulatory roles of these variables in the intact cell were evaluated with 31P NMR and Langendorff perfused rat hearts; in this preparation, the tissue oxygen consumption rate (MVO2) can be varied over a wide range. When the exogenous carbon source was varied, none of the proposed regulatory parameters, i.e., the ATP/ADP ratio, PP, or cytosolic ADP level, were found to be uniquely related to MVO2. Rather, ADP levels at a given MVO2 decreased progressively for the exogenous carbon sources in the following order: glucose, glucose + insulin, palmitate + glucose, lactate, pyruvate + glucose, and octanoate + glucose. In the octanoate and pyruvate groups, MVO2(-1) was linearly dependent upon [ADP]-1 with apparent Km values being in the range previously observed in isolated mitochondria. A similar trend was observed in the MVO2-[Pi] relationship. The present findings suggest that exogenous carbon sources which effectuate deregulation of intramitochondrial NADH generation lower cytosolic ADP and Pi to levels which are limiting to the rate of oxidative phosphorylation. For other carbon sources, the processes controlling the rate of NADH generation also participate in determining the rate of oxidative ATP synthesis. However, this control must be exerted kinetically rather than through a near-equilibrium thermodynamic mechanism as indicated by the present data and prior kinetic studies of the ATP synthetic process in both isolated mitochondria and intact myocardium [La Noue, K. F., et al. (1986) Biochemistry 25, 7667-7675; Kingsley-Hickman, P., et al. (1987) Biochemistry 26, 7501-7510].

Actions of leptin on growth hormone secretagogue-responsive neurones in the rat hypothalamic arcuate nucleus recorded in vitro. In the arcuate nucleus, the growth hormone (GH) secretagogue (GHS)-responsive cells include a subpopulation of the neuropeptide Y (NPY) neurones. It is not known whether these include the orexigenic NPY population that are inhibited by the satiety hormone, leptin. Thus we investigated whether (i) the arcuate nucleus cells electrically excited by GHS are inhibited by leptin and (ii) chronic central leptin infusion alters GHS-induced Fos expression. Of 36 cells recorded from a trimmed hypothalamic slice containing arcuate nucleus, 13 cells were excited by the nonpeptide GHS, CP-459,599. The predominant response of these cells to leptin was inhibitory: six inhibited, three excited and four unresponsive. Similar responses were observed in a population of arcuate cells recorded from a preparation in which synaptic transmission was blocked, suggesting that leptin acts directly on a subpopulation of GHS-responsive neurones. Intracerebroventricular infusion of leptin for 1 week did not alter the number of cells expressing Fos following GHS administration. Thus, while leptin does not appear to influence the central actions of GHS to induce immediate early gene expression, it does act directly on a subpopulation of cells excited by GHS, eliciting mostly inhibitory but also some excitatory responses. It will be interesting to discover the consequences of leptin's inhibitory effects on the hypothalamic circuits excited by GHS, particularly since leptin paradoxically has a stimulatory effect on GH secretion, presumed to reflect a suppression of central NPY pathways.

Imaging Characteristics of a Bladder Wall Paraganglioma. A 65-year-old man with a history of hypertension and nephrolithiasis presented with flank pain. Urographic CT demonstrated a 1.7-cm nodule arising from the bladder wall. The patient was referred for cystourethroscopy. During the procedure, the patient became hypertensive while under general anesthesia. No biopsy or resection was performed. To work up for possible bladder paraganglioma, a I-MIBG scan was ordered, and the patient was referred to endocrinology. On SPECT/CT images, the bladder nodule demonstrates marked uptake of MIBG radiotracer, confirming the diagnosis of a genitourinary paraganglioma arising from the bladder wall.

Impact of soil amendments on reducing phosphorus losses from runoff in sod. Received for publication December 22, 2004. Research was initiated to study the interaction between soil amendments (lime, gypsum, and ferrous sulfate) and dissolved molybdate reactive phosphorus [RP(<0.45)] losses from manure applications from concentrated runoff flow through a sod surface. Four run-over boxes (2.2-m2 surface area) were prepared for each treatment with a bermudagrass [Cynodon dactylon (L.) Pers.] sod surface (using sod blocks) and composted dairy manure was surface-applied at rates of 0, 4.5, 9, or 13.5 Mg ha-1. The three soil amendments were then applied to the boxes. Two 30-min runoff events were conducted and runoff water was collected at 10-min intervals and analyzed for RP(<0.45). Results indicated that the addition of ferrous sulfate was very effective at reducing the level of RP(<0.45). in runoff water, reducing RP(<0.45) from 1.3 mg L(-1) for the highest compost rate with no amendment to 0.2 mg L(-1) for the ferrous sulfate in the first 10 min of runoff. Lime and gypsum showed a small impact on reducing RP(<0.45), with a reduction in the first 10 min to 0.9 and 0.8 mg L(-1), respectively. The ferrous sulfate reduced the RP(<0.45) in the tank at the end of the first runoff event by 66.3% compared with no amendment. In the second runoff event, the ferrous sulfate was very effective at reducing RP(<0.45) in runoff, with no significant differences in RP(<0.45) with application of 13.5 Mg ha(-1) compost compared with no manure application. The results indicate that the addition of ferrous sulfate may greatly reduce RP(<0.45) losses in runoff and has considerable potential to be used on pasture, turfgrass, and filter strips to reduce the initial RP(<0.45) losses from manure application to the environment.

