[Doping and sports].
Doping is widely known as the use of banned substances and practices by athletes in an attempt to improve sporting performances. The term doping likely derives from "dope", an ancient expression referred to a primitive alcoholic drink that was used as a stimulant in South African ceremonial dances; gradually, the term was extended and finally adopted his current significance. There are at least two essential reasons to support the fight against doping: the potential harmful effects on athletes and the depth corruption of the fair competition. An exhaustive list of banned substances and methods has been drawn by the International Olympic Committee and further accepted by other International Sport Authorities and Federations. This list, regularly updated, is basically divided into doping substances (stimulants, narcotic analgesics, anabolic agents, diuretics, peptide and glycoprotein hormones and analogues), doping methods (blood doping, pharmacological, chemical and physical manipulation) and drugs subjected to certain restrictions (alcohol, marijuana, local anesthetics, corticosteroids and beta-blockers). Although there might be some medical conditions, which could legitimate the need of these substances or methods, there is no place for their use in sport. Thus, an athlete's consume of any of these substances or methods will result in disqualification. Aim of the present review is to provide a synthetic description of both the desirable effects and the potentially harmful consequences of the use of some of the major doping substances and methods.


FoxO1 regulates adipose transdifferentiation and iron influx by mediating Tgfβ1 signaling pathway.
Adipose plasticity is critical for metabolic homeostasis. Adipocyte transdifferentiation plays an important role in adipose plasticity, but the molecular mechanism of transdifferentiation remains incompletely understood. Here we show that the transcription factor FoxO1 regulates adipose transdifferentiation by mediating Tgfβ1 signaling pathway. Tgfβ1 treatment induced whitening phenotype in beige adipocytes, reducing UCP1 and mitochondrial capacity and enlarging lipid droplets. Deletion of adipose FoxO1 (adO1KO) dampened Tgfβ1 signaling by downregulating Tgfbr2 and Smad3 and induced browning of adipose tissue in mice, increasing UCP1 and mitochondrial content and activating metabolic pathways. Silencing FoxO1 also abolished the whitening effect of Tgfβ1 on beige adipocytes. The adO1KO mice exhibited a significantly higher energy expenditure, lower fat mass, and smaller adipocytes than the control mice. The browning phenotype in adO1KO mice was associated with an increased iron content in adipose tissue, concurrent with upregulation of proteins that facilitate iron uptake (DMT1 and TfR1) and iron import into mitochondria (Mfrn1). Analysis of hepatic and serum iron along with hepatic iron-regulatory proteins (ferritin and ferroportin) in the adO1KO mice revealed an adipose tissue-liver crosstalk that meets the increased iron requirement for adipose browning. The FoxO1-Tgfβ1 signaling cascade also underlay adipose browning induced by β3-AR agonist CL316243. Our study provides the first evidence of a FoxO1-Tgfβ1 axis in the regulation of adipose browning-whitening transdifferentiation and iron influx, which sheds light on the compromised adipose plasticity in conditions of dysregulated FoxO1 and Tgfβ1 signaling.


Human paraoxonase-1 activity in childhood obesity and its relation to leptin and adiponectin levels.
Childhood obesity is a predisposing factor for adult cardiovascular diseases. Human serum paraoxonase (PON1) may protect against atherosclerosis by hydrolyzing lipid peroxides in oxidized LDL. Alterations and potential correlations of PON1 activities, leptin and adiponectin levels in childhood obesity were studied. We measured PON1 paraoxonase and arylesterase activities, anthropometric parameters, leptin and adiponectin levels in 59 white, obese (obese group-OB: BMI corrected for age: 95.1 +/- 3.5 percentile, age: 11.9 +/- 1.6 y) and 51 normal-weight children (control group-C: BMI corrected for age: 64.1 +/- 8.4 percentile, age: 12.0 +/- 3.9 y). Obese children had significantly lower PON1 paraoxonase (OB: 84.80 (64.33/144.74) U/L versus. C: 99.42 (83.33/152.05) U/L; p < 0.05) and arylesterase activities (OB: 94.40 (82.20/108.70) U/L versus. C: 115.20 (93.70/126.00) U/L; p < 0.01), higher leptin (OB: 37.05 (24.33/53.87) ng/mL versus. C: 4.62 (2.52/17.6) ng/mL; p < 0.0001) and lower adiponectin levels (OB: 7.56 (5.69/12.06) microg/mL versus. C: 11.51 (8.84/14.49) microg/mL; p < 0.001) compared with the normal-weight group. PON1 arylesterase activity showed inverse univariate correlation with leptin (r = -0.29; p < 0.05) and positive correlation with adiponectin levels (r = 0.39; p < 0.01). In multiple regression analysis adiponectin was strongly associated with PON1 arylesterase activity in obese children (beta = 0.45, p < 0.02). Our results emphasize the importance of the investigated metabolic alterations which may have further effects on cardiovascular morbidity and mortality in later adulthood. Altered levels of leptin, adiponectin and PON1 activities may be useful markers beside the general risk factors in childhood obesity.


Screening of mushrooms from the woodlands of Zimbabwe: Occurrence of lectins and partial purification of a mucin specific lectin from Boletus edulis.
Mushrooms are known to possess a diversity of bioactive compounds that include lectins, which are proteins or glycoproteins that bind specifically to cell surface carbohydrates, culminating in cell agglutination. The present study describes the screening of lectin activity from ten local mushrooms, namely, Amanita zambiana, Boletus edulis, Cantharellus heinemannianus, Cantharellus miomboensis, Cantharellus symoensii, Lactarius kabansus, Amanita sp., Coprinus sp., Ganoderma lucidum and Trametes strumosa. The lectin content was detected by the haemagglutination activity of mushrooms against sheep and goat erythrocytes. Among the different mushrooms screened Amanita sp., Boletus edulis and Lactarius kabansus showed high lectin activity (39, 617 and 77 HAU/mg mushroom, respectively). Boletus edulis was used for the haemagglutination inhibition assay. A total of twenty sugars and sugar derivatives, namely, α-lactose, D-glucose, D-mannose, D-raffinose, N-acetyl glucosamine, maltose, melibiose, D-ribose, porcine mucin, D-cellobiose, D-arabinose, α-methyl-D-glucoside, methyl-α-D-mannopyranoside, D-trehalose, L-arabinose, L-sorbose, L-lyxose, β-lactose, DL-xylose, and D-galactose, were used for the haemagglutination inhibition assay. Of the various carbohydrates tested, only porcine mucin was found to be the most potent inhibitor of Boletus lectin. The lectin from Boletus mushroom was partially purified using ammonium sulphate precipitation. The highest lectin activity was observed in the 30%-60% fraction. This study revealed for the first time the occurrence of lectins in the local Zimbabwean mushrooms studied as well as isolation of a novel mucin-specific lectin. The information obtained can be used for further investigation of cell surface sugars, purification and characterisation of glycoproteins and their contribution towards the medicinal properties of local mushrooms.


The comparison of cortical activation patterns by active exercise, proprioceptive input, and touch stimulation in the human brain: a functional MRI study.
Active execution, proprioception, and touch discrimination are important for the execution of movement. In the current study, we attempted to compare the cortical activation patterns of active exercise, proprioceptive input, and touch stimulation in the normal human brain using functional MRI. Nine subjects were recruited for this study. Functional MRI was performed using 1.5-T with three tasks at a fixed rate. The active exercise and proprioceptive input were performed at the metacarpophalangeal joint using a specially equipped apparatus, and touch stimulation was applied on the dorsum of the hand using a rubber brush. We performed analysis using the region of interest (ROI) method, and calculated the laterality index (LI) to assess the relative activity in the ipsilateral versus the contralateral ROI. When active exercise or proprioceptive input were applied, the LI in the primary sensorimotor cortex (SM1) was significantly higher than that of touch stimulation. The supplementary motor cortex, cerebellum, and contralateral SM1 showed stronger activation during active exercise than during proprioceptive input or touch stimulation, and the opposite pattern was observed in the insula. We found that the LIs of active exercise and proprioceptive input were higher than the LI of touch stimulation. This suggest that touch stimulation may be a less lateralized function than active exercise and proprioceptive input.


A Comparison Study of Doctor-Patient Internet Interactions in Traditional and Modern Medicine: Empirical Evidence from Online Healthcare Communities.
Online healthcare platforms serve not just as a medical knowledge-sharing community but also bring about effective interactions between professional physicians and patients. However, it is unclear whether online technology adoption affects such interactions in the same way between traditional Chinese medicine and modern medical departments. By utilizing a large sample of online doctor-patient interaction information from 168,870 doctor-specific interactive webpages recorded in a famous Chinese online healthcare community, this paper studies the differences between 17,513 traditional medicine doctor homepages and 151,357 others from more than 100 different specialty areas. Our chosen platform is representative since it covers about 800,000 physicians working at over 10,000 hospitals across all major provincial regions in China. We document that online medical service users tend to accept and use online health care services. However, patients seeing Chinese medicine doctors exhibit the following unique characteristics. They still prefer choosing doctors according to third-party information and may be reluctant to pay for the current online service price level. This problem is hard to overcome by the platform in the short run. Patients need a long-term process to adapt to the upgraded medical environment gradually. Therefore, establishing a personalized doctor recommendation system has become the most urgent demand presently.


Out of the picture: a study of family drawings by children from step-, single-parent, and non-step families.
Investigated the family drawings of 180 children ages 5 to 7 years in various family settings, including stepfather, single-parent, complex stepfamilies, and 2-parent control families. The relations of family type and biological relatedness to omission of family members and grouping of parents were examined. Children from step- and single-parent families were more likely to exclude family members than children from "control" non-step families, and exclusion was predicted from biological relatedness. Children who were biologically related to both resident parents were also more likely to group their parents together. Omission of family members was found to be associated with children's adjustment (specifically more externalizing and internalizing behavior) as reported by teachers and parents. The results indicate that biological relatedness is a salient aspect of very young children's representations of their families. The association between adjustment and exclusion of family members and grouping of parents indicates that family drawings may be useful research and clinical tools, when used in combination with other methods of assessment.


Epigenetic regulation of microRNA-375 and its role in melanoma development in humans.
To identify epigenetically regulated miRNAs in melanoma, we treated a stage 3 melanoma cell line WM1552C, with 5AzadC and/or 4-PBA. Several hypermethylated miRNAs were detected, one of which, miR-375, was highly methylated and was studied further. Minimal CpG island methylation was observed in melanocytes, keratinocytes, normal skin, and nevus but hypermethylation was observed in patient tissue samples from primary, regional, distant, and nodular metastatic melanoma. Ectopic expression of miR-375 inhibited melanoma cell proliferation, invasion, and cell motility, and induced cell shape changes, strongly suggesting that miR-375 may have an important function in the development and progression of human melanomas.


