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Early postnatal lead exposure: behavioral effects in common tern chicks (Sterna hirundo). Exposure to lead early in life is known to affect behavioral and intellectual development. To develop an animal model we chose the common tern, Sterna hirundo, a species whose early developmental landmarks are well known. One potential for avian models lies in the reliance of birds on visual and acoustic rather than olfactory (and ultrasonic) modes of communication. One randomly chosen member of each of 8 pairs of young common tern chicks was injected with lead nitrate solution at a concentration of 0.2 mg/g. The pairs were not siblings but were matched for age (+/- 1 d) and weight (+/- 3 g). The second member of each pair was injected with an equal volume of sterile saline. Behavioral tests performed examined locomotion, balance and righting response, feeding tasks and begging, depth perception and response on a visual cliff, and behavioral thermoregulation. In each pair the control chick was heavier at 4 wk of age. For most behavioral measures, except begging and movement on a stationary incline, the lead-injected chicks performed less well than the control chicks. When presented with a novel feeding situation (reversal of fish position), the lead-injected chicks required significantly more time to eat the same number of fish. The single injection of lead thus affected a variety of behavioral patterns, with effects apparent within 5 d after injection.

Damage control resuscitation. The early recognition and management of hemorrhage shock are among the most difficult tasks challenging the clinician during primary assessment of the acutely bleeding patient. Often with little time, within a chaotic setting, and without sufficient clinical data, a decision must be reached to begin transfusion of blood components in massive amounts. The practice of massive transfusion has advanced considerably and is now a more complete and, arguably, more effective process. This new therapeutic paradigm, referred to as damage control resuscitation (DCR), differs considerably in many important respects from previous management strategies for catastrophic blood loss. We review several important elements of DCR including immediate correction of specific coagulopathies induced by hemorrhage and management of several extreme homeostatic imbalances that may appear in the aftermath of resuscitation. We also emphasize that the foremost objective in managing exsanguinating hemorrhage is always expedient and definitive control of the source of bleeding.

Improved oral hygiene and Candida species colonization level in geriatric patients. This work consists in improving oral hygiene (OH) for elderly dependent people in long-term hospital care, in order to decrease the degree of colonization and the associated risk of developing oral candidiasis. As this population frequently suffers from such colonization and because it is difficult to install and practice OH care, a study protocol was designed at the request of geriatricians. The objective of the present study was to set up a programme of OH, applied by the care staff, and to monitor oral colonization of by Candida spp. We compared the levels of hygiene and Candida spp. colonization for a group of 110 long-term patients in geriatric departments at T1, when clinical data were collected and oral mycological samples taken before the OH protocol was applied, and at T2, during the postprotocol phase after 3 months of application, when the clinical data and sample collection were repeated. During these 3 months 11 patients died. These patients were excluded from the results, which are presented for matched series of the 99 patients still present at T2. Statistical analysis comparing the clinical and biological parameters at T1 and T2 established that there had been an improvement in OH: the 'adequate' level was reached for 72.4% of patients at T2 compared with 41.8% at T1 (P < 0.001) and the 'very inadequate' level was observed for 9.2% at T2 compared with 27.9% at T1 (P < 0.01). A reduction was observed in the number of patients showing the highest degree of C. albicans and C. glabrata colonization (> 50 colony forming units) from 41.9% at T1 to 24.9% at T2 (P < 0.05) and from 56.4% at T1 to 13.0% at T2 (P < 0.05) respectively. The number of patients with candidiasis fell significantly from 43.2% at T1 to 10.2% at T2. The OH protocol led to an overall decrease in Candida spp. colonization, a significant reduction in the number of candidiasis and an improvement in the level of oral and denture hygiene but vigilance is still necessary concerning OH care and the initial training of staff in specific care of the mouth.

Structural insights into decreased enzymatic activity induced by an insert sequence in mannonate dehydratase from Gram negative bacterium. Mannonate dehydratase (ManD; EC4.2.1.8) catalyzes the dehydration of D-mannonate to 2-keto-3-deoxygluconate. It is the third enzyme in the pathway for dissimilation of D-glucuronate to 2-keto-3-deoxygluconate involving in the Entner-Doudoroff pathway in certain bacterial and archaeal species. ManD from Gram negative bacteria has an insert sequence as compared to those from Gram positives revealed by sequence analysis. To evaluate the impact of this insert sequence on the catalytic efficiency, we solved the crystal structures of ManD from Escherichia coli strain K12 and its complex with D-mannonate, which reveal that this insert sequence forms two α helices locating above the active site. The two insert α helices introduce a loop that forms a cap covering the substrate binding pocket, which restricts the tunnels of substrate entering and product releasing from the active site. Site-directed mutations and enzymatic activity assays confirm that the catalytic rate is decreased by this loop. These features are conserved among Gram negative bacteria. Thus, the insert sequence of ManD from Gram negative bacteria acts as a common inducer to decrease the catalytic rate and consequently the glucuronate metabolic rate as compared to those from Gram positives. Moreover, residues essential for substrate to enter the active site were characterized via structural analysis and enzymatic activity assays.

Limited minocycline neuroprotection after balloon-compression spinal cord injury in the rat. Minocycline (MC), a second-generation tetracycline and anti-inflammatory agent reportedly provides neuroprotection following CNS injury. The objective of this study was to examine the neuroprotective effects of short and long-term MC treatment using balloon-compression spinal cord injury (SCI) in the rat. Rats subjected to SCI were treated with MC for 1 day (1DMC group; total dose 180 mg/kg) or 5 days (5DMC group; total dose 450 mg/kg) or placebo. The effects of MC treatment on locomotor recovery (BBB scale) and spinal cord white and gray matter sparing were evaluated for up to 28 days. Morphometric analysis showed that while MC treatment spared spinal cord white and gray matter rostral to the lesion epicenter in both, 1DMC and 5DMC groups, sparing of white and gray matter areas was not observed caudal to the traumatic lesion. In addition, MC treatment had no effect on final locomotor recovery. Limited improvement of spinal cord post-compression consequences raises questions about the neuroprotection efficiency of MC treatment following compression SCI in the rat.

Constitutive expression of DeltaN-p63alpha isoform in human thymus and thymic epithelial tumours. p63, a member of the p53 family, is involved in the survival and differentiation of reserve/stem cells in different epithelia. To unveil the possible role of p63 in thymic physiology and pathology, we investigated the expression of p63 isoforms in normal thymus, thymomas and other mediastinal tumours. All samples were analysed using immunohistochemistry with three different antibodies: 4A4 antibody recognising all p63 isoforms, p40 antibody reacting only with truncated dominant-negative isoforms (DeltaN-p63) and H-129 antibody recognising all alpha-isoforms. Reverse-transcription polymerase chain reaction (RT-PCR), and real-time PCR analyses were performed on RNA extracted from frozen samples of four thymomas and two primary-mediastinal large-B-cell lymphoma (PMLBCL). In normal thymus, DeltaN-p63alpha was expressed in all cortical and medullary epithelial cells, with decreasing intensity in Hassall's corpuscles. This phenotype was conserved in neoplastic transformation since all 54 investigated thymomas (World Health Organization types A, AB, B1, B2, B3, C) expressed DeltaN-p63alpha (virtually 100% cells). The predominance of DeltaN-p63alpha isoform mRNA was confirmed by real-time PCR. Among other mediastinal tumours, DeltaN-p63alpha was only expressed in those displaying either a stratified epithelial component (teratomas) or epidermoid differentiation (lung carcinoma). Among lymphomas, T-cell-precursor lymphomas did not express p63, whereas most PMLBCL expressed TA-p63alpha (7/8).

Cellular heterogeneity in vertical growth phase melanoma. Melanoma growing as a tumorigenic nodule is one of the most virulent neoplasms to which the flesh is heir. At a considerably small tumor size, it incurs significant risk for widespread metastatic dissemination. There are no effective means of surgical intervention, chemical therapy, or immunologic therapy for advanced and metastatic melanoma. To review the literature and highlight recent cardinal advances in the understanding of melanoma vertical growth, with specific emphasis on how its recognition and characterization may be applied to diagnostic practice and development of novel investigative approaches. Literature review, archival material, personal experience, and research collaborators. The study of tumorigenic melanoma, both in primary lesions and in metastases, is the key to the eventual eradication of this highly virulent neoplasm that may disseminate widely when only occupying the volume of a grain of rice. Morphology often provides the first insight into structure and function. A growing database using meticulous and inclusive criteria to define tumor stem cells in the context of clinically relevant models now indicates that the key to melanoma heterogeneity may reside in a small subpopulation with the ability to self-renew and form tumors despite most cells present being significantly less virulent. Hopefully, from these insights into melanoma tumor progression from radial growth phase to heterogeneous and tumorigenic vertical growth phase will come additional answers to how smart therapies may be developed that specifically target those vertical growth phase cells that most pertain to patient survival.

In vivo formation of codeinone-glutathione adduct: isolation and identification of a new metabolite in the bile of codeine-treated guinea pig. Codeinone-glutathione adduct (CO-GSH) in the bile of guinea pigs given a subcutaneous injection of codeine was isolated and identified. Synthesized authentic CO-GSH was characterized by the mass and nuclear magnetic resonance spectra and used as the standard sample. The metabolite was isolated by preparative high-performance liquid chromatography on a C18 column. The fractions containing the conjugated metabolite were purified using Sep-Pak C18 cartridges. For further purification of the metabolite CO-GSH, a Radial Pak CN column was used. Structure assignment of the metabolite was then performed by fast-atom-bombardment mass spectrometry and 500 MHz Fourier-transform-NMR spectrometric analysis and identified as S-[4,5-epoxy-3-methoxy-17-methyl-6-oxomorphinan-(8S)-yl] glutathione.

Novel cytotoxic drugs: old challenges, new solutions. The discovery of cytotoxic agents was revolutionary for anticancer therapy in the last century, improving survival rates and the quality of life of patients with different types of tumours. However, the development of agents that combine efficacy, safety and convenience remains a great challenge, due to the narrow therapeutic index of some drugs, the fact that they may damage not only cancer cells, but also normal and healthy tissue and the occurrence of resistance, limiting anticancer efficacy. Novel cytotoxic agents have brought certain advantages over the conventional ones, such as shorter administration time, mechanisms to overcome drug resistance and lower incidence of adverse events. In this review we highlight the development of promising novel cytotoxic drugs that will hopefully offer not only gains in efficacy, but also in safety, tolerability and convenience in the treatment of patients with cancer.

[Treatment of adduction cicatricial contracture of the thumb]. The authors discuss the results of treatment of 56 patients with adduction cicatricial contractures of the thumb which developed after severe mechanical, gunshot and thermal injuries. According to the degree of the deformity, 3 degrees of contractures are distinguished and each cells for certain therapeutic tactics. Various types of free and pedicle dermatoplasty and a method of dosed distraction by means of apparatuses designed in the clinic were employed. Among 40 patients who were examined 35 showed good functional and cosmetic results.

The most effective factors to offset sarcopenia and obesity in the older Korean: Physical activity, vitamin D, and protein intake. The aim of this study was to evaluate the effects of the types and levels of physical activity in conjunction with protein intake and vitamin D on sarcopenia and obesity status in an elderly population. Study participants (N = 4452) were ages ≥60 y and included 1929 men and 2523 women who completed a body composition analysis with a dual energy x-ray absorptiometry and provided health and dietary data. Higher appendicular skeletal muscle mass/weight was observed in the non-obese group, although obese participants had greater weights. The non-obese sarcopenia subgroup showed health problems related to insulin resistance and metabolic-related factors compared with the nonsarcopenic group. The total metabolic equivalent was significantly different in both obese categories, regardless of sarcopenic status. The prevalence of obesity, sarcopenia, and sarcopenic obesity relatively increased with a diet deficient of protein intake and vitamin D. These data suggest that sarcopenia had a significant association with metabolic-related factors; physical activity, especially vigorous activity; and protein intake and vitamin D levels in a non-obese elderly population. Therefore, maintaining healthy body weight by means of resistance exercise and enhanced protein intake and vitamin D may help offset sarcopenia in this age group.

A comparative study of allergic and primary irritant contact dermatitis with dinitrochlorobenzene (DNCB) in dogs. Attempts were made to induce allergic contact dermatitis in dogs, a species generally considered poorly responsive to experimental allergic contact dermatitis. Yound Beagles were sensitized to 2,4 dinitrochlorobenzene (DNCB) by multiple intradermal injections. Two weeks after sensitization, these dogs were challenged topically with 0.1% DNCB by a standard closed-patch technique. Sensitization evidenced by various degrees of reaction following challenge was established in all of 14 pups used, while 7 nonsensitized control pups did not react to challenge. Primary irritant contact dermatitis was induced in the skin of nonsensitized Beagle pups by 1%, 5%, and 10% solutions of DNCB. In allergic contact dermatitis the sites of challenge were grossly indurated, erythematous, and edematous. Histologically at these sites there was an infiltration of mononuclear cells which reached maximum intensity at 3 to 4 days. Accumulations of lymphoid cells were marked around sweat galnds and hair follicles. Penetration of leukocytes into these cutaneous adnexa was associated with degenerative processes in their cellular structures. Mononuclear cell infiltration into the epidermis was mild. Spongiosis was observed in the epidermis, but vesicle formation was rare. In primary irritant contact dermatitis gross lesions were characterized by severe erythema, edema, and gangreen of the skin. Microscopically, the main lesions were necrosis of the epidermal cells, separation of the epidermis from the dermis, dermal edema, and massive infiltration of the dermis with polymorphonuclear cells.

