Compliance mismatch and compressive wall stresses drive anomalous remodelling of pulmonary trunks reinforced with Dacron grafts.
Synthetic grafts are often satisfactory employed in cardiac and vascular surgery, including expanded poly(ethylene terephthalate) or expanded poly(tetrafluoroethylene). However, accumulating evidences suggest the emergence of worrisome issues concerning the long-term fate of prosthetic grafts as large vessel replacement. Disadvantages related to the use of synthetic grafts can be traced in their inability of mimicking the elasto-mechanical characteristics of the native vascular tissue, local suture overstress leading to several prosthesis-related complications and retrograde deleterious effects on valve competence, cardiac function and perfusion. Motivated by this, in the present work it is analyzed - by means of both elemental biomechanical paradigms and more accurate in silico Finite Element simulations - the physical interaction among aorta, autograft and widely adopted synthetic (Dacron) prostheses utilized in transposition of pulmonary artery, highlighting the crucial role played by somehow unexpected stress fields kindled in the vessel walls and around suture regions, which could be traced as prodromal to the triggering of anomalous remodelling processes and alterations of needed surgical outcomes. Theoretical results are finally compared with histological and surgical data related to a significant experimental animal campaign conducted by performing pulmonary artery transpositions in 30 two-month old growing lambs, followed up during growth for six months. The in vivo observations demonstrate the effectiveness of the proposed biomechanical hypothesis and open the way for possible engineering-guided strategies to support and optimize surgical procedures.


Association between intimate partner violence against women and HIV infection.
To analyze the association between intimate partner violence against women and infection or suspected infection by the human immunodeficiency virus (HIV). A cross-sectional study was conducted, based on data from questionnaires applied face-to-face and medical records of 2,780 women aged between 15 and 49 years, cared for in Sistema Único de Saúde (Unified Health System) units of the Greater São Paulo area, Southeastern Brazil, in 2001-2002. Women were categorized into: users in treatment because they are "HIV seropositive", those "suspected of having HIV" and others who sought health services for different reasons. Intimate partner violence against women throughout life was categorized according to the severity and recurrence of episodes of violence. The association with the outcome was tested using the Poisson model with robust and adjusted variance for sociodemographic, sexual and reproductive variables. The prevalence of violence was 59.8%. Suffering repeated and severe violence was more closely associated with confirmed HIV infection (PR = 1.91). Violence independent from severity and recurrence of episodes showed greater association with suspected HIV infection (PR = 1.29). Intimate partner violence against women has a key role in situations of suspected and confirmed HIV infection. Thus, it is essential to include its detection, control and prevention as part of the comprehensive care provided for women's health.


Risk factors for graft survival after liver transplantation from donation after cardiac death donors: an analysis of OPTN/UNOS data.
Due to increasing use of allografts from donation after cardiac death (DCD) donors, we evaluated DCD liver transplants and impact of recipient and donor factors on graft survival. Liver transplants from DCD donors reported to UNOS were analyzed against donation after brain death (DBD) donor liver transplants performed between 1996 and 2003. We defined a recipient cumulative relative risk (RCRR) using significant risk factors identified from a Cox regression analysis: age; medical condition at transplantation; regraft status; dialysis received and serum creatinine. Graft survival from DCD donors (71% at 1 year and 60% at 3 years) were significantly inferior to DBD donors (80% at 1 year and 72% at 3 years, p < 0.001). Low-risk recipients (RCRR < or = 1.5) with low-risk DCD livers (DWIT < 30 min and CIT < 10 h, n = 226) achieved graft survival rates (81% and 67% at 1 and 3 years, respectively) not significantly different from recipients with DBD allografts (80% and 72% at 1 and 3 years, respectively, log-rank p = 0.23). Liver allografts from DCD donors may be used to increase the cadaveric donor pool, with favorable graft survival rates achieved when low-risk grafts are transplanted in a low-risk setting. Whether transplantation of these organs in low-risk recipients provides a survival benefit compared to the waiting list is unknown.


Level and determinants of physical activity among school adolescents in Poland.
The recognition of adolescents' physical activity has become one of the serious challenges of the modern times, as a concern about the future health of societies. The major goal of the presented study was to discover the level of physical activity among Polish adolescents aged 16-18, and the factors which condition this level. The investigations were carried out in 2011, among 2,974 school adolescents from various locations in Poland - 1,790 girls (60.2%), and 1,184 boys (39.8%). As a study method, a short version of the IPAQ was applied. The results of the study indicated that a larger number of girls than boys show a low level of physical activity. With respect to activity among boys, higher values of intensive and moderate efforts are noted, while in girls, higher values of activities related to walking. It was confirmed that the level of physical activity does not depend on the place of residence. However, the number of physical exercise classes attended is a significant factor, both among boys and girls. It was also found that adolescents who more frequently lead a sedentary style of life are characterized by a lower level of total physical activity. Sedentary lifestyle (time spent sitting) does not differ among the level of physical activity of girls and of boys, neither with respect to the scope of the total physical activity nor to its three levels (low, moderate, high).


The management of sickle cell crisis pain as experienced by patients and their carers.
This study sought to provide insights into the personal experiences of individuals with sickle cell disorder and nurses involved in the management of painful sickle cell crisis. The sample consisted of 10 patients who experienced hospitalization for the management of pain during sickle cell crisis and 10 nurses who have cared for patients during such crises. The method of data collection used a combination of group and individual interviews, utilizing a 'guided conversation approach'. Data analysis consisted of content analysis of transcribed interviews which resulted in the identification of the following categories of problems: poor pain management, anxieties about pethidine, loss of control, lack of individuality and playing up. The results revealed that pain control during sickle cell crisis is often inadequate, with nurses admitting that they often have to resort to 'trial and error' strategy to manage pain. The findings are discussed in terms of attitudinal and knowledge factors and an individualized approach to pain management.


Morphometric analysis of the odontoid process: using computed tomography--in the Greek population.
A morphometric analysis of the odontoid process of the A2 vertebra, in the Greek population, was conducted using CT scan. We aimed to determine the feasibility to use one or two screws when treating fractures of this anatomic element. One hundred and fifteen patients (57 men) of a mean age of 48 years (16-95 years) underwent a cervical spine CT scan examination. The anterior-posterior and transverse diameters of the odontoid process were measured from the base, at 1-mm interval upward on axial CT images. The length from the tip of the odontoid process to the anterior-inferior angle of the body of the axis was calculated. Data concerning the height and weight of the examined patients were collected. The mean transverse and anterior-posterior distances were found to be 11.46 and 10.45 mm, respectively, for the upper end of the odontoid process. At the neck level of the odontoid process, the equivalent mean values were 11.12 and 8.73 mm, respectively, while at the base, these distances were found to be 13.84 and 12.3 mm, respectively. The mean distance from the tip of the odontoid to its base was 17.25 and 17.28 mm, respectively, while the mean distance from the tip of the dens to the anterior-inferior corner of the axis' body was 39.2 mm. Men showed greater values than women. In this study, it was shown that in the Greek population there is enough room for one 4.5-mm or one 3.5-mm cannulated screw to be used. The application of two 3.5-mm screws is feasible in 58.6 % of the male and 26.3 % of the female population. This confirms that the knowledge of the true dimensions of the odontoid process is of paramount importance before the proper management of fractured dens using the anterior screw technique.


Prediction of alcohol drinking in adolescents: Personality-traits, behavior, brain responses, and genetic variations in the context of reward sensitivity.
Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age=14.37) and again later (mean age=16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced.


Left multicystic dysplastic kidney with contralateral ureteropelvic obstruction: report of one case.
Multicystic dysplastic kidney (MCDK) is a common cause of abdominal mass in neonates. It is frequently associated with malformation of the contralateral kidney, such as ureteropelvic obstruction, etc. Because MCDK is usually functionless, it is important to evaluate the condition of the contralateral kidney. The presence of severe obstruction in the contralateral ureteropelvic junction is life-threatening and prompt treatment should be made to preserve the remaining renal function. We report on a neonate with left MCDK and contralateral ureteropelvic obstruction, presenting as anuria after birth, and also we review the literature.


Warfarin and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation Receiving Dialysis: A Systematic Review and Meta-analysis.
Patients with atrial fibrillation who receive dialysis are at a high risk of ischemic stroke. The role of warfarin in mitigating this risk in patients with atrial fibrillation who receive dialysis is uncertain. Our objective was to examine the safety and efficacy of warfarin in patients who have atrial fibrillation and receive dialysis. We used MedLine, Embase, and the Cochrane Library to conduct a systematic review and meta-analysis of published and unpublished observational and interventional studies related to the use of warfarin in patients with atrial fibrillation who receive dialysis, and provided data on the risk of stroke and/or bleeding outcomes relative to placebo or no anticoagulation therapy. A random effects model was used to calculate pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for these outcomes. No randomized controlled trials met the criteria for inclusion. Fourteen observational studies (20,398 participants) were included in the analysis. The use of warfarin was not associated with ischemic stroke (14 studies; 20,398 participants; aHR, 0.77; 95% CI, 0.55-1.07), intracranial hemorrhage (hemorrhagic stroke; 4 studies; 15,726 participants; aHR, 1.93; 95% CI, 0.93-4.00), gastrointestinal bleeding (3 studies; 14,693 participants; aHR, 1.19; 95% CI, 0.8-1.76), or all-cause mortality (7 studies; 16,172 participants; aHR, 0.89; 95% CI, 0.72-1.11). Observational studies suggest that warfarin was not associated with a clear benefit or harm among patients who have atrial fibrillation and receive dialysis. These estimates were limited by study heterogeneity including the inability to account for a number of important confounders such as the time in the therapeutic range. Because of the high prevalence of atrial fibrillation, stroke, and bleeding complications in this population, well designed clinical trials of warfarin and other anticoagulants are urgently needed.