[Association of polymorphic variants in endothelin-1 (EDN1) genes with the therapy of patients with cutaneous T-cell lymphomas].
The cutaneous T-cell lymphomas (CTCL) are diseases characterised by cutaneous infiltrates of malignant, clonally expanded T-cells. Because individual genetic determination of angiogenetic and antioxidant properties of blood vessels could take part in responsibility to phototherapy in CTCL patients, the association of two frequent polymorphisms in endothelin-1 gene with phototherapy was tested. 77 patients with CTCL, diagnosed and treated at the First Dermatological Clinic of St. Ann's Faculty Hospital Bmo (46 men and 31 women, median age 62, range 28-82 years) were included in the study. Diagnosis of CTCL according to the clinical picture was verified histologically. The genotype distributions and allelic frequencies between CTCL with phototherapy and those without phototherapy were compared. The 4A4A variant of -3A/-4A EDN1 is more frequent in patients treated with phototherapy (8/30 vs. 1/38, OR=10.13; P=0.01). The GA and AA genotypes of G8002A EDN1 polymorphism are more frequent in CTCL patients treated with phototherapy compared to those without it (15/23 vs. 7/32, OR=2.98; P=0.03). Some polymorphic variants in EDN1 genes, a homozygote -4A-4A in -3A/-4A EDN1 and genotypes GA and GG in G8002A EDN1) seem to carry an advantage for phototherapy effectiveness in patients with CTCL.


Cryptogenic Liver Abscess Caused by a K1 Serotype Klebsiella pneumoniae Isolate.
Hypervirulent Klebsiella pneumoniae (hvKp) is a common cause of pyogenic liver abscesses in Asia but is quite uncommon in North America. Among the cases described in North America, only occasional reports have described molecular strain typing to confirm the K1 strain as the causative agent. We report a 56-year-old Hispanic female with no previous intra-abdominal pathology and no recent travel, who presented with subacute abdominal pain and developed bacteremia and monomicrobial pyogenic liver abscess due to a community-acquired K1 serotype K. pneumoniae isolate. In this case, the infection was recognized early, so the patient was successfully treated with percutaneous drainage and prolonged antibiotic therapy. Hvkp can cause severe invasive disease with high morbidity and mortality, and the recent emergence of multidrug resistance in these strains poses a serious threat to public health. In addition, the isolation of a K1 K. pneumoniae strain from a cryptogenic liver abscess in a Hispanic patient with no epidemiologic risk factors raises concern for a wider spread of the hypervirulent strain beyond Asian populations. Therefore, a high index of suspicion for hvKp infection in the Hispanic population can be crucial as the hypervirulent strain is likely to cause severe metastatic infection with significant morbidity and mortality.


The human embryonic stem cell-derived cardiomyocyte as a pharmacological model.
Embryonic stem (ES) cells are specialised cells derived from the early embryo, which are capable of both sustained propagation in the undifferentiated state as well as subsequent differentiation into the majority of cell lineages. Human ES cells are being developed for clinical tissue repair, but a number of problems must be addressed before this becomes a reality. However, they also have potential for translational benefit through its use as a test system for screening pharmaceutical compounds. In the cardiac field, present model systems are not ideal for either screening or basic pharmacological/physiological studies. Cardiomyocytes produced from human ES differentiation have advantages for these purposes over the primary isolated cells or the small number of cell lines available. This review describes the methodology for obtaining cardiomyocytes from human embryonic stem cell-derived cardiomyocyte (hESCM), for increasing the proportion of cardiomyocytes in the preparation and for isolating single embryonic stem cell-derived cardiomyocyte (ESCM) from clusters. Their morphological, contractile and electrophysiological characteristics are compared to mature and immature primary cardiomyocytes. The advantages and disadvantages of the hESCM preparation for long term culture and genetic manipulation are described. Basic pharmacological studies on adrenoceptors and muscarinic receptors in hESCM have been performed, and have given stable and reproducible responses. Prolongation of repolarisation can be detected using hESCM cultured on multielectrode arrays (MEA). Human ESCM have a clear potential to improve model systems available for both basic scientific studies and pharmaceutical screening of cardiac target compounds.


Stress response and humoral immune system alterations related to chronic hypergravity in mice.
Spaceflights are known to induce stress and immune dysregulation. Centrifugation, as hindlimb unloading, is a good ground based-model to simulate altered gravity which occurs during space missions. The aim of this study was to investigate the consequences of a long-term exposure to different levels of hypergravity on the stress response and the humoral immunity in a mouse model. For this purpose, adult C57Bl/6J male mice were subjected for 21 days either to control conditions or to 2G or 3G acceleration gravity forces. Corticosterone level and anxiety behavior revealed a stress response which was associated with a decrease of body weight, after 21-day of centrifugation at 3G but not at 2G. Spleen lymphocyte lipopolysaccharide (LPS) responsiveness was diminished by 40% in the 2G group only, whereas a decrease was noted when cells were stimulated with concanavalin A for both 2G and 3G groups (about 25% and 20%, respectively) compared to controls. Pro-inflammatory chemokines (MCP-1 and IP-10) and Th1 cytokines (IFNγ and IL2) were slightly decreased in the 2G group and strongly decreased in the 3G mouse group. Regarding Th2 cytokines (IL4, IL5) no further significant modification was observed, whereas the immunosuppressive cytokine IL10 was slightly increased in the 3G mice. Finally, serum IgG concentration was twice higher whereas IgA concentration was slightly increased (about 30%) and IgM were unchanged in 2G mice compared to controls. No difference was observed in the 3G group with these isotypes. Consequently, functional immune dysregulations and stress responses were dependent of the gravity level.


Prospects for prevention and amelioration of mental retardation: a guest editorial.
The view of the President's Committee on Mental Retardation (1972) that the incidence of mental retardation can be reduced by 50 percent before the end of the century was critically examined. We concluded that only in the minority of cases, where biomedical etiologies are implicated, is this forecast support by existing trends. The major group of milder cases pose immense difficulties for prevention, and desirable social changes are unlikely to make an immediate impact. We also considered the argument that levels of functioning of most retarded persons can be substantially improved. While research gives a clear indication that this is potentially so, such knowledge is rarely applied. Implications for policy and practice were considered.


Percutaneous Ablation Versus Partial and Radical Nephrectomy for T1a Renal Cancer: A Population-Based Analysis.
Stage T1a renal cell carcinoma (RCC) (tumors <4 cm) is usually curable. Nephron-sparing partial nephrectomy (PN) has replaced radical nephrectomy (RN) as the standard of care for these tumors. Radical nephrectomy remains the first alternative treatment option, whereas percutaneous ablation (PA), a newer, nonsurgical treatment, is recommended less strongly because of the relative paucity of comparative PA data. To compare PA, PN, and RN outcomes. Observational cohort analysis using inverse probability of treatment-weighted propensity scores. Population-based SEER (Surveillance, Epidemiology, and End Results) cancer registry data linked to Medicare claims. Persons aged 66 years or older who received treatment for T1a RCC between 2006 and 2011. PA versus PN and RN. RCC-specific and overall survival, 30- and 365-day postintervention complications. 4310 patients were followed for a median of 52 months for overall survival and 42 months for RCC-specific survival. After PA versus PN, the 5-year RCC-specific survival rate was 95% (95% CI, 93% to 98%) versus 98% (CI, 96% to 99%); after PA versus RN, 96% (CI, 94% to 98%) versus 95% (CI, 93% to 96%). After PA versus PN, the 5-year overall survival rate was 77% (CI, 74% to 81%) versus 86% (CI, 84% to 88%); after PA versus RN, 74% (CI, 71% to 78%) versus 75% (CI, 73% to 77%). Cumulative rates of renal insufficiency 31 to 365 days after PA, PN, and RN were 11% (CI, 8% to 14%), 9% (CI, 8% to 10%), and 18% (CI, 17% to 20%), respectively. Rates of nonurologic complications within 30 days after PA, PN, and RN were 6% (CI, 4% to 9%), 29% (CI, 27% to 30%), and 30% (CI, 28% to 32%), respectively. Ten percent of patients in the PN group had intraoperative conversion to RN. Seven percent of patients in the PA group received additional PA within 1 year of treatment. Analysis of observational data may have been affected by residual confounding by provider or from selection bias toward younger, healthier patients in the PN group. Findings from this older study population are probably less applicable to younger patients. Use of SEER-Medicare linked files prevented analysis of patients who received treatment after 2011, possibly reducing generalizability to the newest PA, PN, and RN techniques. For well-selected older adults with T1a RCC, PA may result in oncologic outcomes similar to those of RN, but with less long-term renal insufficiency and markedly fewer periprocedural complications. Compared with PN, PA may be associated with slightly shorter RCC-specific survival but fewer periprocedural complications. Association of University Radiologists GE Radiology Research Academic Fellowship and Society of Interventional Radiology Foundation.


Identifying expressions of pleasure and displeasure by persons with profound and multiple disabilities.
The aim of this study was to explore a procedure for drafting individualised profiles of how people with profound multiple disabilities express pleasure and displeasure. There were 6 participants with profound multiple disabilities. The procedure involved an observational analysis of videotaped critical incidents by a researcher and a questionnaire for parents and support workers. The procedure is useful for making an individualised profile of the ways a person with profound multiple disabilities expresses his/her pleasure and displeasure. Despite the significant correlation between parents, support workers and the researcher, each has a complementary contribution to make in identifying affective expressions. People with profound multiple disabilities especially use sounds and facial expressions to express pleasure and displeasure and positive or negative moods. The procedure may be useful in services or schools for learning more about the affective communication of these individuals, to determine their specific interests, and to evaluate the effects of living and support characteristics on their wellbeing.


Eosinophilic pustular folliculitis.
Classical eosinophilic pustular folliculitis, or Ofuji's disease, is a chronic and relapsing dermatosis that is predominantly reported in East Asian populations. Clinically, the disease typically begins as small papules, which enlarge and coalesce into a large plaque, usually on the face. The histopathology is characterized by a prominent eosinophilic infiltrate in the dermis with concentration around pilosebaceous units, often with eosinophilic microabscess formation. The differentiation of eosinophilic pustular folliculitis from other eosinophilic dermatoses is practically challenging and requires close clinicopathologic correlation. Eosinophilic pustular folliculitis may also be associated with human immunodeficiency virus infection, various drugs, and some lymphomas and could also be thought of as a nonspecific dermatopathologic pattern in such settings. The cause of classical eosinophilic pustular folliculitis is unknown, although immune processes are almost certain to play a key role in its pathogenesis.