Postoperative orthopaedic blood salvage and reinfusion. Minimal use of homologous blood is a desirable goal for both patients and health care providers. This article discusses one adjunctive technique that is used for the orthopaedic patient, postoperative blood salvage and reinfusion, and the implications for nurses.

Temperature changes of > or = 1 degree C alter functional neurologic outcome and histopathology in a canine model of complete cerebral ischemia. Changes in basal temperature of > or = 1 degree C (e.g., fever-induced hyperthermia or anesthesia-related hypothermia) are a common occurrence in neurologically impaired patients. The current study tested the hypothesis that temperature changes as small as 1 degree C or 2 degrees C would significantly alter post-ischemic functional neurologic outcome and cerebral histopathology. The hypothesis was tested in a canine model of transient, complete cerebral ischemia. After institutional approval, 21 dogs were randomly assigned to one of three temperature-specific groups: (1) a reference group maintained at 37.0 +/- 0.3 degree C (target temperature +/- range); (2) a 38.0 +/- 0.3 degree C group; or (3) a 39.0 +/- 0.3 degree C group (n = 7 per group). Complete cerebral ischemia 12.5 min in duration was produced using an established model of arterial hypotension plus intracranial hypertension. Right atrial and cranial (beneath the temporalis muscles) temperatures were maintained at the target value, beginning 20 min before ischemia and ceasing 1 h postischemia. Thereafter, temperatures were returned to 37.0 +/- 0.3 degree C in all dogs. After discharge from the intensive care environment, all dogs were placed in a temperature-controlled recovery area. Neurologic assessment was performed by a blinded observer at 24, 48, and 72 h postischemia using a 100-point scoring scale. After the 72 h examination (with the dogs anesthetized) or at the time of ischemia-related death, the brains were excised and preserved. The brains subsequently were histologically scored by a neuropathologist who was unaware of the treatment groups. All 21 dogs were included in the analysis of neurologic function; however, only dogs that survived for > or = 24 h postischemia were included in the histopathology analysis. Dogs were well matched for systemic physiologic variables throughout the study, with the exception of temperature. During the 72 h postischemic examination, dogs maintained at 37 degrees C were either normal or near normal. In contrast, dogs maintained at 39 degrees C were either comatose or died from ischemia-related causes. Dogs maintained at 38 degrees C were intermediate between 37 degrees C and 39 degrees C dogs. When compared with the reference group, both 38 degrees C and 39 degrees C dogs had significantly worse neurologic function scores (P < 0.01 and < 0.001, respectively) and histopathology scores (P < 0.01 for both). There also was a significant correlation between neurologic function and histopathology rank scores (rs = 0.96; P < 0.001). Small, clinically relevant changes in temperature (1 degree C or 2 degrees C) resulted in significant alterations in both postischemic neurologic function and cerebral histopathology. Assuming that our results are transferable to humans, the results suggest that, in patients at imminent risk for ischemic neurologic injury, body temperature should be closely monitored. Further, the clinician should aggressively treat all episodes of hyperthermia until the patient is no longer at risk for ischemic neurologic injury.

Energy flows in graphene: hot carrier dynamics and cooling. Long lifetimes of hot carriers can lead to qualitatively new types of responses in materials. The magnitude and time scales for these responses reflect the mechanisms governing energy flows. We examine the microscopics of two processes which are key for energy transport, focusing on the unusual behavior arising due to graphene's unique combination of material properties. One is hot carrier generation in its photoexcitation dynamics, where hot carriers multiply through an Auger type carrier-carrier scattering cascade. The hot-carrier generation manifests itself through elevated electronic temperatures which can be accessed in a variety of ways, in particular optical conductivity measurements. Another process of high interest is electron-lattice cooling. We survey different cooling pathways and discuss the cooling bottleneck arising for the momentum-conserving electron-phonon scattering pathway. We show how this bottleneck can be relieved by higher-order collisions—supercollisions—and examine the variety of supercollision processes that can occur in graphene.

Electrophilic fluorination of stereodefined disubstituted silyl ketene hemiaminals en route to tertiary α-fluorinated carbonyl derivatives. A highly diastereoselective synthesis of tertiary α-fluoro carbonyl compounds is reported in only two chemical steps from a simple alkyne through the reaction of stereodefined fully substituted silyl ketene hemiaminal derivatives with Selectfluor.

Sulfur colloid distribution in normal hips. The normal distribution of Tc-99m sulfur colloid is described in 100 patients with no clinical or radiographic evidence of hip disorders. Two-thirds of the patients had uptake in the femoral neck and some uptake in the femoral head. In the other one-third, no uptake was detected in either femoral head. A high degree of symmetry was noted. Judging both the symmetry and pattern of uptake in both hips is important in evaluating femoral head vasculature after a fracture.

CIDE-A gene expression is decreased in white adipose tissue of growth hormone receptor/binding protein gene disrupted mice and with high-fat feeding of normal mice. Growth hormone's (GH) lipolytic activity in white adipose tissue (WAT) results in decreased body fat in giant GH transgenic mice and increased subcutaneous fat in dwarf growth hormone receptor/binding protein gene-disrupted mice (GHR -/-). We therefore hypothesized that GH action would affect expression of CIDE-A (cell-death-inducing DFF45-like effector-A), a protein found in white adipose tissue (WAT) and involved in lipid metabolism. CIDE-A RNA levels were determined in subcutaneous, retroperitoneal and epididymal adipose tissue isolated from wild-type and GHR -/- mice. The adipose tissue was also analyzed for adipocyte size. We determined that the lack of GH action has depot-specific effects on the levels of CIDE-A RNA and affected adipocyte cell size. CIDE-A expression is significantly reduced in GHR -/- subcutaneous fat compared to wild-type but is not altered in retroperitoneal or epididymal fat. Likewise, adipocytes are significantly enlarged in GHR -/- subcutaneous adipose tissue relative wild-type mice. A high-fat diet also influenced the level of CIDE-A RNA in mouse adipose tissue. The high-fat diet significantly reduced CIDE-A expression in wild-type subcutaneous fat but did not alter CIDE-A expression in subcutaneous fat of GHR -/- mice. The diet also reduced CIDE-A expression in wild-type retroperitoneal fat but the levels of CIDE-A in epididymal fat were unchanged. In contrast, the high-fat diet reduced CIDE-A expression in both retroperitoneal and epididymal fat of GHR -/- mice. These data demonstrate that CIDE-A levels are reduced in two different mouse models of obesity and this reduction may contribute to altered lipid metabolism.

Rheumatic mitral regurgitation. The case for annuloplasty in the pediatric age group. Eight youngsters (five female, three male, ages 10 to 19 years, mean 15 years) with isolated severe rheumatic mitral regurgitation have been subjected to mitral annuloplasty because of limiting symptoms and prominent ECG and X-ray changes. They have been followed for up to 11 years (mean 3.7 years), and 7 have had excellent results. An early (1961) patient had a small annulus and was not a favorable candidate; he had only transient improvement. Seven are greatly improved, have decreased cardiac size (often dramatic), and have improved ECG's. One has undergone successful pregnancy, and none has been limited in activities. The extent and duration of improvement, lack of mortality, and resumption of normal activities by these youngsters indicate surgical success. The essence of childhood and youth is activity and the future life span hopefully long; hence, annuloplasty would appear to be the procedure of choice for severe rheumatic mitral regurgitation in the pediatric age group, avoiding the usual need for anticoagulation and uncertain long-term results associated with mitral valve replacement.

Toxicity effect of dichlorvos on loach (Misgurnus anguillicaudatus) assessed by micronucleus test, hepatase activity analysis and comet assay. Pesticides and other chemicals at environmental concentrations often have detrimental effects. Many aquatic species are particularly threatened because of their susceptibility and also because water environment are often polluted. This study preliminarily evaluated the toxicity effect of dichlorvos (DDVP) on loach (Misgurnus anguillicaudatus) using the methods of micronucleus (MN) test, hepatase activity and comet assay. The tested results showed that indeed very little DDVP had strong toxicity effect on loach and its 50% lethal concentration (LC50) at 24 h, 48 h and 96 h was 8.38 μg l(-1), 7.168 μg l(-1) and 6.411 μg l(-1), respectively; The glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) activity of loach liver decreased; meanwhile, the GPT and GOT activity of loach serum, the MN rate (‰) and three comet parameters of tested fish increased with the increase in the treatment concentration and treatment time of DDVP, and there was significant difference between control group and each treatment group (p < 0.05). These results suggested that DDVP residues might become toxic chemical contaminant in environment and would threaten aquatic and other organisms.

Extracellular phosphomannan as a phosphate reserve in the yeast Kuraishia capsulata. We have found that extracellular phosphomannan is the main phosphate reserve in the yeast Kuraishia capsulata, in contrast to other yeast species effectively absorbing Pi. Under nitrogen starvation, K. capsulata absorbed essentially all Pi from the medium containing 240 mM glucose, 2.5 mM MgSO4, and 11 mM KH2PO4. Inorganic polyphosphate level in the cells was about 14% of the Pi absorbed. Most of the Pi (~60%) was found in the fraction of extracellular phosphomannan that can be used as a carbon and phosphorus source by this yeast in deficient media.

Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase. The function of Nox4, a source of vascular H(2)O(2), is unknown. Other Nox proteins were identified as mediators of endothelial dysfunction. We determined the function of Nox4 in situations of increased stress induced by ischemia or angiotensin II with global and tamoxifen-inducible Nox4(-/-) mice. Nox4 was highly expressed in the endothelium and contributed to H(2)O(2) formation. Nox4(-/-) mice exhibited attenuated angiogenesis (femoral artery ligation) and PEG-catalase treatment in control mice had a similar effect. Tube formation in cultured Nox4(-/-) lung endothelial cells (LECs) was attenuated and restored by low concentrations of H(2)O(2,) whereas PEG-catalase attenuated tube formation in control LECs. Angiotensin II infusion was used as a model of oxidative stress. Compared to wild-type, aortas from inducible Nox4-deficient animals had development of increased inflammation, media hypertrophy, and endothelial dysfunction. Mechanistically, loss of Nox4 resulted in reduction of endothelial nitric oxide synthase expression, nitric oxide production, and heme oxygenase-1 (HO-1) expression, which was associated with apoptosis and inflammatory activation. HO-1 expression is controlled by Nrf-2. Accordingly, Nox4-deficient LECs exhibited reduced Nrf-2 protein level and deletion of Nox4 reduced Nrf-2 reporter gene activity. In vivo treatment with hemin, an inducer of HO-1, blocked the vascular hypertrophy induced by Nox4 deletion in the angiotensin II infusion model and carbon monoxide, the product of HO-1, blocked the Nox4-deletion-induced apoptosis in LECs. Endogenous Nox4 protects the vasculature during ischemic or inflammatory stress. Different from Nox1 and Nox2, this particular NADPH oxidase therefore may have a protective vascular function.

Standardization of U.S. Reference Rh0 (D) Immune Globulin by quantitative automated hemagglutination. An automated hemagglutination procedure was used to assess the relative potency of US Reference Rh0 (D) Immune Globulin, Lot 3, with respect to the International Reference Preparation, WHO Anti-D immunoglobulin, Lot 68/419. A value of 300 international units (IU) of anti-D per ampoule has been assigned to Lot 68/419. In 25 assays, the mean value for Lot 3 was 820 IU anti-D per milliliter when tested in parallel with Lot 68/419.

Beta blockers for acute traumatic brain injury: a systematic review and meta-analysis. Traumatic brain injury (TBI) is associated with a systemic hyperadrenergic state. Through activation of beta adrenoreceptors, catecholamines may induce hypermetabolism and increase both cardiac and cerebral oxygen demands. We conducted a systematic review to appraise the available evidence examining the safety and efficacy of beta blockers in patients with acute TBI. We systematically searched CENTRAL, MEDLINE, EMBASE and the reference lists of relevant articles from database inception until March 19, 2013. The outcomes assessed were in-hospital mortality, functional outcome and quality of life. Common adverse effects of beta blockers were examined including clinically significant hypotension, bradycardia, bronchospasm and congestive heart failure. Data on study outcomes and quality were abstracted in duplicate. The results were summarized descriptively and quantitatively. One randomized controlled trial was found with a high risk of bias. Eight retrospective cohort studies were found with a moderate risk of bias; however, only four of these studies were identified as unique after excluding overlapping cases. The cohort studies reported mortality outcomes; however, none of these included studies assessed functional outcomes or quality of life. Meta-analysis on the cohort studies (n = 4,782 patients) demonstrated that exposure to beta blockers after TBI was associated with a reduction in the adjusted odds of in-hospital mortality by 65 % (pooled adjusted odds ratio 0.35; 95 % CI 0.27-0.45). The current body of evidence is suggestive of a benefit of beta blockers following TBI. However, methodologically sound randomized controlled trials are indicated to confirm the efficacy of beta blockers in patients with TBI.