Musculoskeletal manifestations of Crohn's disease.
The prevalence of musculoskeletal system complaint and involvement in a group of 54 Crohn's disease patients, with a follow-up of 2 to 40 years, was studied and compared to that of a control group of patients with a similar distribution of sex and age. Twenty-four (44%) with Crohn's disease complained of arthralgia in various joints, but only 7.4% had objective findings compatible with joint pathology such as swelling, tenderness, and decreased range of motion. None of them had any serological or radiological evidences of joint damage. No significant correlation was found between patients' complaints/physical signs and age, sex, duration, or severity of Crohn's disease or mode of medical or surgical treatment. In the control group, 46% complained of arthralgia in various joint. The differences in the percentages of arthralgia between the two groups was not significant, although they differed in location of the affected joint. In the Crohn's disease group, a significantly higher proportion of knee, hip, and wrist involvement was observed, while backache was very common in the control group. It is suggested that arthritis in patients with Crohn's disease is an uncommon finding and that arthralgia is just as prevalent as in a matched control group. The pathogenesis of arthralgia in such a condition may be caused by soft tissue involvement.


A randomized trial of telephone-based motivational interviewing for adolescent chronic headache with medication overuse.
Nearly 2% of youths suffer from chronic migraine or chronic tension-type headache (CTTH). A contributing factor in approximately 20%-50% of these youths is medication overuse, which involves taking analgesics three or more times per week for three months. The objective of this study was to test motivational interviewing (MI) as an approach to promote adherence to recommendations regarding not only analgesic overuse but also other aspects of treatment plans. A randomized controlled trial was conducted comparing the experimental condition (standard of care clinic-based treatment with supplemental MI phone calls; N = 24) to a control condition (standard of care clinic-based treatment without these supplemental MI phone calls; N = 23). Four months after enrollment, a research assistant who was blinded to study condition telephoned adolescents inquiring about headache frequency, headache severity, and disability. Headache frequency was lower in the experimental condition versus control condition for those with relatively lower initial levels of headache frequency. In contrast, we did not find greater improvement in headache severity and disability for the experimental condition relative to the control condition. Our findings provided some preliminary, albeit limited, support for MI as an approach to improve outcomes for adolescent medication-overuse headache (MOH).


Multi-infection with helminths in adults from northeast Thailand as determined by post-treatment fecal examination of adult worms.
Six hundred and eighty-one residents from 16 provinces in northeast Thailand who had previously been found positive for Opisthorchis viverrini and Taenia spp. eggs were given 40 mg Praziquantel (Bayer, Germany), per kg body weight. The total stool output for one to three days was collected and examined for adult worms. The prevalence of O. viverrini in this group was 92.4%. The intestinal flukes Echinostoma malayanum, E. ilocanum and E. revolutum were found to be high in males, with 8.3%, 8.1% and 0.8%, respectively. Minute intestinal flukes such as Haplorchis taichui, H. pumilio, H. yokogawai, Phaneropsolus bonnei, Plagiorchis harinasutai, Prosthodendrium molenkampi and Stellantchasmus falcatus were found to be 7.8%, 6.2%, 2.9%, 15.0%, 0.7%, 19.4% and 0.3%, respectively.


A case of Sjögren's syndrome with repeatedly negative findings on lip biopsy.
We report a case of Sjögren's syndrome characterized by keratoconjunctivitis sicca, parotid swelling, reduced salivary flow, and abnormalities on nuclear scanning. Two labial gland biopsies showed complete atrophy. Biopsy of an enlarged submandibular gland revealed lymphoid follicles and glandular replacement consistent with the diagnosis of Sjögren's syndrome. This case supports the concept that a negative finding on labial biopsy does not rule out a diagnosis of Sjögren's syndrome.


Technology for spinal cord injury rehabilitation and its application to youth.
Spinal cord injury (SCI) often results in a sudden, devastating loss of function. SCI is particularly challenging for the pediatric and adolescent populations who, under normal circumstances, are still achieving developmental milestones, but following SCI face additional barriers posed by paralysis and the accompanying secondary complications. Advancing technology in rehabilitation is changing the course of how people with spinal cord injury participate in rehabilitation. Technology plays an ever-increasing role in both restorative and compensatory rehabilitative interventions. While the practical or functional needs of the pediatric patient may differ from those of the adult, technology can and does play a role in restoring function for this population. Applications of technology span broad areas, providing improved options for care in grasp and manipulation, seating and mobility, augmentative and alternative communication, electronic aids to daily living, and computer access and use. This article reviews select applications of technology that have great impact on the functional needs of people with spinal cord injury (SCI): therapeutic and functional stimulation, EMG biofeedback and EMG-triggered stimulation, assistive technology for computer access, and implanted functional electrical stimulation systems. Some of these technologies are already in use in the pediatric population, while some are not - yet have great potential for restoring function in this group. The challenges and potential solutions for implementing these technologies in the pediatric population are discussed.


Firefighter Work Duration Influences the Extent of Acute Kidney Injury.
We tested the hypothesis that elevations in biomarkers of acute kidney injury are influenced by the magnitude of hyperthermia and dehydration elicited by two common firefighter work durations. Twenty-nine healthy adults (10 females) wearing firefighter protective clothing completed two randomized trials where they walked at 4.8 km·h, 5% grade in a 38°C, 50% RH environment. In the short trial, subjects completed two 20-min exercise bouts. In the long trial (LONG), subjects completed three 20-min exercise bouts. Each exercise bout was separated by 10 min of standing rest in an ~20°C environment. Venous blood samples were obtained before and immediately after exercise, and after 1 h recovery. Dependent variables included changes in core temperature, body weight, plasma volume, serum creatinine, and plasma neutrophil gelatinase-associated lipocalin, a marker of renal tubule injury. Changes in core temperature (+2.0°C ± 0.7°C vs +1.1°C ± 0.4°C, P < 0.01), body weight (-0.9% ± 0.6% vs -0.5% ± 0.5%, P < 0.01), and plasma volume (-11% ± 5% vs -8% ± 6%, P < 0.01) during exercise were greater in LONG. Increases in creatinine were higher in LONG postexercise (0.18 ± 0.15 vs 0.08 ± 0.07 mg·dL, P < 0.01) and after recovery (0.21 ± 0.16 vs 0.14 ± 0.10 mg·dL, P < 0.01). Increases in neutrophil gelatinase-associated lipocalin were greater in LONG postexercise (27.0 ± 20.5 vs 12.7 ± 18.0 ng·mL, P = 0.01) and after recovery (16.9 ± 15.6 vs 1.5 ± 15.1 ng·mL, P = 0.02). Biomarkers of acute kidney injury are influenced by the magnitude of hyperthermia and hypovolemia elicited by exercise in the heat.


Mouse embryonic cardiac metabolism under euglycemic and hypoglycemic conditions.
Children of mothers with insulin-dependent diabetic mothers (IDDM) have a 2-4 times higher incidence of congenital birth defects as compared to the general population, including cardiac abnormalities, of unknown etiology. Using rodent embryos to explore potential teratogenic factors of the altered IDDM metabolism, it has been shown that exposure to hypoglycemia in vitro results in a variety of defects, including cardiac malformations. Since pregnant diabetics experience frequent episodes of low blood glucose, it was hypothesized that hypoglycemia may play a role in the generation of heart abnormalities seen in children born to IDDM mothers. Several studies have indicated that during embryogenesis the heart is dependent on glucose for energy production such that under hypoglycemic conditions, insufficient amounts of ATP may be produced resulting in abnormalities. To test this hypothesis, cardiac ATP content was monitored in D10-D12 (plug day = D1) hearts. In addition, the contribution of glycolysis and the Krebs cycle to ATP production was monitored. D10 hearts exposed to euglycemic control conditions were found to be primarily dependent on glycolysis for ATP production from glucose before switching to the Krebs cycle and oxidative phosphorylation for energy production from this substrate on D11. Exposure to hypoglycemia did not alter the timing of this maturation process or deplete cardiac ATP content. However, cardiac lactate levels increased approximately twofold in the presence of hypoglycemia on d10. Since increased concentrations of lactate are harmful to many tissues and have been shown to be detrimental to the adult rat heart, lactic acidosis may explain the origin of cardiac defects produced by hypoglycemia, and not a deficiency of ATP.


Involuntary ureteral micturition resulting from the ectopic opening of the single ureter into the urethra.
The ectopic opening of the single ureter is a rare developmental defect of the urinary system. The authors present a case of the opening displacement of the single ureter to the urethra resulting in ureteral micturition. The successful treatment is a result of the transplantation of the ureter into the bladder.


Determinants of lifetime reproduction in female brown bears: early body mass, longevity, and hunting regulations.
In iteroparous mammals, conditions experienced early in life may have long-lasting effects on lifetime reproductive success. Human-induced mortality is also an important demographic factor in many populations of large mammals and may influence lifetime reproductive success. Here, we explore the effects of early development, population density, and human hunting on survival and lifetime reproductive success in brown bear (Ursus arctos) females, using a 25-year database of individually marked bears in two populations in Sweden. Survival of yearlings to 2 years was not affected by population density or body mass. Yearlings that remained with their mother had higher survival than independent yearlings, partly because regulations prohibit the harvest of bears in family groups. Although mass as a yearling did not affect juvenile survival, it was positively associated with measures of lifetime reproductive success and individual fitness. The majority of adult female brown bear mortality (72%) in our study was due to human causes, mainly hunting, and many females were killed before they reproduced. Therefore, factors allowing females to survive several hunting seasons had a strong positive effect on lifetime reproductive success. We suggest that, in many hunted populations of large mammals, sport harvest is an important influence on both population dynamics and life histories.


Fault classification on vibration data with wavelet based feature selection scheme.
Fault classification based upon vibration measurements is an essential building block of a conditional based health usage monitoring system. Multiple sensors are incorporated to assure the redundancy and to achieve the desired reliability and accuracy. The shortcoming of using multiple sensors is the need to deal with a high dimensional feature set, a computationally expensive task in classification. It is vital to reduce the feature dimension via an effective feature extraction and feature selection algorithm. A simple wavelet based feature selection scheme is proposed herein, uniquely built by local discriminant bases and genetic optimization. This scheme overcomes the disadvantages faced by the existing feature selection methods by producing a generic feature set, reducing the dimensionality of features, and requiring no prior information of the problem domain. The proposed feature selection scheme is based upon the strategy of "divide and conquer" that significantly reduce the computation time without compromising the classification performance. The simulation results show the proposed feature selection scheme provides at least 65% reduction of the total number of features at no cost of the classification accuracy.