Comparative effectiveness research (CER): a summary of AHRQ's CER on therapies for rheumatoid arthritis.
In recent years, the U.S. government has designated funding of several large-scale initiatives for comparative effectiveness research (CER) in health care. The American Recovery and Reinvestment Act (ARRA) of 2009 apportioned more than $1 billion to support CER programs administered by the Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), and the Agency for Healthcare Research and Quality (AHRQ). CER is generally defined as the undertaking of original research or systematic reviews of published literature in order to compare the benefits and risks of different approaches to preventing, diagnosing, or treating diseases. These approaches may include diagnostic tests, medications, medical devices, and surgeries. The overall goals of CER are to support informed health care decisions by patients, clinicians, payers, and policy makers and to apply its evidence to ultimately improve the quality, effectiveness, and efficiency of health care. To (a) provide managed care professionals with general definitions of CER, specifically as it is administered by AHRQ; (b) discuss the importance of CER to clinical and managed care pharmacists; and (c) summarize key methods and findings from AHRQ's 2007 comparative effectiveness review on therapies for rheumatoid arthritis (RA). As supported by AHRQ, CER is conducted in order to synthesize comprehensive evidence on the comparative benefits and harms of treatment interventions. The findings from comparative effectiveness reviews can thus contribute to informing therapeutic strategies and treatment decisions. In 2007, a multitude of RA treatment options and studies motivated AHRQ to commission a systematic comparative effectiveness review. Conducted by investigators at the RTI-University of North Carolina Evidence-Based Practice Center, the review included comparisons of synthetic disease-modifying antirheumatic drugs (DMARDs), biologic agents, synthetic DMARDs versus biologic agents, and various combination therapies. Head-to-head comparisons of synthetic DMARDs generally revealed no significant differences in long-term clinical and radiographic outcomes, or in functional capacity or health-related quality of life. Two nonrandomized prospective cohort studies and 1 open-label effectiveness trial reported no differences in ACR20 and ACR50 response rates in patients treated with the tissue necrosis factor (TNF)-alpha inhibitors etanercept and infliximab. Comparisons of TNF-alpha inhibitors generally indicated no significant differences in rates of adverse events, including serious infections, and no increases in rates over time. In comparisons of a biologic agent combined with methotrexate versus a biologic agent alone, combination therapies were generally associated with better clinical response rates and better outcomes of functional capacity and quality of life. The most common adverse events observed in studies on biologic agents were diarrhea, headache, nausea, rhinitis, injection site reactions, and upper respiratory tract infections.


Seasonality of birth in patients with childhood Type I diabetes in 19 European regions.
Differences in seasonality of birth patterns between the general population and the group who develop Type I (insulin-dependent) diabetes mellitus indicate that environmental factors operating around the antenatal and perinatal period could be important. We investigated whether the same unsual patterns in seasonality of birth observed in children with Type I diabetes in Great Britain could also be found in other European populations. Population-based incidence cohorts of children diagnosed with Type I diabetes under 15 years of age from 1989 onwards were analysed. Previously reported data sets from Great Britain were also included together with data on children diagnosed over an additional 5 year period (1988-1992). To assess the role of seasonality in diabetes, we used the method of Walter and Elwood to examine monthly birth figures for each country or region. Outside of Great Britain, no seasonality of birth was seen for any single or combination of European countries. Significant sinusoidal patterns were observed in Scotland, Yorkshire and Leicester, although the peak for Leicester appeared around autumn rather than spring. There was little evidence that sex or age at diagnosis played a part in differences in seasonal patterns, either overall or for any individual country. We found no uniform seasonal pattern of birth in childhood diabetes patients across European populations, either overall or according to sex and age. This study provides no consistent evidence that environmental factors, which vary from season to season, have any influence on the fetal or neonatal life to determine the onset of Type I diabetes. However, a study of seasonality that takes into account possible changes both over time and over geographical areas could provide more insights.


The impact of in-vehicle cell-phone use on accidents or near-accidents among college students.
With in-vehicle use of cell phones rapidly increasing, the safety of young drivers, who represent 14% of licensed drivers but 26% of drivers involved in fatal crashes, may be disproportionately threatened. The authors used a questionnaire to examine the association between in-vehicle cell-phone use and accidents or near-accidents among 1,291 conveniently recruited college students in 4 states. Of the 1,185 respondents who were drivers, 87% had a cell phone, and 86% of the cell-phone owners reported talking while driving at least occasionally. Of the 762 reported accidents or near-accidents, 21% (n = 159) involved at least 1 of the drivers talking while driving. Chi-square tests and logistic regression analyses showed that the frequency, not the duration, of drivers talking while driving was related to experiencing accidents or near-accidents. Differences between drivers who used cell phones and nonusers in unsafe driving behaviors and attitudes were also examined, and target groups for intervention efforts against talking on a cell phone while driving are suggested.


Neurologic recovery after penetrating craniocerebral war injury.
From June 1, 1991, until December 31, 1992, 116 patients with penetrating craniocerebral war injuries inflicted at the east Slavonian front were treated at the Osijek University Hospital. There were 26 (22.4%) gunshot wounds and 90 (77.6%) wounds inflicted by explosive devices and projectiles. Four years after the injury, a study of the survivors' condition was carried out. No difference was recorded in the survival rate between the patients with gunshot wounds compared with explosive wounds. Rehabilitation produced good results in the survivors, in the prevention of both acute and chronic complications and permanent damage. Older age, lower Glasgow Coma Scale, and level of consciousness were found to be prognostic indicators of outcome.


Percutaneous endoscopic gastrostomy: a review of indications, complications and outcome.
Percutaneous endoscopic gastrostomy (PEG) was first described in 1980 as an effective method of feeding via the stomach in situations where oral intake is not possible. Its simplicity has led to its potential use in areas of dubious clinical benefit. Our unit has faced a major increase in referrals for PEG insertion over the last 2 years. For this reason we decided to audit our PEG insertion procedures with regard to indications, complications, outcome and follow up. We studied 168 patients who had an initial PEG insertion during the period 1 February 1996-31 January 1998. The medical records of these patients were reviewed with regard to the procedure, antibiotic use and complications. All patients (or carers or next of kin) were contacted by telephone to provide details regarding late complications and follow up. There were 87 females and 81 males (aged 16-98 years, median age 70 years). At 2 years, 67% were alive. The most frequent indication for PEG insertion was a neurological condition, the commonest being stroke. Most patients received either ticarcillin/clavulanic acid or cephazolin antibiotic prophylaxis before and after the procedure. In six patients (3.6%) infection at the PEG site required intravenous antibiotics. Four of these six patients did not have antibiotic prophylaxis. Only two deaths could be directly related to the procedure. Three died within 7 days of the procedure due to unrelated medical complications. Sixteen patients died within 1 month, the majority of these patients did not leave hospital. One-fifth of the patients (35/168) had their PEG removed due to the re-establishment of oral feeding, with median time of use, 4.3 months. It is a safe, effective feeding method in the elderly, but experience with case selection, the procedure and careful follow up remain essential. The use of prophylactic antibiotics resulted in few significant infections of the PEG site. Up to one-fifth of patients will require their PEG only for a short term.


MICA-G129R: A bifunctional fusion protein increases PRLR-positive breast cancer cell death in co-culture with natural killer cells.
Breast cancer cells were reported to up-regulate human prolactin receptor (PRLR) to assist their growth through the utilization of prolactin (PRL) as the growth factor, which makes PRLR a potential therapeutic target for breast cancer. On the other hand, advanced cancer cells tend to down-regulate or shed off stress signal proteins to evade immune surveillance and elimination. In this report, we created a fusion protein consisting of the extracellular domain of MHC class I chain-related protein (MICA), a stress signal protein and ligand of the activating receptor NKG2D of natural killer (NK) cells, and G129R, an antagonistic variant of PRL. We hypothesize that the MICA portion of the fusion protein binds to NKG2D to activate NK cells and the G129R portion binds to PRLR on breast cancer cells, so that the activated NK cells will kill the PRLR-positive breast cancer cells. We demonstrated that the MICA-G129R fusion protein not only binds to human natural killer NK-92 cells and PRLR-positive human breast cancer T-47D cells, but also promotes NK cells to release granzyme B and IFN-γ and enhances the cytotoxicity of NK cells specifically on PRLR-positive cells. The fusion protein, therefore, represents a new approach for the development of breast cancer specific immunotherapy.


Borna disease virus RNA in immunocompromised patients in southwestern France.
Borna disease virus (BDV) is a neurotropic RNA virus with a wide host range. Human infections, although controversial, have been described in Europe, Asia, and the United States. The present study investigated the existence of BDV infections in immunocompromised human beings, namely, 82 human immunodeficiency virus (HIV)-infected and 80 therapeutically immunosuppressed patients. BDV p40 RNAs were detected in peripheral white blood cells with reverse transcription-nested PCR and hybridization in, respectively, 11 (13.41%) and 1 (1.25%) of the two groups of patients. BDV p24 RNAs were identified in only one of those. BDV RNA was detected in the absence of any neuropsychiatrical illness, suggesting that BDV infections may occur in asymptomatic carriers. The severity and particularity of cellular immunosuppression could explain the significantly increased detection of BDV RNA in HIV-infected patients.


Role of poFUT1 and O-fucosylation in placental angiogenesis†.
Trophoblast cells are critical to placental angiogenesis in the first trimester of pregnancy. Dysfunction of trophoblast leads to defective vascular remodeling and impaired angiogenesis, which is believed as the major cause of placental insufficiency and pregnancy failure. Protein O-fucosyltransferase 1 (poFUT1) is mainly responsible for O-fucosylated glycan biosynthesis on glycoproteins, and poFUT1 deficiency causes embryonic lethality in mice. However, the expression and function of poFUT1 in trophoblast-mediated human placental vessel formation remain unclear. In the current study, we showed that fewer blood vessels were observed in the villi and decidua of miscarriage patients than in normal pregnancy women. The expression of poFUT1 was decreased in the trophoblast cells of miscarriage patients compared with normal pregnancy women. Employing HTR/SVneo cells and an in vivo chorioallantoic membrane assay, we demonstrated that poFUT1 promoted the proliferation, migration ability, and angiogenesis potential of trophoblast cells. The results also indicated that poFUT1 upregulated O-fucosylation on uPA, facilitated the binding of uPA and uPAR, activated the RhoA signaling pathway, and further enhanced the angiogenic capacity of trophoblast cells. Our study provides new evidence for a relationship between poFUT1/O-fucosylation and placental angiogenesis. These findings may provide potential diagnostic biomarkers and targeted therapies for miscarriage patients.


