Cerebellar growth, volume and diffusivity in children cooled for neonatal encephalopathy without cerebral palsy.
Children cooled for HIE and who did not develop cerebral palsy (CP) still underperform at early school age in motor and cognitive domains and have altered supra-tentorial brain volumes and white matter connectivity. We obtained T1-weighted and diffusion-weighted MRI, motor (MABC-2) and cognitive (WISC-IV) scores from children aged 6-8 years who were cooled for HIE secondary to perinatal asphyxia without CP (cases), and controls matched for age, sex, and socioeconomic status. In 35 case children, we measured cerebellar growth from infancy (age 4-15 days after birth) to childhood. In childhood, cerebellar volumes were measured in 26 cases and 23 controls. Diffusion properties (mean diffusivity, MD and fractional anisotropy, FA) were calculated in 24 cases and 19 controls, in 9 cerebellar regions. Cases with FSIQ ≤ 85 had reduced growth of cerebellar width compared to those with FSIQ > 85 (p = 0.0005). Regional cerebellar volumes were smaller in cases compared to controls (p < 0.05); these differences were not significant when normalised to total brain volume. There were no case-control differences in MD or FA. Interposed nucleus volume was more strongly associated with IQ in cases than in controls (p = 0.0196). Other associations with developmental outcome did not differ between cases and controls.


Structure and thermal properties of salicylate-based-protic ionic liquids as new heat storage media. COSMO-RS structure characterization and modeling of heat capacities.
During this research, we present a study on the thermal properties, such as the melting, cold crystallization, and glass transition temperatures as well as heat capacities from 293.15 K to 323.15 K of nine in-house synthesized protic ionic liquids based on the 3-(alkoxymethyl)-1H-imidazol-3-ium salicylate ([H-Im-C1OC(n)][Sal]) with n = 3-11. The 3D structures, surface charge distributions and COSMO volumes of all investigated ions are obtained by combining DFT calculations and the COSMO-RS methodology. The heat capacity data sets as a function of temperature of the 3-(alkoxymethyl)-1H-imidazol-3-ium salicylate are then predicted using the methodology originally proposed in the case of ionic liquids by Ge et al. 3-(Alkoxymethyl)-1H-imidazol-3-ium salicylate based ionic liquids present specific heat capacities higher in many cases than other ionic liquids that make them suitable as heat storage media and in heat transfer processes. It was found experimentally that the heat capacity increases linearly with increasing alkyl chain length of the alkoxymethyl group of 3-(alkoxymethyl)-1H-imidazol-3-ium salicylate as was expected and predicted using the Ge et al. method with an overall relative absolute deviation close to 3.2% for temperatures up to 323.15 K.


Dexamethasone suppressible hyperaldosteronism in a child with nephrosclerosis.
A 9 year old Mexican boy presented with severe hypertension, hypokalaemia and features suggesting acute glomerulonephritis. Nephrosclerosis was present on renal biopsy. Aldosterone levels were unresponsive to variations in dietary salt intake and plasma renin activity was suppressed. Following oral dexamethasone therapy (2 mg/day), plasma aldosterone decreased to undetectable levels, serum potassium normalized and plasma renin activity gradually increased. Dexamethasone also restored the normal responsiveness of the renin-aldosterone system to postural stimuli. The patient exhibited a marked response to a single dose of ACTH with a rise in plasma aldosterone. Long-term blood pressure control and normal potassium levels have been achieved with oral prednisone therapy (5 mg/day) for a period of one year. This case of dexamethasone suppressible hyperaldosteronism (DSH) illustrates that the degree of hypertension in this syndrome may produce severe renal microvascular lesions. DSH should be considered in all children who present with low renin hypertension.


"Even though they insult us, the delivery they give us is the greatest thing": a qualitative study contextualizing women's experiences with facility-based maternal health care in Ethiopia.
Globally, amidst increased utilization of facility-based maternal care services, there is continued need to better understand women's experience of care in places of birth. Quantitative surveys may not sufficiently characterize satisfaction with maternal healthcare (MHC) in local context, limiting their interpretation and applicability. The purpose of this study is to untangle how contextual and cultural expectations shape women's care experience and what women mean by satisfaction in two Ethiopian regions. Health center and hospital childbirth care registries were used to identify and interview 41 women who had delivered a live newborn within a six-month period. We used a semi-structured interview guide informed by the Donabedian framework to elicit women's experiences with MHC and delivery, any prior delivery experiences, and recommendations to improve MHC. We used an inductive analytical approach to compare and contrast MHC processes, experiences, and satisfaction. Maternal and newborn survival and safety were central to women's descriptions of their MHC experiences. Women nearly exclusively described healthy and safe deliveries with healthy outcomes as 'satisfactory'. The texture behind this 'satisfaction', however, was shaped by what mothers bring to their delivery experiences, creating expectations from events including past births, experiences with antenatal care, and social and community influences. Secondary to the absence of adverse outcomes, health provider's interpersonal behaviors (e.g., supportive communication and behavioral demonstrations of commitment to their births) and the facility's amenities (e.g., bathing, cleaning, water, coffee, etc) enhanced women's experiences. Finally, at the social and community levels, we found that family support and material resources may significantly buffer against negative experiences and facilitate women's overall satisfaction, even in the context of poor-quality facilities and limited resources. Our findings highlight the importance of understanding contextual factors including past experiences, expectations, and social support that influence perceived quality of MHC and the agency a woman has to negotiate her care experience. Our finding that newborn and maternal survival primarily drove women's satisfaction suggests that quantitative assessments conducted shortly following delivery may be overly influenced by these outcomes and not fully capture the complexity of women's care experience.


Prevalence and risk factors for cervical and lumbar spondylosis in interventional electrophysiologists.
The volume and complexity of interventional electrophysiology procedures have increased greatly over the last 20 years. Anecdotal reports from Canada and elsewhere have suggested an important prevalence of neck and back problems in interventional electrophysiologists. To quantify the scope of neck and back problems, we surveyed 70 interventional electrophysiologists in Canada using an electronic survey with in person and email reminders. We also surveyed an age- and gender-matched group of noninterventional cardiologists. We received responses from a total of 58 of 70 interventional electrophysiologists (response rate 82.8%). There was a significantly higher prevalence of cervical spondylosis among electrophysiologists compared to matched noninterventional cardiologists (20.7% compared to 5.5%, P = 0.033). There was a trend for increased prevalence of lumbar spondylosis (25.9% compared to 16.7%, P = 0.298). Among electrophysiologists, those with cervical spondylosis were older (49.83 ± 10.48 years compared to 44.57 ± 9.20, P = 0.092) and had worked in the specialty for longer in comparison to unaffected physicians (19.67 ± 10.06 years compared to 13.37 ± 8.97 years, P = 0.039). All other variables including gender, height, weight, BMI, type of lead, weekly average lead time, and % of time standing in electrophysiology laboratory were not different. On multivariable analysis there were no independent predictors of disease. There is a significant increased prevalence of cervical spondylosis among interventional electrophysiologists. Programs to improve ergonomics and minimize time spent wearing lead are needed. The same vigilance that is used to ensure radiation safety in the laboratory should be applied to create ergonomic safety.


An anti-smoking project instituted by senior nursing students in a rural community.
The Health Council of Hawkins County, Tennessee, received a State Tobacco Prevention grant to institute an anti-smoking program in the county schools. The program chosen was called TarWars and encompasses a prohealth tobacco-free program curriculum. The goal was to discourage tobacco use among the nation's youth by focusing on tobacco's short-term ill effects. Because the program encourages community involvement, nursing students from East Tennessee State University, Johnson City, identified volunteers from the Hawkins County Retired Teachers Association to develop a teaching program for use in the first year of the program and as well as in subsequent years of the TarWars curriculum. A pretest and posttest were given to the students to assess the program's success. The objectives of the grant were that 80% of the students would be able to name three negative effects associated with tobacco use and three positive effects of not using tobacco. The goal was met when 91% could identify negative effects and 89% could identify three positive effects of not using tobacco.


Prevalence and Associated Factors of Erectile Dysfunction among Married Men in Vietnam.
Sexuality is an essential part of life; however, erectile dysfunction (ED) has been one of the most common complaints among men with sexual health issues all over the world. ED includes dysfunction in erection and penile erectile pain. In Vietnam, ED is a subject a not readily discussed. Thus, relatively little is known about ED among Vietnamese men. To identify the prevalence of ED and its associated variables and the need for treatment of ED among married men in Vietnam. This was a cross-sectional study. A total sample size included 746 married men, aged 20-60 years, living in four representative wards of the Hue City and randomly selected by systematic sampling methods. Respondents completed a self-reported questionnaire. The International Index of Erectile Function (IIEF-5) scale was used to determine ED severity, and the Depression Anxiety Stress Scales (DASS-21) was used to measure depression, anxiety, and stress. Quality of life was assessed using the WHO Quality of Life score (WHOQoL). A multivariate logistic regression model was used to determine the relationships between independent variables and ED. Mean age of married men was 44.3 ± 8.7. Two-thirds (66.9%) of respondents experienced ED symptoms. In terms of severity, 40.8% reported mild ED; 20.3% mild-moderate ED; 5.0% moderate ED; and 0.8% severe ED. Depression, anxiety, and stress problems were 5.0, 3.6, and 2.8%, respectively. One-third (33.1%) of the respondents reported having low quality of life, and 32.6% reported having medium quality of life. The vast majority (86.9%) had consensual sex with their wives/partners. Variables associated with increased IIEF-5 score were increased WHOQoL score, increased body mass index (BMI), religion, and no consumption of alcohol. Increasing age, disease history, increased anxiety, and no consensual sex with their wife/partner were associated with a lower IIEF-5 score. If experiencing ED, 55.5% would seek help from medical doctors, 55.1% discussed it with their wives/partners, and 23.1% turned to their friends for help. The prevalence of ED was high, although only 5.8% experienced moderate to severe ED. The key factors associated with ED were age, religion, disease history, BMI, alcohol consumption, anxiety, quality of life, and consensual sex with their wives/partners. Sexual health education should be more specifically targeted for men, including the provision of local sexual health-care services for men.