Improvement in peripheral nerve function after one year of Sorbinil. The effect of 250 mg day-1 of the aldose reductase inhibitor, Sorbinil, upon peripheral nerve function was assessed in 23 adult diabetics with clinical neuropathy. Sorbinil was given for 4 weeks to 10 subjects, while 13 received placebo in this double-blind study. Open label treatment with Sorbinil was then continued for 52 weeks in 10 of the 23 subjects. Red cell sorbitol, hemoglobin A1c, vibratory sensation, median nerve sensory and motor conduction velocities were measured at 0, 4 and 52 weeks. There were no measurable changes in peripheral nerve function after 4 weeks of Sorbinil treatment. After 52 weeks significant improvement was found in the median nerve motor and sensory conduction velocities. This was associated with no change in blood glucose control but a reduction of erythrocyte sorbitol levels.

Minimizing wound contamination in a 'clean' surgery: comparison of chlorhexidine-ethanol and povidone-iodine. There is limited work analyzing the efficacy of different antiseptics in reducing wound contamination by the skin flora during hernia repair and its influence on the incidence of wound infection, which continues to be a major problem in the developing world. This study was designed to test if chlorhexidine-ethanol has superior antimicrobial efficacy compared with povidone-iodine. In a prospective randomized trial, the efficacy of chlorhexidine-ethanol and povidone-iodine in the reduction of colony counts of the skin flora and the incidence of surgical site infection was compared. Both povidone-iodine and chlorhexidine-ethanol produced significant reduction in the skin bacterial colony counts, from 18.66 x 10(2) to 2.34 x 10(2) colony-forming units with povidone-iodine (59%) and from 12.34 x 10(2) to 0.93 x 10(2) colony-forming units (82%) with chlorhexidine-ethanol. Infection rates with the use of povidone-iodine and chlorhexidine-ethanol groups were not significantly different (9.5 vs. 7.0; p = 0.364). The reduction in colony counts in those who developed infection was only 15.6% compared with 77.1% in those who did not develop infection. The antibacterial efficacy of chlorhexidine-ethanol and povidone-iodine is comparable in open hernia repair.

A Yersinia pestis YscN ATPase mutant functions as a live attenuated vaccine against bubonic plague in mice. Yersinia pestis is the causative agent responsible for bubonic and pneumonic plague. The bacterium uses the pLcr plasmid-encoded type III secretion system to deliver virulence factors into host cells. Delivery requires ATP hydrolysis by the YscN ATPase encoded by the yscN gene also on pLcr. A yscN mutant was constructed in the fully virulent CO92 strain containing a nonpolar, in-frame internal deletion within the gene. We demonstrate that CO92 with a yscN mutation was not able to secrete the LcrV protein (V-Antigen) and attenuated in a subcutaneous model of plague demonstrating that the YscN ATPase was essential for virulence. However, if the yscN mutant was complemented with a functional yscN gene in trans, virulence was restored. To evaluate the mutant as a live vaccine, Swiss-Webster mice were vaccinated twice with the ΔyscN mutant at varying doses and were protected against bubonic plague in a dose-dependent manner. Antibodies to F1 capsule but not to LcrV were detected in sera from the vaccinated mice. These preliminary results suggest a proof-of-concept for an attenuated, genetically engineered, live vaccine effective against bubonic plague.

[Distribution characteristics of heavy metals in soil profile of facility vegetable fields]. Taking the facility vegetable fields having been planted for 1-12 years and the adjacent wheat land in Shouguang City of Shandong Province as test objects, this paper studied the distribution characteristics of arsenic (As), cadmium (Cd), copper (Cu), zinc (Zn), chromium (Cr), and nickel (Ni) in their soil profiles (0-150 cm). With the increase of soil depth, the test heavy metals contents in the soil profiles all had a decreasing trend, and in the same soil layers, the contents were obviously higher in facility vegetable fields than in wheat land. Comparing with those in the same soil layers of wheat land, the average contents of As, Cd, Cu, Zn, Cr, and Ni in 0-20 and 120-150 cm soil layers of facility vegetable fields were 35.0%, 146.2%, 65.6%, 36.4%, and 21.5%, and 10.6%, 178.5%, 19.4%, 20.2%, 15.2%, and 9.3% higher, respectively, and the average contents of the heavy metals in 20-120 cm soil layer of facility vegetable fields were also higher in some degree. In the 0-20 cm soil layer of facility vegetable fields, the Cd, Cu, and Zn contents had significant positive correlations with planting years (P < 0.05), with the accumulation rates of Cd, Cu, and Zn being 0.027, 1.153, and 2.830 mg x kg(-1) x a(-1), respectively. In facility vegetable fields, the test six heavy metals contents were significantly positively correlated with the contents of soil organic carbon and total nitrogen, and the Cd, Cu, Zn, and Cr contents were significantly correlated with the content of soil total phosphorus (P < 0.01). Applying organic fertilizer could induce the heavy metals accumulation in the soils of facility vegetable fields to some extent.

Monoclonal antibodies against a specific surface determinant on malarial (Plasmodium knowlesi) merozoites block erythrocyte invasion. Twelve hybridoma cell lines secreting monoclonal antibodies against Plasmodium knowlesi merozoites have been produced. Antibodies from 3 of the 12 lines agglutinated merozoites. The 2 monoclonal antibodies (13C11 and 16F8) that markedly agglutinated merozoites blocked merozoite invasion of erythrocytes. Of these 2 lines, the one that induced the most agglutination also blocked invasion most effectively. The third monoclonal antibody (53B3) caused minimal agglutination of merozoites and did not block invasion, nor did the other 9 nonagglutinating antibodies. The 2 blocking monoclonal antibodies bound to antigens around the entire surface of merozoites, as demonstrated by immunoelectron microscopy, and precipitated a single biosynthetically labeled protein of apparent m.w. of 250,000. None of the nonagglutinating lines precipitated this protein. Monoclonal antibodies 13C11 and 16F8 reacted with a common antigenic determinant on a Malaysian and a Philippine strain of P. knowlesi in that they blocked invasion and precipitated a 250,000 m.w. protein from both. Sera from immune monkeys also precipitated this 250,000 m.w. protein.

A novel HLA-B*51 allele (B*5116) identified by nucleotide sequencing. We report here an additional HLA-B*51 variant designated HLA-B*5116. Detected by an abnormal serological reactivity pattern, this variant was identified as a B*51 allele by polymerase chain reaction using sequence-specific primers (PCR-SSP) and characterized by nucleotide sequencing. The new variant sequence match closely with the classical HLA-B*5101 excepted two adjacent nucleotide substitutions at positions 216 and 217 of the third exon and the subsequent Leucine to Glutamic acid change at codon 163 of the alpha2 domain (CTG-->GAG). This new variant was not detected in three different ethnic groups (French, Algerian and Lebanese) suggesting a very rare frequency.

[The effect of caerulein on gastric mucosal blood-flow and gastric secretion (author's transl)]. The effect of Caerulein, a decapeptide produced from the skin of the Australian frog Hyla caerulea, on the mucosal blood-flow and the gastric acid secretion as well as the pepsin secretion has been investigated in 15 patients. Caerulein administered at a dose rate of 0.1 mug/kg-h significantly inhibited the gastric mucosal blood-flow (p greater than 0.005) and the acid secretion (0.05 greater than p greater than 0.01), which had been stimulated by pentagastrin at a dose rate of 1.5 mug/kg-h. The pepsin secretion stimulated with pentagastrin also decreased, but not significantly. Caerulein at the above mentioned dose rate however caused a slight but not significant increase of the acid secretion stimulated by 40 mug histamine/kg-h. At the same time, gastric mucosal blood-flow and pepsin output decreased slightly but not significantly. Caerulein given alone stimulates acid secretion, yet it causes a significant reduction of the acid output when administered together with pentagastrin. This response has to be explained by the fact, that the similar chemical structure of pentagastrin and caerulein leads to a competitive inhibition. The mucosal blood-flow of the stomach measured with the heat-clearance technique also decreases with the administration of caerulein after pentagastrin stimulation. The fact that the mucosal blood-flow remains unchanged after the administration of histamine, suggests that the reduction in mucosal blood-flow observed with pentagastrin is a consequence and not the cause of the acid inhibition occurring at the same stage.

[Anomalies of the skull in cleidocranial dysplasia]. The description of the otorhinolaryngeal and craniofacial anomalies in patients with cleidocranial dysplasia. For this study, 26 patients with cleidocranial dysplasia were examined after their medical history had been recorded. The main focus was placed on otorhinolaryngological and orthodontic findings. The portion of spontaneous mutations in our patient population was 46.1%. All patients exhibited otorhinolaryngological and craniofacial anomalies. While single ENT-anomalies were expressed in 76.9%-92.3% of the patients, the craniofacial findings were distributed over 84.6%-92.3%. The expression of this rare disorder is variable and its symptomatology not always distinct. Otorhinolaryngological and craniofacial anomalies are often apparent. Appropriate treatment can significantly contribute to an improvement in the patient's quality of life. In cases of ambiguous findings, we recommend consultation with an experienced clinician as well as genetic counselling.

Novel selective inhibitor of Leishmania (Leishmania) amazonensis arginase. Arginase is a glycosomal enzyme in Leishmania that is involved in polyamine and trypanothione biosynthesis. The central role of arginase in Leishmania (Leishmania) amazonensis was demonstrated by the generation of two mutants: one with an arginase lacking the glycosomal addressing signal and one in which the arginase-coding gene was knocked out. Both of these mutants exhibited decreased infectivity. Thus, arginase seems to be a potential drug target for Leishmania treatment. In an attempt to search for arginase inhibitors, 29 derivatives of the [1,2,4]triazolo[1,5-a]pyrimidine system were tested against Leishmania (Leishmania) amazonensis arginase in vitro. The [1,2,4]triazolo[1,5-a]pyrimidine scaffold containing R1 = CF3 exhibited greater activity against the arginase rather than when the substituent R1 = CH3 in the 2-position. The novel compound 2-(5-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)hydrazinecarbothioamide (30) was the most potent, inhibiting arginase by a non-competitive mechanism, with the Ki and IC50 values for arginase inhibition estimated to be 17 ± 1 μm and 16.5 ± 0.5 μm, respectively. These results can guide the development of new drugs against leishmaniasis based on [1,2,4]triazolo[1,5-a]pyrimidine derivatives targeting the arginase enzyme.

Temporal arteritis. Temporal arteritis, a vasculitis, affects the large- and medium-sized arteries. This disorder has a largely unknown etiology and mainly occurs in older patients. Headache is the predominant symptom with diplopia usually appearing shortly after. Clinicians must be aware of temporal arteritis because blindness occurs in up to 50% of untreated or misdiagnosed patients.

Sexuality in cancer and palliative care 1: Effects of disease and treatment. All cancers and related treatments have the potential to affect sexuality and sexual function. This may result from impaired body function or altered body image, or from the emotional and psychological distress that often accompany diagnosis and treatment. It is increasingly acknowledged that issues surrounding sexuality are an important factor in quality of life for patients with cancer, and that sexuality is a legitimate area of concern for nurses in oncology and palliative care. However, issues relating to sexuality remain among the most poorly addressed in cancer care--possibly owing to lack of knowledge and expertise. There are also societal norms, myths and assumptions that may prevent nurses from broaching these issues. To provide this component of care, nurses need to have good communication skills, an open and non-judgmental approach, and knowledge of the potential ramifications of disease and treatment on sexuality.

[Progress and perspectives in bone research]. Structural integrity and strength of bone is maintained by a balance between bone resorption and bone formation. The balance in bone remodeling process is maintained by factors including mechanical stress, calcium-regulating hormones and sex hormones. Changes in physiological regulators of bone remodeling such as reduction in mechanical stress, aging and reduction in sex hormones, or an increase in pathological factors such as glucocorticoid and inflammatory cytokines cause disturbances in bone remodeling process. Disturbances in bone remodeling not only reduce the bone volume but also deteriorate material as well as structural properties of bone, resulting in a reduction in bone strength. Mechanisms of how bone resorption is initiated at the surface of damaged or aged bone, and how bone resorption is coulpled to bone formation are under active investigation. Increasing the understanding of physiological regulation and pathological conditions of bone remodeling should be able to develop new therapeutic approaches to osteoporosis and other metabolic bone diseases.

Occurrence of polycyclic aromatic hydrocarbons in dust emitted from circulating fluidized bed boilers. Occurrence of polycyclic aromatic hydrocarbons (PAHs) in granulometric fractions of dust emitted from a hard coal fired circulating fluidized bed (CFB) boiler was investigated. The dust was sampled with the use of a Mark III impactor. In each fraction of dust, by using gas chromatography (GC), 16 selected PAHs and total PAHs were determined and the toxic equivalent B(a)P (TE B(a)P) was computed. The results, recalculated for the standard granulometric fractions, are presented as concentrations and content of the determined PAHs in dust. Distributions of PAHs and their profiles in the granulometric dust fractions were studied also. The PAHs in dust emitted from the CFB boiler were compared with those emitted from mechanical grate boilers; a distinctly lower content of PAHs was found in dust emitted from the former.