Cytotoxic T lymphocyte antigen 4 decreases humoral and cellular immunity by adenovirus to enhance target GFP gene transfer in C57BL/6 mice.
Adenoviruses (Ad) are once potential and promising vectors for gene delivery, but the immunogenicity attenuates its transfer efficiency. Cytotoxic T lymphocyte antigen 4 (CTLA-4) can inhibit T cell immunity. Thus, we aimed to study the effect of CTLA-4 in the process of Ad-mediated gene transfer. The C57BL/6 mice were injected by Ad vectors at twice, and CTLA-4 was administrated after the first Ad injection. Then, the CD3(+)CD4(+) T cells and circulating levels of IL-2, IL-4, and anti-Ad IgG were decreased by CTLA-4, while Ad generated immune responses. The green fluorescence protein (GFP) expressions of tissues were enhanced by CTLA-4 till injection of Ad at twice. Our results indicate that CTLA-4 can inhibit humoral and cellular immunity by adenovirus generation to enhance GFP delivery, and provide a potential way to assist in Ad-mediated gene transfer.


High-performance liquid chromatography-mass spectrometry method for determination of anagrelide in human plasma.
This paper describes a simple, fast and sensitive liquid chromatography-mass spectrometry method for quantification of an anti-thrombocythemic agent, anagrelide in human plasma. The samples were subjected to a liquid-liquid extraction after addition of a buffer and an internal standard. Chromatography was performed on an Inertsil ODS2 column and the extract was injected onto a HPLC system coupled with mass spectrometric detection. Linear responses for standards were observed from 50 to 7500 pg/ml. The accuracy of intra-assay and inter-assay were in the ranges 4.3-4.4% and 4.8-5.6%, respectively. The method is simple and reproducible with a run time of less than 2 min.


[Reporting guidelines are also useful for readers of medical research publications: CONSORT, STARD, STROBE and others].
Over the last few years reporting guidelines for research papers have had increasing attention and use. They comprise recommendations and checklists, developed by expert groups consisting of researchers, methodologists and journal editors. They aim at ensuring the transparent description of research results. Following the CONSORT statement for the reporting of randomized controlled trials (RCTs), other reporting guidelines such as STARD for diagnostic accuracy studies, STROBE for observational studies and QUOROM for systematic reviews of RCTs have been published. This article discribes the concept of reporting guidelines for research reports and discusses searches of the international literature based on them. Selected reporting guidelines of particular interest are presented in detail. Nowadays, reporting guidelines exist for different areas of research and types of studies. The EQUATOR network (www.equator-network.org) offers a comprehensive overview. Other reporting guidelines are being prepared. It has been shown for some guidelines, in particular the CONSORT statement that they contribute to an improvement in reporting medical research. Existing guidelines should be assesed regularly for their timeliness and, if necessary, be updated. Reporting guidelines contribute to the improvement of the quality of medical research publications. They offer advice how to interpret and critically appraise the medical literature for authors but also for journal editors, reviewers and critical readers.


Separate effects of moisture content and water activity on the hyphal extension of Penicillium rubens on porous media.
To prevent indoor fungal growth, understanding the moisture relations of fungi is a key element. Indoor moisture is quantified by the relative humidity (RH). RH controls the water activity of the indoor materials that fungi grow on, a well-studied parameter known to limit fungal growth. RH, however, also controls the amount of water present in these materials, the moisture content. The significance of the moisture content of these materials to indoor fungal growth is currently overlooked. In the work reported here, growth experiments with the indoor fungus Penicillium rubens on gypsum substrates were performed to test whether the moisture content influences growth on porous materials. Second, we report the development of a video microscopy method that for the first time quantified hyphal growth on a porous material. It is found that a higher moisture content leads to earlier colonization and higher hyphal extension rates. This is a fundamental step in unravelling the effect of RH on indoor fungal growth. The real-time monitoring of colonization of gypsum provides a new view of growth on indoor surfaces.


Computer-derived image compositing.
A computer-derived composite image is obtained of the details contained in successive photomicrographs taken by optical sectioning of the collagen networks in the pulmonary interalveolar wall. Three-dimensional information is therefore contained in a two-dimensional portrayal, providing a basis for computer digital analysis otherwise not readily available.


Lectin histochemical detection of sulfoglycans in the zona pellucida of mammalian antral oocytes.
Sulphated esters are important to increase effectiveness of specific biological activities of carbohydrates. Biochemical studies revealed the presence of distinct sulphated glycoproteins in mammal zona pellucida (ZP) that bind proacrosin and thus participate in the sperm-egg fusion processes. In the present study, 6 lectin-horseradish peroxidase conjugates (SBA, PNA, RCA-I, GSA-IB4, GSA-II and DBA) were used in combination with desulphation and sialidase digestion to identify sulphocarbohydrates in the terminal and/or subterminal position of oligosaccharide side chains of glycoproteins in the ZP of bovine, ovine, caprine and porcine antral oocytes. In particular, we identified the following terminal sulphoglycans located in the outer layer of the ZP only: SO4-GalNAc in bovine ZP; SO4-Galbeta1,3GalNAc in bovine and ovine ZP; SO4-Galbeta1,4GlcNAc in bovine, ovine and caprine ZP; SO4-alpha-Gal in bovine, caprine and porcine ZP. Subterminal sulphoglycans linked to sialic acid residues were evenly distributed throughout the entire thickness of the ZP: Neu5Ac-SO4-Galbeta1,3GalNAc in bovine and porcine ZP; Neu5Ac-SO4-Galbeta1,4GlcNAc in caprine ZP; Neu5Ac-SO4-alpha-Gal in porcine ZP; Neu5AcSO4-GlcNAc in bovine ZP. The results demonstrate that the chemical composition of the ZP differs among species determining the species-specificity of gamete interactions.


Health in the workplace.
General good health and the prevention of specific "non-occupational" disease, in addition to protection against occupational disease and injury, are already part of the aim and function of occupational health services. They are justified, if at all, mostly on the grounds of intangible benefits the virtue of which is not questioned. Concern over health costs and financial constraints are forcing industry to justify health expenditure. Yet, the health programmes can be justified, and industry has some obligation to adopt them.


Appendicular arthropathy.
The radiographic examination plays an extremely important role in the diagnosis of appendicular arthropathies. Accurate diagnosis can be made by observing the radiographic abnormalities in the bones surrounding the joint involved and the distribution of the abnormalities within the joint or the body.


Pulling smarties out of a bag: a Headed Records analysis of children's recall of their own past beliefs.
The work reported provides an information processing account of young children's performance on the Smarties task (Perner, J., Leekam, S.R., & Wimmer, H. 1987, Three-year-olds' difficulty with false belief: the case for a conceptual deficit. British Journal of Developmental Psychology, 5, 125-137). In this task, a 3-year-old is shown a Smarties tube and asked about the supposed contents. The true contents, pencils, is then revealed, and the majority of 3-year-olds cannot recall their initial belief that the tube contained Smarties. The theoretical analysis, based on the Headed Records framework (Morton, J., Hammersley, R.J., & Bekerian, D.A. 1985, Headed records: a model for memory and its failures, Cognition, 20, 1-23), focuses on the computational conditions that are required to resolve the Smarties task; on the possible limitations in the developing memory system that may lead to a computational breakdown; and on ways of bypassing such limitations to ensure correct resolution. The design, motivated by this analysis, is a variation on Perner's Smarties task. Instead of revealing the tube's contents immediately after establishing the child's beliefs about it, these contents were then transferred to a bag and a (false) belief about the bag's contents established. Only then were the true contents of the bag revealed. The same procedure (different contents) was carried out a week later. As predicted children's performance was better (a) in the 'tube' condition; and (b) on the second test. Consistent with the proposed analysis, the data show that when the computational demands imposed by the original task are reduced, young children can and do remember what they had thought about the contents of the tube even after its true contents are revealed.


Bottom-up versus top-down effects on ciliate community composition in four eutrophic lakes (China).
Previous studies have shown that ciliate plankton is generally controlled by food resources (e.g., algae) and predators (e.g., metazooplankton). Among lakes with similar trophic levels but different distributions of phyto- and metazooplankton, the main forces acting on ciliate assemblages may be different. We investigated the relationship between ciliate communities and bottom-up versus top-down variables based on a survey of four subtropical eutrophic lakes (China). Two of the lakes (Chaohu, Taihu) are located on the Mid-lower Yangtze Plain near sea level, and the other two (Dianchi, Xingyunhu) on the Yunnan-Kweichow Plateau at 1700 m above sea level. Blooms of cyanobacteria developed during summer in Lakes Chaohu and Taihu and throughout the year in Lakes Dianchi and Xingyunhu. Ciliate functional feeding groups differed significantly between lakes. The results of canonical correspondence analysis (CCA) and variation partitioning showed that cyanobacteria significantly influence ciliate species, whereas 'edible' algae (cryptophytes, diatoms) and cladocerans were the important variables in explaining the ciliate community structure of Lakes Dianchi and Xingyunhu compared with Lakes Taihu and Chaohu. Our results highlight the importance of consistent cyanobacterial blooms in shaping the ciliate community in subtropical eutrophic shallow lakes by interacting with top-down and bottom-up factors.


Comprehensive outsourcing biobanking facility to serve the international research community.
The validity of results from biomarker studies using archived specimens depends on the integrity of the specimens and the manner in which they are collected, processed, and stored. The management of a huge amount of biomaterial generated from research studies and clinical trials is becoming a very demanding task and many organizations are facing the choice between in-house storage and processing and outsourcing some activities. Storage and logistic functions are the prime targets for outsourcing, because to sustain these critical assets organizations must have the expertise, the dedicated qualified personnel, the proper quality control programs, and available resources to fulfill the mandatory requirements to maintain the integrity of the samples. External biobanks are dedicated and certified infrastructures (ISO, GMP, etc.) that apply efficient logistic and shipping activities, use validated standard operating procedures, install appropriate monitoring back-up systems, and, most of all, have room for expansion. Thus, the choice between in-house biobanking and outsourcing cannot be exclusively based on a financial decision; it must also consider (i) type of collection/project, (ii) logistic complexity (number and locations of collection sites), (iii) safety requirements, (iv) functional expertise, and (v) business priorities.