Assessment of the individual fracture risk of the proximal femur by using statistical appearance models.
Standard diagnostic techniques to quantify bone mineral density (BMD) include dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography. However, BMD alone is not sufficient to predict the fracture risk for an individual patient. Therefore, the development of tools, which can assess the bone quality in order to predict individual biomechanics of a bone, would mean a significant improvement for the prevention of fragility fractures. In this study, a new approach to predict the fracture risk of proximal femora using a statistical appearance model will be presented. 100 CT data sets of human femur cadaver specimens are used to create statistical appearance models for the prediction of the individual fracture load (FL). Calculating these models offers the possibility to use information about the inner structure of the proximal femur, as well as geometric properties of the femoral bone for FL prediction. By applying principal component analysis, statistical models have been calculated in different regions of interest. For each of these models, the individual model parameters for each single data set were calculated and used as predictor variables in a multilinear regression model. By this means, the best working region of interest for the prediction of FL was identified. The accuracy of the FL prediction was evaluated by using a leave-one-out cross validation scheme. Performance of DXA in predicting FL was used as a standard of comparison. The results of the evaluative tests demonstrate that significantly better results for FL prediction can be achieved by using the proposed model-based approach (R = 0.91) than using DXA-BMD (R = 0.81) for the prediction of fracture load. The results of the evaluation show that the presented model-based approach is very promising and also comparable to studies that partly used higher image resolutions for bone quality assessment and fracture risk prediction.


Omega-3 fatty acid supplementation reduces one-year risk of atrial fibrillation in patients hospitalized with myocardial infarction.
Current strategies for avoiding atrial fibrillation (AF) are of limited value. We aim to assess the relationship between omega-3 fatty acids (n-3 PUFA) and AF occurrence in post-myocardial infarction (MI) patients. A population study, linking hospital discharge records, prescription databases, and vital statistics, was conducted and included all consecutive patients with MI (ICD-9: 410) in six Italian local health authorities over a 3-year period. A propensity score (PS)-based, 5-to-1, greedy 1:1 matching algorithm was used to check consistency of results. Sensitivity analysis was performed to assess the robustness of findings. N-3 PUFA reduced the relative risk of the hospitalization for AF [hazard ratio (HR) 0.19, 95% CI 0.07-0.51] and was associated with a further and complementary reduction in all-cause mortality (HR 0.15, 95% CI 0.05-0.46). PS-based matched analysis and sensitivity analysis confirmed the main results. n-3 PUFA reduced both all-cause mortality and incidence of 1-year AF in patients hospitalized with MI.


Application of a capillary gas chromatographic-selected-ion recording mass spectrometric technique to the analysis of diethylstilbestrol and its phosphorylated precursors in plasma and tissues.
A method for the analysis of diethylstilbestrol (DES) which is suitable for pharmacokinetic studies has been developed using capillary gas chromatographic (GC) separation and detection with selected-ion mass spectrometry (MS). This technique has been applied to a variety of samples including human plasma samples and extracts of animal tissues including prostate and liver. To investigate the pharmacokinetics of stilphostrol (diethylstilbestrol diphosphate) we have modified the GC-MS method in two ways. One modification involves a dual assay for DES; the first a direct assay, and the second after hydrolysis of a sample with alkaline phosphatase. The difference in these values is the amount of phosphorylated DES present. The other modification separates stilphostrol and DES using a reversed-phase, ion-paired high-performance liquid chromatographic method followed by alkaline phosphatase hydrolysis followed by the GC-MS method. The details of these three methods are described and some representative data are shown.


Does presentation format at the Pediatric Academic Societies' annual meeting predict subsequent publication?
The validity of research presented at scientific meetings continues to be a concern. Presentations are chosen on the basis of submitted abstracts, which may not contain sufficient information to assess the validity of the research. The objective of this study was to determine 1) the proportion of abstracts presented at the annual Pediatric Academic Society (PAS) meeting that were ultimately published in peer reviewed journals; 2) whether the presentation format of abstracts at the meeting predicts subsequent full publication; and whether the presentation format was related to 3) the time to full publication or 4) the impact factor of the journal in which research is subsequently published. We assembled a list of all abstracts submitted to the PAS meetings in general pediatrics categories in 1998 and 1999, using both CD-ROM and journal publications. In each year, we chose up to 80 abstracts from each presentation format ("publish only," "poster," "poster symposium," "platform presentation"). We chose either 1) all abstracts in each format or 2) when there were >80 abstracts, a random selection of 80 of them. We assessed each selected abstract for subsequent full publication by searching Medline in March 2003; if published, then we recorded the journal, month, and year of publication. We used logistic and linear regression to determine whether publication, time to publication, and the journal's impact factor were associated with the abstract's presentation format. Overall, 44.6% of abstracts presented at the PAS meeting achieved subsequent full publication within 4 to 5 years. There were significant differences between the rates of subsequent full publication of abstracts submitted but not chosen for presentation at the meeting (22.2%) and those that were chosen for presentation in poster sessions (40.0%), poster symposia (44.1%), and platform presentations (53.8%). There were no meaningful differences between the presentation formats in their mean time to publication and their mean journal impact factor. PAS meeting attendees and the press should be cautious when interpreting the presentation format of an abstract as a predictor of either its subsequent publication in a peer-reviewed journal or the impact factor of the journal in which it will appear.


Antibody-free isolation of rare cancer cells from blood based on 3D lateral dielectrophoresis.
We present an antibody-free approach for the high-purity and high-throughput dielectrophoretic (DEP) isolation of circulating tumour cells (CTCs) from blood in a microfluidic chip. A hydrodynamic sheath flow is designed upstream in the chip to direct the suspension samples to the channel side walls, thus providing a queue to allow DEP-induced lateral displacements. High-throughput continuous cancer cell sorting (maximum flow rate: ~2.4 mL h(-1), linear velocity: ~4 mm s(-1)) is achieved with a sustained 3D lateral DEP (LDEP) particle force normal to the continuous through-flow. This design allows the continuous fractionation of micro/nanosized particles into different downstream subchannels based on the differences in their different critical negative DEP strengths/mobilities. The main advantage of this separation strategy is that increasing the channel length can effectively increase the throughput proportionally. The effective separation of rare cancer cells (<0.001%) from diluted human blood in a handheld chip is demonstrated. An enrichment factor of 10(5) and a recovery rate of ~85% from a 0.001% cancer cell sample are achieved at an optimal flow rate of 20 μL min(-1) passing through a 6 cm long LDEP channel with an appropriate voltage at a frequency of 10 kHz. A higher throughput of 2.4 mL h(-1) is also achieved with a 13 cm long metal-based microchannel.


Serotype 1-specific monoclonal antibody-based antigen capture immunoassay for detection of circulating nonstructural protein NS1: Implications for early diagnosis and serotyping of dengue virus infections.
Rapid diagnosis and serotyping of dengue virus (DV) infections are important for timely clinical management and epidemiological control in areas where multiple flaviviruses are endemic. However, the speed and accuracy of diagnosis must be balanced against test cost and availability, especially in developing countries. We developed a specific antigen capture enzyme-linked immunosorbent assay (ELISA) for early detection and serotyping of DV serotype 1 (DV1) by using well-characterized monoclonal antibodies (MAbs) specific to nonstructural protein 1 (NS1) of DV1. With this assay, a total of 462 serum specimens from clinically probable DV1-infected patients during the DV1 epidemic in Guangdong, China, in 2002 and 2003 were analyzed. DV1 NS1 was detectable in blood circulation from the first day up to day 18 after onset of symptoms, with a peak at days 6 to 10. The sensitivity of DV1 NS1 detection in serum specimens with reference to results from reverse transcriptase PCR was 82%, and the specificity was 98.9% with reference to 469 healthy blood donors. No cross-reactions with any of the other three DV serotypes or other closely related members of the genus Flavivirus (Japanese encephalitis virus and Yellow fever virus) were observed when tested with the clinical specimens or virus cultures. These findings suggest that the serotype-specific MAb-based NS1 antigen capture ELISA may be a valuable tool for early diagnosis and serotyping of DV infections, while also providing a standardized assay for the analysis of a great number of clinical samples with convenience and cost-effectiveness.


Superior transduction of mouse hematopoietic stem cells with 10A1 and VSV-G pseudotyped retrovirus vectors.
The inefficient transduction of human hematopoietic stem cells (HSC) with amphotropic retroviral vectors has been an obstacle to gene therapy for hematopoietic diseases. We have previously reported low levels of amphotropic retrovirus receptor (Pit-2) mRNA and higher levels of gibbon ape leukemia virus (GALV) or 10A1 retrovirus receptor (Pit-1) mRNA in mouse and human HSC. The vesicular stomatitis virus (VSV-G) uses an abundant membrane phospholipid as a receptor. We hypothesized that transduction of HSC requires relatively high levels of retrovirus receptor molecules. Because mouse HSC can be efficiently transduced by ecotropic virus through the abundant ecotropic receptor, the mouse is an ideal model to compare receptor levels and transduction. We have developed a cotransduction assay where ecotropic retrovirus transduction is a positive internal control for downstream steps in retrovirus transduction. A comparison of mouse HSC transduction with amphotropic, 10A1, and VSV-G envelopes showed that the level of amphotropic and 10A1 receptor mRNA in HSC correlated with the frequency of transduction. Transduction with VSV-G vectors was similar to that with 10A1 vectors. We conclude that the level of retrovirus receptor on HSC is critical for HSC transduction and that GALV or VSV-G vectors would be better for human HSC transduction.


Induction of cytochrome P450-mediated detoxification of xanthotoxin in the black swallowtail.
Xanthotoxin is a phototoxic allomone found in many of the host plants of the black swallowtail,Papilio polyxenes (Lepidoptera: Papilionidae). When added to the diet of final instar larvae, xanthotoxin can induce the cytochrome P450 monooxygenase (P450) activity in midgut microsomes by which it is detoxified. Induction is dose-dependent, increasing sevenfold when larvae feed on parsley treated topically with xanthotoxin at 0.5 or 1.0% fresh weight. Although xanthotoxin exerts much of its toxic effects when photoactivated by ultraviolet light, induction of P450 activity did not differ in the presence or absence of ultraviolet light. Despite a 4.7-fold induction of xanthotoxin-metabolizing P450 activity, total P450 content measured in the same microsomal samples did not increase significantly. These data indicate that multiple forms of P450 exist in the black swallowtail midgut and that they are differentially induced by xanthotoxin.