Creating a "win-win" home care agency-university partnership. This article describes the experiences of the home care agency-university partnership, identifies cooperative activities and resultant clinical and cost outcomes, and cites future collaborative plans. The authors also outline home care agency and university characteristics that contribute to successful partnerships and tips for initiating such relationships.

Nanoscaled Amorphous TiO2 Hollow Spheres: TiCl4 Liquid Droplet-Based Hydrolysis Fabrication and Strong Hollow Structure-Enhanced Surface-Enhanced Raman Scattering Effects. A very simple route is developed for fast fabrication of nanosized amorphous titanium dioxide (TiO2) hollow spheres (THPs) just via dropping the pure four titanium chloride (TiCl4) liquid droplets into deionized water at around room temperature. The THPs, at around 80 nm in mean diameter, can be formed within a few seconds after dropping TiCl4 droplets into water. The shell layers of the obtained THPs are amorphous and porous in structure with a porosity of 58-80% and show a linear increase in thickness with the size of THPs. Further experiments have revealed that the reaction temperature, initial pH value, and size of the TiCl4 droplet are crucial to the formation, size, productivity, and microstructure of the THPs. A model is proposed on the basis of the fragmentation of liquid droplets, hydrolysis-induced formation, and inward growth of TiO2 shell layers, which can well describe the formation of the THPs. Importantly, such amorphous nanoscaled THPs have exhibited some strong hollow structure-enhanced performances. Typically, the THP-built film shows the highest reflectivity in the visible region compared to the other structured TiO2 films. Especially, if it supports the film of the Au nanoparticle, the surface-enhanced Raman scattering effect is significantly enhanced by more than 1 order of magnitude. This work provides not only a simple and quick fabrication method for the THPs but also a new member for their family.

The genetic and molecular basis of congenital cataract. Congenital cataracts are one of the most treatable causes of visual impairment and blindness during infancy, with an estimated prevalence of 1 to 6 cases per 10,000 live births. Approximately fifty percent of all congenital cataract cases may have a genetic cause. All three types of Mendelian inheritance have been reported for cataract; however, autosomal dominant transmission seems to be the most frequent. The transparency and high refractive index of the lens are achieved by the precise architecture of the fiber cells and the homeostasis of the lens proteins in terms of their concentration, stability, and supramolecular organization. Research on hereditary congenital cataract led to the identification of several classes of candidate genes that encode proteins such crystallins, lens specific connexins, aquaporine, cytoskeletal structural proteins, and developmental regulators. The purpose of this study was to review the literature on the recent advances made in understanding the molecular genetic basis of congenital cataracts.

Use-dependent block with tetrodotoxin and saxitoxin at frog Ranvier nodes. II. Extrinsic influence of cations. Use-dependent declines of Na+ currents in myelinated frog nerve fibres were measured during a train of depolarizing pulses in solutions containing tetrodotoxin (TTX) or saxitoxin (STX). The following effects of external monovalent (Na+), divalent (Ca2+, Mg2+) and trivalent (La3+) cations on use dependence were found: Increasing the Ca2+ concentration from 2 to 8 mM shifts its voltage dependence by 20 mV whereas no significant use-dependent decline occurred at 0.2 mM Ca2+. Doubling the external Na+ concentration in 0.2 mM Ca2+ solutions did not initiate phasic block. External Mg2+ ions induced a smaller, and La3+ ions a larger, use dependence. The time constants of the current decline were 4-fold greater in 1.08 mM La3+. The static block of Na+ currents by La3+ could be directly demonstrated by the relief of block during a train of pulses. The results are qualitatively explained by a toxin binding site at the Na+ channel whose affinity for TTX or STX depends on 1) the gating conformation of the channel, probably the inactivation and ii) the occupancy of a blocking site by di- or trivalent external cations.

[Multidrug resistance of cancer cells mediated by ABC superfamily transporters]. ATP-binding cassette(ABC) superfamily transporters, including P-glycoprotein and MRP, actively transport various structurally dissimilar chemotherapeutic compounds out of cancer cells and confer multidrug resistance. Members of ABC superfamily which may extrude anti-cancer drugs are still expanding, thus the importance of these proteins are further increasing for cancer chemotherapy. Multidrug resistance will be acquired either by the induction of expression of ABC superfamily transporters or by mutations of ABC superfamily genes which cause amino acids substitutions. We recently found that amino acid substitutions in the first predicted transmembrane domain of P-glycoprotein increase the ability to confer resistance to important anti-cancer drugs adriamycin and VP-16. The mechanisms for drug recognition and transport of human P-glycoprotein and MRP are discussed.

Efficacy of tapentadol prolonged release for pre- and post-operative low back pain: a prospective observational study. Low back pain (LBP) is a highly prevalent chronic pain condition with a neuropathic component of pain that limits the benefits of classical opioids. Tapentadol is an innovative drug for the treatment of chronic severe pain, with a dual mechanism of action combining µ-opioid receptors agonism and noradrenaline re-uptake inhibition (NRI). Its efficacy is equal to that of strong opioids, with a better tolerability profile and a consequently lower risk of treatment discontinuation. The aim of this study was to evaluate the analgesic efficacy and tolerability of tapentadol prolonged release (PR) vs. other analgesics in patients with moderate-to-severe neuropathic low back pain, before and after back surgery. The primary endpoints of the study were the rate of response to treatment, measured as ≥30% reduction in pain intensity on the Numeric Rating Scale (NRS), and tapentadol PR efficacy for pain relief. The secondary endpoints were the improvements of the neuropathic component of pain and of sleep quality. A total of 40 patients were enrolled in the study, receiving either tapentadol PR (n=21, 52.5%) or other analgesics (n=19, 47.5%), both before and after surgery. The rate of response to treatment was statistically in favor of tapentadol PR (p<0.01). The reduction in pain intensity was statistically significant in the group treated with tapentadol PR, both before and after surgery (p<0.01), with a complete resolution of pain 90 days after surgery. The quality of sleep after surgery improved more in patients treated with tapentadol PR than in the comparator group (p<0.01), with 100% of the patients reporting a "good" sleep quality 2 months after surgery. Tapentadol PR was well tolerated by all patients, and its efficacy for pain relief was also confirmed in our small group of "real-life" patients with chronic, severe low back pain. Overall, the tolerability of this treatment may help to improve patients' quality of life, which is frequently compromised because of pain and its related comorbidities.

Genetics of craniosynostosis: genes, syndromes, mutations and genotype-phenotype correlations. Craniosynostosis is a very heterogeneous group of disorders, in the etiology of which genetics play an important role. Chromosomal alterations are important causative mechanisms of the syndromic forms of craniosynostosis accounting for at least 10% of the cases. Mutations in 7 genes are unequivocally associated with mendelian forms of syndromic craniosynostosis: FGFR1, FGFR2, FGFR3, TWIST1, EFNB1, MSX2 and RAB23. Mutations in 4 other genes, FBN1, POR, TGFBR1 and TGFBR2, are also associated with craniosynostosis, but not causing the major clinical feature of the phenotype or with an apparently low penetrance. The identification of these genes represented a great advance in the dissection of the genetics of craniosynostosis in the last 15 years, and today they explain the etiology of about 30% of the syndromic cases. The paucity in the identification of genes associated with this defect has partly been due to the rarity of familial cases. In contrast, very little is known about the molecular and cellular factors leading to nonsyndromic forms of craniosynostosis. Revealing the molecular pathology of craniosynostosis is also of great value for diagnosis, prognosis and genetic counseling. This chapter will review (1) the chromosomal regions associated with syndromic forms of the malformation, (2) the genes in which a large number of mutations have been reported by independent studies (FGFR1, FGFR2, FGFR3, TWIST1 and EFNB1) and (3) the molecular mechanisms and genotype-phenotype correlations of such mutations.

Prevalence of anxiety, depression and quality of life in HTLV-1 infected patients. The HAM/TSP caused by HTLV-1 infection usually affects patients to disabling states, and sometimes can lead them to paraplegia presenting symptoms of depression and anxiety, impacting on quality of life. The purpose of this study was to evaluate the frequency of depression and anxiety and its impact on quality of life in HTLV-1-infected TSP/HAM patients. This was a cross-sectional study including 67 asymptomatic (control group) and 63 with TSP/HAM subjects. The instruments used were a demographic questionnaire, scales for anxiety and depression diagnosis (BDI and BAI), questionnaire for the assessment of Quality of Life of the World Health Organization (WHOQOL-Brief) and neurological scale to measure the disability level (Osame's Disability Status Scale). All patients had HTLV-I diagnosis by serological and molecular approaches, monitored at Instituto de Infectologia Emílio Ribas from May 2008 to July 2009. Data were analyzed statistically by frequencies, the Mann-Whitney test and the Spearman correlation test. Data among groups were analyzed and correlated with functional and severity aspects. The results showed that patients with HAM/TSP compared to asymptomatic carriers had higher rates of depression (p < 0.001) and anxiety (p < 0.001), and impairment on quality of life in the areas of: dissatisfaction with health (p < 0.001), physical (p < 0.001) and the environment (p = 0.003). The main factors that correlated with levels of depression and anxiety and the domains of the WHOQOL-brief were: education, family income and social class. A well conducted evaluation and counseling may help in treatment, for a better quality of life of these patients.

Teenage parenting and child abuse: are they related? The relationship between teenage parenting and child abuse is examined in terms of three methodological problems that must be considered in assessing this relationship. Four data sets illustrative of the methodological difficulties are described. Results suggest that the hypothesized association between teenage pregnancy and child abuse may be confounded by the association of each variable with social class.

Human beta defensin-3 engineered keratinocyte sheets constructed by a magnetic force-based tissue engineering technique. A multilayered keratinocyte sheet overexpressing human beta defensin-3 (HBD-3) gene was prepared by the magnetic force-based tissue engineering technique. The cell sheet demonstrated significant antimicrobial activity, indicating that the therapeutic introduction of HBD-3 gene into cell sheets may provide a new gene therapy strategy for infectious diseases.

Partial purification and characterization of protein tyrosine kinases from normal tissues. Three membranous protein tyrosine kinases (PTKs) have been partially purified from human placenta and pig brain. The two placental enzymes (PTK-1 and -2) are distinct with respect to solubility in detergents, molecular weight, and enzymatic properties. The brain protein tyrosine kinase resembles placental PTK-1 with respect to molecular weight and some kinetic properties. However, stimulation of brain PTK is greater with Mn2+ than with Mg2+ whereas placental PTK-1 gives higher rates with Mg2+ than with Mn2+. All three enzymes are inhibited about 50% by 0.1 M NaCl. A monoclonal antibody raised in vitro against the brain enzyme inhibits brain PTK as well as placental PTK-2, but has no effect against PTK-1 or pp60src. It thus appears that these three enzymes are distinct entities that differ from each other both kinetically and immunologically. With synthetic tyrosine-glutamic acid polymers as a substrate, protein tyrosine kinase activity can be detected in crude extracts of membranes.

Can membrane progesterone receptor α on T regulatory cells explain the ensuing human labour? Progesterone acts as an immunosteroid by contributing to the establishment of a pregnancy-protective milieu. It seems that it is the responsibility of progesterone to evade the inflammatory events that lead to parturition. T regulatory lymphocytes (Treg cells) could further explain the inhibition of the inflammatory mechanisms that lead to labour through the rapid action of progesterone on this cell subset. We investigated Treg cells and the membrane progesterone receptor α (mPRα) in these immune cells with in relationship to human parturition. This pilot cohort study was conducted in a single-centre tertiary obstetrical unit with 20 normal pregnant women. Variation in the absolute and relative frequency of CD4(+) T cells, Treg cells, and of mPR(α+) Treg cells was calculated by flow cytometry on three occasions (second and third trimesters; delivery day). Our results show that during normal pregnancy there is a generalised increase in Treg cells and mPR(α+) Treg cells, from the second to the third trimesters (23.4% vs. 52.3% and 4.3% vs. 8.3%, respectively). On the contrary, on delivery day, compared with the values in the third trimester, there is a sudden decrease in both Treg cells (52.3% vs. 17.4%) and mPR(α+) Treg cells (8.3% vs. 6.1%). Our findings suggest that human labour may develop as a consequence of a decline in mPR(α+) Treg cells, which reduces progesterone anti-inflammatory action through Treg cells.

Uterine sarcomas: a clinicopathologic study. A series of 48 cases with initial diagnosis of uterine sarcoma was reviewed to evaluate the validity of histologic criteria. The influence of pathologic and clinical prognostic factors and treatment modalities were examinated. The 32 patients included in this retrospective study after pathologic review had 5-year overall survival rate of 13.1%. Surgical pathological staging was demonstrated to be a significant prognostic factor, since patients with FIGO stage I-II disease had 33.5% actuarial survival rate whereas no patient with stage III-IV disease was alive at 37 months. Histological type, age and menopausal status did not significantly influence survival. Presence of heterologous elements and lymphovascular invasion were associated with a poor prognosis in the subgroup of patients with mixed mesodermal tumors. Median survival for patients receiving adjuvant treatment was 25 months compared to 19 months for those undergoing no adjuvant therapy.