Raloxifene blocks estradiol induction of the serotonin transporter and 5-hydroxytryptamine2A receptor in female rat brain.
Sex steroids have potent effects on mood, mental state and cognition. Our previous findings and those of others suggest that these effects may be due at least in part to estradiol actions on central serotonergic mechanisms. Specifically, estradiol-17beta in its acute positive feedback mode for gonadotropin release in the female rat induces expression of the genes for the 5-hydroxytryptamine(2A) receptor (5-HT(2A)R) and the serotonin transporter (SERT) in the dorsal raphe nucleus (DRN). This is accompanied by an increase in the densities of 5-HT(2A)R and the SERT in forebrain regions which in the human are concerned with the control of mood, mental state, cognition and emotion. Here we report that raloxifene, a benzothiophene and selective estrogen receptor modulator (SERM), completely blocked estradiol stimulation of brain 5-HT(2A)R and SERT expression in acutely ovariectomized rats. Raloxifene also blocked the estrogen-induced surge of luteinizing hormone. Treatment of acutely ovariectomized rats with raloxifene alone increased the density of SERT sites in the mid-frontal cortex and decreased the density of 5-HT(2A)R in the posterior olfactory tubercle. The inhibitory effects of raloxifene on acute estrogen-induction of central serotonergic mechanisms were similar to those of tamoxifen even though there are major differences between the two SERMs in their affinity for the two estrogen receptor subtypes and their actions on the uterus. These findings provide robust evidence that estradiol induction of the 5-HT(2A)R and the SERT in brain is mediated by nuclear estrogen receptors. Our data may provide the basis for obtaining a better understanding of the effects of sex steroids on mood and mental state in the human and the possible rational development of congeners of sex steroids for the treatment of mental disorders.


miR-124 radiosensitizes human esophageal cancer cell TE-1 by targeting CDK4.
Radiotherapy is one of the most important treatments for esophageal cancer, but radioresistance remains a major challenge. Previous studies have shown that microRNAs (miRNAs or miRs) are involved in human cancers. miR-124 has been widely reported in various cancers and it is intimately involved in proliferation, cell cycle regulation, apoptosis, migration, and invasion of cancer cells. The aim of this study was to explore the relationship between the miR-124/cyclin-dependent kinase 4 (CDK4) axis and the radiosensitivity of esophageal cancer cells. In this study, we identified the reduced expression of miR-124 in 18 paired esophageal cancer tissues compared to their matched normal tissues. In order to investigate the physiological role of miR-124 in esophageal cancer, the cell counting kit-8 (CCK-8) assay and wound healing assay were performed, and the results suggest that miR-124 overexpression decreases tumor growth and aggression. Next, we detected the effects of ectopic miR-124 expression on the apoptosis of an esophageal cancer cell line (TE-1) following radiotherapy. Using the CCK-8 assay and Hoechst 332528 stain, we found that ectopic expression of miR-124 led to a higher percentage of apoptotic cells. Finally, we identified that CDK4 is a direct target of miR-124 in TE-1 cells using target prediction algorithms and a luciferase reporter assay. Moreover, western blot assay confirmed that CDK4 was downregulated during miR-124 transfection. Taken together, we illustrate that the miR-124/CDK4 axis plays an important role in radiation sensitivity of human esophageal cancer cells by targeting CDK4.


[Mortality in a district hospital--an indicator for efficiency].
The paper presents mortality in surgical units of a second referral hospital from Galati. During 2003 year there have been recorded 190 deaths, most of them being reported by neurosurgery department (132). Hospital mortality varied from 2.8 deaths per 100 inpatients in neurosurgery to 0 deaths in urology and obstetrics-gynecology department. The surgical procedure with the highest number of deaths has been craniotomy (133). The death risk during operation was very low for most of surgical procedures, medium in the first 24 hours and high after 48 hours.


Differential expression of two calmodulin genes in response to physical and chemical stimuli.
Two different calmodulin (CaM) cDNAs (MBCaM-1 and MBCaM-2) were isolated from a vigna radiata lambda gt11 library by screening with a heterologous Arabidopsis cDNA probe (TCH-1). Both cDNAs are 85% homologous inside the coding region but are highly divergent outside this region. The polypeptides encoded by MBCaM-1 and MBCaM-2 are identical except for two conservative substitutions at positions 7 and 10. Southern analysis revealed that both cDNAs are encoded by different genes. Expression studies revealed different patterns of expression of both genes. MBCaM-1 mRNA exhibited a dramatic transient increase in response to touch, while MBCaM-2 expression showed a steady but small increase as compared to MBCaM-1. When plants were grown in complete darkness MBCaM-1 was undetectable and MBCaM-2 exhibited very low levels of expression. One hour after exposure of etiolated seedlings to light MBCaM-1 showed no change, while MBCaM-2 expression was increased. After a 6 h exposure to light there was an induction of both MBCaM-1 and MBCaM-2; however, the magnitude of this increase was much greater for MBCaM-2. When plants were grown under a 16 h light/8 h dark cycle the mRNA levels for MBCaM-1 were lower during the light period and increased during the beginning of the night cycle, while MBCaM-2 showed no change. Plants treated with indole-3-acetic acid had a peak in MBCaM-1 expression 6 h after treatment initiation with a slight decline 3 h after the peak, while MBCaM-2 showed a steady but small increase over time as compared to MBCaM-1. When plants were subjected to salt stress they showed an increase in MBCaM-1 expression 2 h after treatment initiation reaching a maximum after 4 h with no further increase after 6 h, while MBCaM-2 remained unchanged over the time course.


HIV type 1 molecular epidemiology among high-risk clients attending the Thai Red Cross Anonymous Clinic in Bangkok, Thailand.
Several studies have reported an increasing number of non-CRF01_AE infections in high-risk groups in Thailand suggesting a more complex HIV-1 epidemic. This study assessed the complexity of the HIV epidemic among high-risk clients tested for HIV-1 at the Thai Red Cross Anonymous Clinic (TRCAC) between July 1, 2006 and February 28, 2007. HIV-1 genotypes were determined from plasma of infected subjects (n = 401) by the multiregion hybridization assay (MHAbce, v.2). Univariate and multivariate logistic regression analyses were used to determine risk factors associated with HIV prevalence and non-CRF01_AE infection. The estimated overall HIV prevalence was 14.1%: 25.3% among men who have sex with men (MSM), 18.4% among heterosexual women, and 9.6% among heterosexual men. Among the risk factors found to be associated with HIV prevalence were age (25-29 years), risk behavior (MSM), marital status (not single), education (less than high school), and inconsistent condom use. Overall, non-CRF01_AE strains accounted for 18.9% of the infections: 25.3% among MSM and 14.8% and 20.4% among heterosexual women and men, respectively. Our results indicate a concentrated and genetically complex HIV epidemic among Thai MSM. These findings advocate for targeted intervention and prevention measures among high-risk populations in Thailand.


Diagnostic accuracy of outpatient endocervical curettage using conventional and Vabra curettage of the cervix.
With the object of examining the diagnostic accuracy of and pain reaction to endocervical curettage (ECC) either by using a new instrument, Vabra mc cervix, or with a conventional 3 mm metal curette, 298 patients with histologically verified cervical intraepithelial neoplasia (CIN) or cytological suspicion have been involved in a consecutive prospective randomized trial. One hundred and forty-eight patients underwent curettage with the Vabra instrument (vabrasio) followed by conventional curettage; 150 underwent the same procedure, but in reverse order. In 114 patients, CIN was ascertained in one or both trials. Vabra mc cervix found normal histology in 23 of these patients (20%), whereas conventional curettage showed normal histology in 58 patients (51%). Quantitatively, Vabra mc cervix extracted significantly more tissue material than did conventional curettage. The pain intensity when using of Vabra mc cervix was less severe. The present study showed diagnostic accuracy of Vabra mc cervix to be 80% (95% confidence limits: 63.38-80.73), compared with 49% (95% confidence limits: 35.17-54.35) when using conventional curettage.


The synthesis of mycobacterial dimycoloyl diarabinoglycerol based on defined synthetic mycolic acids.
Complex mixtures of natural dimycoloyl diarabinoglycerols isolated from mycobacteria have been shown to be both potent immune signalling agents and potentially valuable antigens in the serodiagnosis of mycobacterial infections. We now report the highly stereocontrolled synthesis of diacyl l-glycerol-(1'→1)-β-d-arabinofuranosyl-α-d-arabinofuranosides based on simple fatty acids and single defined synthetic mycolic acids. NMR analysis confirmed that the synthetic core was identical to that in natural mixtures.


The tify family previously known as ZIM.
The ZIM domain was originally identified in the ZIM protein (BAA97679; Zinc-finger protein expressed in Inflorescence Meristem). Since then it has been found in other proteins and the corresponding genes have been grouped into a plant-specific family. However, the family lacks consistency in its classification among different databases. Here, we try to clarify this incongruity by presenting an overview of the Arabidopsis proteins having this domain. The presented genome-wide survey can be seen as a start point to reveal the unknown function of these proteins. Furthermore, because of the confusing ZIM nomenclature being used at present, we propose to rename the domain and family as tify, after the most conserved amino acid motif characterizing the members of this family.


[Endoscopic surgery of the sinus: own experiences].
In the Clinic of Otolaryngology Central Clinical Hospital Military School of Medicine in Warsaw in years 1992-1996 there were performed 187 endoscopic operations of nose and paranasal sinuses. Authors analised own material paying particular attention to indications, benefits and failures of these operations. Authors postulate that indications for clinical diagnostic and therapeutic procedures of this technique should be considerably extended in diseases of nose and paranasal sinuses. The application of endoscopic sinus surgery in our Clinic decreased the number of more extended operations of paranasal sinuses.


Cachexia-like symptoms predict a worse prognosis in localized t1 renal cell carcinoma.
Although cachexia is a common sequela of advanced and metastatic renal cell carcinoma (RCC), cachexia-like symptoms may also represent a paraneoplastic finding. We assessed the prognostic significance of these symptoms in patients with stage T1 RCC. Using the kidney cancer database at our institution 250 patients were identified who underwent partial or radical nephrectomy for T1N0M0 RCC between 1989 and 2001. The prognostic significance of the symptoms present at diagnosis and findings on preoperative laboratory evaluation were examined. Mean and median followup was 33 and 43 months, respectively. Malaise, weight loss, anorexia and hypoalbuminemia were cachexia related findings that were significant predictors of worse disease specific survival (DSS). DSS in patients with 1 vs greater than 1 cachexia related symptoms was not significantly different (p = 0.077). Therefore, any patient with at least 1 cachexia related finding was considered to be positive for cachexia and cachexia occurred in 37 (14.8%). Cachexia was associated with significantly worse recurrence-free survival (HR 3.03, p = 0.032) and DSS (HR 4.39, p = 0.011) even after controlling for tumor size, grade and performance status. The 5-year survival rate in patients with low grade (1 or 2) tumors with and without cachexia was 91% and 81%, respectively. The 5-year survival rate in patients with high grade (3 or 4) tumors with and without cachexia was 75% and 55%, respectively. Cachexia-like symptoms independently predict a worse prognosis in patients with T1 RCC. Patients with cachexia (malaise, weight loss, anorexia and hypoalbuminemia), especially when associated with high grade tumors, should be considered for clinical trials of adjuvant therapies.