Human keratinocytes respond to osmotic stress by p38 map kinase regulated induction of HSP70 and HSP27.
Human skin is exposed to an environment that varies in humidity from 100 to 0%, leading to seasonal variations in the condition of the skin. Exposure to a low humidity environment creates an osmotic gradient across the stratum corneum, which is known to modulate cutaneous barrier function. Heat shock proteins protect against stress-induced destabilization of proteins. We investigated whether osmotic shock (sorbitol) induced a heat shock protein response in normal human keratinocytes, and used heat shock as a positive control. Both heat shock and osmotic stress (200 and 300 mM sorbitol) clearly induced heat shock proteins 70 and 27 mRNA levels. The induction of heat shock protein 70 mRNA levels by osmotic stress peaked at 16 h and persisted until 24 h, whereas upregulation of heat shock protein 70 mRNA levels by heat peaked at 2 h and returned to baseline levels by 6 h. Sorbitol also increased heat shock protein 70 levels in a concentration-dependent manner. The kinetics of heat shock protein 27 mRNA induction by osmotic stress and heat were similar with peak induction at 6 h. The mitogen activated protein kinase family of proteins plays an important part in the coordination of gene responses to various stress conditions. We have demonstrated that the p38 mitogen activated protein kinase was strongly activated by 200 mM and 300 mM sorbitol. The specific p38 mitogen activated protein kinase inhibitor PD169316 almost completely blocked heat shock protein 70 mRNA induction by 200 mM and 300 mM sorbitol and completely suppressed heat shock protein 27 mRNA induction with 200 mM sorbitol. PD169316 also counteracted upregulation of heat shock protein 70 levels by sorbitol. These data indicate that keratinocytes respond to osmotic stress by p38 mitogen activated protein kinase regulated induction of heat shock proteins. This molecular pathway may be relevant for the mechanisms regulating the response of human skin to variations in environmental humidity.


Using a Poverty Simulation Exercise in Mental Health Nursing.
Simulation exercises can be used to provide poverty-related content that might be lacking in traditional clinical settings. A descriptive qualitative study design was used to examine the use of a poverty simulation in mental health nursing. Thematic analysis of reflective journals indicated students viewed the poverty simulation as a positive, realistic, and informative learning experience; had a better understanding of how poverty impacts health; and expressed changes in attitudes toward providing care. Results from this study suggest poverty simulations can be used to illustrate key concepts taught in mental health nursing, including empathy, advocacy, and refrainment from judging patients.


Ubiquitin‑like protein FAT10 regulates DNA damage repair via modification of proliferating cell nuclear antigen.
In response to DNA damage, proliferating cell nuclear antigen (PCNA) has an important role as a positive regulator and as a scaffold protein associated with DNA damage bypass and repair pathways by serving as a platform for the recruitment of associated components. As demonstrated in the present study, the ubiquitin‑like modifier human leukocyte antigen F locus adjacent transcript 10 (FAT10), which binds to PCNA but has not previously been demonstrated to be associated with the DNA damage response (DDR), is induced by ultraviolet/ionizing radiation and VP‑16 treatment in HeLa cells. Furthermore, DNA damage enhances FAT10 expression. Immunoprecipitation analysis suggested PCNA is modified by FAT10, and the degradation of FATylated PCNA located in the cytoplasm is regulated by the 26S proteasome, which is also responsible for the upregulation of nuclear foci formation. Furthermore, immunofluorescence experiment suggested FAT10 co‑localizes with PCNA in nuclear foci, thus suggesting that FATylation of PCNA may affect DDR via the induction of PCNA degradation in the cytoplasm or nucleus. In addition, immunohistochemistry experiment suggested the expression levels of FAT10 and PCNA are enhanced in HCC tissues compared with healthy liver tissues; however, the expression of FAT10 is suppressed in regenerated liver tissues, which express high levels of PCNA, thus suggesting that the association between FAT10 and PCNA expression is only exhibited in tumor tissues. In conclusion, the results of the present study suggest that FAT10 may be involved in DDR and therefore the progression of tumorigenesis.


Fine needle aspiration cytology of adult perineal rhabdomyosarcoma: a case report.
Adult perineal soft tissue sarcomas are rare. Fewer than 30 cases have been reported, and all were diagnosed after surgical resection by histologic examination. Below we report a case in which the diagnosis was established preoperatively by fine needle aspiration (FNA). A 27-year-old man presented with a firm, midline, perineal mass. Magnetic resonance imaging showed a 3-cm, enhancing mass that was considered neoplastic. FNA biopsy, followed by cytologic examination, revealed moderately cellular aspirates composed of discohesive, small, blue cells with scant cytoplasm, high nuclear/cytoplasmic ratios and pleomorphic nuclei with irregular nuclear contours; uniform, hyperchromatic chromatin; and occasional mitotic figures. Frequent naked nuclei and scattered cells with more abundant, dense cytoplasm and eccentric nuclei were also noted. The diagnosis of rhabdomyosarcoma was favored on FNA and was corroborated by immunohistochemical stains for desmin, myogenin and CD56. Upon surgical resection, the diagnosis of alveolar rhabdomyosarcoma was confirmed histologically and immunophenotypically. FNA is a useful tool in diagnosing soft tissue lessions of the perineum, including rare primary tumors, such as adult rhabdomyosarcoma. In this case, early identification avoided incisional biopsy and directed appropriate extirpative surgery and reconstruction considerations.


Wrinkle- and Edge-Adsorption of Aromatic Compounds on Graphene Oxide as Revealed by Atomic Force Microscopy, Molecular Dynamics Simulation, and Density Functional Theory.
In this work, the favorable adsorption sites of aromatic compounds (ACs) on graphene oxide (GO) are characterized with both experimental and theoretical approaches. The results show that ACs exhibit a strong preference in adsorbing near the wrinkles and edges. Further analyses reveal that the edge-adsorption is mainly guided by the stronger π-π interaction near edges, accompanied by a stronger hydrogen bond interaction between carboxyl groups and ACs. Additionally, the water-mediated steric hindrance and flexibility of carboxyl groups also contribute to the edge-adsorption. A higher density of atoms and electrons is the main mechanism for the wrinkle-adsorption, and structural investigations indicate that the roughness serving as a steric hindrance for the ACs migration also contributes to the wrinkle-adsorption. This wrinkle- and edge-adsorption pattern will shed light on the design of GO-related environmental materials.


[Clinical evaluation of surgical treatment of Graves' disease].
Five hundred and thirteen surgical patients with Graves' disease from 1970 to 1983 were subjected to this study. They were divided into three groups by period in which operation was performed; 1st period from 1970 to 1974, 2nd from 1975 to 1979, and 3rd from 1980 to 1983. Postoperative thyroid function was evaluated. The weight of remnant thyroid was the greatest in the first period and the smallest in the third. There were no differences of frequency of postoperative complications among these periods in spite of remarkable decrease of weight of remnant thyroid tissue in the third period. Remission of thyroid function, was most frequently observed in the group of the remnant thyroid weight from 4 to 8 grams. Recurrence of hyperthyroidism was frequently observed in the group of the greatest weight of remnant thyroid and hypothyroid state was frequently observed in the group of the smallest remnant thyroid. These results indicate that the remnant thyroid weight may be one of the most crucial factors which influence on the postoperative functional state of patients with Graves' disease, and remnant thyroid tissue weighing from 4 to 8 grams may be the most appropriate in subtotal thyroidectomy.


Neuropeptides in hypertension: role of neuropeptide Y and calcitonin gene related peptide.
1. The effect of neuropeptide Y (NPY) on cardiovascular function at three levels of the noradrenergic axis where the peptide is known to co-exist with noradrenaline (NA) and or adrenaline (A) was studied in normotensive Sprague-Dawley (SD), Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). 2. In the perfused mesenteric arterial bed, NPY and the structurally similar peptide intestinal polypeptide (PYY) decreased the periarterial nerve stimulation induced release of NA and potentiated the increase in perfusion pressure to nerve stimulation or exogenously applied agonists (e.g. angiotensin, vasopressin, phenylephrine). In contrast to NPY and PYY, C-terminal NPY fragments inhibited NA release and produced a parallel decrease in perfusion pressure thus supporting the concept of Y1 (post) and Y2 (pre) NPY receptors. 3. In the mesenteric artery of SHR the prejunctional inhibitory effect of NPY was attenuated while the postjunctional response was enhanced. 4. Following intrathecal (Int) injection of NPY, there was a decrease in blood pressure, total peripheral resistance (predominantly by a decrease in mesenteric vascular resistance) and renal nerve activity. The depressor effect of Int NPY was attenuated in the SHR. 5. Unilateral injections of NPY into the posterior hypothalamic nucleus increased blood pressure, hindquarter and renal vascular resistance and renal nerve activity. The pressor effect was enhanced in the SHR. 6. Periarterial nerve stimulation of the perfused mesenteric artery produced a frequency dependent vasodilation in beds pretreated with guanethidine and precontracted with methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of upper endoscopy on satisfaction in patients with previously uninvestigated dyspepsia.
In patients with uninvestigated dyspepsia who undergo endoscopy, the presence of abnormal findings guides subsequent management. However, upper endoscopy is "negative" in the majority of these patients, and the value of endoscopy in these individuals has been questioned. This study evaluated the impact of endoscopy on patient satisfaction in patients with previously uninvestigated dyspepsia. The study was a secondary analysis of data obtained from a double-blind, randomized placebo-controlled trial, evaluating a 6-week course of omeprazole versus placebo in 140 patients with uninvestigated dyspepsia who were followed for up to 1 year. The setting was the primary care outpatient clinics at the Houston Veterans Affairs Hospital. Participants had to be 18 years of age or older with at least a 1-week history of dyspepsia (epigastric discomfort) without alarm features. Satisfaction was measured at each visit with the Severity of Dyspepsia Assessment, a validated, reliable dyspepsia-related health measure that has a satisfaction scale (scores 2-23; higher scores indicate greater satisfaction). Patients unresponsive to empiric therapy with placebo or omeprazole based on predefined criteria underwent endoscopy. Severity of Dyspepsia Assessment satisfaction scores were analyzed for 5 visits: 2 closest in time to, but before, the day of endoscopy (Times 1 and 2); immediately before endoscopy (Time 3); and the 2 visits closest in time after endoscopy (Times 4 and 5). After determining there was no difference in treatment failure rates between patients who received placebo or omeprazole, data from these groups were combined. The mean Severity of Dyspepsia Assessment satisfaction scores for Times 1 through 5 in all patients who underwent endoscopy were compared as well as for subgroups with positive and negative endoscopic findings with a repeated-measures analysis of variance. Data on all 5 visits were available in 62 patients, 36 of whom had a negative endoscopy. For all patients the mean scores for Time 2 (8.5; 95% CI [7.4, 9.6]), and Time 3 (7.6; 95% CI [6.6, 8.6]) were significantly lower than those for Time 4 (13.7; 95% CI [12.2, 15.3]) and Time 5 (14.4; 95% CI [12.9, 15.9]). The mean score for Time 1 (11.1; 95% CI [9.5, 12.6]) was significantly lower than the mean score for Time 5. Similar significant improvements in satisfaction scores were observed in subgroups with negative and positive findings. In patients with previously uninvestigated dyspepsia, endoscopy leads to improved patient satisfaction regardless of the endoscopic findings.