Peculiarities of cardiovascular disease in women. In a review article peculiarities of cardiovascular disease among women are considered. The analysis of published data showed that cardiovascular disease (CVD) is common in women. Gender-specific risk factors include oral contraceptives and menopause. Clinical manifestations, major causes of various forms of cardiovascular disease in women are revealed. It was found that women most often than men have coronary micro vascular disease - X Syndrome, which affects the tiny coronary arteries. Coronary microvascular dysfunction is prevalent in women with chest pain. There is a greater prevalence of no coronary causes of chest pain in the female population, and chest pain is frequently accompanied by abdominal pain, dyspnea, nausea, fatigue, and greater functional disability. Women tend to suffer from more single vessel and two-vessel disease as opposed to the three-vessel disease seen more often in men. It is concluded that specific research is required to identify risk factors of cardiovascular disease in women in Georgia.

[Bacterial overgrowth of slides and electron microscopic grids in the surface film of water and ooze deposits]. Distinct bacterial growth can be discerned in the surface water film on semisubmerged slides in the laboratory conditions. The thickness of growth depends on the content of organic substances in water. The growth is found also in natural brine if the content of salts is 127--230 g per litre. A great variety of aqueous bacteria is seen, by means of electron microscopy, on electron-microscopic nets submerged in the surface water layer. New bacterial forms have been found in natural brine. Many creeping bacteria cover slides at the water-ooze interface.

Planning for a second (23 valent) generation pneumococcal vaccine. With special reference to new developments in our understanding of the structure and biology of polysaccharides. The epidemiologic and experimental data upon which the proposed second and more expanded formulation for the pneumococcal capsular polysaccharide was based has been reviewed. The use of a functional (opsonization) and quantitative (radioimmunoassay) for assaying the human serum antibody response in order to predict the efficacy of pneumococcal vaccine should permit further examination of its usefulness in various clinical settings. New developments in the area of improved pneumococcal and other polysaccharide vaccines were examined.

Recognition of amplitude-modulation patterns in the presence of a distractor. I. Effects of correlation and frequency relation. Listeners' ability to compare the amplitude modulation pattern of 200- and 500-Hz targets when distractors that were also amplitude modulated were presented simultaneously was evaluated. The amplitude modulations of the distractors were either uncorrelated, partially correlated, or fully correlated with the amplitude modulations of the comparisons. Relative to the case of no distractor, performance tended to decrease when a distractor was present, and the degree of interference increased as the modulation correlation between the comparisons and distractors decreased. Although the interference was greater when the comparisons and distractors were separated by 50 Hz, there was also significant interference when the separation was 300 Hz. Whether the comparison was higher or lower in frequency than the distractor had no overall effect. However, the effect of modulation correlation was greater when comparisons were higher than distractors rather than lower. Patterns of interference are compared to those found in studies of modulation detection and discrimination interference, and implications for the use of multiple-band signals that carry the amplitude envelopes from different spectral regions of a speech signal to convey speech are discussed.

Serum metabolome biomarkers associate low-level environmental perfluorinated compound exposure with oxidative /nitrosative stress in humans. Previous in vivo and in vitro studies have linked perfluorinated compound (PFC) exposure with metabolic interruption, but the inter-species difference and high treatment doses usually make the results difficult to be extrapolated to humans directly. The best strategy for identifying the metabolic interruption may be to establish the direct correlations between monitored PFCs data and metabolic data on human samples. In this study, serum metabolome data and PFC concentrations were acquired for a Chinese adult male cohort. The most abundant PFCs are PFOA and PFOS with concentration medians 7.56 and 12.78 nM, respectively; in together they count around 81.6% of the total PFCs. PFC concentration-related serum metabolic profile changes and the related metabolic biomarkers were explored by using partial least squares-discriminant analysis (PLS-DA). Respectively taking PFOS, PFOA and total PFC as the classifiers, serum metabolome can be differentiated between the lowest dose group (1st quartile PFCs) and the highest PFC dose group (4th quartile PFCs). Ten potential PFC biomarkers were identified, mainly involving in pollutant detoxification, antioxidation and nitric oxide (NO) signal pathways. These suggested that low-level environmental PFC exposure has significantly adverse impacts on glutathione (GSH) cycle, Krebs cycle, nitric oxide (NO) generation and purine oxidation in humans. To the best of our knowledge, this is the first report investigating the association of environmental PFC exposure with human serum metabolome alteration. Given the important biological functions of the identified biomarkers, we suggest that PFC could increase the metabolism syndromes risk including diabetes and cardiovascular diseases.

Amino acid sequence similarity between the terminal protein of hepatitis B virus and predicted hepatitis delta virus gene product. The comparative analysis of primary and secondary structures, and hydropathy plots of hepatitis B virus (HBV) and hepatitis delta virus (HDV) proteins was carried out. Two short regions belonging to the HBV terminal protein were shown to be homologous to two regions; one encoded by HDV ORF5, and the other encoded by small ORF of the HDV antigenomic RNA strand. We propose a new protein containing both these regions may be synthesized in HDV infected cells. Striking structural homology between the terminal protein of HBV and this predicted protein called HDAg' of HDV may indicate a possible functional similarity. We hypothesize the HDAg' may interact with and inhibit the polymerase activity of HBV.

Ulnar stress reaction from crutch use following amputation for tibial osteosarcoma. Stress fractures of the ulnar diaphysis occur most commonly in association with upper-limb dominated sports. Their occurrence in association with crutch use is rare. Following a review of the world literature we report the third such case in a patient using crutches following above knee amputation for recurrent tibial osteosarcoma. MRI was performed to rule out metastatic disease.

Inhibition of coxsackievirus B3 carrier state infection of cultured human myocardial fibroblasts by ribavirin and human natural interferon-alpha. As enterovirus infections of the heart cause myocarditis and eventually congestive heart failure, the antiviral activity of ribavirin was studied in coxsackie virus B3 (CVB3)-infected carrier cultures of human myocardial fibroblasts. Cultures were infected 7 days before application of ribavirin and effects were evaluated over a period of 16 days by plaque assays and in situ hybridization. Compared to the low antiviral activity in HeLa cells, ribavirin was highly active in reducing infectious virus yields in human myocardial fibroblasts, for example, to 2.0 x 10(3) pfu/ml with 25 microg/ml and to 1.3 x 10(2) pfu/ml with 50 microg/ml (4.3 x 10(4) pfu/ml in infected controls). Moreover, 100 microg ribavirin/ml completely suppressed infectious virus progeny in two of three cultures, and reduced the number of infected cells from 14.3 to 0.3% as determined by in situ hybridization, whereas up to 3200 microg ribavirin/ml did not result in a significant cytotoxic effect. Interaction with interferon-alpha (IFN-alpha) was additive to slightly synergistic in reducing the number of infected cells and virus yields. In conclusion, our results suggest a cell-specific high activity of ribavirin in human myocardial fibroblasts and indicate the importance of using organ-specific cells for testing antiviral agents in myocarditis. Furthermore, the usefulness of in situ hybridization for determining the long term effects of antivirals in carrier state cell cultures was demonstrated.

Isolation of pseudorabies virus from trigeminal ganglia of a latently infected sow. A 2-year-old sow with a relatively low virus-neutralization (VN) titer (1:8) against pseudorabies virus (PRV) was brought to the National Animal Disease Center for observation and study. The sow was kept in isolation for approximately 6 weeks, and repeated nasal and tonsillar swabs for virus isolation and blood samples for VN tests were obtained during this interval. At the end of 5 weeks' observation, the sow was injected IM with 200 mg of dexamethasone and was euthanatized 1 week later. Parts of the two trigeminal ganglia, tonsillar tissue, and nasal secretions were cultured in porcine kidney cells. The rest of the trigeminal ganglia was extracted with phenol and tested for presence of the PRV-DNA genome by hybridization with tritiated complementary RNA. The PRV was isolated from the trigeminal ganglia only, and the PRV genome was demonstrated in the same tissue. This latently infected sow was a potential shedder of PRV.

Three-dimensional ultrasonography using the minimum transparent mode in obstructive biliary diseases: early experience. To assess the feasibility of three-dimensional ultrasonography using the minimum transparent mode in patients with obstructive biliary disease. Fourteen patients with obstructive jaundice underwent three-dimensional ultrasonography after conventional two-dimensional ultrasonography before interventional procedures. Three-dimensional images reconstructed by the minimum transparent mode were evaluated and compared with direct cholangiography. The minimum transparent mode images were compared with the two-dimensional ultrasonographic images to determine whether additional information was obtained. The level of obstruction was correctly depicted in all patients, and a dilated common bile duct, common hepatic duct, gallbladder, and main intrahepatic ducts were well visualized on minimum transparent mode images. The findings on minimum transparent mode images were well correlated with those on cholangiography; however, the perspective of the whole biliary tree on minimum transparent mode images was inferior to that on cholangiography in all cases. The overall image quality of minimum transparent mode images was poor in 6 patients, fair in 3, good in 4, and excellent in 1. The biliary anatomy was more objectively visualized on the minimum transparent mode images than conventional two-dimensional ultrasonographic images. Three-dimensional ultrasonography using the minimum transparent mode appears to be clinically feasible. The biliary anatomy was more objectively visualized on the minimum transparent mode images than conventional two-dimensional ultrasonographic images. Further technical development is needed to improve imaging resolution.

An even hover-reading of Freud: The work of metaphor. It is posited that the 'elasticity' of Freud's texts evokes an 'evenly hovering' stance in the reader in order to draw out from his writings the multilayered and latent meanings, which often subvert his manifest discourse. This elasticity is exemplified in the metaphor - a central feature of psychoanalytic epistemology. This hypothesis is tested through a close reading of a text that precisely announces itself on the manifest level as a series of straightforward prescriptions, 'Recommendations to Physicians Practicing Psychoanalysis' (1912). And we find that his use of metaphors (culminating in the telephone metaphor) glides into unexpected and surprising (unconscious) spaces, thus mirroring the analytic process that is the subject of Freud's paper. The text proves itself to be as slippery as the psyche it studies, and for which an 'evenly hovering' stance is best suited for both the reader and for the clinician to be receptive to the workings of the metaphor that reveals unique psychoanalytic truths.

Epizootic of equine influenza in 1969 in Poland. Epidemiological observations on the course and spread of equine influenza in Poland during the 1969 epizootic were carried out. The dynamics of the spread of the disease in the country are shown graphically by voivodship. The disease incidence and mortality rates for the entire country are also shown. The highest incidence of disease and mortality rates were found to be in November 1969. A/equi-2/Warsaw/69 was identified as the causal virus. It caused the largest epizootic in the country since 1954.

Physiologic rationale for multiple sodium pump isoforms. Differential regulation of alpha 1 vs alpha 2 by ionic stimuli. A number of important themes emerge from our compartmental analyses of Na,K-ATPase biosynthesis in response to ionic stimuli. The ubiquitous alpha 1 beta 1 type sodium pump evolved to generate and maintain transmembrane Na+ and K+ gradients, and there are cell-type specific mechanisms of increasing synthesis and decreasing degradation to control surface expression of this important "housekeeping" enzyme. Expression of alpha 2 beta-type sodium pumps may have evolved in cells designated as K+ storehouses to facilitate maintenance of extracellular K+ in the presence of K+ restriction. Finally, the specialized distribution of Na,K-ATPase (and related E1-E2 type pumps) along the renal epithelia allows for monitoring and fine control of extracellular K+ and Na+ (volume). Many interesting questions remain to be answered, and we now have the probes and techniques needed to answer them.

Partial anomalous pulmonary venous connection to the superior vena cava. Repair of partial anomalous pulmonary venous connection (PAPVC) to the high portion of the superior vena cava (SVC) may be complicated by atrial arrhythmia and obstruction of the pulmonary veins or SVC. We reviewed our experience with the modified Warden technique, in which the SVC was transected and anastomosed to the right atrial appendage with anterior augmentation of pedicled autologous pericardial flap, and the atrial septum was directly displaced to the SVC orifice. Twenty of 51 patients with PAPVC underwent this technique. Mean age was 11.9 years. Follow-up averaged 6.5 years. To quantify the height of insertion of anomalous pulmonary veins, the distance between the highest anomalous pulmonary venous orifice and SVC-right atrial junction was indexed by thoracic vertebral body height (height index). All patients are alive in sinus rhythm. No patients exhibited pulmonary venous obstruction, and mean flow was 0.61 mL. Mean flow of SVC return was 0.79 mL. The SVC occlusion occurred in 2 patients who had persistent left SVC with a good communicating vein. Three patients whose height index exceeded 2.5 successfully underwent catheter intervention at the SVC channel. Midterm results with the modified Warden technique were satisfactory. Patients with particularly high insertion of anomalous pulmonary veins should be treated and followed with specific caution for preserving an unobstructed caval pathway.