Protecting human security: proposals for the G7 Ise-Shima Summit in Japan. In today's highly globalised world, protecting human security is a core challenge for political leaders who are simultaneously dealing with terrorism, refugee and migration crises, disease epidemics, and climate change. Promoting universal health coverage (UHC) will help prevent another disease outbreak similar to the recent Ebola outbreak in west Africa, and create robust health systems, capable of withstanding future shocks. Robust health systems, in turn, are the prerequisites for achieving UHC. We propose three areas for global health action by the G7 countries at their meeting in Japan in May, 2016, to protect human security around the world: restructuring of the global health architecture so that it enables preparedness and responses to health emergencies; development of platforms to share best practices and harness shared learning about the resilience and sustainability of health systems; and strengthening of coordination and financing for research and development and system innovations for global health security. Rather than creating new funding or organisations, global leaders should reorganise current financing structures and institutions so that they work more effectively and efficiently. By making smart investments, countries will improve their capacity to monitor, track, review, and assess health system performance and accountability, and thereby be better prepared for future global health shocks.

Liver Transplant From a Donor With Situs Inversus Totalis Using Orthotopic and Retroversus Technique: A Case Report. Situs inversus totalis is an infrequent genetic malformation affecting 0.01% of the population and consists of the total rotation of the organs 180 degrees, generating the so-called mirror-image reversal. For many years donors with this pathology were discouraged from organ donation. We present a case of hepatic and renal transplantation using the 2 techniques described, orthotopic and retroversus. The recipient was a 69-year-old man with end-stage liver and kidney disease due to alcoholism and diabetes, respectively, and a Model for End-Stage Liver Disease score of 32. There was no mismatch between recipient and donor. The implant started with the piggy-back technique using the retroversus technique, generating a tense portal vein anastomosis due to the superior situation of the elements of the hepatic hilum, so it was decided to undo suprahepatic anastomosis with the orthotopic technique, rotating the liver on its axis, without complications. Roux-en-Y hepaticojejunoanastomosis was carried out. The patient was discharged 15 days after surgery with normalization of renal function. Although both techniques must be taken into account, the one that fits best for a particular recipient should be used, given the particularities of size and shape of the liver graft. This can take some art and creativity from the surgical team.

Software for the data analysis of the arrival-timing monitor at SACLA. X-ray free-electron laser (XFEL) pulses from SPring-8 Ångstrom Compact free-electron LAser (SACLA) with a temporal duration of <10 fs have provided a variety of benefits in scientific research. In a previous study, an arrival-timing monitor was developed to improve the temporal resolution in pump-probe experiments at beamline 3 by rearranging data in the order of the arrival-timing jitter between the XFEL and the synchronized optical laser pulses. This paper presents Timing Monitor Analyzer (TMA), a software package by which users can conveniently obtain arrival-timing data in the analysis environment at SACLA. The package is composed of offline tools that pull stored data from cache storage, and online tools that pull data from a data-handling server in semi-real time during beam time. Users can select the most suitable tool for their purpose, and share the results through a network connection between the offline and online analysis environments.

Efficacy, safety, and risk-benefit analysis of adjuvant interferon alfa-2b in melanoma. A recently completed Eastern Cooperative Oncology Group trial, E1684, has shown that adjuvant therapy with high-dose recombinant interferon alfa-2b (rIFN-alpha 2b) has a significant impact on relapse-free and overall survival in melanoma patients at high risk of recurrence. Adjuvant rIFN-alpha 2b increased the median overall survival to 3.82 years in the treatment group compared with 2.78 years with observation and yielded a 5-year survival rate of 46% versus 37% with observation. This is the first adjuvant therapy to significantly extend survival in this patient population (P = .0023, one-sided). The response to therapy was greatest among those patients with clinical evidence of nodal metastasis. The toxicity associated with this regimen was substantial but tolerable. Approximately 78% of patients treated with rIFN-alpha 2b experienced grade 3 or greater toxicity, and dose modifications were required for 37% and 36% of patients in the induction or maintenance phase, respectively. Quality-of-life-adjusted survival analysis has shown that, despite the toxicity associated with rIFN-alpha 2b therapy, the quality-of-life-adjusted time gained with rIFN-alpha 2b therapy outweighs the reduced quality of life associated with treatment toxicity and relapse. These data support the use of high-dose rIFN-alpha 2b as adjuvant therapy in melanoma patients at high risk of recurrence.