Promoting participation in physical activity through Snacktivity: A qualitative mixed methods study.
Public health guidance acknowledges the benefits of physical activity of any duration. We have proposed a whole-day approach to promoting physical activity called Snacktivity™, which encourages frequent 2-5 minute 'activity snacks' of moderate-to-vigorous intensity. Using repeated semi-structured interviews and a think aloud protocol, this study aimed to understand participants' experiences of integrating Snacktivity™ into daily life, to provide insights to refine the delivery of Snacktivity™ interventions. Physically inactive adults recruited via primary care and a community health service engaged with an intervention to encourage Snacktivity™ over three weeks, which included using a Fitbit and linked mobile phone app (SnackApp). Participants took part in semi-structured interviews on two occasions during the intervention, with a sub-group participating in a think aloud study. Three study data sets were generated and independently explored using inductive thematic analysis, with findings combined into a single set of themes. Eleven adults participated in the interview study who were interviewed twice (total interviews completed n = 21, 1 participant declined the second interview), of whom six completed the think aloud study (total voice recordings n = 103). Three main themes emerged from the combined data; lived experience of participating in Snacktivity™, motivation for Snacktivity™ and experiences with the Snacktivity™ technology. Participants undertook a variety of activity snacks, utilising their environment, which they believed improved their psychological wellbeing. Participants were enthusiastic about Snacktivity™, with some stating that activity snacks were more accessible than traditional exercise, but perceived they were often prevented from doing so in the presence of others. Participants were mostly enthusiastic about using the Snacktivity™ technology. Participants were able to incorporate Snacktivity™ into their lives, particularly at home, and found this approach acceptable. Participants felt they experienced health benefits from Snacktivity™ although barriers to participation were reported. This study offers insights for translating guidance into practice and supporting people to become more physically active.


Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease.
Parkinson's disease is a relentlessly progressive neurodegenerative disease. Breakdown of compensatory mechanisms influencing putaminal dopamine processing could contribute to the progressive motor symptoms. We studied a cohort of 78 subjects (at baseline) with sporadic Parkinson's disease and 35 healthy controls with multi-tracer positron emission tomography scans to investigate the evolution of adaptive mechanisms influencing striatal dopamine processing in Parkinson's disease progression. Presynaptic dopaminergic integrity was assessed with three radioligands: (i) [(11)C](±)dihydrotetrabenazine, to estimate the density of vesicular monoamine transporter type 2; (ii) [(11)C]d-threo-methylphenidate, to label the dopamine transporter; and (iii) 6-[(18)F]fluoro-L-DOPA, to assess the activity of aromatic amino acid decarboxylase and storage of 6-[(18)F]-fluorodopamine in synaptic vesicles. The subjects with Parkinson's disease and the healthy controls underwent positron emission tomography scans at the initial visit and after 4 and 8 years of follow-up. Non-linear multivariate regression analyses with random effects were utilized to model the longitudinal changes in tracer values in the putamen standardized relative to normal controls. We found evidence for possible upregulation of dopamine synthesis and downregulation of dopamine transporter in the more severely affected putamen in the early stage of Parkinson's disease. The standardized 6-[(18)F]fluoro-L-DOPA and [(11)C]d-threo-methylphenidate values tended to approach [(11)C](±)dihydrotetrabenazine values in the putamen in later stages of disease (i.e. for [(11)C](±)dihydrotetrabenazine values <25% of normal), when the rates of decline in the positron emission tomography measurements were similar for all the markers. Our data suggest that compensatory mechanisms decline as Parkinson's disease progresses. This breakdown of compensatory strategies in the putamen could contribute to the progression of motor symptoms in advanced disease.


Neonatal lamb vigour is improved by feeding docosahexaenoic acid in the form of algal biomass during late gestation.
To determine whether feeding a sustainable, algal source of docosahexaenoic acid (DHA) to sheep during late pregnancy would improve neonatal lamb vigour, 48 English mule ewes, of known conception date, were divided into four treatment groups. For the last 9 weeks of gestation, ewes received one of two dietary supplements: either a DHA-rich algal biomass providing 12 g DHA/ewe per day, or a control supplement based on vegetable oil. The four dietary treatment groups (n = 12) were: control supplement for the duration of the trial (C), DHA supplement from 9 to 6 weeks before parturition (3 week), DHA supplement from 9 to 3 weeks before parturition (6 week) and DHA supplement for the duration of the trial (9 week). Dietary supplements were fed alongside grass silage and commercial concentrate. There was a tendency for gestation length to be extended with increased duration of DHA supplementation (P = 0.08). After parturition, the concentrations of eicosapentaenoic acid (EPA) and DHA in ewe and lamb plasma and colostrum were elevated in line with increased periods of DHA supplementation. Lambs from the 6-week and 9-week groups stood significantly sooner after birth than lambs from the C group (P < 0.05). These data show that neonatal vigour may be improved by the supplementation of maternal diets with DHA-rich algal biomass and that this beneficial effect depends upon the timing and/or duration of DHA allocation.


Albendazole treatment of pulmonary hydatid cysts in naturally infected sheep: a study with relevance to the treatment of hydatid cysts in man.
Albendazole was given orally to sheep with naturally occurring live pulmonary and hepatic cysts. The viability of pulmonary cysts was established before treatment by thoracotomy and needle puncture. Both 10 and 20 mg/kg/day doses were found effective in that no viable protoscoleces were found after six weeks' treatment in either group while untreated controls still had viable cysts. In addition, treated animals showed macroscopic and electron microscopic changes. Bone marrow toxicity probably occurred in two sheep.


Effect of time and duration of untreated psychosis on cognitive and social functioning in Chinese patients with first-episode schizophrenia: A 1-year study.
Duration of untreated psychosis (DUP) is believed to exert a deleterious effect on cognitive and social function. However, to date, results remain inconclusive. To investigate the effect of time and DUP on cognitive and social functioning in first-episode schizophrenia (FES) subjects in Shanghai, China. FES patients were subjected to a comprehensive neuropsychological battery, the Personal and Social Performance scale (PSP) and the Positive and Negative Symptoms Scale (PANSS) at baseline, 6 month and 1 year. DUP was defined as the time from onset of first psychotic symptoms to first contact made with psychiatric services. Though the rate of non-completers in our observational study was relatively high (40%), we did not find any significant differences between the completers and non-completers (P-values > 0.05). Significant impairments in verbal learning and memory and executive function were noted over the course of 1 year. Meanwhile, social function improved significantly over the course of 1 year. Although, DUP did not share any significant relationship with cognitive or social function the effect estimate (range: - 0.03 to 0.02) of an increase of 1 month in DUP was clinically non-negligible in this study. In Chinese FES patients, the longitudinal course of cognitive function tends to worsen in verbal learning and memory, executive function and motor speed, while that of social function tends to improve. DUP was not found to be associated with cognitive or social deterioration in Chinese FES.


Immune effects of blood transfusion.
Blood is a complicated tissue that has been routinely applied over the past century. Since the recognition of the principles of species specificity (1818) and major compatibility for red cell antigens (1900), considerable attention has been given in the second half of this century to leukocyte-determined immune effects following transfusion. Most reactions are febrile and nonhemolytic and show, in limited situations, true relation to immune activity of transfused white blood cells. The complete picture is not yet finished; however, the more important immune effects are stimulation and modulation, tolerance and suppression. Here most work done is ex vivo and in animal experiments. Little clinical evidence has been obtained or assessment done. Most publications therefore relate to laboratory work, extrapolating results to the bedside. The most interesting publication over the review period with regard to the core immune effects of blood transfusion relates to measured concentrations of active, soluble molecules like HLA class I and II and Fas ligand molecules and to their in vitro immunomodulating effect as well as effects on induction of apoptosis. Stored red cell preparations show an increase in soluble molecules and death of viable leukocytes. Platelet preparations show similar phenomena, although information on numbers of white blood cells and storage conditions are lacking. The authors propose selective use of these aged components in specific clinical settings to allow immune suppression, induction of cell anergy, and apoptosis, whereas fresher products not showing increased levels of soluble molecules could be applied in clinical settings in which immunosuppression is not wanted. No reference is found to scientifically support and substantiate the global universal leukodepletion movement.


Giant T4 rectal carcinoma mimicking urinary bladder adenocarcinoma accurately diagnosed by immunohistochemistry and successfully treated with total pelvic exenteration: report of a case.
A 54-year-old man, with the chief complaints of hematuria, pollakisuria, and pneumaturia, was referred to our hospital, with a diagnosis of giant urinary bladder adenocarcinoma with massive invasion to the rectum. On the basis of the radiological diagnosis and findings of hematoxylin and eosin (H&E) of biopsy specimens, it was difficult to conclude whether the adenocarcinoma originated in the bladder or in the rectum. The immunohistochemical staining of the biopsy specimens showed cytokeratin 7 (CK7)(-) and CK20(+), which supported the notion that the adenocarcinoma possibly originated from the rectum. Although the prognosis of T4 bladder adenocarcinomas has been reported to be quite poor in comparison with that of transitional cell carcinomas, the postoperative prognosis of T4 rectal adenocarcinomas has been reported to be more favorable and such tumors are recommended to be surgically resected. Because no distant metastasis was detected, the patient underwent total pelvic exenteration with a reconstruction of the ileal conduit. Although the resected tumor measured 12 cm in diameter with n1 metastasis, the radial margin was cancer-negative, and the tumor was curatively resected. The immunohistochemical diagnosis of the resected tumor showed carcinoembryonic antigen(+), CK7(-), CK20(+), thrombomodulin(-), and uroplakin(-), which supported the rectal origin. At present the patient is undergoing postoperative adjuvant chemotherapy for rectal cancer.