Assignment of five loci from human chromosome 8q onto sheep chromosome 9.
Using a chromosomally characterized minipanel of sheep x hamster cell hybrids, five new loci, including carbonic anhydrase II (CA2), calbindin 1 (28 kDa) (CALB1), corticotropin releasing hormone (CRH), cytochrome P450 11B subfamily XIB (steroid-11-beta-hydroxylase), polypeptide 1 (CYP11B1), and interleukin 7 (IL7), have been assigned to sheep chromosome 9. A homolog of CA2 was detected on sheep chromosome 1. CRH was regionally localized to sheep 9q23-->q28 by in situ hybridization. This study assigns chromosome 9 as the sheep equivalent of cattle chromosome 14 and indicates that CALB1, CYP11B1, and IL7, which have not been mapped on the cattle genome, are likely to be present on cattle chromosome 14. It also shows by comparative genome analysis that a large segment of human chromosome 8q is highly conserved in sheep chromosome 9 and cattle chromosome 14. Based on these data, we propose that sheep chromosome 9 be recognised as the equivalent of cattle chromosome 14.


The impact of carbohydrate-active enzymes on mediating cell wall polysaccharide-tannin interactions in a wine-like matrix.
Tannins are present in grape skins and seeds from where they are transferred into the must-wine matrix during the maceration stages of winemaking. However, tannin transfer is often incomplete. This could be due, among other reasons, to tannins becoming bound to grape cell wall polysaccharides, including soluble polymers, which are released during vinification and are present in high concentrations in the must/wine. The use of cell wall deconstructing enzymes offers the possibility of reducing these interactions, releasing more tannins into the final wine. The main aim of this study was to evaluate the optimal addition (individually, in combination or sequentially) of hydrolytic enzymes that would prevent tight polysaccharide-tannin associations. The use of comprehensive microarray polymer profiling (CoMPP) methodology provided key insights into how the enzyme treatments impacted the grape cell wall matrix and tannin binding. The results demonstrated that polygalacturonase + pectin-lyase promoted the highest release of tannins into solution.


Advocacy and the nurse manager.
This paper analyses the advocacy role of the nurse manager, defining terms and emphasizing the need for a rational appraisal of risks before advocacy is undertaken. Power analysis is offered as a theoretical basis for estimating risk and for tactical planning. Outcomes from a small-scale qualitative research study are also presented, in order to stimulate a wider debate on the principles underpinning safe and ethical practice in advocacy.


[Mitral valve prolapse and type II mucopolysaccharidosis. Report of two familial cases].
Type II mucopolysaccharidosis (Hunter's disease) is a hereditary condition due to a deficit of a lysosome specific hydrolase (iduronate sulfatase) inducing an accumulation of dermatane-sulphate and heparane-sulphate in certain organs. Cardiac involvement is constant in this disease and manifests itself essentially by aortic valve stenosis and insufficiency and/or mitral insufficiency which is progressive, irreversible and life-threatening. Two brothers of Portuguese nationality suffering from a so-called slight form of this disease had classical mucopolysaccharide infiltration of their aortic valves. The elder brother, aged 11, had severe aortic insufficiency associated with mild stenosis requiring treatment with vasodilator drugs. The younger, aged 8, had asymptomatic mild aortic regurgitation. Curiously, mitral valve prolapse with regurgitation was present in both children. The association of mitral valve prolapse and type II mucopolysaccharidosis, without other typical cardiac involvement, has only been reported once in the literature.


Five-Antigen Fluorescent Bead-Based Assay for Diagnosis of Lyme Disease.
The systematically difficult task of diagnosing Lyme disease can be simplified by sensitive and specific laboratory tests. The currently recommended two-tier test for serology is highly specific but falls short in sensitivity, especially in the early acute phase. We previously examined serially collected serum samples from Borrelia burgdorferi-infected rhesus macaques and defined a combination of antigens that could be utilized for detection of infection at all phases of disease in humans. The five B. burgdorferi antigens, consisting of OspC, OspA, DbpA, OppA2, and the C6 peptide, were combined into a fluorescent cytometric bead-based assay for the detection of B. burgdorferi antigen-specific IgG antibodies. Samples from Lyme disease patients and controls were used to determine the diagnostic value of this assay. Using this sample set, we found that our five-antigen multiplex IgG assay exhibited higher sensitivity (79.5%) than the enzyme immunoassay (EIA) (76.1%), the two-tier test (61.4%), and the C6 peptide enzyme-linked immunosorbent assay (ELISA) (77.2%) while maintaining specificity over 90%. When detection of IgM was added to the bead-based assay, the sensitivity improved to 91%, but at a cost of reduced specificity (78%). These results indicate that the rational combination of antigens in our multiplex assay may offer an improved serodiagnostic test for Lyme disease.


Perceptions and knowledge regarding the COVID-19 pandemic between U.S. and China: a mixed methods study.
SARS-CoV-2, a new coronavirus first reported by China on December 31st, 2019, has led to a global health crisis that continues to challenge governments and public health organizations. Understanding COVID-19 knowledge, attitudes, and practices (KAP) is key for informing messaging strategies to contain the pandemic. Cross-national studies (e.g.: comparing China to the U.S.) are needed to better understand how trans-cultural differences may drive differences in pandemic response and behaviors. The goal of the study is to compare knowledge and perceptions of COVID-19 between adults in China and the U.S. These data will provide insight into challenges these nations may face in coordinating pandemic response. This is a convergent mixed methods study comparing responses from China and the U.S. to a multinational COVID-19 KAP online survey. The survey included five quantitative constructs and five open-ended questions. Chinese respondents (n = 56) were matched for gender, age, education, perceived social standing, and time of survey completion with a U.S. cohort (n = 57) drawn from 10,620 U.S. Quantitative responses were compared using T-test & Fisher-Exact tests. Inductive thematic analysis was applied to open-ended questions. Both U.S. and Chinese samples had relatively high intention to follow preventive behaviors overall. Differences in intended compliance with a specific recommendation appear to be driven by the different cultural norms in U.S. and China. Both groups expressed trepidation about the speed of COVID-19 vaccine development, driven by concern for safety among Chinese respondents, and concern for efficacy among U.S. The Chinese cohort expressed worries about other countries' passive handling of the pandemic while the U.S. cohort focused on domestic responses from individuals and government. U.S. participants appeared more knowledgeable on some aspects of COVID-19. Different perspectives regarding COVID-19 origins were identified among the two groups. Participants from both samples reported high trust in health professionals and international health organizations. Mixed methods data from this cross-national analysis suggests sociocultural differences likely influence perceptions and knowledge of COVID-19 and its related public health policies. Discovering and addressing these culturally-based differences and perceptions are essential to coordinate a global pandemic response.


Systems for care of hypertension in the United States.
Control of hypertension in recent clinical trials varies from 48% to 65%. However, in community care of hypertension in the United States, estimates of control of hypertension are far lower. The United States has no single system of care; however, several care systems can be identified for comparison, such as the Department of Veterans Affairs, managed care organizations, and the Indian Health Service. This review compares control of hypertension in certain centers in these systems with that achieved in clinical trials and in the community at large. Certain components of care systems are assessed for their contribution to the control of hypertension. The author concludes that for community control of hypertension to approach that achieved in clinical trials, the use of physician extenders, together with reduced or minimal cost of medication, improved education of providers with feedback, and computerization of management systems will be needed. In addition, specific interventions targeted to medically underserved groups will be required.


Chagas disease awareness among Latin American immigrants living in Los Angeles, California.
Approximately 300,000 persons have Chagas disease in the United States, although almost all persons acquired the disease in Latin America. We examined awareness of Chagas disease among Latin American immigrants living in Los Angeles, California. We surveyed 2,677 persons (age range = 18-60 years) in Los Angeles who resided in Latin America for at least six months. A total of 62% of the participants recalled seeing triatomines in Latin America, and 27% of the participants reported triatomine bites at least once per year while living abroad. A total of 86% of the participants had never heard of Chagas disease. Of persons who had heard of Chagas disease, 81% believed that it was not serious. More than 95% of those who had heard of Chagas disease would want to be tested and treated. Most Latin American immigrants living in Los Angeles recalled exposure to vectors of Chagas disease. However, they have little knowledge of this disease. Increasing awareness of Chagas disease is needed in this high-risk population.


[Genetic analysis of 35 microsatellite loci in 5 lineages of xishuangbanna miniature pig inbred line].
The polymorphism of 35 microsatellites in 5 lineages of Xishuangbanna small-ear miniature pig inbred line (XMI) was analysed. Nmuber of alleles of each lineage was counted, and rates of homozygote for 35 microsatellite loci in 5 lineages were calculated. According to gene frequencies of 35 microsatellites polymorphism information content (PIC) and mean heterozygosity were calculated for each lineage, and genetic distances between these lineage were estimated. The dendrograms were obtained based on genetic distances. The results suggest that rates of homozygote in these lineage are all high, and that is the highest in lineage 151. The results also suggest that polymorphism information content and mean heterozygosity in all the lineages are low. Composition of alleles of each lineage was quite different and the genetic relationship between lineages accorded with the process of inbred line. So it is suggested that the inbreeding degree of 5 lineages of XMI are all high, and the richness of genetic diversity is lower than general commercial pig breeds. It also shows each lineage has been different groups with individual genes.