Contact-force radiofrequency ablation of non-paroxysmal atrial fibrillation: improved outcomes with increased experience. Clinical trials have failed to reliably show improved outcomes with utilization of contact-force sensing (CFS) radiofrequency (RF) ablation catheters. It is unknown whether the unfavorable outcomes observed in these trials are attributable to inexperience with CFS technology. To compare catheter ablation outcomes of stepwise linear ablation with versus without CFS technology and to assess the impact of operator experience with CFS technology on procedural outcomes. Clinical outcomes were evaluated in 228 consecutive NPAF patients undergoing first-time left atrial ablation using a stepwise linear approach. Arrhythmia recurrence was assessed using 2-week event monitors at 3-month intervals following index ablation. A total of 228 patients were included in our study. There was no statistically significant difference in risk of recurrent atrial arrhythmias at 12 and 24 months between CFS and non-CFS patients (p = 0.5 and p = 0.169). The time to recurrence of atrial arrhythmias at 24 months in the second half of CFS patients was significantly lower when compared to both the first half of CFS patients (p = 0.002) and non-CFS patients (p = 0.005). While there was no difference in overall outcomes between CFS and non-CFS ablation using a stepwise linear approach in patients with NPAF, procedural efficacy of the second half of CFS patients was significantly improved compared to both the first half of CFS patients and all non-CFS patients. Lack of benefit seen in clinical trials using CFS technology may be related to operator inexperience with CFS ablation catheters at the time of the trials.

[Procalcitonin (PCT), contemporary indicator of infection and inflammation]. Procalcitonin is a protein synthesized during sepsis and inflammation. In these states, its production is stimulated by inflammatory mediators and bacterial toxins. Routine determination of PCT concentration is useful in the rapid detection and monitoring of bacterial and fungal infections. The article presents the latest meta-analysis and clinical reports on the use of the PCT and comparison of its diagnostic sensitivity and specificity with other indicators of inflammation and infection in both neonates and in the adult population. Synthesis, properties and metabolism of PCT and the available methods and conditions of the determination are discussed. Presented data indicate a high sensitivity and specificity of PCT determinations, especially in bacterial infection and, what is very important, short duration of the assay and the use of a small sample volume. Assess the dynamics of changes in the concentrations of PCT can provide information not only about the course of infection but also facilitates the decision to introduce and then to discontinue antibiotic therapy.

Interactions between fluoroquinolones, Mg2+, DNA and DNA gyrase, studied by phase partitioning in an aqueous two-phase system and by affinity chromatography. The primary target of fluoroquinolones has been identified as the enzyme DNA gyrase, but the mechanism of action of these antibacterial agents is still a matter of controversy. Using partitioning in aqueous polyethylene glycol (PEG)-dextran systems, the affinities of several fluoroquinolones for DNA were determined with accuracy and at equilibrium. It was proved that the binding was strongly dependent on the ability of the drugs to bind Mg2+, with KA values of about 40 000 l mol-1, but was poorly related to the antibacterial activity [minimal inhibitory concentration (MIC) and gyrase inhibition]. Using affinity chromatography on immobilized fluoroquinolone, it was shown that DNA gyrase was unable to bind fluoroquinolones in the absence of DNA, but that a DNA-quinolone-gyrase complex was formed in the presence of Mg2+.

Transfection of rabbit articular chondrocytes by the calcium phosphate procedure: Improvement of efficiency and reproducibility. The understanding of cartilage disorders relies on the possibility of studying mechanisms which monitor the regulation of matrix protein genes through introducing efficiently and in a reproducible manner these genes, or their regulatory regions, into cells. To this end, we attempted to improve the transfection efficiency of rabbit articular chondrocytes by the calcium phosphate procedure. Transfection efficiencies were assessed by measuring the expression of the Lac Z reporter gene encoding β-galactosidase using anin situ staining (X-gal staining) and an enzymatic assay (β-galactosidase assay).Results revealed that addition of 4 U ml(-1) of hyaluronidase before and during transfection increases by 2 to 4-fold the transfection efficiency of rabbit articular chondrocytes. Furthermore, we demonstrated that the use of a "giant" calcium phosphate DNA coprecipitate gives a higher transfection efficiency and much more reproducible results than those obtained with classical small volumes of precipitates.

Noise at the crossover from Wigner liquid to Wigner glass. Using a simple classical model for interacting electrons in two dimensions with random disorder, we show that a crossover from a Wigner liquid to a Wigner glass occurs as a function of charge density. The noise power increases strongly at the crossover and the characteristics of the 1/f(alpha) noise change. When the temperature is increased, the noise power decreases. We compare these results with recent noise measurements in systems with two-dimensional metal-insulator transitions.

Additional complexity within the HLA-D region: sequence analysis of two new DRw13-DQw7 haplotypes. HLA-DRB1 is by far the most polymorphic locus within the HLA-D region with now well over 40 alleles. Nearly one fourth of these alleles are subtypes of DRw6, and these are in most cases undetectable by routine typing procedures. In this paper we present the molecular characterization of two new Caucasian DRw13-DQw7 haplotypes by DNA sequencing of the polymorphic first domain exons of DRB1 and DRB3 loci. The first haplotype, DRB1*1301-DRB3*0101-DQB1*0301, has arisen by a recombination between locus DRB1 from a DRw13-DQw6 haplotype and DQA1 from a DR4-DQw7 haplotype, as determined by DNA sequencing, DQ oligotyping, and restriction fragment length polymorphism typing. The second haplotype, DRB1*1305-DQB1*0301, is characterized by the novel DRB1*1305 allele differing from DRB1*1301 by three amino acids. It probably arose by a gene conversion event between a DRw13-DQw6 allele and DRB1*1101. This allele represents a DRw11/DRw13 hybrid DR molecule with a DRw13 serological epitope in the second hypervariable region and a Dw5 cellular epitope in the third hypervariable region. As determined by sequencing of locus DRB3, this allele is associated with DRw52b. Our molecular analysis of the complex HLA-DRw13 group now allows unambiguous DNA typing of all five DRw13 alleles with seven oligonucleotides, a significant improvement in the context of organ transplantation.

Fetal lung maturity in complicated pregnancy, as predicted from microviscosity of amniotic fluid. We measured the microviscosity of amniotic fluid between 28 and 40 weeks of gestation in 252 normal pregnancies and in 172 pregnancies complicated by factors known to influence fetal lung maturation, including chronic high blood pressure, pregnancy-induced hypertension, diabetes mellitus, and therapy with betamethasone. Comparison of the microviscosity value distributions and regression analysis indicated significantly lower microviscosity values in hypertensive disorders, in Class D and Classes F or R diabetes, and after 48 h of treatment with betamethasone. Few changes were observed in Classes A, B, or C diabetes. These observations are consistent with the accelerated maturation of surfactant observed in chronic intrauterine stress and the lower incidence of hyaline membrane disease reported after glucocorticoids.

Bio-mimetically synthesized Ag@BSA microspheres as a novel electrochemical biosensing interface for sensitive detection of tumor cells. The use of a novel cytosensor, comprised of bio-mimetically synthesized Ag@BSA composite microspheres, for the detection of KB cells (a model system) is described. The Ag@BSA composite microspheres were immobilized on Au electrodes via Au-thiol bonds. Scanning electron microscopy (SEM), atomic force microscopy (AFM) and transmission electron microscopy (TEM) images revealed that the Ag@BSA were well-dispersed microspheres with an average diameter of 500 nm, including the monolayer of BSA. The immobilization of Ag@BSA composite microspheres onto Au electrodes is thought to increase the electrode surface area and accelerate the electron transfer rate while providing a highly stable matrix for the convenient conjugation of target molecules (such as folic acid) and the prolonged incubation of cells. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) studies showed that the fabricated cytosensor was able to detect KB cells ranging from 6.0×10(1) to 1.2×10(8) cells mL(-1) with a lower detection limit of 20 cells mL(-1). Due to its facile synthesis, high stability and reproducibility and cytocompatibility, the novel cytosensor described here could find multifarious uses in applications, such as cancer diagnosis, drug screening and cell adhesion studies.

Impact of metformin-induced gastrointestinal symptoms on quality of life and adherence in patients with type 2 diabetes. Gastrointestinal (GI) symptoms are common in patients with type 2 diabetes mellitus (T2DM). This study assesses the impact of 1) metformin on GI symptoms and health-related quality of life (HRQoL) and 2) metformin-associated GI symptoms on medication adherence in patients with type 2 diabetes newly beginning therapy. Patients with T2DM aged>or=18 years starting metformin from January to June 2007 who filled their prescriptions for >or=3 months were identified from a health benefits company database. Via telephone, GI symptom impact was evaluated in a 360-patient sample using the validated Bowel Symptom Questionnaire and Medical Outcomes Study 36-Item Short-Form Health (SF-36) survey. Adherence was assessed using the medication possession ratio (MPR). Logistic regression adjusting for demographic and clinical covariates was used to assess the relationship between GI symptoms and MPR<80%. The most and least common GI symptoms reported were diarrhea (62.1%) and retching (21.1%), respectively. Most GI symptoms were associated with lower physical and mental HRQoL (P<0.05). Most changes in specific HRQoL reached the minimum important difference of 3 points. Bloating, nausea, and abdominal pain were significantly associated with MPR<80%. Adjustment for demographic, clinical, and HRQoL factors made these relationships less evident. Metformin-associated GI symptoms in patients with T2DM lead to lower physical and mental HRQoL, which may result in patient nonadherence or physician reluctance to optimally titrate the metformin dose.

Relationship between dose rate and oxygen enhancement ratio. Born [1] concluded that the D0 values of dose-effect curves from cells irradiated under chronically hypoxic conditions were not much influenced by the dose rate and that the oxygen enhancement ratio was decreased from 3.9 at 3.64 Gy. min-1 to 1.8 at 0.07 Gy.min-1. These conclusions, however, are not supported by properly performed experiments. Comments on the paper by Born [1] are provided and a method of obtaining realistic oxygen enhancement ratios at low dose rates is described.

Thermal-changeable complex-refractive-index spectra of merocyanine aggregate films. Thermal behaviors of complex refractive index of merocyanine (MC) Langmuir-Blodgett (LB) films have been investigated with absorption spectrum measurements, which are obtained from the Kramers-Kronig (K-K) analysis. The complex-refractive-index spectra with an anomalous dispersion around a J-aggregate absorption band of MC molecules are changed by annealing temperatures. This thermal characteristic is attributed to the annealing-changeable MC J-aggregates. The MC J-aggregates in the LB films collapse in the annealing and become a monomer state. The refractive-index dispersion decreased with the collapse of MC J-aggregates. These behaviors are confirmed from the reflection spectrum measurements under the different conditions of incident light to the MC film samples.

Histogenesis of the mouse pyloric mucosa with special reference to the development of surface mucous cells and pylorocytes, and the formation of the generative zone. The distribution of proliferative cells and maturation of epithelial cells were studied in the pyloric mucosa of developing mice by 3H-thymidine autoradiography, carbohydrate histochemistry and electron microscopy. The formation of the gastric foveola and pyloric gland were seen to begin as an invagination in the epithelial surface and/or the formation of intraepithelial cavity on day 13 of gestation (day E13). Surface mucous cells and pylorocytes were first identified on day E16 by carbohydrate staining as well as by their fine structure. Both types of cells rapidly acquired abundant membranous organelles and secretory granules within the first postnatal day, maturing in fine structure by day 28. Proliferative cells were distributed over the epithelium by day E15, while they were rarely found at the mucosal surface after day E16. Concomitantly with the elongation of foveolae and glands during postnatal development, the proliferative capability of surface mucous cells diminished from the foveolae and that of pylorocytes from the glands, respectively; the generative zone was restricted to the isthmus by day 21, as in the adult animal. These results reveal that the histogenesis of the mouse pyloric mucosa is accomplished by the end of the weaning period.

Intravenous levodopa in hallucinating Parkinson's disease patients: high-dose challenge does not precipitate hallucinations. In five nondemented Parkinson's disease patients with daily visual hallucinations, we tested whether high-dose IV levodopa (LD) infusions precipitated hallucinations. Two infusion paradigms were studied, each with 1.5-mg/kg hourly dose for 4 hours--steady infusion and pulse infusion of the full hour dose over 5 minutes each hour. In both protocols, plasma LD levels changed significantly during the infusion protocol. The cumulative area under the curve was equivalent for the two infusions. All patients remained alert, and none developed visual hallucinations. The two patients with peak-dose dyskinesias on oral LD developed prominent dyskinesias during the infusion. Visual hallucinations do not relate simply to high levels of LD or to sudden changes in plasma levels.

X-irradiation of equine peripheral blood lymphocytes stimulated with phytohaemagglutinin in vitro. Small lymphocytes were isolated from the peripheral blood of horses and incubated at 37 degrees C in Eagle's medium supplemented with 20 per cent foetal calf serum. The addition of phytohaemagglutinin (PHA) to the cultures resulted in: increased RNA and protein synthesis; the enlargement of the small lymphocyte into a lymphoblast-like cell; the initiation of DNA synthesis, and cell division. When survival was measured 24 hours after X-irradiation by means of phase-contrast microscopy, the lymphoblast-like cell was much more radio-resistant (D0 = 250 rad) than the small lymphocyte (D0 = 20 rad). This increase in radioresistance, however, was not observed until 12-24 hours after PHA treatment. To investigate which of the changes occurring during the transformation of the small lymphocyte was responsible for the increased resistance to irradiation, the percentage of cells surviving irradiation was compared with the percentage of cells incorporating significant amounts of 3HTdR, 3H-UR, or 3H-leucine at the time of irradiation. For this comparison, a dose of 100 rad was used because 100 rad killed essentially all of the small lymphocytes, but less than 35 percent of the cells which had become radioresistant from the PHA treatment. The results indicated that the increase in radioresistance was not associated with DNA synthesis, but instead correlated with the increase in RNA and protein synthesis which the cells had attained at the time of irradiation.