The functional anatomy of Gilles de la Tourette syndrome.
Gilles de la Tourette syndrome (GTS) holds a prime position as a disorder transgressing the brittle boundaries of neurology and psychiatry with an entangling web of motor and behavioral problems. With tics as the disorder's hallmark and myriads of related signs such as echo-, pali- and coprophenomena, paralleled by a broad neuropsychiatric spectrum of comorbidities encompassing attention deficit hyperactivity disorder, obsessive-compulsive disorder and self-injurious behavior and depression, GTS pathophysiology remains enigmatic. In this review, in the light of GTS phenomenology, we will focus on current theories of tic-emergence related to aberrant activity in the basal ganglia and abnormal basal ganglia-cortex interplay through cortico-striato-thalamocortical loops from an anatomical, neurophysiological and functional-neuroimaging perspective. We will attempt a holistic view to the countless major and minor drawbacks of the GTS brain and comment on future directions of neuroscientific research to elucidate this common and complex neuropsychiatric syndrome, which merits scientific understanding and social acceptance.


Manipulating meat quality and composition.
Meat quality describes the attractiveness of meat to consumers. The present paper focuses on two major aspects of meat quality, tenderness and flavour. Both aspects of quality can be influenced by nutrition, principally through its effects on the amount and type of fat in meat. In several countries, high levels of intramuscular fat (marbling fat), i.e. above 30 g/kg muscle weight in longissimus, are deemed necessary for optimum tenderness, although poor relationships between fat content and tenderness have generally been found in European studies, where fat levels are often very low, e.g. below 10 g/kg in UK pigs. Muscle lipid may be a marker for red oxidative (type 1) muscle fibres which are found at higher concentrations in tender muscles and carcasses. Nutritional treatment can be used to manipulate the fatty acid content of muscle to improve nutritional balance, i.e. increase the polyunsaturated (PUFA): saturated fatty acid value and reduce the n-6:n-3 PUFA value. Increasing PUFA levels may also change flavour because of their greater susceptibility to oxidative breakdown and the generation of abnormal volatile compounds during cooking. This situation particularly applies to the n-3 PUFA which are the most unsaturated meat lipids. In pigs, a concentration of 3 mg alpha-linolenic acid (18:3)/100 mg in muscle and fat tissue fatty acids can easily be achieved by including whole linseed in the diet. This level has led to abnormal odours and flavours in some studies, but not in others. In cattle and sheep, feeding whole linseed raised 18:3 concentrations in muscle fatty acids from about 0.7 mg/100 mg to > 1 mg/100 mg. As with pigs, this diet also increased levels of long-chain n-3 PUFA formed from 18:3, including eicosapentaenoic acid (20:5). Although this increase led to greater oxidative breakdown of lipids during storage and the generation of large quantities of lipid-derived volatile compounds during cooking, there were no deleterious effects on odour or flavour. When 18:3 levels are raised in lamb and beef because of grass feeding, the intensity of the flavours increases in comparison with grain-fed animals which consume and deposit relatively more linoleic acid (18:2). In ruminants, very high levels of 18:2 produced by feeding protected oil supplements cause the cooked beef to be described as oily, bland or pork-like.


Diversification in sexual and asexual organisms.
Sexual reproduction has long been proposed as a major factor explaining the existence of species and species diversity. Yet, the importance of sex for diversification remains obscure because of a lack of critical theory, difficulties of applying universal concepts of species and speciation, and above all the scarcity of empirical tests. Here, we use genealogical theory to compare the relative tendency of strictly sexual and asexual organisms to diversify into discrete genotypic and morphological clusters. We conclude that asexuals are expected to display discrete clusters similar to those found in sexual organisms. Whether sexuals or asexuals display stronger clustering depends on a number of factors, but in at least some scenarios asexuals should display a stronger pattern. Confounding factors aside, the only explanation we identify for stronger patterns of diversification in sexuals than asexuals is if the faster rates of adaptive change conferred by sexual reproduction promote greater clustering. Quantitative comparisons of diversification in related sexual and asexual taxa are needed to resolve this issue. The answer should shed light not only on the importance of the different stages leading to diversification, but also on the adaptive consequences of sex, still largely unexplored from a macroevolutionary perspective.


Towards smart polymeric drug carriers: self-assembling γ-substituted polycaprolactones with highly tunable thermoresponsive behavior.
Synthesis and ring opening polymerization of a new γ-substituted ε-caprolactone monomer, γ-(2-methoxyethoxy)-ε-caprolactone is reported. Amphiphilic diblock copolymers comprised of poly[γ-(2-methoxyethoxy)-ε-caprolactone] and thermosensitive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone} as the hydrophobic and hydrophilic blocks, respectively, were prepared. The copolymers exhibited fully biodegradable backbones and highly tunable thermoresponsive behavior in the range of 31-43 °C. Additionally, the copolymers were shown to self-assemble in aqueous media above their respective critical micelle concentrations, on the order of 10-2 g L-1. Due to their thermosensitive, self-assembling, and biodegradable properties, these copolymers demonstrate potential for the use in polymeric micellar drug delivery systems.


Intermittently increased repetitive work intensity and neuromuscular function in the cold.
This study evaluated whether cold-induced deterioration in neuromuscular function can be restored by intermittently increasing the workload. We examined the level of muscular strain, agonist-antagonist co-activation, the occurrence of EMG gaps and neuromuscular efficiency in wrist flexor and extensor muscles at 21°C (TN) and 4°C (C(10)) with a 10%MVC workload. During second exposure to 4°C (C(50)) the workload was increased every fourth minute to 50%MVC. The results indicated that muscular strain and co-activation was the highest and the amount of EMG gaps and neuromuscular efficiency the lowest at C(10). By intermittently increasing the workload at C(50) we were able to reduce muscular strain and co-activation (p<0.05) and induce a trend like increase in EMG gaps and enhance neuromuscular efficiency in relation to C(10) (NS). It may be concluded that intermittently increasing the workload, i.e. breaking the monotonous work cycle was able to partially restore neuromuscular function.


PET/MRI of atherosclerosis.
Myocardial infarction and stroke are the most prevalent global causes of death. Each year 15 million people worldwide die due to myocardial infarction or stroke. Rupture of a vulnerable atherosclerotic plaque is the main underlying cause of stroke and myocardial infarction. Key features of a vulnerable plaque are inflammation, a large lipid-rich necrotic core (LRNC) with a thin or ruptured overlying fibrous cap, and intraplaque hemorrhage (IPH). Noninvasive imaging of these features could have a role in risk stratification of myocardial infarction and stroke and can potentially be utilized for treatment guidance and monitoring. The recent development of hybrid PET/MRI combining the superior soft tissue contrast of MRI with the opportunity to visualize specific plaque features using various radioactive tracers, paves the way for comprehensive plaque imaging. In this review, the use of hybrid PET/MRI for atherosclerotic plaque imaging in carotid and coronary arteries is discussed. The pros and cons of different hybrid PET/MRI systems are reviewed. The challenges in the development of PET/MRI and potential solutions are described. An overview of PET and MRI acquisition techniques for imaging of atherosclerosis including motion correction is provided, followed by a summary of vessel wall imaging PET/MRI studies in patients with carotid and coronary artery disease. Finally, the future of imaging of atherosclerosis with PET/MRI is discussed.


Data on the effect of high-pressure torsion processing on secondary cast Al-10%Si- Cu piston alloy: Methods, microstructure and mechanical characterizations.
The dataset presented here shows the microstructure and mechanical properties of secondary (recycled) cast aluminum-silicon (Al-Si) piston alloys processed through severe plastic deformation technique, known as high-pressure torsion (HPT). The HPT processing was undertaken for 1/4, 1/2, 1 and 10 turns of the lower anvil (rotating at constant speed of 1rpm) while the upper anvil maintained at a normal pressure of 3.0 GPa. The data on microstructural evolution obtained at the central region and edge of the circular (disk) HPT sample were obtained using optical and scanning electron microscopy and these data are presented here. The data on the analysis of the particle shape, sizes and distribution from the micrographs using ImageJ software are also presented. Data on mechanical properties characterized using Vickers microhardness measurement across the surface of HPT sample are also shown. Pictures depicting the microhardness measurement scheme, high-pressure torsion facility and sample nomenclature are presented.


Molecular basis for the inhibition of human alpha-thrombin by the macrocyclic peptide cyclotheonamide A.
The macrocyclic peptide cyclotheonamide A (CtA), isolated from the marine sponge Theonella sp., represents an unusual class of serine protease inhibitor. A complex of this inhibitor with human alpha-thrombin, a protease central to the bioregulation of thrombosis and hemostasis, was studied by x-ray crystallography. This work (2.3-A resolution) confirms the structure of CtA and reveals intimate details about its molecular recognition within the enzyme active site. Interactions due to the "Pro-Arg motif" (Arg occupancy of the S1 specificity pocket; formation of a hydrogen-bonded two-strand antiparallel beta-sheet with Ser214-Gly216) and the alpha-keto amide group of CtA are primarily responsible for binding to thrombin, with the alpha-keto amide serving as a transition-state analogue. A special interaction with the "insertion loop" of thrombin (Tyr60A-Thr60I) is manifested through engagement of the hydroxyphenyl group of CtA with Trp60D as part of an "aromatic stacking chain." Biochemical inhibition data (Ki values at 37 degrees C) were obtained for CtA with thrombin and a diverse collection of serine proteases. Thus, CtA is just a moderate inhibitor of human alpha-thrombin (Ki = 0.18 microM) but a potent inhibitor of trypsin (Ki = 0.023 microM) and streptokinase (Ki = 0.035 microM). The relative lack of potency of CtA as a thrombin inhibitor is discussed with respect to certain structural features of the enzyme complex. We also report the total synthesis of CtA, by a convergent [2 + 3] fragment-condensation approach, to serve the preparation of cyclotheonamide analogues for structure-function studies.