[Comparative study of platinum complexes in athymic mice with human tumors].
Tumoricidal activity of Soviet-synthesized oxoplatinum and cycloplatam was shown to influence human tumor strains (melanoma, cancer of the kidney, Burkitt's lymphoma) transplanted to nude mice. Their therapeutic effect was associated with lymphopenia; however, they did not suppress the chemically determined activity of succinate dehydrogenase and alpha-glycerophosphate dehydrogenase.


[Scanning electron microscopic observation of interactions of vaginal epithelial cells with Candida albicans and Lactobacillus crispatus].
Objective: To investigate interactions of vaginal epithelial cells (VEC) with Candida albicans and the protective effect of Lactobacillus crispatus on VEC. Methods: VK2/E6E7 VEC cell line was cultured. Candida albicans and Lactobacillus crispatus suspension were prepared respectively. Ultrastructural morphological changes of VEC infected with Candida albicans and treated with Lactobacillus crispatus were observed by scanning electron microscope (SEM). Results: Candida albicans invaded into VEC mainly through endocytosis after an early infection of 6 hours. Pseudopods of VEC increased, contacted and covered the surface of pseudohyphae. After 12 hours infection, active penetration developed into the predominant invasion mechanism. Candida albicans directly penetrated through VEC, destroyed the surface structures, and even led to cell death. A reduction of pseudopods on VEC was observed. After co-incubation with Lactobacillus crispatus, SEM revealed a morphological recovery of VEC and destruction of pseudohyphae. Conclusion: s Candida albicans invade VEC mainly through endocytosis and active penetration. Lactobacillus crispatus could utilize occupying effect to exert protective effect on VEC during the infection with Candida albicans.


Oridonin: targeting programmed cell death pathways as an anti-tumour agent.
Oridonin, an active diterpenoid isolated from traditional Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis- and autophagy-inducing activity and relevant molecular mechanisms in cancer therapy. Apoptosis is a well known type of cell death, whereas autophagy can play either pro-survival or pro-death roles in cancer cells. Accumulating evidence has recently revealed relationships between apoptosis and autophagy induced by oridonin; however, molecular mechanisms behind them remain to be discovered. In this review, we focus on highlighting updated research on oridonin-induced cell death signalling pathways implicated in apoptosis and autophagy, in many types of cancer. In addition, we further discuss cross-talk between apoptosis and autophagy induced by oridonin, in cancer. Taken together, these findings open new perspectives for further exploring oridonin as a potential anti-tumour agent targeting apoptosis and autophagy, in future anti-cancer therapeutics.


Comorbid depression and risk of cardiac events and cardiac mortality in people with diabetes: A systematic review and meta-analysis.
To examine the association of comorbid occurrence of diabetes and depression with risk of cardiovascular endpoints including cardiovascular mortality, coronary heart disease and stroke. A systematic review and metaanalysis. We searched PUBMED/MEDLINE, Medscape, Cochrane Library, CINAHL, EMBASE and Scopus databases assessing cardiac events and mortality associated with depression in diabetes up until 1 December 2018. Pooled hazard ratios were calculated using random- effects models. Nine studies met the inclusion criteria. The combined pooled hazard ratios showed a significant association of cardiac events in people with depression and type 2 diabetes, compared to those with type 2 diabetes alone. For cardiovascular mortality the pooled hazard ratio was 1.48 (95% CI: 1.185, 1.845), p = 0.001, for coronary heart disease 1.37 (1.165, 1.605), p < 0.001 and for stroke 1.33 (1.291, 1.369), p < 0.001. Heterogeneity was high in the meta-analysis for stroke events (I-squared = 84.7%) but was lower for coronary heart disease and cardiovascular mortality (15% and 43.4% respectively). Meta-regression analyses showed that depression was not significantly associated with the study level covariates mean age, duration of diabetes, length of follow-up, BMI, sex and ethnicity (p < 0.05 for all models). Only three studies were found that examined the association of depression in type 1 diabetes, there was a high degree of heterogeneity and data synthesis was not conducted for these studies. We have demonstrated a 47.9% increase in cardiovascular mortality, 36.8% increase in coronary heart disease and 32.9% increase in stroke in people with diabetes and comorbid depression. The presence of depression in a person with diabetes should trigger the consideration of evidence-based therapies for cardiovascular disease prevention irrespective of the baseline risk of cardiovascular disease or duration of diabetes.


[Inhibition of 3H-TdR-incorporation in tumor cells after application of cytotoxic drugs as an indicator of therapeutical efficacy (author's transl)].
In 36 Walker-ascites-carcinosarcoma bearing rats the reduction of 3H-TdR-incorporation into tumor cells after cytotoxic treatment as an potential prognostic factor for efficacy of chemotherapy was tested. Twelve rats each were i.p. treated with 1 mg/kg bw. DDP resp. 0.8 mg/kg bw. adriamycin. Twelve rats were injected with 0.2 mg phs. NaCl and served as control. Survival of rats served as criterion of therapeutic efficacy. There was a significant correlation between reduction of 3H-TdR-uptake in tumor cells after cytotoxic therapy and survival.


The benefits of combined anti-platelet treatment in carotid artery stenting.
To assess the benefits of a combined anti-platelet regime of aspirin and clopidogrel in carotid artery stenting. A randomised controlled trial was performed comparing aspirin and 24-h heparin with aspirin and clopidogrel for patients undergoing carotid artery stenting. Outcome measures included 30-day bleeding and neurological complications and 30-day stenosis rates. Bleeding complications (groin haematoma or excessive bleeding at the groin site) occurred in 17% of the heparin and 9% of the clopidogrel group (p=0.35; n.s). The neurological complication rate in the 24-h heparin group was 25% compared to 0% in the clopidogrel group (p=0.02). The 30-day 50-100% stenosis rates were 26% in the heparin group and 5% in the clopidogrel group (p=0.10; n.s). The dual anti-platelet regime has a significant impact on reducing adverse neurological outcomes without an additional increase in bleeding complications. This study was terminated prematurely due to an unacceptable level of complications in the heparin arm of the trial.


In vitro and in vivo efficacy of sulfo-carrabiose, a sugar-based cosmetic ingredient with anti-cellulite properties.
Most of adult women exhibit cellulite on the hips, buttock and thighs. Although extracellular matrix and lymphatic system disorders can increase its appearance, cellulite basically results from an excessive fat storage in the adipose tissue which exerts considerable pressure on the surrounding skin tissue and creates a dimpled irregular appearance. Caffeine, the most widely used anti-cellulite ingredient, favours fat break-down by inhibiting the phosphodiesterase enzyme and encouraging a high intracellular level of cAMP. A series of studies has shown that spermine and spermidine, two ubiquitous polyamines, encouraged fat storage and slowed fat break-down in the adipose tissue. Besides, it was shown that heparan sulfate glycosaminoglycans had a strong affinity for polyamines. To design a new cosmetic ingredient with anti-cellulite properties, we used molecular modelling to screen several ingredients with a structure similar to that of heparan sulfate glycosaminoglycans. This way, we identified sulfo-carrabiose as a potent molecule for trapping spermine and spermidine. These virtual results were first confirmed in tubo where sulfo-carrabiose was shown to dose-dependently inactivate spermine and spermidine. In vitro, adipocytes cultured with sulfo-carrabiose exhibited a significant reduction of lipogenesis and a significant increase of lipolysis. When sulfo-carrabiose was incorporated in a cosmetic formula, significant improvements were observed in thigh circumference, with better results than those obtained with caffeine after 28 days of use. Furthermore, a combination of caffeine and sulfo-carrabiose led to results significantly better than those obtained with caffeine alone. As measured by fringe projection, thigh volume was also significantly reduced after sulfo-carrabiose treatment. Finally, the appearance of cellulite assessed by clinical evaluation was also significantly reduced within 28 days.


Interactions between growth hormone, insulin-like growth factor I, and basic fibroblast growth factor in melanocyte growth.
Melanocytes, highly differentiated neural crest-derived cells, are located in the basal layer of the epidermis, where they play a role in protecting against UV damage in the skin. Previous studies suggest that both growth hormone (GH) and the insulin-like growth factor I (GH/IGF-I) system may be important for melanocyte growth and function. We have therefore characterized the role of the GH/IGF system in melanocyte growth in vitro and its interaction with the local growth factor basic fibroblast growth factor (bFGF). Analysis of the effects of GH, IGF-I, and bFGF and combinations of these growth factors on melanocyte growth in vitro revealed that 1) GH stimulates the growth of melanocytes when combined with IGF-I, des(1-3)IGF-I [an analog of IGF-I that has a reduced binding affinity for IGF-binding proteins (IGFBPs)], or bFGF, either separately or in combination; 2) in contrast to the lack of effect of GH or bFGF alone, both IGF-I and des(1-3)IGF-I enhance melanocyte growth in a dose-dependent manner; and 3) IGF-I is more efficacious in eliciting a growth response at low concentrations compared to des(1-3)IGF-I. Using Western ligand blotting, affinity cross-linking, immunoprecipitation, RIA, and Northern analysis, we show that cultured human melanocytes synthesize and secrete minimal amounts of IGFBP. IGFBP-4 is the major IGFBP produced by these cells when cultured in complete growth medium or in the presence of either IGF-I or des(1-3)IGF-I alone. In conclusion, these studies provide support for a role for both GH and IGF-I in the growth of human melanocytes in vitro, involving synergy with bFGF. Low levels of melanocyte-derived IGFBP-4 may play a role in enhancing the modulation of IGF action.