Use of synthetic peptides as immunogens for developing a vaccine against human chorionic gonadotropin. Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced by the placental trophoblast soon after conception and is essential for successful gestation in women. A vaccine against this hormone has been developed for the purposes of birth control and the treatment of hormone-related diseases. Synthetic peptides representing the native primary structure of the hCG beta subunit have been coupled to protein carriers to produce immunogens. Several peptides, representing varying lengths from the C-terminus of the beta subunit, were synthesized and their ability to elicit antibodies reactive to hCG and able to neutralize hCG activity in vivo was tested. A peptide representing the 37 amino acids of the C-terminal end of the beta subunit was selected as the vaccine antigen and diphtheria toxoid was selected as the carrier for the first prototype vaccine. Procedures for coupling a specified number of peptide molecules to each carrier molecule in a reproducible fashion were developed. The immunogen is mixed with an adjuvant compound and the mixture administered in an oil-in-water emulsion. Significant levels of antibodies to hCG have been elicited in several species and a marked reduction in the fertility of immunized baboons has been observed. Extensive evaluations of vaccine safety have been conducted and Phase I clinical trials have been proposed to test its utility for human birth control. Possible applications of the hCG vaccine to health problems other than birth control are being considered.

The catalytic subunit of cAMP-dependent protein kinase: prototype for an extended network of communication. The protein kinase catalytic core in essence comprises an extended network of interactions that link distal parts of the molecule to the active site where they facilitate phosphoryl transfer from ATP to protein substrate. This review defines key sequence and structural elements, describes what is currently known about the molecular interactions, and how they are involved in catalysis.

Levan production by Zymomonas mobilis in batch and continuous fermentation systems. Levan production in batch and continuous fermentation systems by Zymomonas mobilis B-14023 was investigated. The culture medium used in both of the fermentation systems contained sucrose and various organic nitrogen sources. Maximum concentration of levan was produced with yeast extract among the nitrogen sources tested. Response surface methodology was used to investigate the effects of three factors on the concentration of levan in batch cultures of Z. mobilis. Maximum levan concentration was 40.2 g/L and this concentration was reached at the optimum levels of process variables, which were 299.1 g/L initial substrate concentration, 42.3 h incubation time, and initial pH 6.0. Continuous fermentation experiments were done in packed bed bioreactor using Ca-alginate immobilized Z. mobilis cells. The highest levan concentration (31.8 ± 0.21 g/L) was obtained at a dilution rate of 0.14 h(-1) while maximum volumetric productivity (6.556 g/(Lh)) was obtained at a dilution rate of 0.22 h(-1). Increasing the dilution rate resulted in decreased levan and increased residual sugar concentrations.

Is post-mortem ultrasonography a useful tool for forensic purposes? To investigate the interest of post-mortem ultrasonography in the diagnosis of pathological background, and manner and cause of death. Post-mortem ultrasonography exams were carried out on 38 fresh human adult cadavers referred to the Department of Forensic Medicine and Pathology (Garches, France). Data obtained from ultrasonography were independently compared with further forensic autopsy findings. Two important limitations relative to ultrasound utilization appeared: hyper-echoic abdominal and thoracic walls, with gas distension of the whole digestive tube and subcutaneous tissues (due to precocious putrefactive gas releasing); and difficulty in accessing lateral and posterior structures (i.e. liver, spleen, kidneys, lung bases, aorta) due to rigor mortis and evident non-compliance of the subject. Post-mortem diagnoses (moderate ascites, gallbladder stones, bladder globe, chronic kidney disease, cirrhosis, thyroid gland cysts and hypertrophy, intrauterine device), were strongly limited. False negative diagnoses comprised fatty liver, pleural effusion, thoracic aortic dissection, and focal organ and/or soft tissues lesions (for example, wounds or infarcts). According to the results, post-mortem ultrasonography seems to have a very limited role for forensic purposes. Other post-mortem utilizations are cited, proposed, and discussed.

Deconvolution of long-pulse lidar signals with matrix formulation. A deconvolution technique for deriving more resolved signals from lidar signals with typical CO(2) laser pulses is proposed, utilizing special matrices constructed from the temporal profile of laser pulses. It is shown that near-range signals can be corrected and small-scale variations of backscattered signals can be retrieved with this technique. Deconvolution errors as a result of noise in lidar data and in the laser pulse profile are also investigated numerically by computer simulation.