[New sites in the hemagglutinin composition of epidemic variants of the influenza virus A (H3N2) from 1989-1990]. Immunological analysis of the antigenic structure of hemagglutinin of newly isolated variants of influenza (H3N2) virus carried out using monoclonal and monospecific antibodies to individual antigenic sites of hemagglutinin showed the 1989-1990 isolates to be markedly different in their antigenic properties from the variants isolated in previous years. Sites with new antigenic properties were determined in hemagglutinin of the isolates. Wide variability was found in the region of three immunodominant sites. The fact of circulation in the human population of influenza viruses of one subtype with different antigenic structures within the limits of one epidemic season was established.

Contrast agents in magnetic resonance imaging of the liver: present and future. New contrast agents are being developed by drug companies to better image the liver magnetic resonance imaging (MRI). They can be divided into hepatobiliary agents (Gd-EOB-DTPA, Gd-BOPTA, Mangafodipir) and nanoparticulate agents directed to the reticulo-endothelial system (ferumoxides, SHU 555A). After intravenous injection, all these agents concentrate in the liver and induce profound signal changes. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver-lesion conspicuity is enhanced, leading to a better visualization of the lesion. After a description of the principal pharmacokinetic characteristics of the compounds, this review paper summarizes the utility of the agents in the detection and characterization of focal liver diseases.

A novel gene required for cercosporin toxin resistance in the fungus Cercospora nicotianae. Cercosporin, a photosensitizing perylenequinone toxin produced by the plant pathogenic Cercospora fungi, generates the highly toxic singlet oxygen (1O2) upon exposure to light. Cercosporin shows broad toxicity against a wide range of organisms, including bacteria, fungi, plants, and animals; however, Cercospora fungi are resistant to its effects. A novel gene, crg1 (cercosporin-resistance gene) was isolated from a wild-type strain of C. nicotianae by genetic complementation of a C. nicotianae mutant (CS10) which is cercosporin sensitive and down-regulated in cercosporin production. Sequence analysis indicated that crg1 encodes a putative protein of 550 amino acids with four putative transmembrane helical regions, however CRG1 shows no strong similarity to any other protein in sequence databases. Northern analysis identified two transcripts (4.5 and 2.6 kb) that are unaffected by the presence of light or cercosporin. Southern analysis demonstrated that crg1 is present in a single copy in the C. nicotianae genome and can be detected only in Cercospora species. Targeted disruption of crg1 resulted in mutants that, like CS10, are sensitive to cercosporin. However, unlike CS10, crg1 disruption mutants are not down-regulated in toxin production. Both CS10 and the crg1 disruption mutants are unaffected in their response to other 1O2-generating photosensitizers, suggesting that CRG1 functions specifically against cercosporin, rather than against 1O2.

Signs of impaired cognitive function in adolescents with marginal cobalamin status. Lack of cobalamin may lead to neurologic disorders, which have been reported in strict vegetarians. The objective of this study was to investigate whether cognitive functioning is affected in adolescents (aged 10-16 y) with marginal cobalamin status as a result of being fed a macrobiotic diet up to an average age of 6 y. Data on dietary intake, psychological test performance, and biochemical variables of cobalamin status were collected from 48 adolescents who consumed macrobiotic (vegan type) diets up to the age of 6 y, subsequently followed by lactovegetarian or omnivorous diets, and from 24 subjects (aged 10-18 y) who were fed omnivorous diets from birth onward. Thirty-one subjects from the previously macrobiotic group were cobalamin deficient according to their plasma methylmalonic acid concentrations. Seventeen previously macrobiotic subjects and all control subjects had normal cobalamin status. The control subjects performed better on most psychological tests than did macrobiotic subjects with low or normal cobalamin status. A significant relation between test score and cobalamin deficiency (P: = 0.01) was observed for a test measuring fluid intelligence (correlation coefficient: -0.28; 95% CI: -0.48, -0.08). This effect became more pronounced (P: = 0.003) within the subgroup of macrobiotic subjects (correlation coefficient: -0.38; 95% CI: -0.62, - 0.14). Our data suggest that cobalamin deficiency, in the absence of hematologic signs, may lead to impaired cognitive performance in adolescents.

Liposome-supported enzymatic peritoneal dialysis. Compared to hemodialysis, peritoneal dialysis represents a more straightforward and less invasive alternative, though current solutions are not as effective. Herein, the feasibility of liposome-supported enzymatic peritoneal dialysis (LSEPD) is explored to increase the functionality of peritoneal dialysis for the model indication acute alcohol poisoning. Enzyme-loaded liposomes (E-Liposomes) containing alcohol metabolizing enzymes, alcohol oxidase and catalase, are developed and their in vitro and in vivo performances investigated. The E-Liposomes outperform the free enzymes in stability, overcoming the thermal instability of alcohol oxidase and enhancing the in vitro ethanol elimination, which is further accelerated by hydrogen peroxide, due to the rapid generation of oxygen by catalase. Compared to the free enzymes, the E-Liposomes exhibit reduced systemic exposure and organ distribution. In a rodent ethanol intoxication model, LSEPD enhances ethanol metabolism as evidenced by an increased acetaldehyde production, ethanol's primary metabolite. In conclusion, LSEPD presents an innovative platform to temporarily enhance xenobiotic metabolism, in view of the improved enzyme stability and peritoneal retention.

[Environment, nutrition and intellectual development]. The differential effects of malnutrition and psychosocial cultural deprivation (PSAC) upon intellectual performance and psychomotor development were studied in 52 preschool children attending nursery schools in urban Santiago (Chile). Nutritional status was evaluated according to Gómez, intellectual performance according to Weschler's scale (WISP and WISC tests), psychomotor development according to the Denver Developmental Screening Test and PSAC according to a numerical scale constructed from maternal I.Q.; socioeconomic status (Graffar) and a psychological questionnaire the correlational analysis, undernutrition was assigned a single value calculated from the severity and duration of the disease. An inverse correlation of - 0.36 existed between malnutrition and intellectual performance, and of - 0.39 between malnutrition and psychomotor development. Also, there was an inverse and significant correlation of - 0.73 between PSAC and psychomotor development; there was no correlation between PSAC and intellectual performance. Verbal I.Q. was more affected (r = - 0.52) than manual I.Q. (r = - 0.18) and children malnourished during the first 6 months of life attained lower scores of I.Q. than normals. The duration of malnutrition (mild in all cases) had no influence upon subsequent I.Q. This study was the basis for a rehabilitation program (educational-nutritional) to be applied in preschool children from nonprivileged areas.

Imaging-based planning for spine surgery. The planning of decompressive and reconstructive spine surgery is based on clinical findings and diagnostic imaging. The evaluation of segmental instability, but also of the risk of destabilization following a needed decompression of the spinal canal and/or neural foramina make complex spine surgery a challenge, bearing in mind the risk of failures in case of an inadequate operation. The insufficient correlation between imaging and clinical symptoms originating from the spine and its nerve roots has been frustrating for some decades. This review focuses on the new upright, dynamic-kinetic, i.e., "functional" MRI and its ability to detect load- and motion-dependent disc herniations, stenosis, instabilities, and combinations of these pathologies not seen during recumbent imaging.

Glycosylated hemoglobin and the risk of microalbuminuria in patients with insulin-dependent diabetes mellitus. The risk of microalbuminuria in patients with insulin-dependent diabetes mellitus (IDDM) is thought to depend on the degree of hyperglycemia, but the relation between the degree of hyperglycemia and urinary albumin excretion has not been defined. We measured urinary albumin excretion in three random urine samples obtained at least one month apart from 1613 patients with IDDM. Microalbuminuria or overt albuminuria was considered to be present if the ratio of albumin (in micrograms) to creatinine (in milligrams) was 17 to 299 or > or = 300, respectively, for men and 25 to 299 or > or = 300, respectively, for women. Measurements of glycosylated hemoglobin (hemoglobin A1) obtained up to four years before the urine testing were used as an index of hyperglycemia. Twelve percent of the patients had overt albuminuria and were excluded from subsequent analyses. The prevalence of microalbuminuria was 18 percent in patients with IDDM. It increased with increasing postpubertal duration of diabetes and, within each six-year interval of disease duration, it increased nonlinearly with the hemoglobin A1 value. For hemoglobin A1 values below 10.1 percent, the slope of the relation was almost flat, whereas for values above 10.1 percent, the prevalence of microalbuminuria rose steeply (P < 0.001). For example, as the hemoglobin A1 value increased from 8.1 to 10.1 percent, the odds of microalbuminuria increased by a factor of 1.3, but as the value increased from 10.1 to 12.1 percent, the odds were increased by a factor of 2.4. The risk of microalbuminuria in patients with IDDM increases abruptly above a hemoglobin A1 value of 10.1 percent (equivalent to a hemoglobin A1c value of 8.1 percent), suggesting that efforts to reduce the frequency of diabetic nephropathy should be focused on reducing hemoglobin A1 values that are above this threshold.

[Aggressive cutaneous T-cell lymphoma associated with the presence of Epstein-Barr virus. 2 cases]. The factors of prognosis of the cutaneous T-cell lymphomas are less well known as those of the B-cell lymphomas and the role of the Epstein-Barr virus (EBV) is not yet definitively evaluated. Two male patients aged 62 and 82 years had a mycosis fungoides with a lethal outcome. The first patient had mutilating facial tumors; the RNA m of EBV and the genome of EBV were demonstrated in the diseased skin. The second patient had an erythrodermic course with enlarged peripheral lymph nodes and circulating Sézary's cells; the genome of EBV was demonstrated by PCR in the diseased skin. The role of the EBV has already been demonstrated in peripheral aggressive T-cell lymphomas. In the mycosis fungoides, the EBV is associated with the lesions in 0 to 32 p. cent according to the published series. EBV associated T-cell lymphomas have a poor survival rate and the EBV infection may be associated with the expression of the multidrug resistant gene-1 (MDR-1) and the risk of a terminal hemophagocytosis. In our both patients the presence of the EBV in the lymphocytes of the skin lesions is also an argument in favour of the pathogenic role of the virus.

Characterization of Gq family G proteins GL1 alpha (G14 alpha), GL2 alpha (G11 alpha), and Gq alpha expressed in the baculovirus-insect cell system. The alpha subunits of Gq family G proteins, GL1 alpha (G14 alpha), GL2 alpha(G11 alpha), and Gq alpha were expressed with G protein beta 1 and gamma 2 subunits in insect cells using a baculovirus system. The trimeric forms of G proteins, GL1 (GL1 alpha beta gamma), GL2 (GL2 alpha beta gamma), and Gq (Gq alpha beta gamma), were solubilized by 1% sodium cholate and purified by sequential chromatography on three kinds of columns. GL1, GL2, and Gq activated phospholipase C-beta purified from bovine brain in the presence of aluminum fluoride to the same extent. Muscarinic acetylcholine receptor m1 subtype stimulated the guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) binding to GL1, GL2, and Gq in the presence of similar concentrations of carbamylcholine. When m1 receptor, G protein, and phospholipase C-beta were reconstituted in lipid vesicles, each subtype of Gq family G proteins mediated the activation of phospholipase C-beta by carbamylcholine in the presence of either 1 microM GTP gamma S or 1 mM GTP. Phospholipase C-beta stimulated the GTPase activity of GL1, GL2, and Gq in the presence of m1 receptor and carbamylcholine but did not stimulate the GTPase activity of GO. Protein kinase C phosphorylated m1 receptor and phospholipase C-beta, but the phosphorylation did not significantly affect the ability of the m1 receptor to stimulate phospholipase C-beta in the reconstitution system of purified proteins.

The effect of actinomycin D on the formation of gametangia and mitosporangia in Allomyces. The effect of actinomycin on gametangium and mitosporangium production in Allomyces arbuscula and A. macrogynus has been investigated. Male gametangium production was not more sensitive to actinomycin than female development. Actinomycin at 20 mug/ml added at the commencement of induction was completely inhibitory. The process became insensitive to actinomycin just before the first septum was laid down.

p18(Hamlet) mediates different p53-dependent responses to DNA-damage inducing agents. Cells organize appropriate responses to environmental cues by activating specific signaling networks. Two proteins that play key roles in coordinating stress responses are the kinase p38alpha (MAPK14) and the transcription factor p53 (TP53). Depending on the nature and the extent of the stress-induced damage, cells may respond by arresting the cell cycle or by undergoing cell death, and these responses are usually associated with the phosphorylation of particular substrates by p38alpha as well as the activation of specific target genes by p53. We recently characterized a new p38alpha substrate, named p18(Hamlet) (ZNHIT1), which mediates p53-dependent responses to different genotoxic stresses. Thus, cisplatin or UV light induce stabilization of the p18(Hamlet) protein, which then enhances the ability of p53 to bind to and activate the promoters of pro-apoptotic genes such as NOXA and PUMA leading to apoptosis induction. In a similar way, we report here that p18(Hamlet) can also mediate the cell cycle arrest induced in response to gamma-irradiation, by participating in the p53-dependent upregulation of the cell cycle inhibitor p21(Cip1) (CDKN1A).