Abnormal calcium homeostasis in heart failure with preserved ejection fraction is related to both reduced contractile function and incomplete relaxation: an electromechanically detailed biophysical modeling study.
Heart failure with preserved ejection fraction (HFpEF) accounts for about 50% of heart failure cases. It has features of incomplete relaxation and increased stiffness of the left ventricle. Studies from clinical electrophysiology and animal experiments have found that HFpEF is associated with impaired calcium homeostasis, ion channel remodeling and concentric left ventricle hypertrophy (LVH). However, it is still unclear how the abnormal calcium homeostasis, ion channel and structural remodeling affect the electro-mechanical dynamics of the ventricles. In this study we have developed multiscale models of the human left ventricle from single cells to the 3D organ, which take into consideration HFpEF-induced changes in calcium handling, ion channel remodeling and concentric LVH. Our simulation results suggest that at the cellular level, HFpEF reduces the systolic calcium level resulting in a reduced systolic contractile force, but elevates the diastolic calcium level resulting in an abnormal residual diastolic force. In our simulations, these abnormal electro-mechanical features of the ventricular cells became more pronounced with the increase of the heart rate. However, at the 3D organ level, the ejection fraction of the left ventricle was maintained due to the concentric LVH. The simulation results of this study mirror clinically observed features of HFpEF and provide new insights toward the understanding of the cellular bases of impaired cardiac electromechanical functions in heart failure.


Nomenclatural changes on some Mediterranean Aphaenogaster Mayr, 1853 taxa (Hymenoptera, Formicidae).
The ant genus Aphaenogaster Mayr, 1853 is especially diverse in the West-Palearctic region, where its taxonomy is still problematic for several groups. Among other issues, there is a redundancy of valid taxa compared to the number of species whose validity is currently sustained by any evidence. Names that do not represent taxa with clearly defined identities complicate specimen identification and add confusion to biodiversity databases and checklists. Based on a review of the available literature information on several taxa, and the study of both type and non-type material, the following taxonomic changes are proposed: i) A. mauritanica Dalla Torre, 1893 should be considered a senior synonym of A. gibbosa homonyma Emery, 1921 syn. nov. and of A. foreli Cagniant, 1996 syn. nov. (the Maghrebian populations of the pallida group hitherto considered to represent A. foreli should be attributed to A. dulcineae Emery, 1924); ii) A. pallida (Nylander, 1849) should be considered a senior synonym of A. leveillei Emery, 1881 syn. nov. and of A. leveillei laurenti Santschi, 1939 syn. nov.; iii) A. sangiorgii (Emery, 1901) should be considered a senior synonym of A. finzii Müller, 1921 syn. nov. and A. radchenkoi Kiran & Tezcan, 2008 syn. nov.; iv) A. sardoa Mayr, 1853 should be considered a senior synonym of A. sardoa ujhelyii Szabó, 1910 syn. nov. and A. sardoa anoemica Santschi, 1910 syn. nov.; v) A. subterraneosplendida André, 1883 should be considered a senior synonym of A. sicula Emery, 1908 syn. nov.; vi) A. subterraneoides Emery, 1881 should be considered a senior synonym of A. subterraneoides armeniaca Arnol'di, 1968 syn. nov. These changes will reduce the gap between nomenclature and actual understanding of species diversity, while synonymized names may be resurrected if supporting evidence is discovered.


Effects of training dose on the relationship between discriminative-stimulus and self-reported drug effects of d-amphetamine in humans.
The aim of the present experiment was to examine the relationship between the discriminative-stimulus and self-reported effects of drugs in humans. To accomplish this aim, nine healthy adult volunteers (four females, five males) were trained to discriminate between placebo and 10 mg d-amphetamine (low-dose group) or 20 mg d-amphetamine (high-dose group). After acquiring the placebo-amphetamine discrimination, a range of doses of d-amphetamine (1.25-20 mg) was tested to determine if they shared discriminative stimulus effects with the training dose. Participants in the low-dose group exhibited a significant leftward shift in the dose-response function for discrimination performance, which is concordant with previous preclinical and human drug discrimination studies that assessed the effects of training dose. Consistent with the drug discrimination findings, participants in the low-dose group exhibited a significant leftward shift in the dose-response function for several self-reported drug effects (e.g., Like the Drug and Stimulated). However, several other self-reported drug effect items were not significantly influenced by training condition (e.g., Anxious/Nervous and Bad Effects). These results suggest that the discriminative-stimulus and self-reported drug effects of d-amphetamine overlap, but are not isomorphic. Furthermore, these results illustrate that behavioral history significantly influences subsequent drug effects in humans.


D-lysergic acid-activating enzyme from the ergot fungus Claviceps purpurea.
A D-lysergic acid-activating enzyme from the ergot fungus Claviceps purpurea was purified about 145-fold. The enzyme was able to catalyse both the D-lysergic acid-dependent ATP-pyrophosphate exchange and the formation of ATP from D-lysergic acid adenylate and pyrophosphate. Both reactions were also catalysed to a decreased but significant extent with respect to dihydrolysergic acid. The molecular mass of the enzyme was estimated to lie between 135 and 140 kDa. The involvement of the enzyme in the biosynthesis of ergot peptide alkaloids is discussed.


Impact of psoriasis disease severity and special area involvement on patient-reported outcomes in the real world: an analysis from the CorEvitas psoriasis registry.
The impact of psoriasis in special areas (i.e., scalp, nails, palms, soles, genitals) on patient physical functioning, health-related quality of life (HRQoL), and work abilities has not been fully characterized. We assessed associations between disease severity and special area involvement in psoriasis symptoms, HRQoL, and work/activity impairment. Patients with psoriasis from the CorEvitas Psoriasis Registry who initiated systemic treatment between 04/2015-06/2020 were included. Outcomes were change from baseline in psoriasis symptoms, Dermatology Life Quality Index (DLQI), and work/activity impairment at 6 months stratified by baseline disease severity and special area involvement. Among 2620 patients, increasing disease severity was associated with worsening patient-reported outcomes. Patients with (46.0%; N = 1205) versus without (54.0%; N = 1415) psoriasis in special areas reported greater HRQoL and work/activity impairment. Over 6 months, patients with unchanged or worsening disease severity had reduced HRQoL and increased symptom severity; incremental increases in patient HRQoL and decreases in symptom severity were associated with improved disease severity. Higher disease severity and special area involvement was associated with worse outcomes and impaired work abilities. These data highlight the significant impact that adequate treatment of severe psoriasis and/or special area involvement may have on patient HRQoL and function.


The nature of the in vivo sodium and chloride uptake mechanisms through the epithelium against sodium and of bicarbonate against chloride.
The Chilean frog, Calyptocephallela gayi, placed in dilute NaCl solutions may pump Na(+) and Cl(-) at very different rates depending on the kind of bath solutions in which it was preadapted. Furthermore, Na(+) and Cl(-) may be absorbed from solutions in which the accompanying coion, such as sulfate and choline, respectively, is impermeant. In all these cases it is obligatory to postulate the existence of two ionic exchange mechanisms, Cl(-) and Na(+), being exchanged against endogenous anions and cations, respectively. It has been determined that Na(+) is exchanged against endogenous H(+) and that Cl(-) is exchanged against HCO(3) (-). In animals pumping Na(+) and Cl(-) from dilute NaCl solutions Na(+) or Cl(-) uptake may be selectively inhibited, while the flux of the accompanying ion remains unchanged. This is considered to be an additional proof that both Na(+) and Cl(-) fluxes are always independent. The role of the ionic exchange mechanisms in the direct regulation of the Na(+) and Cl(-) levels in the internal medium is discussed as well as their relationship in the regulation of the acid-base equilibrium; other physioecological considerations have been treated.


Hepatitis non A, non B. Manifestations and implications of acute and chronic disease.
Application of sensitive radioimmunoassays for the detection of hepatitis A and B viruses has demonstrated that up to 25% of cases of acute sporadic hepatitis and up to 90% of cases of posttransfusion hepatitis cannot be classified by etiologic agent and warrant designation as non-A, non-B hepatitis. Epidemiologic studies have indicated a pattern of transmission similar to that of hepatitis B virus, with predominance of parenteral routes of spread. Spontaneous resolution of acute infection fails to occur in up to 60% of patients; a chronic asymptomatic but infectious carrier state is recognized. Although the chronic hepatitis is usually mild, a potential for progression to cirrhosis has been described. Transmission studies in chimpanzees have suggested the existence of at least two non-A, non-B agents, which produce strain-specific ultrastructural changes in the hepatocyte and confer a homologous immunity. Multiple assay systems for detecting putative viral antigens have been developed, but their specificity has not been confirmed. Elimination of blood procured by contract from commercial blood banks diminishes the risk of posttransfusion hepatitis and is recommended for prophylaxis. Although the effectiveness of immune serum globulin in the prevention of sporadic disease has not been established, its administration should be considered after exposure to incriminated blood, in spouses during the acute illness, and in neonates of infected mothers.


A sib-pair strategy for the use of restriction fragment length polymorphisms to study the mode of transmission of type II diabetes.
Three models for explaining the joint distribution of DNA insertional elements and type II diabetes in sibships are given as potential candidates for resolving the mode of transmission for this common non-Mendelian disorder. While the distributions predicted from all models are subject to the same rigid marginal constraints, only two models can be considered genetic (a combined major locus multifactorial background model and a two-locus model). A sequential probability ratio test is proposed to distinguish between these two models. Once the probands have been ascertained and using realistic parameter estimates, it is shown that, on the average, fewer than 100 affected sib-pairs are required to reach a decision at the 1% significance level with 99% power.


Pulse dynamics of a passively mode-locked Bi-doped fiber laser.
The pulse evolution in Bi-doped soliton fiber laser with slow and fast saturable absorber has been studied both experimentally and numerically. Semiconductor saturable absorbers with balanced slow and fast absorption recovery mechanisms exhibit a bi-temporal recovery dynamics which permits both reliable start-up of passive mode-locking and short pulse generation and stabilization. The pulse dynamics within the Bi fiber laser cavity have been investigated.