Prostate biopsy quality is independent of needle size: a randomized single-center prospective study.
To evaluate sample quality, prostate cancer detection rate and biopsy morbidity in transrectal ultrasound (TRUS)-guided prostate biopsy (PBx) using 16- or 18-gauge Tru-Cut needles. Patients undergoing TRUS PBx were consecutively randomized with a 1:1 ratio into two study arms: group A (16-gauge needle) and group B (18-gauge needle). Core fragmentation and small specimen length (<10 mm) rate were the sample quality criteria. Three consecutive visual analog scale tests for pain and the Clavien surgical classification complications grading for rectal bleeding were used to evaluate TRUS PBx morbidity. Overall, 250 patients were evaluated. No statistically significant difference between 16- and 18-gauge biopsy needles was recorded for cancer detection rate (29.6 vs. 30.4%, p = 0.890), core fragmentation rate (5 vs. 7%, p = 0.425) and shorter specimen (2 vs. 2%, p = 0.309). Pain control was similar in the two groups during the biopsy, 30 min after biopsy and the evening of the same day. Very small or absent bleeding was the more frequent complication observed in each group. Prostate detection rate and sample quality were not influenced by needle size. A 16-gauge needle biopsy does not increase TRUS PBx morbidity.


Structure of cDNAs encoding the triple-helical domain of murine alpha 2 (VI) collagen chain and comparison to human and chick homologues. Use of polymerase chain reaction and partially degenerate oligonucleotide for generation of novel cDNA clones.
Type VI collagen cDNAs of human and avian origin were recently obtained and characterized by screening cDNA libraries in lambda phage. Based on the published sequences of these cDNAs, we constructed partially degenerate oligonucleotide primers that we used in polymerase chain reactions for the generation of alpha 2(VI) collagen clones of murine origin. As template, we used cDNA derived from murine total RNA. We amplified, cloned and sequenced a 1043-bp fragment that contains the coding sequence for the entire triple-helical domain except for the first two amino acids that are Gly-Pro in both man and chicken. Comparison of the nucleotide and derived amino acid sequences revealed 84.6% and 92.5% identity between mouse and man at the DNA and protein levels, respectively. Comparison with chicken sequences showed 72% and 79.1% identity. The third base usage showed a distinct preference for A in the glycine codons for the three species; whereas, U is preferred in all human fibrillar collagen genes previously defined. The preference for third base codon in Y position prolines is U for the alpha 2(VI) collagen as it is for the human fibrillar collagen genes. A single cysteine at position 89, two Arg-Gly-Asp sequences, and one triple helix-interruption are conserved in mouse, man and chicken. Comparison of hydropathy plots showed great similarity between those of murine and human alpha 2(VI) collagen chains and to a lesser extent between murine and chick. Northern blot hybridization of murine poly A+ RNA with a nick-translated radiolabeled alpha 2(VI) collagen probe detected one major transcript of 3.7 kb.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro comparison of the antifungal activities of R34,000, miconazole and amphotericin B.
In vitro susceptibilities of 78 isolates of pathogenic filamentous fungi to the imidazole compounds R34,000 and miconazole and to amphotericin B were determined using an agar dilution technique. Allescheria boydii, Sporothrix schenckii and the dematiaceous fungi (Cladosporium, Fonsecaea and Phialophora spp.) were most susceptible to miconazole with minimum inhibitory concentration (MIC) values ranging from less than or equal to 0.25 to 32 microgram/ml and with geometric mean MIC (G-MIC) values of 0.56-1.24 microgram/ml. Isolates of Aspergillus fumigatus were more susceptible to amphotericin B and miconazole than to R34,000 with G-MIC values of 1.20 and 3.48 microgram/ml, respectively. Coccidioides immitis, Histoplasma capsulatum and Blastomyces dermatitidis were highly susceptible to all three drugs (G-MICs greater than 1 microgram/ml); R34,000 was the most active of the three compounds against C. immitis (G-MIC = 0.44 microgram/ml).


[Colorimetric assay of perfluorooctanesulfonate based on gold nanoparticles].
For the property of persistent, bioaccumulation and genetic toxicity, perfluorooctanesulfonate (PFOS) is classified as a sort of persistent organic pollutants (POPs). It is significant to develop a novel assay for the determination of PFOS. In this work, we create a new colorimetric assay for PFOS in which the positively-charged gold nanoparticles (AuNPs) work as a nano-probe. This method works on the aggregation of AuNPs induced by PFOS via electrostatic interaction. The stable monodisperse AuNPs coated by cysteamine present color of red wine and the addition of PFOS can make the monodispersed AuNPs aggregated resulting in the color change from wine red to reddish purple with a red-shift in ultraviolet-visible absorption spectrum. The experimental results show that AuNPs has a characteristic absorption peak (524 nm), as well as a wide absorption peak (650 nm) and the absorption signal intensity is proportional to the PFOS content in a range of 0. 8-8. 0 µmo .l L-1. According to these, we developed a method based on ultraviolet-visible absorption and colorimetric to detect PFOS with the detection limit of 80 nmol . L-1. The scanning electron microscope (SEM) was investigated and the photos show that the stable AuNPs are made and the degree of AuNPs aggregation is related with PFOS concentration. The effect tests of coexisting substances in system show that common anions had less impact on the system and inorganic metal ions had some interference, which can be get rid of by cat- ion exchange resin in real sample. This assay was applied to detect PFOS in tap water with a recovery range of 87. 5%-118% and RSD 4. 4%. It is a novel application of AuNPs-based probe for PFOS detection. The proposed method has more advantages such as rapidity, low-cost and simplicity than conventional ones. In addition, it has the visual sensing function and the difference of color can be sensed by naked eyes directly, which produce ideas of real-time colorimetric strategies of nanoprobe application in environmental pollutant detection.


Construction of plasmids, estimation of plasmid stability, and use of stable plasmids for the production of poly(3-hydroxybutyric acid) by recombinant Escherichia coli.
Plasmids containing the Alcaligenes eutrophus poly(3-hydroxybutyric acid) (PHB) biosynthetic genes were constructed for the production of PHB in Escherichia coli and plasmid stability was investigated by repeated subculturing without antibiotic pressure. Both pSYL101 (high copy) and pSYL102 (medium copy) were unstable during the subcultures. Higher instability was observed when cells were accumulating PHB. Segregational instability was aggravated by the faster growth of plasmid-free cells and by appearance of non-dividing cells harboring large amount of PHB during the fed-batch culture. Two derivatives, pSYL103 and pSYL104, were then developed by cloning the parB locus of plasmid R1 into pSYL102 and pSYL101, respectively. They showed 100% stability even during PHB synthesis and accumulation over 110 generations. All four plasmids were structurally stable. The final cell mass, PHB concentration, and PHB per dry cell weight (P/X, w/w, %) of 101.4 g l-1, 81.2 g l-1, and 80.1%, respectively, were obtained in 39 h by high cell density culture of XL1-Blue (pSYL104). The final PHB concentration was lower using XL1-Blue (pSYL103), which suggested that high gene dosage was required for the synthesis and accumulation of PHB to a high concentration in E. coli.


Dissection of human allostimulatory determinants with cloned T cells: stimulation inhibition by monoclonal antibodies TU22, 34, 35, 36, 37, 39, 43, and 58 against distinct human MHC class II molecules.
Alloantigenic determinants causing secondary lymphoproliferative responses of primed T cells were investigated by blocking stimulation with monoclonal antibodies TU22, 34, 35, 36, 37, 39, 43, and 58 binding differentially to HLA-DR and SB or MB associated molecules. In particular, the use of cloned and functionally defined T cell responders greatly facilitated the assignment of stimulator-level inhibition caused by these antibodies. Thus, a novel way of functional "mapping" for stimulatory epitopes for sets of clones with restimulation specificities associated with HLA-D, SB, MB, or hitherto unidentified class II determinants is presented here. This considerably helps to elucidate the distinct immunoregulatory roles of the three major class II alloantigen systems thus far defined.


Effect of morphine on the rat gastrointestinal cholinergic enzymes.
Male Sprague-Dawley rats weighing approximately 225 g and maintained under controlled lighting and temperature conditions, were used in this experiment. Animals were given morphine (10 mg/kg, i.p.) either at 10:00 hr or at 22:00 hr. One hour later, treated animals with their proper control were sacrificed and the mucosa of the stomach, duodenum, ileum and colon were separated and assayed for acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities. Data obtained indicate that morphine administration during the light phase resulted in a significant increase (p less than 0.01) in AChE activity in the colon, with no significant effect on the stomach, duodenum or the ileum. There was also significant increase (p less than 0.05) in ChAT activity in the stomach and the duodenum as a result of morphine administration during the light phase, with no effect on other tissues studied. During the dark phase, there were no significant changes observed in AChE activity of all tissues examined following morphine administration. However, the determination of ChAT activity during the dark phase, following morphine treatment, showed a significant increase (p less than 0.01) in the duodenum and the ileum, with a significant decline (P less than 0.05) in the colon. Results obtained from this study indicate that gastrointestinal changes seen after morphine administration could be due to changes in the activity of the cholinergic enzymes and these changes may be diurnally controlled.


[Pulmonary infection in the emphysematous bulla due to Mycobacterium szulgai diagnosed by percutaneus needle aspiration].
A 73-year-old male was admitted to our hospital because of productive cough and infiltrate on the chest roentogenogram. The underlying diseases was found to be multiple myeloma. He received a physical examination in June, 1996. The chest X-ray and CT scan on admission showed an infiltrative shadow with multiple bulla in the left upper lung field. Internal use of antibiotics and drip infusion of IPM/CS were ineffective. The chest X-ray showed air-fluid level in left upper peripheral bullous lesion and a percutaneus needle aspiration of the lung was performed. The specimen was pus with blood and microscopical examination of smears revealed no acid-fast bacilli, but Mycobacterium szulgai was isolated and identified by DNA-DNA hybridization method. The patient was treated with isoniazid and rifampicin, and improved in a few months. There are a few case reports of pulmonary infection due to M. szulgai associated with emphysematous bulla of the lung in Japan. M. szulgai infection of the lung is similar to M. kansasii infection in respect to clinical features (improvement of chest abnormal shadow, efficacy of drug).