Late infective endocarditis of an atrial septal occluder device presenting as a cystic mass.
We report an atypical echocardiographic presentation of a vegetation in a patient with late infective endocarditis of an atrial septal defect (ASD) occluder device. Transesophageal echocardiography demonstrated a penduculated mass attached to the left atrial side of the occluder device. This mass presented as an oscillating echo free area surrounded by a membrane attached to the device by a thin stalk. At time of surgical excision, the lesion did not present as a spherical cyst. It was assumed that the content of the echo free mass had already emptied into the left atrium. Histopathology diagnosed the mass as a vegetation. The contribution of contrast echocardiography to the evaluation of intracardiac masses is briefly discussed.


Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis.
This study examines the effect of interstitial inflammation and interstitial fibrosis and tubular atrophy on renal survival in lupus nephritis. Baseline characteristics, initial (n = 301) and repeat biopsies (n = 94) and clinical outcomes for patients with biopsy-proven lupus nephritis from 1998 to 2014 were retrospectively collected from the medical record. Clinical and morphologic variables were evaluated using a Cox proportional hazards model and multiple imputation to address missing data. Renal survival was defined as the time from initial biopsy to end-stage renal disease [estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2], dialysis or transplant. A total of 218 patients had follow-up and Class IV had worse renal survival, especially in patients with active and chronic glomerular lesions {relative to non-IV; Class IV-A: hazard ratio [HR] 0.92 [95% confidence interval (CI) 0.41-2.04], Class IV-AC: HR 5.02 [95% CI 2.70-9.36]}. Interstitial inflammation grade [relative to interstitial inflammation <5%; interstitial inflammation 5-25%: HR 2.36 (95% CI 1.13-4.91), interstitial inflammation 25-50%: HR 3.84 (95% CI 1.53-9.62), interstitial inflammation >50%: HR 7.67 (95% CI 3.75-15.67)] and increased interstitial fibrosis and tubular atrophy (IFTA) category [relative to IFTA <5%; IFTA 5-25%: HR 3.93 (95% CI 1.58-9.75), IFTA 25-50%: HR 4.01 (95% CI 1.37-11.70), IFTA >50%: HR 13.99 (95% CI 4.91-39.83)] predicted worse renal survival among all patients and those with Class IV on initial and repeat biopsy (n = 94) in a dose-dependent manner. Interstitial inflammation grade and IFTA category were significant predictors of renal survival in a multivariable model adjusted for age, gender, race, ethnicity and serum creatinine. Interstitial inflammation and IFTA independently affect renal survival and grading these lesions stratifies risk within the International Society of Nephrology and Renal Pathology Society classification of lupus nephritis.


Ottawa prenatal educator e-survey: Experiences and perceptions of public health nurses and allied childbirth educators.
Prenatal education provides opportunities for health promotion of healthy behaviors and risk reduction. Quality and coherence with prenatal health promotion best practices depend on an individual class instructor. The objective of our study was to document the experiences, practices, and perceptions of our diverse Ottawa, Canada community of prenatal educators. In this quantitative, mixed methods e-survey conducted in Ottawa, Canada, prenatal educators were asked to describe their prenatal class settings, delivery formats, content, perceptions of pregnant women, and recommendations. Data were analyzed by descriptive statistics and thematic content analysis. Respondents included public health nurses and a diverse group of "allied childbirth educators" (ACE). Topics related to pregnancy, labor, and postpartum issues were well addressed; however, established and emerging risks to pregnancy were omitted. Nurses were more likely to discuss lifestyle risks to pregnancy and general prenatal health promotion, whereas ACE respondents emphasized informed consent and individualized counseling. Women marginalized by social exclusion including Indigenous women, immigrants, and women with disabilities were perceived as missing from prenatal educational settings. Heterogeneity of prenatal education provides opportunities for collaboration; however, established and emerging risk factors to pregnancy are neglected topics. Addressing the needs of diverse communities of pregnant women requires timely, evidence-based, inclusive, and culturally safe delivery of prenatal health promotion.


Design and Analysis of Particulate Matter Air-Microfluidic Grading Chip Based on MEMS.
Atmospheric particulate matter (PM) air-microfluidic grading chip is the premise for realizing high-precision PM online monitoring. It can be used as an indispensable basis for identifying pollution sources and controlling inhalable harmful substances. In this paper, based on aerodynamic theory and COMSOL numerical analysis, a two-stage PM air-microfluidic grading chip with cut-off diameters of 10 μm and 2.5 μm was designed. The effects of chip inlet width (W), main flow width (L), second channel width (S), and split ratio (Q1/Q) on PM classification efficiency were analyzed, and optimized design parameters were achieved. The collection efficiency curves were plotted according to PM separation effects of the chip on various particle sizes (0.5-15 μm). The results indicate that the chip has good separation effect, which provides an efficient structural model for the PM micro-fluidization chip design.


Myoelectric activation and kinetics of different plyometric push-up exercises.
The kinetic and myoelectric differences between 3 types of plyometric push-ups were investigated. Twenty-seven healthy, physically active men served as subjects and completed both familiarization and testing sessions. During these sessions, subjects performed 2 series of 3 plyometric push-up variations in a counterbalanced order according to the following techniques: Countermovement push-ups (CPUs) were push-ups performed with the maximum speed of movement; jump push-ups (JPUs) were similar to clapping push-ups; and fall push-ups (FPUs) required kneeling subjects to drop and then attempt to return to their initial position. Vertical ground reaction forces were determined by using a force plate. Myoelectric activity was recorded by means of electromyography. Impact force and impact rate of force development were significantly (p < 0.05) higher for FPUs than for JPUs. The maximum rate of force development was higher for CPUs (p < 0.05) than for JPUs, and the maximum force was higher for the CPUs than for the FPUs (p < 0.05). There were differences among exercises for the mean muscle activation of the pectoralis major (PM; p < 0.001), triceps brachii (p < 0.001), external oblique (p < 0.005) and anterior deltoid (p < 0.001), and in the maximum muscle activation of the PM (p < 0.001). Plyometric push-ups with countermovement achieved a higher maximum force and rate of force and did not cause impact forces. Thus, this type of push-up exercise may be regarded as the best for improving explosive force. The FPU exercise achieved higher levels of muscular activation in the agonist and synergist muscle groups, and greater impact forces and impact force development rates.


[The Effect of recombinant adiponectin on apoptosis induced by t-BHP in human umbilical vein endothelial cells].
To investigate the protective effect and possible mechanism of recombinant adiponectin on apoptosis in Human Umbilical Vein Endothelial Cells (HUVECs) induced by tert-butyl hydroperoxide (t-BHP). HUVECs were cultured in vitro and apoptosis was induced by t-BHP. On this basis, HUVECs were transfected with adenovirus carrying adiponectin prior to exposure to t-BHP, to further explore the protective effect of adiponectin on apoptosis induced by t-BHP. The percentage of cell viability was determined by MTT assay. The apoptotic rate was evaluated by fluorescence microsopic analysis with Hochest/PI staining. The protein levels of p-JNK, JNK and Caspase 3 were detected by Western blot. Following t-BHP 100 μmol/L administration for 8 h, the ratio of apoptotic cells was increased. Western blot revealed that the protein levels of p-JNK and active caspase 3 were increased(P<0.01) compared to the control group. When cells were pretreated by adenovirus with adiponectin, the apoptosis rate and protein levels of p-JNK and active caspase 3 were decreased significantly(P<0.01). Continuous exposure to t-BHP induced apoptosis in HUVECs. Recombinant adiponectin protected HUVECs from apoptosis induced by t-BHP, which was correlated with the downregulation of p-JNK and active Caspase 3.


Myometrial invasion and lymph node metastasis in endometrioid carcinomas: tumor-associated macrophages, microvessel density, and HIF1A have a crucial role.
Myometrial invasion is an independent prognostic parameter of the endometrioid carcinomas which correlates with the risk of metastasis to pelvic and/or paraaortic lymph nodes. Recognition of myometrial invasion is sometimes difficult. In fact, myoinvasion is overdiagnosed in routine practice in as many as 25% of the cases. Recently, it has been observed that tumor-associated macrophages stimulate angiogenesis and promote cancer dissemination. Tumor macrophages (CD163), microvessel density (CD31), and hypoxia inducible factor 1 α subunit (HIF1A) were investigated in 64 primary endometrioid carcinomas with (50 cases) and without (14 cases) myometrial invasion as well as in the corresponding regional lymph nodes metastases of 20 of the myoinvasive tumors. Endometrioid carcinomas with myometrial invasion showed higher number of CD163-tumor macrophages and greater microvessel density than endometrioid carcinomas without myometrial invasion (P=0.000 and P=0.000, respectively). In carcinomas confined to the corpus uteri (stage I), expression of HIF1A was associated with deep myoinvasion (stage IC) (P=0.006). There was a significant relationship between microvessel density and CD163-macrophages both in the myoinvasive and nonmyoinvasive tumors. On the other hand, high-grade endometrioid carcinomas had more macrophage infiltrates and microvessels than low-grade tumors (P=0.03 and P=0.07). Also, there was a positive correlation between CD163-macrophages and microvessel density in the primary tumors and their corresponding regional lymph node metastases. These findings link increased microvessel proliferation to stromal macrophage infiltrate and suggest that enhanced tumor angiogenesis, triggered by stromal macrophages, regulates the progression of endometrioid carcinomas. The identical stroma microenvironment found in the primary and the corresponding metastatic tumor suggests that tumor stroma response is determined by the intrinsic biology of the tumor.


Tailored mechanosensitive nanogels release drugs upon exposure to different levels of stenosis.
Owing to the unhealthy lifestyle and genetic susceptibility of today's population, atherosclerosis is one of the global leading causes of life-threatening cardiovascular diseases. Although a rapid intervention is required for severe blood vessel constrictions, a systemic administration of anticoagulant drugs is not the preferred method of choice as the associated risk of bleeding complications is high. In this study, we present mechanosensitive nanogels that exhibit tunable degrees of disintegration upon exposure to different levels of stenosis. Those nanogels can be further functionalized to encapsulate charged drug molecules such as heparin, and they efficiently release their cargo when passing stenotic constrictions; however, passive drug leakage in the absence of mechanical shear stress is very low. Furthermore, heparin molecules liberated from those mechanosensitive nanogels show a similar blood clot lysis efficiency as the free drug molecules, which demonstrates that drug encapsulation into those nanogels does not interfere with the functionality of the cargo. Thus, the hemocompatible and mechanoresponsive nanogels developed here represent a smart and efficient drug delivery platform that can offer safer solutions for vascular therapy.