MUC1 expression in Sjogren's syndrome, KCS, and control subjects.
To quantify and compare human mucin 1 (MUC1) protein and mRNA expression in tears and conjunctival epithelial cells collected from Sjogren's syndrome (SS), non-Sjogren's keratoconjunctivitus sicca (KCS) and non-dry eyed (NDE) control subjects. Seventy-six subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 KCS (confirmed by symptoms and Schirmer scores < or = 10 mm) and 26 NDE. Tears were collected using an eye-wash technique. Impression cytology was used to gather protein and mRNA from conjunctival epithelial cells. Soluble and membrane bound MUC1 were quantified via western blotting and MUC1 mRNA was quantified by real time qPCR. The SS group demonstrated significantly higher concentrations of soluble MUC1 (0.12 +/- 0.11 [SS]; 0.013 +/- 0.02 [KCS; p=0.001]; 0.0023 +/- 0.0024 [NDE; p<0.001]) and MUC1 mRNA (3.18 +/- 1.44 [SS]; 1.79 +/- 1.18 [KCS; p<0.05]; 1.60 +/- 0.74 [NDE; p<0.05]) compared to both KCS and NDE groups. Soluble MUC1 expression was also higher in the KCS group compared to the NDE group (p=0.02), where as MUC1 mRNA expression was similar in both KCS and NDE groups. Membrane bound MUC1 expression differed only between the SS and NDE groups (0.005 +/- -0.003 [SS]; 0.003 +/- 0.002 [NDE; p=0.002]). These results demonstrate that SS subjects express greater quantities of MUC1 protein and mRNA compared to both KCS and control subjects. Increased soluble MUC1 expression was also found in KCS subjects compared to controls. Membrane bound MUC1 was present in higher concentration in SS versus NDE only. These significant changes in MUC1 expression may represent compensatory or protective responses to chronic insult to the ocular surface.


Near-Infrared Afterglow Luminescent Aggregation-Induced Emission Dots with Ultrahigh Tumor-to-Liver Signal Ratio for Promoted Image-Guided Cancer Surgery.
Afterglow imaging through the collection of persistent luminescence after the stopping of light excitation holds enormous promise for advanced biomedical uses. However, efficient near-infrared (NIR)-emitting afterglow luminescent materials and probes (particularly the organic and polymeric ones) are still very limited, and their in-depth biomedical applications such as precise image-guided cancer surgery are rarely reported. Here, we design and synthesize a NIR afterglow luminescent nanoparticle with aggregation-induced emission (AIE) characteristics (named AGL AIE dots). It is demonstrated that the AGL AIE dots emit rather-high NIR afterglow luminescence persisting over 10 days after the stopping of a single excitation through a series of processes occurring in the AIE dots, including singlet oxygen production by AIE luminogens (AIEgens), Schaap's dioxetane formation, chemiexcitation by dioxetane decomposition, and energy transfer to NIR-emitting AIEgens. The animal studies reveal that the AGL AIE dots have the innate property of fast afterglow signal quenching in normal tissues, including the liver, spleen, and kidney. After the intravenous injection of AGL AIE dots into peritoneal carcinomatosis bearing mice, the tumor-to-liver ratio of afterglow imaging is nearly 100-fold larger than that for fluorescence imaging. The ultrahigh tumor-to-liver signal ratio, together with low afterglow background noise, enables AGL AIE dots to give excellent performance in precise image-guided cancer surgery.


[Preliminary evaluation of the antiviral activity of the aqueous extract of Phyllanthus orbicularis vs HIV-1 infection].
The antiviral activity of the aqueous extract of Phyllanthus orbicularis, a member of the Euohorbiacea family, against the simple herpes virus typel was evaluated in cellular culture, specifically in fibroblasts of human prepucium, and in an animal model, Balb-c mice. The extracelullar effect of the extract on HIV-1 proved to be effective. A selective index of 44 was obtained, which shows a possible virucidal action on the particle. In the trial in vivo, the topical administration of the aqueous extract (12 mg/kg) reduced significantly the development of lesions in mice subcutaneously infected with HIV-1 (1 x 106 UFP). These results suggest the consideration of Phyllanthus orbicularis as a possible anti-HIV-1 candidate


The experience of mental health consumers as researchers.
The purpose of this study was to examine the experiences of six mental health consumers who were involved in paid employment as researchers in the mental health field. Semi-structured interviews were conducted with these individuals in order to identify any benefits experienced as a result of their employment and to identify special needs that should be considered when employing consumers. Although consumers felt they had benefitted from their employment, several unmet needs were identified. The study findings support both the benefits experienced by mental health consumers who are employed as researchers and the necessity of providing meaningful opportunities for them to give feedback on their experience.


Signal pathway profiling of prostate cancer using reverse phase protein arrays.
Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro-survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phospho-specific endpoints revealed changes in cellular signaling events through disease progression and between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient-tailored therapy.


Hyperinsulinemia and hyperglucagonemia in fasted rats during liver regeneration.
The two pancreatic hormones, insulin and glucagon, have been implicated as hepatotrophic factors for the regenerating liver after partial hepatectomy. Similar to previous studies, hyperglucagonemia and hypoinsulinemia were noted following major liver resection of initially well-fed rats. In contrast to well-fed animals, rats fasted for 24 h prior to surgery to deplete hepatic glycogen and establish low basal insulin levels developed both portal venous hyperglucagonemia and hyperinsulinemia after 67% hepatectomy. Elevation of basal portal venous levels of the two hormones suggested enhanced pancreatic secretion of insulin and glucagon in response to acute liver injury in fasted animals. Because polypeptide hormones must bind to specific hepatic cell membrane receptors to exert their hepatotrophic influences, basal portal-systemic venous differences of insulin and glucagon and glucose-elicited portal-hepatic venous insulin differences were evaluated. The evidence implies that hepatic extraction and, therefore, cell membrane receptor binding of both insulin and glucagon by regenerating livers were enhanced even though portal venous levels of the two hormones were elevated.


Mechanism of NaCl transport-stimulated prostaglandin formation in MDCK cells.
Recently we have found that stimulation of NaCl transport in high-resistance MDCK cells enhances their prostaglandin formation. In the present study, we investigated the mechanisms by which prostaglandin formation could be linked to the ion transport in these cells. We found that stimulation of transport caused a transient stimulation of prostaglandin formation lasting 5-10 min. The rise in prostaglandin formation was paralleled by a rise of free intracellular arachidonic acid. Analysis of membrane lipids revealed that the rise of free arachidonic acid was paralleled by a loss of arachidonic acid from polyphosphoinositides. We failed to obtain indications for the stimulation of calcium-dependent phospholipase A2. However, we did obtain evidence that the incorporation of arachidonic acid into phospholipids was diminished during stimulation of ion transport, indicating a decreased rate of reesterification. Despite the fact that there was no significant fall in total cellular ATP on stimulation of ion transport, we found a high and transient rise of lactate production of the cells on stimulation of the ion transport indicating an alteration of the ADP/ATP ratio. Moreover, prostaglandin formation and lactate formation were linearly correlated in this situation. When glucose utilization was inhibited by mannoheptulose, the rise in lactate formation was abolished, whereas that of PG formation was unaltered, indicating that lactate formation and prostaglandin formation were not causally linked on stimulation of ion transport. Our results suggest that an increase in the rate of sodium chloride transport by MDCK cells stimulates formation by an inhibition of reesterification of free arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of an iPad-based Speech-Generating Device Infused into Instruction with the Picture Exchange Communication System for Adolescents and Young Adults with Severe Autism Spectrum Disorder.
This study used a multiple baseline, single-subject research design to investigate the efficacy of an iPad®-based speech-generating device (SGD). The iPad was equipped with the SPEAKall!® application to function as a SGD. SGDs are a form of aided augmentative and alternative communication (AAC) allowing a user to communicate using digitized and/or synthesized speech. Instruction followed a modified version of the intervention phases from the Picture Exchange Communication System (PECS). This modified PECS protocol was implemented with two adolescents and one young adult between the ages of 14 and 23. All three participants were diagnosed with severe autism spectrum disorder and little to no functional speech. Dependent measures included the ability to request for edible and tangible items as the primary measure, and the ability to engage in natural speech production as an ancillary measure to determine simultaneous, additive effects on speech acquisition. Results indicated increases in requesting behaviors for all three participants across intervention and maintenance phases. Once participants mastered requesting of edible items, they were able to generalize the skill to tangible items. However, mixed results were found when targeting natural speech production. Based on the current findings, the infusion of an iPad-based SGD into PECS instruction may be effective in increasing initial requesting skills; however, a facilitative effect on increasing speech acquisition cannot necessarily be expected for every participant.


The Child Behavior Checklist Dysregulation Profile in Preschool Children: A Broad Dysregulation Syndrome.
Children with concurrent impairments in regulating affect, behavior, and cognition can be identified with the Anxious/Depressed, Aggressive Behavior, and Attention Problems scales (or AAA scales) of the Child Behavior Checklist (CBCL). Jointly, these scales form the Dysregulation Profile (DP). Despite persuasive evidence that DP is a marker for severe developmental problems, no consensus exists on the preferred conceptualization and operationalization of DP in preschool years. We addressed this concern by testing and validating the factor structure of DP in a group of predominantly clinically referred preschool children. Participants were 247 children (195 boys and 52 girls), aged 3.5 to 5.5 years. Children were assessed at baseline and 18 months later, using parent and teacher reports, a clinical interview with parents, behavioral observations, and neuropsychological tasks. Confirmatory factor analysis showed that a bifactor model, with a general DP factor and 3 specific factors representing the AAA scales, fitted the data better than a second-order model and a one-factor model for both parent-reported and teacher-reported child problem behavior. Criterion validity analyses showed that the DP factor was concurrently and longitudinally associated with markers of dysregulation and clinically relevant criteria, whereas the specific factors representing the AAA scales were more differentially related to those criteria. DP is best conceptualized as a broad syndrome of dysregulation that exists in addition to the specific syndromes as represented by the AAA scales. Implications for researchers and clinicians are discussed.