Effects of nitroglycerin on the diagnostic accuracy of electrocardiogram-gated coronary computed tomography angiography.
To evaluate the effect of nitroglycerin on the diagnostic accuracy of electrocardiogram-gated coronary computed tomography (CT) angiography in patients with suspected coronary artery disease. Computed tomography angiography was performed on 76 patients using a 16-slice CT scanner. Forty-six patients received a sublingual nitroglycerin 1 minute before CT scanning (the NTG group), but the other 30 did not (the non-NTG group). No statistically significant differences were evident between these 2 groups in terms of clinical and demographic characteristics. Significant stenosis (> or =50% diameter reduction) as determined by CT was evaluated according to patient-based and segment-based analyses, and results were compared with conventional coronary angiographic findings. In addition, segments of the coronary artery were reclassified by segment luminal size into proximal, mid, and distal segments, and the diagnostic accuracies of the NTG and non-NTG approaches were evaluated in these segments. Differences in heart rate, and systolic and diastolic blood pressures before and after using nitroglycerin were 1.0 +/- 2.4 beats per minute, -8.3 +/- 14.4 mm Hg, and -4.6 +/- 10.6 mm Hg, respectively. Sensitivity, specificity, and positive and negative predictive values in the NTG group were higher than in the non-NTG group by patient-based analysis (P = 0.25) and by segment-based analysis (P < 0.05). In addition, based on the luminal size of each segment, diagnostic accuracy in the NTG group was significantly higher for proximal segments than in the non-NTG group (96.7% vs 89.7%; P < 0.05). The use of nitroglycerin was found to be safe and to improve the diagnostic accuracy of coronary CT angiography for the evaluation of coronary artery disease.


Edetate Disodium as a Polysorbate Degradation and Monoclonal Antibody Oxidation Stabilizer.
Polysorbates are frequently used in biotherapeutic formulations. Interest in assessing their stability, in particular the impact of their degradation products on the stability of therapeutic proteins, has been steadily growing in the past decade. The work presented summarizes a case study of a monoclonal antibody formulation that demonstrated a simultaneous loss of polysorbate and an increase in methionine oxidation. Spiking studies were conducted to determine both the cause and a potential mitigation for the monoclonal antibody (mAb) oxidation and polysorbate 80 (PS80) loss. The results indicated that a different source material exhibited different rates of mAb oxidation and PS80 loss and that in all evaluated materials, the addition of edetate disodium to the formulation mitigated both observed issues. The mAb was assessed for the presence of lipases and lipoprotein lipase was detected at low levels. It is proposed that edetate disodium was effective in mitigating the mAb oxidation and PS80 loss by chelating calcium in the formulation and therefore decreasing the activity of the lipases.


Practicing a Structured Continuous Key-Pressing Task: Motor Chunking or Rhythm Consolidation?
An experiment is reported on the effects of extensive practice in a task in which subjects (N = 36) pressed a succession of nine keys with nine separate fingers, each key press in response to a corresponding stimulus. The order of the key presses remained constant over practice. Key-pressing cycles followed each other without interruption. A stimulus was usually presented immediately upon depressing the previous key, but in the structured conditions a stimulus was preceded at either two (the 45 group) or three (the 333 group) positions by a 750-ms response-stimulus interval (RSI). This partitioned the sequence into three response groups for subjects in the 333 condition and into two response groups for subjects in the 45 condition. On occasion, all subjects performed in the unstructured condition, in which RSls were zero. Interkey times in this condition clearly reflected the position of the 750-ms RSls in the structured conditions. This suggests that motor chunks developed in the structured conditions were also used in the unstructured condition. Rhythm-based control, as proposed by Summers (1975), was rejected as an explanation for this effect because group-start-within-group ratios exceeded 2:1 and because the theory of rhythm-based control could not predict intervals in the unstructured 45 condition. Unstructured within-group intervals were slower than structured within-group intervals, which effect was more pronounced in the 333 than in the 45 condition. Also, the initial element of the unstructured four-key group was faster than the initial element of the unstructured three-key group. These and other findings (a) accord with the notion that in unstructured sequences preparing a forthcoming response group concurs with the execution of the preceding group and (b) suggest that shorter groups are more slowed by concurrent preparation for the forthcoming group than are longer groups.


A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.
Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10(-9)), 4q26 (rs6858698, P = 3.07 × 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.


Epworth sleepiness scale scores and adverse pregnancy outcomes.
Snoring is associated with adverse pregnancy outcomes including gestational hypertensive disorders, gestational diabetes, and Cesarean deliveries. The purpose of this study was to assess whether excessive daytime sleepiness (EDS) assessed by Epworth Sleepiness Scale (ESS) increases the risk of these complications further. Following institutional review board approval and informed consent, English-speaking women in the immediate postpartum period were systematically selected and recruited. Women answered a survey that included questions regarding symptoms of sleep-disordered breathing (SDB) using the multivariable apnea prediction index and excessive daytime sleepiness using ESS. Pregnancy and fetal outcomes were collected by review of medical records. Standard statistical analysis with multivariable logistic regression was performed. ESS was evaluated both as a continuous variable and with various cutoffs given that pregnant women are likely more sleepy at baseline than the general population. In patients who underwent planned Cesarean delivery, mean ESS was significantly higher than in those with uncomplicated vaginal delivery, even after adjusting for confounders (adjusted odds ratio (aOR), 1.08; 95 % CI, 1.01-1.15; p = 0.02). There was no significant association between EDS (defined as ESS of >10) and gestational diabetes or gestational hypertensive disorders in snorers or non snorers. However, a significant association with gestational diabetes was found in patients with an ESS of >16 compared to those with an ESS of ≤16, even after multiple adjustments (aOR, 6.82; 95 % CI, 1.19-39.27), but the number of subjects in an ESS of >16 category was small. There is an increased association between women with higher ESS and planned Cesarean delivery. Severe EDS was associated with gestational diabetes in pregnant women in a small sample size. Future studies in larger samples need to confirm the association of severe EDS and gestational diabetes and elucidate potential mechanisms of the links with adverse outcomes.


Autoradiographic analysis of [3H]Ryanodine binding sites in rat brain: regional distribution and the effects of lesions on sites in the hippocampus.
Quantitative and qualitative autoradiographic methods together with lesion approaches were used to determine the distribution of [3H]ryanodine binding sites in rat brain and the neuronal localization of these sites in the hippocampus. In normal animals, levels of [3H]ryanodine binding sites ranged from a low of about 1 fmol/mg tissue in subcortical structures to a high of 12-18 fmol/mg tissue in subregions of the hippocampus and the olfactory bulb. Relatively high densities of sites (5-9 fmol/mg tissue) were also seen in the olfactory tubercle, most areas of the cerebral cortex, accumbens nucleus, striatum, lateral septal nuclei, pontine nucleus, superior colliculus and granule cell layer of the cerebellum. Specific binding was undetectable in white matter. In experimental animals, intracerebral injections of kainic acid caused neuronal degeneration and a near total depletion of [3H]ryanodine binding sites in the dentate gyrus and in fields CA1, CA2 and CA3 of the hippocampus. Injections of kainic acid that left dentate granule cells largely intact while destroying all neurons in field CA3 had no effect on binding sites in the dentate gyrus. However, these lesions substantially reduced the density of binding in field CA3, leaving a narrow band of sites outlining the position of the degenerated CA3 pyramidal cells. Mechanical knife-cut lesions that severed the granule cell mossy fiber input to field CA3 reduced the density of binding sites in the CA3 region. The results indicate that [3H]ryanodine binding sites in brain are heterogeneously distributed and suggest that a proportion of these sites in the hippocampus may be contained in mossy fiber terminals where a presumptive calcium channel/ryanodine receptor complex may be involved in the regulation of calcium mobilization and/or neurotransmitter release.


Cloning of NAD-SDH cDNA from plum fruit and its expression and characterization.
A full-length cDNA consisting of 1444 bp for NAD dependent sorbitol dehydrogenase (NAD-SDH) was cloned from fruit of plum (Prunus salicina var. cordata cv. Younai) by means of RT-PCR and RACE. The cDNA containing an open reading frame (ORF) of 1101 bp encoded a polypeptide of 367 amino acid residues. The maltose binding protein fusion SDH (MBP-SDH) was expressed and partially purified from Escherichia coli cells, and biochemical properties of MBP-SDH and SDH cleaved from the fusion protein by factor Xa were characterized. The MBP-SDH had the specific affinity for NAD and was able to oxidize sorbitol, xylitol, l-ribitol and mannitol but not ethyl alcohol, arabitol and other polyols. The optimum pH for the oxidation of sorbitol and the reduction of fructose was 9.0 and 7.0, respectively; the maximum reaction rate occurred when temperature increased up to 50 °C in the presence of sorbitol. The MBP-SDH with a subunit of 80 kDa appears to be a hexamer. Its molecular weight was 478.6 kDa estimated by gel filtration and 493.2 kDa estimated using native linear gradient PAGE. The K(m) values for sorbitol, NAD, fructose and NADH were 95.86 mM, 0.31 mM, 1.04 M and 0.038 mM, respectively. However, when MBP was cleaved from the fusion enzyme, the SDH exists as a homotetramer with the native molecular weight of 164.8 kDa estimated by gel filtration. The K(m) values were 111.8 mM, 0.35 mM, 1.25 M and 0.048 mM for sorbitol, NAD, fructose and NADH, respectively. The MBP-SDH and the SDH were similar with respect to their kinetic characteristics despite their difference in quaternary structures.


Increased serum phenytoin concentration following influenza vaccination.
The effect of influenza vaccination on serum phenytoin concentration was studied in a group of long-term care patients with epilepsy. The subjects in this study were 15 men and 1 woman with a mean age of 76.7 years. All were white, receiving long-term phenytoin therapy for seizure disorders, on stable antiepileptic regimens for a minimum of eight weeks, and scheduled to receive an influenza vaccination. Baseline phenytoin concentrations were determined one or two days before vaccination. Subjects were vaccinated subcutaneously with 0.5 ml of an inactivated whole-virion trivalent influenza vaccine. Phenytoin therapy was maintained, and serum concentrations were determined on days 7 and 14 following the vaccination. Assays were performed with a standard enzyme immunoassay technique. No significant increases in mean serum phenytoin concentrations were observed on days 7 or 14 following vaccination. However, temporary increases of 46-170% occurred in four subjects, and in two of these subjects, the increases in serum phenytoin concentration could best be attributed to the influenza vaccination. Serum phenytoin concentrations may be temporarily increased in some individuals after influenza vaccination.