Problems and proposals for the surveillance and control of sexually transmitted diseases associated with pelvic inflammatory disease in South America. In South America, the number of women at risk for gonococcal pelvic inflammatory disease has increased greatly along with the incidence rates for gonorrhea. Further information is needed on the epidemiologic aspects of gonorrhea and PID in order to develop programs for optimal control of sexually transmitted disease (STD). We think that the control of STD, including PID, requires improvement of four basic factors: professional training in STD, management of STD by all levels of health care services, laboratory diagnostic services, and public education in STD.

Colon cancer in a 14-year-old female with turner syndrome: report of a case. A 14-year-old female with Turner syndrome (karyotype 45,X) had a history of abdominal pain with distention, constipation, and fever. She was first operated on for the suspicion of appendicitis, failed to improve, and was later hospitalized for further investigation and treatment. Studies demonstrated an obstructing tumor of the transverse colon, and an emergency laparotomy was performed. The final diagnosis was a signet-ring cell carcinoma of the colon with diffuse peritoneal dissemination and metastasis to paracolic lymph nodes. On the basis of this case, we report the association of Turner syndrome with malignancies and also some aspects of colon cancer in childhood.

Histochemical reactivity of peanut lectin-horseradish peroxidase conjugate. A peanut lectin-horseradish peroxidase (PL-HRP) conjugate has been applied to histochemical staining of paraffin sections of various mouse organs. The PL-HRP conjugate has selectively reacted with secretory bodies, the Golgi zone, and the apical cell surface in various cell types. Some positive sites, including lingual and tracheal serous glands, Brunner's glands, and the brush border of the proximal straight nephron, contained periodic acid-Schiff (PAS)-positive glycoconjugate with no affinity for basic reagents. The stored secretion in these sites was interpreted as containing neutral glycoprotein with terminal galactose residues which could, in part at least, account for the PAS reactivity. Duodenal goblet cells, which exhibited basophilia attributable to sulfate esters, also bound PL-HRP. As the binding was affected by prior sialidase digestion, the secretory glycoprotein in the duodenal goblet cells was judged to contain oligosaccharides with sulfate esters and terminal galactose uncapped by sialic acid. All sites known from their basophilia to form sialomucin failed to stain with the PL-HRP conjugate, but consistently gained reactivity following sialidase digestion and were inferred, therefore, to possess glycoproteins with oligosaccharide side chains containing subterminal galactose and terminal sialic acid. Lingual mucous glands, known to secrete a mucosubstance with basophilic properties indicative of the presence of sulfate esters but not sialic acid, stained with PL-HRP only after sialidase digestion and, accordingly, were reinterpreted as containing both sulfate esters and terminal galactose-sialic acid dimers. Staining of gastric surface epithelium demonstrated a srongly PAS-reactive neutral glycoprotein, and that of goblet cells in the cecum disclosed PAS-positive sulfated glycoprotein. The latter two sites lacked PL-HRP affinity without or with prior sialidase treatment and apparently possessed neither terminal galactose residues nor galactose-sialic acid dimers. PL-HRP affinity was observed exclusively in the Golgi cisternae of some epithelial cells, thus indicating that galactose occurs transiently as a terminal residue in this site. A few histologic sites, such as pancreatic and gastric zymogen cells and renal tubules, were devoid of both PAS reactivity and basophilia indicative of the presence of complex carbohydrate but stained strongly with the PL-HRP conjugate by means which are not understood. Galactose in the PL-HRP solution blocked or reversed the PL-HRP binding in most of the structures with an affinity for the conjugate, supporting the conclusions that the reagent is specific for galactosyl residues.

Factors associated with technical difficulty of endoscopic submucosal dissection for early gastric cancer that met the expanded indication criteria: post hoc analysis of a multi-institutional prospective confirmatory trial (JCOG0607). There are few reports on the technical difficulty of gastric endoscopic submucosal dissection (ESD). The aim of this study was to investigate the factors associated with the technical difficulty of ESD for early gastric cancer (EGC) using the data from the multicenter non-randomized confirmatory trial of expanded indication criteria of ESD (JCOG0607). The major inclusion criteria were as follows: (1) histologically proven intestinal-type adenocarcinoma; (2) cT1aN0M0; (3) lesion without finding of ulcer (UL-negative) with > 2 cm in size, or UL-positive with ≤ 3 cm; (4) age 20-75 years. The difficult case was defined as ESD taking ≥ 120 min, piecemeal resection, and/or developing perforation during procedure. Between June 2007 and October 2010, 470 patients were enrolled from 29 institutions. Median procedure time was 79 (range 14-462) min, and it was ≥ 120 min in 127 patients. Twelve patients developed perforation during ESD, and the procedure time was ≥ 120 min in 9 of them. Therefore, 130 patients (27.7%) were identified as difficult cases. Multivariable analysis showed that UL-negative with > 5 cm (vs. UL-negative with ≤ 3 cm, odds ratio, 24.993; 95% CI 6.130-101.897, p < 0.0001) had the largest odds ratio and followed by UL-negative with 3-5 cm upper or middle portion of stomach and age ≤ 60 years were significantly associated with difficulty. UL-negative lesion with > 3 cm, upper or middle portion of stomach and age ≤ 60 years were independent factors associated with technical difficulty of ESD for EGC. Trial registered number was UMIN000000737.

Validity of self-reported waist and hip circumferences in men and women. Recent epidemiologic evidence indicates an association between fat distribution and many diseases. To assess the validity of circumference measurements obtained by self-report, the authors analyzed data from 123 men aged 40-75 years and 140 women aged 41-65 years, drawn from two large ongoing prospective studies. On mailed questionnaires, subjects were asked to measure and record their weight and waist and hip circumferences. These data were compared with standardized measurements taken approximately six months apart by technicians who visited participants at their homes. Crude Pearson correlations between self-reported waist circumferences and the average of two technician-measured waist circumferences were 0.95 for men and 0.89 for women. Similar correlations for hip measurements were 0.88 for men and 0.84 for women, and for waist-to-hip ratios, 0.69 for men and 0.70 for women. After adjusting for age and body mass index (kg/m2), correlations for waist-to-hip ratios were 0.55 for men and 0.58 for women. Correlations became stronger after correcting for random within-person variability from daily or seasonal fluctuations. Self-reported and measured weights were highly correlated: 0.97 for men and 0.97 for women. Self-reported waist, hip, and weight measurements appear reasonably valid. The moderate degree of measurement error for the ratio of self-reported waist and hip circumferences, however, implies that previously reported associations based on self-report of these measures may have been appreciably underestimated.

A clinical training model for students: intensive treatment of stuttering using prolonged speech. This study describes a practical model for improving the quality of Speech-Language Pathology (SLP) education on a clinical setting in a Bulgarian University. During this study, adults who stutter (AWS) received intensive treatment (IT) to increase fluent speech. The intensive treatment was delivered by students trained in the SLP Master's degree program "Logopedics Management in Fluency and Voice Disorders". The La Trobe University intensive program of prolonged speech was implemented. SLP students were trained and delivered the IT for AWS, under supervision in all stages. The treatment followed a clinical modeling pattern. The primary outcomes were measured according to (i) percent of syllables stuttered (%SS) within and outside the stuttering research center of the university; (ii) self-reported inventory scores; and (iii) speech naturalness score evaluations from pre-treatment, immediately following treatment, 11 months post-treatment, and 18 months after the intensive treatment using stutter-free speech samples. The outcomes were reported for the overall IT program delivered by the SLP Master students. The treatment delivered by students can ensure objective speech outcomes. The evidence-based practice model allowed students to develop and master specific clinical skills in establishing fluent speech by applying a prolonged speech technique. During the IT experience, students began to incorporate elements of evidence-based practice (EBP), clinical expertise, and consider values held by AWS. After four outcome-sessions, the AWS developed self-consciousness about the quality of their prolonged speech during controlled fluent patterns. The participants produced objective speech fluency data and statistically significant differences before and immediately after the IT regarding %SS and overall speech naturalness.

An engineered Pseudomonas putida can simultaneously degrade organophosphates, pyrethroids and carbamates. Agricultural soils are often polluted with a variety of pesticides. Unfortunately, natural microorganisms lack the capacity to simultaneously degrade different types of pesticides. Currently, synthetic biology provides powerful approaches to create versatile degraders. In this work, a biosafety strain Pseudomonas putida KT2440 was engineered for simultaneous degradation of organophosphates, pyrethroids, and carbamates, enhanced oxygen-sequestering capability, and real-time monitoring by targeted insertion of four pesticide-degrading genes, vgb, and gfp into the chromosome using a scarless genome-editing method. The resulting recombinant strain, designated as P. putida KTUe, could completely degrade 50mg/L methyl parathion, chlorpyrifos, fenpropathrin, cypermethrin, carbofuran and carbaryl within 30h when incubated in M9 minimal medium supplemented with 20g/L glucose. In soil remediation studies, all the tested six pesticides (50mg/kg soil each) were completely removed in soils inoculated with P. putida KTUe within 15days. Moreover, Vitreoscilla hemoglobin (VHb)-expressing P. putida KTUe grew faster than P. putida KTUd without VHb expression under oxygen-limited conditions, suggesting that VHb may enhance the capability of this recombinant strain to sequester oxygen. Furthermore, the green fluorescence was observed on the P. putida KTUe cells, suggesting that this green fluorescent protein (GFP)-marked strain may be tracked by fluorescence during bioremediation. Therefore, this recombinant strain may serve as a promising candidate for in situ bioremediation of soil contaminated with multiple pesticides. This work not only underscores the value of P. putida KT2440 as an ideal host for bioremediation but also highlights the power of synthetic biology for expanding the degradation capability of natural degraders.

STAT3-induced WDR1 overexpression promotes breast cancer cell migration. WD repeat domain 1 (WDR1), a protein that assists cofilin-mediated actin filament disassembly, is overexpressed in the invading front of invasive ductal carcinoma (IDC), but its implication of overexpression and how to be regulated have not been studied. In our study, we demonstrated that STAT3 bound to the 5' upstream sequence (-1971 to -1964), a putative promoter region, of WDR1 gene, and its activation induced WDR1 overexpression in breast cancer cells. The exogenous overexpression of WDR1 increased the migration of MDA-MB-231, which was attenuated by WDR1 knockdown. In the analysis of breast cancer patients, WDR1 overexpression was associated with a shorter distant metastasis-free survival (DMFS), more specifically in basal-like tumors.

Roles of the ccoGHIS gene products in the biogenesis of the cbb(3)-type cytochrome c oxidase. In many bacteria the ccoGHIS cluster, located immediately downstream of the structural genes (ccoNOQP) of cytochrome cbb(3) oxidase, is required for the biogenesis of this enzyme. Genetic analysis of ccoGHIS in Rhodobacter capsulatus demonstrated that ccoG, ccoH, ccoI and ccoS are expressed independently of each other, and do not form a simple operon. Absence of CcoG, which has putative (4Fe-4S) cluster binding motifs, does not significantly affect cytochrome cbb(3) oxidase activity. However, CcoH and CcoI are required for normal steady-state amounts of the enzyme. CcoI is highly homologous to ATP-dependent metal ion transporters, and appears to be involved in the acquisition of copper for cytochrome cbb(3) oxidase, since a CcoI-minus phenotype could be mimicked by copper ion starvation of a wild-type strain. Remarkably, the small protein CcoS, with a putative single transmembrane span, is essential for the incorporation of the redox-active prosthetic groups (heme b, heme b(3 )and Cu) into the cytochrome cbb(3) oxidase. Thus, the ccoGHIS products are involved in several steps during the maturation of the cytochrome cbb(3) oxidase.

Lipase catalyzed synthesis of neutral glycerides rich in micronutrients from rice bran oil fatty acid distillate. Neutral glycerides with micronutrients like sterols, tocopherols and squalene may be prepared from cheap raw material like rice bran oil fatty acid distillate (RBO FAD). RBO FAD is an important byproduct of vegetable oil refining industries in the physical refining process. Glycerides like triacylglycerols (TAG), diacylglycerols (DAG) and monoacylglycerols (MAG) containing significant amounts of unsaponifiable matter like sterols, tocopherols and hydrocarbons (mainly squalene) may certainly be considered as novel functional food ingredients. Fatty acids present in RBO FAD were esterified with glycerol of varying amount (1:0.33, 1:0.5, 1:1 and 1:1.5 of FAD : glycerol ratio) for 8 h using non-specific enzyme NS 40013 (Candida antartica). After esterification the product mixture containing mono, di- and triglycerides was purified by molecular distillation to remove excess free fatty acids and also other volatile undesirable components. The purified product containing sterols, tocopherols and squalene can be utilized in various food formulations.