Electric energy generator.
This study reports an extremely cost-effective mechanism for converting wind energy into electric energy using piezoelectric bimorph actuators at small scale. The total dimensions of the electric energy generator are 5.08 x 11.6 x 7.7 cm3. The rectangular, box-shaped body of the overall structure is made using 3.2-mm thick plastic. Slits are made on two opposite faces of the box so that two columns and six rows of bimorph actuators can be inserted. Each row of bimorph actuators is separated from each other by a gap of 6 mm, and the two columns of bimorphs are separated from each other by a gap of 6.35 mm. In between the two columns, a cylindrical rod is inserted consisting of six rectangular hooks. The hooks are positioned in such a way that each of them just touches the two bimorphs on either side in a particular row. As the wind flows across the generator, it creates a rotary motion on the attached fan that is converted into vertical motion of the cylindrical rod using the cam-shaft mechanism. This vertical motion of the cylindrical rod creates oscillating stress on the bimorphs due to attached hooks. The bimorphs produce output voltage proportional to the applied oscillating stress through piezoelectric effect. The prototype fabricated in this study was found to generate 1.2 mW power at a wind speed of 12 mph across the load of 1.7 komega.


[The frequency of irregular erythrocyte antibodies (author's transl)].
Investigations to demonstrate irregular erythrocyte antibodies showed an increase in the number of sensitizations due to blood transfusions as well as an increase of the antibodies anti-E and anti-Kell. A reorganization of the blood transfusion system should be considered. It seems necessary to detect patients with irregular antibodies as early as possible. This should be done by follow-up investigations after blood transfusion and by antibody screening tests before transfusion. Blood groups estimated previously should not be relied upon during subsequent hospital admissions.


Combination approaches in NSCLC involving immune checkpoint inhibitors.
Immune checkpoint inhibition has been proven to be highly efficacious in NSCLC and associated with durable responses in a limited number of patients. Chemotherapy and targeted therapies, which have also expanded rapidly in this field lead to high response rates and improved survival although inevitably resistance occurs and hence treatment failure. There is increasing evidence showing that chemotherapy and targeted therapy interplay with the immune system including exerting effects on tumor cells and the host immune cells. Naturally combining both of these treatment modalities to induce cytotoxic effects on tumor cells to release tumor antigens and priming of the immune system should in turn lead to enhanced anticancer activity. This review will explore some of the preclinical rationale and clinical trial data we have to date on combining various systemic therapies with immunotherapies.


Serum levels of lysozyme in term and preterm newborns.
Serum lysozyme levels were studied in term babies at the time of delivery and again between 7th and 30th postnatal days, and in preterm babies on the 1st, 3rd, and 5th postnatal days. Levels in term babies at delivery (mean 2.28 mug/ml) were similar to those found in adults, but they fell between the 7th and 30th postnatal days. In premature babies lysozyme levels on the first day of live (mean (0.82 mug/ml) were lower than in term babies. They tended to rise during the first 5 days, by which time they had reached levels found in term babies between the 7th and 30th days. The low lysozyme levels in preterm and in term babies after the first few days of life may contribute to the poor ability of the newborn baby to localize infection and to kill bacteria extracellularly.


Transient responses of heart rate, arterial pressure, and head movement at the beginning of eating in awake cats.
Time courses of heart rate (HR), arterial pressure (AP), and head movement at the beginning of eating were analyzed in conscious cats. The cats were trained to eat when movements of their body trunks were restrained. Food was presented for 10 sec at intervals of 100 sec. With the abrupt presentation of food, a head-down movement occurred immediately and thereafter eating started with a mean latency of 1.6 sec. During eating HR increased by 22% from the preeating value and AP was elevated by 11%. To determine the time relation between the onset of eating and the change in each variable in response to eating, mean time courses of HR, AP, and head movement were obtained from 7-40 trials in each cat. The head-down movement preceded the onset of eating by 1.3 sec. The increase in HR preceded the onset of eating by 0.2 sec; the change in AP followed it by 3-4 sec. This indicated that the increase in HR was not induced reflexly either by food intake or by the change in AP. After administration of hexamethonium, the changes in HR and AP in response to eating were abolished, although eating was evoked by the food presentation. Additionally, the increase in HR was also reduced by propranolol and atropine. Thus, the acceleration of HR at the beginning of eating may be induced by central activation of the autonomic nervous system.


Prevention of ankle sprains.
Two different methods for the prevention of ankle joint injuries in soccer were tested. Coordination training on an ankle disk improves functional stability and postural control, whereas an orthosis provides mechanical support. Both techniques reduce the frequency of ankle sprains in soccer players with previous ankle problems. The orthosis is an alternative to taping, and can be used during the rehabilitation period after injury or when playing on uneven ground. Coordination training on an ankle disk ought to be included in the rehabilitation of ankle injuries to prevent functional instability. It may also be done prophylactically by players with previous ankle problems in order to break the vicious circle of recurrent sprains and feeling of giving way.


Copper induces Cu-ATPase ATP7A mRNA in a fish cell line, SAF1.
Copper transporting ATPase, ATP7A, is an ATP dependent copper pump present in all vertebrates, critical for the maintenance of intracellular and whole body copper homeostasis. Effects of copper treatment on ATP7A gene expression in fibroblast cells (SAF1) of the sea bream (Sparus aurata) were investigated by qRT-PCR and by a medium density microarray from a closely related species, striped sea bream (Lithognathus mormyrus). To discriminate between the effects of Cu and other metals, SAF1 cells were exposed to sub-toxic levels of Cu, Zn and Cd. Expression of Cu homeostasis genes copper transporter 1 (CTR1), Cu ATPase (ATP7A), Cu chaperone (ATOX1) and metallothionein (MT) together with the oxidative stress markers glutathione reductase (GR) and Cu/Zn superoxide dismutase (CuZn/SOD) were measured 0, 4 and 24 hours post-exposure by qRT-PCR. Microarray was conducted on samples from 4 hours post Cu exposure. Cu, Zn and Cd increased MT and GR mRNA levels, while only Cu increased ATP7A mRNA levels. Microarray results confirmed the effects of Cu on ATP7A and MT and in addition showed changes in the expression of genes involved in protein transport and secretion. Results suggest that ATP7A may be regulated at the transcriptional level directly by Cu and by a mechanism that is different from that exerteted by metals on MT genes.


Apolipoprotein C-III-1 activates lysosomal sphingomyelinase in vitro.
Apolipoprotein (apo)C-III-1 from human very low density lipoprotein stimulates 14-fold the activity of lysosomal sphingomyelinase from human fibroblasts. At the sphingomyelin concentrations tested, maximal stimulation was obtained with 5 microM apoC-III-1 or apoC mixture. Apolipoproteins A-I, A-II, B, and C-I conferred little or no stimulation. Sphingomyelinase was stimulated 20-fold by lysophosphatidylcholine with an optimum concentration of 70 microM using 0.3 mM substrate. Sphingomyelinase activity was inhibited by concentrations of apoC-III-1 and lysophosphatidylcholine three- to fivefold above stimulatory levels. Triton X-100 activated sphingomyelinase 300-fold with a pH optimum of 5.0, while the pH optimum with the biological activators was 4.0. These results raise the possibility of an in vivo activity for the biological activators. The proteins that enter lysosomes as part of a lipoprotein complex may activate lysosomal enzymes that degrade the lipid components.


Characterization of a novel topoisomerase I mutation from a camptothecin-resistant human prostate cancer cell line.
In this study, we characterized the structure and function of topoisomerase I (top1) protein in the camptothecin (CPT)-resistant prostate cancer cell lines, DU-145/RC0.1 and DU-145/RC1 (RC0.1 and RC1, respectively). Both of the cell lines were previously selected by continuous exposure to 9-nitro-CPT. The RC0.1 and RC1 cells have high cross-resistance to CPT derivatives including SN-38 and topotecan, but are not cross-resistant to the non-top1 inhibitors etoposide, doxorubicin, and vincristine. Although the top1 protein levels were not decreased in the resistant cells compared with the parental cells, CPT-induced DNA cleavage was markedly reduced in the RC0.1 and RC1 nuclear extracts. The resistant-cell-line nuclear extracts also demonstrated top1 catalytic activity and resistance to CPT, in in vitro assays. Reverse transcription-PCR products from the resistant cell lines were sequenced, and revealed a point mutation resulting in a R364H mutation in the top1 of both RC0.1 and RC1. No wild-type top1 RNA or genomic DNA was detected in the resistant cell lines. Using a purified recombinant R364H top1, we found that the R364H mutant top1 was CPT resistant and fully active. In the published top1 crystal structure, the R364H mutation is close to the catalytic tyrosine and other well-known mutations leading to CPT resistance.


Mortality, mental disorders and addiction: a 5-year follow-up of 82 homeless men in Stockholm.
A 5-year follow-up study was performed on 82 homeless men, with mental problems, who had been contacted by an outreach team run by the Social welfare administration of Stockholm 1995/1996. Data have been collected from the Cause of Death Register, death certificates, forensic autopsy reports, hospital medical reports, Hospital Discharge Register, interviews with social workers and with those men who were able to participate. The standardized mortality ratio (SMR) was 4.7 times higher than expected. The highest mortality was found in the group where drug addiction was dominant; 46% had died. In the group of men with severe psychiatric disorders, with diagnosis such as schizophrenia, none had died. Compared with the others, they had spent less time in homelessness. Among the survivors, 75% were still homeless at the follow-up in spite of considerable treatment interventions from the social services and health authorities. Residential institutions or treatment seemed to have some protective effect concerning misuse, diseases and injuries. Among the still homeless, the mental health problems combined with substance use problems had increased with 17%. The life and housing situation for the whole group seemed not to have improved, even if fewer of them were staying in hostels for homeless people.