Occupational risk factors for sarcoidosis in African-American siblings.
To determine whether certain occupations and occupationally related exposures were associated with a history of sarcoidosis in African-American siblings. We collected occupational data from 921 African Americans in 273 sibships that had been identified through a sarcoidosis case. Among the 648 siblings of sarcoidosis index cases enrolled, 30 (4.6%) also had a history of sarcoidosis. A detailed job history was obtained for any job held for > or = 6 months throughout the subject's life. Having a usual occupation in education (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07 to 4.44), in metal machining (OR, 7.47; 95% CI, 1.19 to 47.06), and ever working in metalworking, not elsewhere classified (OR, 2.05; 95% CI, 1.14 to 3.70) were associated with increased sarcoidosis risk. Occupations ever held in the transportation services industry (OR, 12.71; 95% CI, 1.32 to 122.56) and usual occupations in the retail trade industry (OR, 0.49; 95% CI, 0.27 to 0.88) also were associated with sarcoidosis risk. Specific occupational exposures that were associated with sarcoidosis included titanium (OR, 3.15; 95% CI, 1.02 to 9.68) and vegetable dust (OR, 1.82; 95% CI, 1.01 to 3.27), and indoor exposure to high humidity (OR, 1.51; 95% CI, 1.13 to 2.02), water damage (OR, 1.50; 95% CI, 1.11 to 2.03), or musty odors (OR, 1.78; 95% CI, 1.32 to 2.40) for > 1 year. Individuals who work in occupations with potential metal exposures or in workplaces with high humidity may be at an increased risk for sarcoidosis, but the complexity of occupationally related exposures makes it difficult to identify specific agents by using job titles as a surrogate for exposure. A more detailed exposure assessment of such jobs, along with the incorporation of genetic risk factors, should help to uncover the complex etiology of sarcoidosis.


Variable Neighborhood Search with Cost Function Networks To Solve Large Computational Protein Design Problems.
Computational protein design (CPD) aims to predict amino acid sequences that fold to specific structures and perform desired functions. CPD depends on a rotamer library, an energy function, and an algorithm to search the sequence/conformation space. Variable neighborhood search (VNS) with cost function networks is a powerful framework that can provide tight upper bounds on the global minimum energy. We propose a new CPD heuristic based on VNS in which a subset of the solution space (a "neighborhood") is explored, whose size is gradually increased with a dedicated probabilistic heuristic. The algorithm was tested on 99 protein designs with fixed backbones involving nine proteins from the SH2, SH3, and PDZ families. The number of mutating positions was 20, 30, or all of the amino acids, while the rest of the protein explored side-chain rotamers. VNS was more successful than Monte Carlo (MC), replica-exchange MC, and a heuristic steepest-descent energy minimization, providing solutions with equal or lower best energies in most cases. For complete protein redesign, it gave solutions that were 2.5 to 11.2 kcal/mol lower in energy than those obtained with the other approaches. VNS is implemented in the toulbar2 software. It could be very helpful for large and/or complex design problems.


Prediction models for transfer of arsenic from soil to corn grain (Zea mays L.).
In this study, the transfer of arsenic (As) from soil to corn grain was investigated in 18 soils collected from throughout China. The soils were treated with three concentrations of As and the transfer characteristics were investigated in the corn grain cultivar Zhengdan 958 in a greenhouse experiment. Through stepwise multiple-linear regression analysis, prediction models were developed combining the As bioconcentration factor (BCF) of Zhengdan 958 and soil pH, organic matter (OM) content, and cation exchange capacity (CEC). The possibility of applying the Zhengdan 958 model to other cultivars was tested through a cross-cultivar extrapolation approach. The results showed that the As concentration in corn grain was positively correlated with soil pH. When the prediction model was applied to non-model cultivars, the ratio ranges between the predicted and measured BCF values were within a twofold interval between predicted and measured values. The ratios were close to a 1:1 relationship between predicted and measured values. It was also found that the prediction model (Log [BCF]=0.064 pH-2.297) could effectively reduce the measured BCF variability for all non-model corn cultivars. The novel model is firstly developed for As concentration in crop grain from soil, which will be very useful for understanding the As risk in soil environment.


[The value of corpus cavernosum sonography following administration of vasoactive substances in the diagnosis of patients with erectile impotence].
In 70 Patients with erectile dysfunction, ultrasound examination of both corpora cavernosa after intracavernous injection of papaverine was done using B-scan, Duplex scan and Doppler color. B-scan can detect morphological disease in a penis profundis, the higher degrees of cavernous muscle myopathia, and disease of the tunica albuginea. For the analysis of pulse curve and the measurement of blood-flow velocity, the Duplex scan is necessary. Doppler color imaging enables ultra sonographic examination of a dorsalis and a penis profundis and can detect intracavernous vascular pathology. The results show that ultrasonography is an important diagnostic tool in patients with erectile dysfunction. A differentiated therapeutic strategy can be based on this examination, especially when revascularization procedures are being discussed. Additionally, better follow-up of patients under self-injection therapy is possible.


Mediators in psychological treatment of social anxiety disorder: individual cognitive therapy compared to cognitive behavioral group therapy.
According to cognitive-behavioral models of social anxiety disorder (SAD), four of the important maintaining mechanisms are avoidance, self-focused attention, anticipatory processing and post-event cognitive processing. Individual cognitive therapy (ICT) and cognitive behavioral group therapy (CBGT) both have substantial empirical support. However, it is unclear whether they achieve their effects by similar or different mechanisms. The aim of this study was to investigate whether changes in the four maintenance processes mediate clinical improvement in ICT and CBGT for SAD. We analyzed data from participants (N = 94) who received either ICT or CBGT in two separate RCTs. The results showed that ICT had larger effects than CBGT on social anxiety and each of the four potential mediators. More pertinently, moderated mediation analyses revealed significant between-treatment differences. Whereas improvement in ICT was mainly mediated by reductions in avoidance and self-focused attention, improvement in CBGT was mediated by changes in self-focused attention and in anticipatory and post-event processing. These results support the importance of the putative mediators, but suggest that their relative weights are moderated by treatment type.


Toxicity and adaptation of Dictyosphaerium chlorelloides to extreme chromium contamination.
Metals are often spilled by industries into inland water environments, with adverse consequences. Numerous papers have reported that heavy metals produce massive destruction of algae. Nevertheless, algal populations seem to become tolerant when they have had previous exposures to heavy metals. Because the mechanisms allowing heavy metal tolerance of algae are not yet known, the present study analyzed the effect of hexavalent chromium on growth and photosynthetic performance of Dictyosphaerium chlorelloides, stressing on the adaptation mechanisms to chromium contamination. Growth and photosynthetic performance of algal cells were inhibited by Cr(VI) at 10 mg/L, and the 72-h median inhibition concentration was established as 1.64 and 1.54 mg/L, respectively. However, after further incubation for a three month period in an environment with 25 mg/L of chromium, some rare, chromium-resistant cells occasionally were found. A Luria-Delbrück fluctuation analysis was performed to distinguish between resistant algae arising from rare, spontaneous mutations and resistant algae arising from physiological adaptation and other adaptive mechanisms. Resistant cells arose only by spontaneous mutations before the addition of chromium, with a rate of 1.77 x 10(-6) mutants per cell division. From a practical point of view, the use of both chromium-sensitive and chromium-resistant genotypes could make possible a specific algal biosensor for chromium.


[Development of early erythroid precursors (BFUe) from mouse bone marrow in a serum-free culture media. Effect of hemin].
In culture medium containing albumin, iron saturated transferrin, phospholipids, cholesterol and erythropoietin, BFUe growth requires foetal Calf serum. Without serum the BFUe development is advantageously restored by the addition of hemin associated with spleen conditioned medium. In erythropoietin supplemented serum-free medium the growth of primitive erythroid precursor cells is closely dependent on growth factor supply found in spleen conditioned medium. Using this medium allows us to clearly distinguish between the respective effects of erythropoietin and of BPA on erythroid progenitor cells.


Clinical pharmacology and malaria.
The role of clinical pharmacology in improving the prevention and treatment of malaria is reviewed. A series of general and specific issues is discussed, concentrating on risk-benefit and cost-effectiveness. The techniques of clinical pharmacokinetics play an important role in the optimal use of drugs and this is illustrated by studies on quinine and proguanil. In discussing amodiaquine toxicity, the role of the pharmacologist and the chemist in designing out drug toxicity lends hope for producing a new generation of antimalarial drugs.


Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.
In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups.


Minilaparoscopic fundoplication: technical adaptations and initial experience.
Gastroesophageal reflux disease (GERD) is a highly prevalent disease. Treatment is divided into lifestyle modifications, medical and surgical treatment. Surgical laparoscopy is the gold standard treatment. In the last decade, there were an extensive research on procedures, less aggressive than laparoscopy and with better esthetic results. Minilaparoscopy is "reemerging" as a safe, effective and with excellent cosmetic results in selected patients treated for gastroesophageal reflux disease. We present a serie of 27 patients treated for GERD by minilaparoscopic laparoscopy. Between October 2009 July 2011 a total of 27 patients underwent fundoplication by minilaparoscopy. It is used one 10mm trocar, a telescope of 30 degrees and four 3 mm trocars at regular positions. Regular surgical steps are done with no modifications. Cardiac tape, suture needles, and eventually extracting bag, gauze, are placed and taken out through the umbilical port. With these technical adjustments, we can perform the procedure safely and effectively, similarly to standard laparoscopic technique. Of the 27 patients, 22 were female and 5 male. The average body mass index was 25.5 kg/m². Hiatal hernias were small (<3 cm) in 24 patients. Mean operative time was 60 minutes. In all cases the hiatoplasty was performed with simple or 'x' stitches of 2.0 Ethibond. There was no need for conversion to standard laparoscopy or open surgery. The length of hospital stay was less than or equal to 24 hours in all patients. In this series of patients there were no postoperative complications. We did not observe any complication of the surgical wound. There were no evidence of recurrence of symptoms or endoscopic changes. Hiatoplasty associated with fundoplication using minilaparoscopic instruments is safe, feasible and effective. If compared to other "new access", has a spectacular esthetic results. Can be done with only minor technical adjustments, for any experienced laparoscopic surgeon, and is perfectly adaptable to our financial reality.