The radiographic appearance of complications following Nissen fundoplication.
Seventy patients had an upper gastrointestinal examination following Nissen fundoplication for reflux esophagitis associated with hiatal hernia. Thirty-nine were asymptomatic and the fundoplication appeared normal. Of the 31 patients with symptoms (dysphagia, pain, or vomiting), 15 had spontaneous relief and demonstrated a normal postsurgical radiographic appearance of the stomach. The other 16 had both persistent symptoms and radiographic abnormalities, including 5 stenoses, 3 recurrent hernias, and 8 pouch deformities of the fundus. The roentgenographic features and etiology of these surgical failures are discussed and the importance of the radiographic examination in discerning successful surgical repair from failure despite similar postsurgical symptoms is stressed.


CLINICAL MANAGEMENT OF LOCALIZED BCG ADVERSE EVENTS IN CHILDREN.
BCG adverse events (BCG-AE) are rare conditions with no well-established treatment. This study aims to describe clinical characteristics and outcome of localized BCG-AE. Children with BCG-AEs who were treated at the Reference Center for Special Immunobiologicals of the Federal University of São Paulo from 2009 to 2011 were included. Patients were followed monthly until 3 months after healing. One hundred and twenty-seven patients with localized BCG-AE were followed: 67 (52.7%) had suppurative lymphadenitis; 30 (23.6%) injection-site abscess; five (3.9%) had enlarged lymph node > 3 cm; four (3.1%) had ulcer > 1 cm; and one (0.8%) had a local bacterial infection. Five patients (3.9%) had more than one BCG-AE simultaneously. Fifteen patients (11.8%) had atypical manifestations: seven wart-like lesions; five BCG reactivations; two other dermatologic lesions and one with vasomotor phenomenon. Isoniazid was used in 96 patients with typical BCG-AE (85.7%) until lesion resolution which took place 3.1 months later (in median); the healing rate was 90.6%. Patients with atypical manifestations had an individual approach. Regarding the outcome, 105/112 patients with typical AE and 13/15 patients with atypical AE had resolution of BCG-AE. Localized BCG-AE caused by BCG Moreau RJ had positive outcome when treated with a short course of isoniazid. Atypical BCG-AE are not infrequent.


Three-coordinated boron-11 chemical shifts in borates.
Despite the importance of (11)B nuclear magnetic resonance (NMR) in structural studies of borate glasses, no clear means of correlating NMR parameters with the number of nonbridging oxygens on three-coordinate boron has been demonstrated. In this work, a series of anhydrous, polycrystalline, binary borates has been examined by (11)B magic-angle spinning (MAS) NMR to obtain precise measurements of their three-coordinate boron isotropic chemical shifts. The shifts generally increase with the replacement of bridging oxygens by nonbridging oxygens, ranging from 14.6 ppm in crystalline B(2)O(3) to 22.5 ppm in magnesium orthoborate. The underlying physical basis for this trend is satisfactorily accounted for by considering second neighbor effects using bond valence sums. These data are supportive of a structural model for B(2)O(3) glass in which 72% of the boron atoms are in rings. High-field MAS NMR experiments (B(0) = 18.8 T) indicate that the boron shielding is anisotropic, with greater anisotropy measured for three-coordinate borons possessing one or two nonbridging oxygens, than for those with zero or three nonbridging oxygens.


The first asymmetric ring-expansion carbonylation of meso-epoxides.
The first asymmetric ring-expansion carbonylation of meso-epoxides to β-lactones is reported. Two structurally diverse chiral Cr(III) chloro complexes in conjunction with Co(2)(CO)(8) were shown to be competent catalytic systems for this transformation, displaying significant levels of asymmetric induction of up to 56% ee.


Cyclin dependent kinase inhibitors prevent apoptosis of postmitotic mouse motoneurons.
Recent evidence suggests that apoptosis in post-mitotic neurons involves an aborted attempt of cells to re-enter the cell cycle which is characterized by increased expression of cyclins, such as cyclin D1, prior to death. However, such cyclins activation prior to apoptotic cell death remains controversial. Many neurological disorders are characterized by neuronal loss, particularly amyotrophic lateral sclerosis (ALS). ALS is a motoneuronal degenerative condition in which motoneuron loss could be due to an inappropriate return of these cells in the cell cycle. In the present study, we observed that deprivation of neurotrophic factor in purified motoneuron cultures induces an apoptotic pathway. After neurotrophic factor withdrawal, DAPI (4,6-diamidin-2-phenylindol dichlorohydrate) staining revealed the presence of nuclear condensation, DNA fragmentation, and perinuclear apoptotic body. Similarly, release of apoptotic microparticles and activation of caspases-3 and -9 were observed within the first hours following neurotrophic factor withdrawal. Next, we tested whether inhibition of cell cycle-related cyclin-dependent kinases (cdks) can prevent motoneuronal cell death. We showed that three cdk inhibitors, olomoucine, roscovitine and flavopiridol, suppress the death of motoneurons. Finally, we observed early increases in cyclin D1 and cyclin E expression after withdrawal of neurotrophic factors. These findings support the hypothesis that after removal of trophic support, post-mitotic neuronal cells die due to an attempt to re-enter the cell cycle in an uncoordinated and inappropriate manner.


Limited sampling strategies for monitoring tacrolimus in pediatric liver transplant recipients.
To develop and validate limited sampling strategies (LSSs) for tacrolimus in pediatric liver transplant recipients. Thirty-six 12-hour pharmacokinetic profiles from 28 pediatric liver transplant recipients (0.4-18.5 years) were collected. Tacrolimus concentrations were measured by immunoassay and area under the curve (AUC0-12) was determined by trapezoidal rule. LSSs consisting of 1, 2, 3, or 4 concentration-time points were developed using multiple regression analysis. Eight promising models (2 per category) were selected based on the following criteria: r2 ≥ 0.90, inclusion of trough concentration (C0), and time points within 4 hours postdose. The predictive performance of these LSSs was evaluated in an independent set of data by measuring the mean prediction error and the root mean squared prediction error. Five models including 2-4 time points predicted AUC0-12 with a ±15% error limit. Bias (mean prediction error) and precision (root mean squared prediction error) of LSS involving C0, C1, and C4 (AUCpredicted = 9.30 + 3.69 × C0 + 2.19 × C1 + 4.69 × C4) were -4.98% and 8.29%, respectively. Among single time point LSSs, the model using C0 had a poor correlation with AUC0-12 (r2 = 0.53), whereas the one with C4 had the highest correlation with tacrolimus exposure (r2 = 0.84). Trough concentration is a poor predictor of tacrolimus AUC0-12 in pediatric liver transplant recipients. However, LSSs using 2-4 concentration-time points obtained within 4 hours postdose provide a reliable and convenient method to predict tacrolimus exposure in this population. The proposed LSSs represent an important step that will allow the undertaking of prospective trials aiming to better define tacrolimus target AUC in pediatric liver transplant recipients and to determine whether AUC-guided monitoring is superior to C0-based monitoring in terms of efficacy and safety.


Ecological study based on the distribution of recent foraminifers from southeast of Buenos Aires province, Argentinean Continental Shelf.
The study about the distribution of benthic foraminifers in relationship with the type of substrate is presented. Samples of surface sediments from 15 to 60 m of depth from the southeast coast of the province of Buenos Aires (40º 30´ - 42ºS), Argentina were analysed. The foraminiferal assemblage was constituted by forty-eight species that belong to 22 genera. It was characterized mostly by the free-living style, epifaunal microhabitats, oxic levels and a detritivore trophic strategy. Based on statistical analysis, three zones were determinated: at 15 m depth , characterized mainly by Buccella peruviana (d´Orbigny), and species of Bolivina reflected a littoral environment with sandy sediments and the most important clay contribution, whereas it also presented the lowest oxygen levels were determinated; between 24-48 m depth, associted by Ammonia parkinsoniana (d´Orbigny), Buccella peruviana and Quinqueloculina seminula (Linné), this zone displayed an oxygenated environment with coarse grainsize from inner shelf where local water circulation may explain the high energy observed; and the last one located between 36 to 58 m of depth was characterized by Buccella peruviana, Ammonia parkinsoniana, Elphidium macellum (Fichtel Moll), Cibicides dispars (d´Orbigny) and Cibicides aknerianus (d´Orbigny) regflecting an inner shelf environment with sandy sediments, the lowest water temperature and the highest oxygen levels.


A critical test of the hippocampal theta model of anxiolytic drug action.
Hippocampal theta rhythms have been associated with a number of behavioural processes, including learning, memory and arousal. Recently it has been argued that the suppression of hippocampal theta is a valid indicator of anxiolytic drug action. Like all such models, however, it has relied almost exclusively on the experimental effects of well-known, clinically proven anxiolytic compounds for validation. The actual predictive validity of putative models of anxiolytic drug action, however, cannot be rigorously tested with this approach alone. The present study provides a stringent test of the predictive validity of the theta suppression model, using the drug phenytoin (50 mg/kg and 10 mg/kg), and a positive comparison compound, diazepam (2 mg/kg). Phenytoin has two important properties that are advantageous for assessing the validity of the theta suppression model: 1) it is a standard antiepileptic drug with no known anxiolytic effects, and 2) its primary mechanism of action is through suppression of the persistent sodium current, an effect that should also suppress hippocampal theta. Because of the latter property, we also directly compared the effects of phenytoin in the theta suppression model with its effects in the most widely tested behavioural model of anxiolytic drug action, the elevated plus-maze. While an anxiolytic-like effect of phenytoin in the theta suppression model might be expected simply due to its suppressive effects on sodium channel currents, anxiolytic effects in both tests would provide strong support for the predictive validity of the theta suppression model. Surprisingly, phenytoin produced clear anxiolytic-like effects in both neurophysiological and behavioural models, thus providing strong evidence of the predictive validity of the theta suppression model. This article is part of a Special Issue entitled 'Anxiety and Depression'.


[Consensus conferences in Israel--a collaborative model for national policy making].
The determination of an integrated national policy on controversial issues is a challenge for health systems worldwide. A common method to reach agreements for national policies in different countries throughout the world is group discussion that involves all stakeholders. A structured model of discussion on medical technologies started in the 1970s, mostly in North America, spreading to Europe and in the last decade also crossed borders to India, South America and Israel. Public discussion in the format of a consensus conference is a complex process that includes a thorough literature review for technology assessment, combining academic information using a technique of close consultation with experts, extensive panel discussion and dialogue with representatives of the public. At the end of the process a broad consensus is determined facilitating national-level policy implementation. The multiple factors involved, the issues addressed, the nature of the health system where the intended results will be applied, as well as political and social characteristics, produce variations among different countries. Therefore, this process requires flexibility in adjusting the classic model according to the awakening needs. The advantages of this method include encouraging the appropriate utilization of existing technologies, contemporary assessment by leading experts, aligning between all involved parties, public sharing and more. The initial model of the consensus conference was implemented in an orderly, systematic, structured process which allowed broad discussion, and many factors for thorough preparation. The disadvantages are its complexity, length and cost. In order to cope with the dynamics of the health system in israel, forcing policymakers to make decisions in real time, parts of the model were adjusted to address the issues arising in the system. Hence, a new process was developed--a derivative of the original Israeli model, with an emphasis on professional reviews, group discussion, and involvement of leading factors in the system. The participation of patients and the public in the process requires a thorough examination.


Serum homocysteine and physical exercise in patients with Parkinson's disease.
Hyperhomocysteinemia is a major risk factor for cerebral and peripheral vascular diseases, as well as cortical and hippocampal injury, including an increased risk of dementia and cognitive impairment. Elevated serum homocysteine (Hcy) concentrations are common in patients with Parkinson's disease (PD) who have been treated with levodopa; however, physical exercises can help reduce Hcy concentrations. The aim of the present study was to compare serum Hcy levels in patients with PD who partook in regular physical exercises, sedentary PD patients, and healthy controls. Sixty individuals were enrolled in the present study across three groups: (i) 17 patients who did not partake of any type of exercise; (ii) 24 PD patients who exercised regularly; and (iii) 19 healthy individuals who did not exercise regularly. All participants were evaluated by Hoehn and Yahr scale, the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab and England scale (measure daily functionality). The serum levels of Hcy were analyzed by blood samples collected of each participant. An analysis of variance and a Tukey's post hoc test were applied to compare and to verify differences between groups. Pearson's correlation and stepwise multiple regression analyses were used to consider the association between several variables. Mean plasma Hcy concentrations in individuals who exercised regularly were similar to those in the healthy controls and significantly lower than those in the group that did not exercise at all (P= 0.000). In addition, patients who did not exercise were receiving significantly higher doses of levodopa than those patients who exercised regularly (P= 0.001). A positive relationship between levodopa dose and Hcy concentrations (R(2) = 0.27; P= 0.03) was observed in patients who did not exercise, but not in those patients who exercised regularly (R(2) = 0.023; P= 0.15). The results of the present study suggest that, even with regular levodopa therapy, Hcy concentrations in PD patients who exercise regularly are significantly lower than in patients who do not exercise and are similar Hcy concentrations in healthy controls.


Pacesetter potential of the human gastroduodenal junction.
The pacesetter potential of the gastric antrum and proximal duodenum has been recorded in man by electrodes placed under the serosal coat of the gut. The typical 3 cycle/min of the stomach was found to be conducted across the pylorus into the first part of the duodenum at a rate (2 cm/sec) about four times as fast as its conduction in the more proximal antrum (0.5 cm/sec). A 3 cycle/min pacesetter potential could be detected as far distally in the duodenum as 10 cm from the pylorus.


Real-World Analysis of the Aging Effects on Visual Field Reliability Indices in Central 10-2 Tests.
We investigated the influence of aging on the reliability indices of visual field (VF) testing using a large dataset of central 10-2 program tests, including 6674 VF tests, which consisted of 1782 eyes of 1094 Japanese subjects (the mean age ± standard deviation was 66.6 ± 14.1 years). All of the combinations for each parameter, except for the pairs between age and fixation losses (FLs) or false positives (FPs) and between pattern standard deviation (PSD) and FPs, had significant correlations (p < 0.0001). Among the reliability indices, the false negatives (FNs) had the strongest correlation against age (the correlation coefficient was ρ = 0.21). Each reliability index changes differently with aging. The FLs were the highest in the first 10 s and remained constant after 20 s. The FNs remained constant for 60 s and rose steeply after 70 s. The FPs reached their highest value in 10 s and remained constant after 40 s. In mixed-effect regression analyses in 40-year-old or older subjects, older age was significantly associated with higher FNs (p < 0.0001) but not with FLs (p = 0.9014) and FPs (p = 0.9267). Compared to central 30-2 VF testing, central 10-2 VF tests were associated with smaller FLs (p < 0.0001) and FPs (p < 0.0001). In central 10-2 testing, age-related deterioration was seen in FNs but not in FLs and FPs. Choosing the 10-2 program over the 30-2 program can be effective in reducing the FL, especially in older cases with severe VF loss. This study highlighted the relationships between age and each reliability index in central 10-2 VF testing.


Impact of Teacher Incentive Intervention on Students' Vision Healthcare Uptake: A Cluster-Randomized Controlled Trial.
Less than one-third of rural Chinese children with refractive error own or wear eyeglasses. To study the effect of teacher incentives on the acceptance of vision care offered to rural students with uncorrected refractive error, we conducted a cluster-randomized controlled trial in 18 townships in one county in Shaanxi Province. Primary and junior high schools within each township were assigned to either intervention (all teachers received an incentive) or control (no teacher incentives were offered) groups. A total of 42 schools were assigned to either the intervention group (13 schools) or the control group (29 schools). Teachers in the intervention group could elect to receive high-value (sunglasses worth USD 148), moderate-value (eyeglasses worth USD 89), or cash incentives (USD 35) if ≥70% of eligible students (uncorrected visual acuity (VA) ≤ 6/12 in both eyes and corrected VA ≤ 6/9.5 in both eyes) in the teacher's class visited a program-affiliated vision center (VC) within 60 days after their vision screening. Among 8238 students, 3401 (41.2%, of which 53.0% were girls with a mean age of 12 (SD 1.75)) met the enrollment criteria and were randomly allocated to the intervention (n = 1645, 49.0%) and control groups (n = 1579, 51.0%). Among these, 3224 (94.8%) completed the study and underwent analysis. Nearly equal numbers of students had classroom teachers selecting the high-value (n = 524, 31.9%), moderate-value (n = 582, 35.4%), and cash incentives (n = 539, 32.8%). The rate of the acceptance of offered vision care was significantly higher in the intervention group (382/1645 = 23.2%) compared to the control group (172/1579 = 10.9%, 95% confidence interval for observed difference 12.3%, p < 0.001). Teacher incentives appeared effective in improving Chinese rural school-aged children's uptake rate of vision services provided by county hospital-based VCs.


[Systematic review of the effectiveness and indications of antidigoxin antibodies in the treatment of digitalis intoxication].
Cardiac glucoside intoxication is a frequent medical problem given the following: the very narrow therapeutic range, its use in advanced aged patients, in patients with altered renal function, and because of interaction with other drugs. There are two types of digitalis intoxication: one that appears as a complication of the treatment with digitalis, and the other as a result of an accidental ingestion or in suicide attempt. The objective of this study was to review and assess the level of scientific evidence on the effectiveness and the indications of use of Fab fragments of antidigoxine antibodies. A systematic bibliographic search in the following databases was made: MEDLINE, The Cochrane Library, The Iowa Drug Information Service, Embase, LMS/R&D Insight, and Indice Médico Español. The selected papers were classified according to their level of scientific evidence. Abstracts of 252 references were reviewed. In the reviewed bibliography no controlled, randomized trials were found. Most of the studies found are descriptions of case series or single cases that were treated with antidigoxin Fab fragments. These types of studies provide little or no scientific evidence to speak of. None of the treatment regimes with antidigoxin antibody Fab fragments so far proposed have proven to be valid in a controlled, randomized clinical trial. There is a very high level of concordance among the studies reviewed with regards to the efficacy and the indications for the use of Fab fragments in severe acute accidental digitalis intoxication and in suicide attempts. Regarding those intoxications that result in patients undergoing digitalis therapy, usual therapeutic approach is traditional treatment and the monitorization of the severity of the intoxication.


Impact of adrenal versus ovarian androgen ratio on signs and symptoms of polycystic ovarian syndrome.
The aim of this study was to examine the effect of adrenal versus ovarian androgen (dehydroepiandrosterone sulfate/total testosterone [DHEAS/TT]) on clinical presentation and related metabolic disturbances in Turkish women with polycystic ovarian syndrome (PCOS). Two hundred eighty PCOS cases were taken into the study. For all cases, the DHEAS/TT ratio was calculated. The median value of this ratio was 4.40. Patients with an androgen ratio lower than 4.40 were included in Group 1 and cases with a ratio higher than 4.40 were Group 2. The two groups were compared in terms of hormonal, biochemical and clinical parameters. Body mass index and waist circumference were lower, the Ferriman-Gallwey score was higher and the cycle length was shorter in Group 2. High DHEAS level was associated with better lipid profiles and lower levels of inflammatory markers, meaning good metabolic control in these women, in spite of increased hirsutism rates. In patients with PCOS, both androgens are usually high in proportion to each other. Therefore, it would be more meaningful to use the DHEAS/TT ratio for an assessment of the metabolic and phenotypic effects of PCOS.


Production of fertile zebrafish (Danio rerio) possessing germ cells (gametes) originated from primordial germ cells recovered from vitrified embryos.
This study aimed to produce fertile zebrafish (Danio rerio) possessing germ cells (gametes) that originated from cryopreserved primordial germ cells (PGCs). First, to improve the vitrification procedure of PGCs in segmentation stage embryos, dechorionated yolk-intact and yolk-removed embryos, the PGCs of which were labeled with green fluorescent protein, were cooled rapidly after serial exposures to equilibration solution (ES) and vitrification solution (VS), which contained ethylene glycol, DMSO, and sucrose. Yolk removal well prevented ice formation in the embryos during cooling and improved the viability of cryopreserved PGCs. The maximum recovery rate of live PGCs in the yolk-removed embryos vitrified after optimum exposure to ES and VS was estimated to be about 90%, and about 50% of the live PGCs showed pseudopodial movement. Next, to elucidate the ability of cryopreserved PGCs to differentiate into functional gametes, PGCs recovered from the yolk-removed embryos (striped-type) that were vitrified under the optimum exposure to ES and VS were transplanted individually into 218 sterilized recipient blastulae (golden-type). Two days after the transplantation, 7.5% (14/187) of morphologically normal embryos had PGC(s) in the genital ridges. Six (5 males and 1 female) of the 14 recipient embryos developed into mature fish and generated progeny with characteristics inherited from PGC donors. In conclusion, we demonstrated the successful cryopreservation of PGCs by vitrification of yolk-removed embryos and the production of fertile zebrafish possessing germ cells that originated from the PGCs in vitrified embryos.