Sublethal enteroviral infection exacerbates disease progression in an ALS mouse model.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor neuron system associated with both genetic and environmental risk factors. Infection with enteroviruses, including poliovirus and coxsackievirus, such as coxsackievirus B3 (CVB3), has been proposed as a possible causal/risk factor for ALS due to the evidence that enteroviruses can target motor neurons and establish a persistent infection in the central nervous system (CNS), and recent findings that enteroviral infection-induced molecular and pathological phenotypes closely resemble ALS. However, a causal relationship has not yet been affirmed. Wild-type C57BL/6J and G85R mutant superoxide dismutase 1 (SOD1G85R) ALS mice were intracerebroventricularly infected with a sublethal dose of CVB3 or sham-infected. For a subset of mice, ribavirin (a broad-spectrum anti-RNA viral drug) was given subcutaneously during the acute or chronic stage of infection. Following viral infection, general activity and survival were monitored daily for up to week 60. Starting at week 20 post-infection (PI), motor functions were measured weekly. Mouse brains and/or spinal cords were harvested at day 10, week 20 and week 60 PI for histopathological evaluation of neurotoxicity, immunohistochemical staining of viral protein, neuroinflammatory/immune and ALS pathology markers, and NanoString and RT-qPCR analysis of inflammatory gene expression. We found that sublethal infection (mimicking chronic infection) of SOD1G85R ALS mice with CVB3 resulted in early onset and progressive motor dysfunction, and shortened lifespan, while similar viral infection in C57BL/6J, the background strain of SOD1G85R mice, did not significantly affect motor function and mortality as compared to mock infection within the timeframe of the current study (60 weeks PI). Furthermore, we showed that CVB3 infection led to a significant increase in proinflammatory gene expression and immune cell infiltration and induced ALS-related pathologies (i.e., TAR DNA-binding protein 43 (TDP-43) pathology and neuronal damage) in the CNS of both SOD1G85R and C57BL/6J mice. Finally, we discovered that early (day 1) but not late (day 15) administration of ribavirin could rescue ALS-like neuropathology and symptoms induced by CVB3 infection. Our study identifies a new risk factor that contributes to early onset and accelerated progression of ALS and offers opportunities for the development of novel targeted therapies.


Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life.
Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aim of the study was to determine the prevalence and predictors of vitamin D deficiency in an IBD cohort. It was hypothesized that vitamin D deficiency is associated with increased disease activity and lower health-related quality of life (HRQOL). This was a retrospective cohort study. Harvey-Bradshaw index and ulcerative colitis disease activity index were used to assess disease activity. Short Inflammatory Bowel Disease Questionnaire scores were used to assess HRQOL. Multivariate logistic regression was used to identify independent predictors of vitamin D deficiency and its association with disease activity and HRQOL. The study included 504 IBD patients (403 Crohn's disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with older age (P = .004) and older age at diagnosis (P = .03). Vitamin D deficiency was associated with lower HRQOL (regression coefficient -2.21, 95% confidence interval [CI], -4.10 to -0.33) in CD but not UC (regression coefficient 0.41, 95% CI, -2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71). Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.


Studies of inactivated influenza virus vaccines in hospital employees: reactogenicity and absenteeism.
The impact of a mass influenza vaccination program on the operation of a major medical center was evaluated in adult volunteer employees who were given either ether-split or whole-virus bivalent influenza vaccine in a double-blind manner by jet-injector gun. Each volunteer completed a reaction information form, nurses monitored temperatures, and data on absenteeism of the employees of the Nursing Service and the Building Management Service were collected. The results of this study demonstrated that the mass campaign did not adversely affect absenteeism. However, the whole-virus vaccine caused significantly more local, systemic, and febrile reactions thant the split-virus vaccine. Purified inactivated influenza virus vaccines can be given in a mass campaign to hospital personnel without adversely affecting the operation of the hospital.


BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation.
Blood vessel epicardial substance (BVES/Popdc1) is a junctional-associated transmembrane protein that is underexpressed in a number of malignancies and regulates epithelial-to-mesenchymal transition. We previously identified a role for BVES in regulation of the Wnt pathway, a modulator of intestinal stem cell programs, but its role in small intestinal (SI) biology remains unexplored. We hypothesized that BVES influences intestinal stem cell programs and is critical to SI homeostasis after radiation injury. At baseline, Bves(-/-) mice demonstrated increased crypt height, as well as elevated proliferation and expression of the stem cell marker Lgr5 compared to wild-type (WT) mice. Intercross with Lgr5-EGFP reporter mice confirmed expansion of the stem cell compartment in Bves(-/-) mice. To examine stem cell function after BVES deletion, we used ex vivo 3D-enteroid cultures. Bves(-/-) enteroids demonstrated increased stemness compared to WT, when examining parameters such as plating efficiency, stem spheroid formation, and retention of peripheral cystic structures. Furthermore, we observed increased proliferation, expression of crypt-base columnar "CBC" and "+4" stem cell markers, amplified Wnt signaling, and responsiveness to Wnt activation in the Bves(-/-) enteroids. Bves expression was downregulated after radiation in WT mice. Moreover, after radiation, Bves(-/-) mice demonstrated significantly greater SI crypt viability, proliferation, and amplified Wnt signaling in comparison to WT mice. Bves(-/-) mice also demonstrated elevations in Lgr5 and Ascl2 expression, and putative damage-responsive stem cell populations marked by Bmi1 and TERT. Therefore, BVES is a key regulator of intestinal stem cell programs and mucosal homeostasis. Stem Cells 2016;34:1626-1636.


Does Suprapubic Stimulation in Infants Facilitate Collection of a Clean Catch Urine Specimen?
Review of recent evidence with translation to practice for the advanced practice nurse (APN) role is presented using a case study module for "Faster Clean Catch Urine Collection (Quick Wee Method) From Infants: Randomised Controlled Trial." This prospective study enrolled 344 infants between 1 and 12 months of age seeking care in an emergency department with a complaint that led to the ordering of a clean catch urine specimen. Use of the Quick Wee procedure yielded clean catch urine specimens without the use of an invasive procedure. Variables of interest were time to specimen collection and patient and provider satisfaction with procedure. Study subjects in the intervention group voided spontaneously within 5 min more often than subjects in the usual care group. This study highlights the important role of the APN in ordering clean catch urine specimen collection and avoidance of invasive procedures.


Pharmacokinetic study of metopimazine by oral route in children.
Metopimazine (MPZ) is an antiemetic considered as a currently used drug. In France, it has become the leading antiemetic mediator due to its good tolerance, however, its pharmacokinetics has never previously been studied in children. MPZ was administered by oral route to 8 children with a single dose of 0.33 mg/kg during an endocrine exploration using stimuli well known for its adverse emetic effects. We used biological remnants from sera following an hGH test in order to obtain the MPZ pharmacokinetics. Plasmatic concentrations of MPZ and the active acid metabolite AMPZ, were quantified by HPLC-MS/MS during a 270 min test period. MPZ is quickly absorbed with a median C max of 17.2 ng/mL at one hour and its half-life is 2.18 h. The plasmatic concentrations of AMPZ were higher than MPZ with a median C max of 76.3 ng/mL, a T max to 150 min and its concentration was approximately maintained at 50 ng/mL from 1 to 4 h. The plasmatic concentrations in children are similar to those observed in adults. No adverse effects, nausea or vomiting occurred during the trial. Therefore, these results confirm the MPZ dosage that should be used in children under 15 kg administered as 0.33 mg/kg up to 3 times a day.


University students' satisfaction with, interest in improving, and receptivity to attending programs aimed at health and well-being.
The purpose of this pilot study is to investigate students' (a) satisfaction with nine health constructs, (b) interest in improving these health areas, and (c) receptivity to participating in programming targeting these areas. The study sample is composed of 1,778 undergraduate students from a Canadian university. Students complete a five-page paper-and-pencil questionnaire assessing the above objectives along a 5-point Likert-type scale. Students are most satisfied with their social health and report their lowest satisfaction with physical activity (M = 3.16, SD = 1.09). Overall, students are most interested in enhancing their physical activity (M = 4.10, SD = 0.79), followed by both body image (M = 3.94, SD = 0.89) and dietary habits (M = 3.94, SD = 0.85), and are receptive to programs aimed at improving their level of physical activity (M = 3.62, SD = 0.98) and body image (M = 3.42, SD = 1.63). A preference for physical activity level and body image improvement among university students is revealed and should be considered of paramount importance by campus-based health promotion practitioners.


Pharmacologic evidence for 5-HT1A receptors associated with human retinal pigment epithelial cells in culture.
The authors investigate the possible presence of 5-hydroxytryptamine (5-HT1) type serotonin receptors negatively coupled to adenylate cyclase activity in cultured human retinal pigment epithelial (RPE) cells. Adenylate cyclase activity was assessed by the determination of cellular adenosine 3':5' cyclic monophosphate (cAMP) levels and the effects of serotonin on both basal and forskolin-stimulated cAMP levels studied. Serotonin at 100 microM had no effect on the basal levels of cAMP in cultured human RPE cells, but attenuated by 43.6% the stimulation in cAMP production induced by forskolin (5 microM). This effect was dose dependent for serotonin with half-maximal inhibition (EC50) occurring at approximately 1.5 x 10(-9) M. The 5-HT1 receptor agonist 8-hydroxy [2-di-n-propylamino] tetralin (8-OH DPAT), buspirone, 5-carboxyamidotryptamine, and RU24969 mimicked the inhibitory effect of serotonin in a dose-dependent manner. The actions of serotonin and 8-OH DPAT (10 microM) were dose-dependently attenuated by the serotonergic antagonists spiroxatrine, propranolol, and spiperone. Pretreatment of RPE cell cultures with pertussis toxin abolished the serotonin-induced reduction of forskolin-elevated cAMP levels. Stimulation of cAMP production by the beta-adrenoceptor agonist isoproterenol at 0.1 microM, but not at 10 microM or 100 microM, also was attenuated by serotonin (100 microM), whereas cAMP production induced by the adenosine receptor agonist 5'-[N-ethyl]-carboxamidoadenosine (NECA) at 1 microM, 10 microM, and 100 microM was unaffected. Serotonin and 8-OH DPAT dose-dependently inhibited isoproterenol-stimulated (0.1 microM) cAMP production with EC50 values of approximately 10 microM, and pertussis toxin pretreatment partially blocked these effects. Cultured human RPE cells possess 5-HT1A receptors negatively coupled to cAMP production through a pertussis toxin-sensitive G protein. These receptors show differential effects on forskolin-, isoproterenol-, and NECA-stimulated cAMP production, which may reflect a unique spatial distribution of receptor proteins or the phenotypic heterogeneity of RPE cells that is the result of or that is preserved in culture.


Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures.
Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4-22.6%) that associates with reduced spine BMD (P=1.0 × 10(-11), β=-0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6 × 10(-10), β=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus.