Fyn Kinase regulates GluN2B subunit-dominant NMDA receptors in human induced pluripotent stem cell-derived neurons

NMDA receptor (NMDAR)-mediated fast excitatory neurotransmission is implicated in a broad range of physiological and pathological processes in the mammalian central nervous system. The function and regulation of NMDARs have been extensively studied in neurons from rodents and other non-human species, and in recombinant expression systems. Here, we investigated human NMDARs in situ by using neurons produced by directed differentiation of human induced pluripotent stem cells (iPSCs). The resultant cells showed electrophysiological characteristics demonstrating that they are bona fide neurons. In particular, human iPSC-derived neurons expressed functional ligand-gated ion channels, including NMDARs, AMPA receptors, GABAA receptors, as well as glycine receptors. Pharmacological and electrophysiological properties of NMDAR-mediated currents indicated that these were dominated by receptors containing GluN2B subunits. The NMDAR currents were suppressed by genistein, a broad-spectrum tyrosine kinase inhibitor. The NMDAR currents were also inhibited by a Fyn-interfering peptide, Fyn(39-57), but not a Src-interfering peptide, Src(40-58). Together, these findings are the first evidence that tyrosine phosphorylation regulates the function of NMDARs in human iPSC-derived neurons. Our findings provide a basis for utilizing human iPSC-derived neurons in screening for drugs targeting NMDARs in neurological disorders

How many sentinel nodes should be harvested in oral squamous cell carcinoma?

The number of harvested lymph nodes when performing sentinel lymph node (SLN) biopsy remains controversial. The aim of this study was to examine the maximum number of nodes to be harvested for histopathological analysis. We also wanted to determine if the level of radioactivity within a SLN or its size were indicators for the likelihood of nodal metastases. The SLNs from 34 neck dissection specimens from patients with T1/T2 N0 oral and oropharyngeal carcinomas were included. Altogether 76 SLNs were measured for radioactivity and lymph node dimensions and volume. Tumour was identified in 16 of 76 nodes (positive nodes), and the remaining 60 nodes were free from tumour (negative nodes). In 9 of 16 cases, metastases were in the hottest node. Two patients had more than one positive SLN: the first and fourth hottest in one and the second and fourth hottest nodes in another contained tumour. However, all patients would have been staged accurately if only the hottest three sentinel nodes had been retrieved. Lymph nodes that contained tumour had a greater maximum diameter than non-metastatic SLNs. To stage the neck accurately, only the three hottest lymph nodes required sampling

Upper body movement analysis of multiple limb asymmetry in 367 clinically lame horses

Background Compensatory lameness is common in horses and evaluation can be challenging. Objectives To investigate patterns of compensatory movements in clinical cases with fore- or hindlimb lameness before and after diagnostic analgesia. Study design Retrospective clinical study. Methods Multiple limb lameness of 367 horses was characterised by type (push-off, impact or mixed), limb (fore- or hindlimb in predominant lameness) and side (ipsi- or contralateral in concurrent lameness) using a body-mounted inertial sensor (BMIS). Diagnostic analgesia was performed until the percentage improvement of the vector sum in forelimb lameness and the mean difference of the maximum or minimum pelvic height (PDmax or PDmin) in hindlimb lameness was >= 50%. Linear mixed model and post-estimation of effects were performed by contrast command with multiple comparisons adjusted by Bonferroni method. Correlation of pre- and post-analgesia of all head and pelvis asymmetry parameters was tested with Spearman's rank correlation. Results Improvement in vector sum per mm after diagnostic analgesia in forelimb impact lameness positively correlated with decrease in PDmax in contralateral mixed lameness (0.187 mm, r = .58, P < .05). Improvement in PDmin per mm after diagnostic analgesia in hindlimb mixed and PDmax in hindlimb push-off lameness decreased vector sum in ipsilateral forelimb impact lameness by 0.570 and 0.696 mm, respectively (P < .05), with no positive correlation. Main limitations A variety of cases with inhomogeneous distribution of lameness patterns was investigated retrospectively, therefore, it is impossible to distinguish between true multiple limb lameness and compensatory lameness in this clinical material. Conclusions Various asymmetry patterns of concurrent lameness were seen in horses with naturally occurring primary forelimb impact lameness with contralateral compensatory hindlimb lameness with a mixed component being the most common. In horses with hindlimb lameness, compensatory movements were seen in ipsilateral forelimbs, mostly as an ipsilateral impact lameness during straight line trot

Systematic review and meta-analysis: prevalence of alcohol use among young people in eastern Africa.

OBJECTIVE: Systematic review and meta-analysis of published studies of alcohol use among young people (age 15-24 years) in eastern Africa to estimate prevalence of alcohol use and determine the extent of use of standardised screening questionnaires in alcohol studies. METHODS: Five databases (MEDLINE, EMBASE, Global Health, Africa-wide, and PsycINFO) were searched for publications until 30th June 2013. Results were summarised using the guidelines on preferred reporting items for systematic reviews and meta-analyses (PRISMA) and on quality assessment using the modified quality assessment tool for systematic reviews of observational studies (QATSO). Heterogeneity was assessed using the I(2) statistic (DerSimonian-Laird). RESULTS: We identified 2785 potentially relevant studies, of which 56 were eligible for inclusion. Only two studies (4%) used the standardised Alcohol Use Disorder Identification Test (AUDIT) questionnaire, and six studies (13%) used the Cut down, Annoyed, Guilt, Eye opener (CAGE) questionnaire. The reported median prevalence of alcohol use was ever-use 52% [interquartile range (IQR): 20-58%], use in the last month 28% (IQR: 17-37%), use in the last year 26% (IQR: 22-32%), and problem drinking as defined by CAGE or AUDIT 15% (IQR: 3-36%). We observed high heterogeneity between studies, with the highest prevalence of ever use of alcohol among university students (82%; 95%CI: 79-85%) and female sex workers (66%; 95%CI: 58-74%). Current use was most prevalent among male sex workers (69%; 95%CI: 63-75%). CONCLUSIONS: Reported alcohol use and problem drinking were common among diverse groups of young people in eastern Africa, indicating the urgent need for alcohol-focused interventions in this population. Few studies have used standardised alcohol screening questionnaires. Epidemiological research to investigate alcohol-focused interventions in young people should aim to apply such questionnaires that should be validated for use in this population

Predictors of Unrecognized HIV Infection Among Poor and Ethnic Men Who Have Sex with Men in Los Angeles

This study evaluates associations between unrecognized HIV infection and demographic factors, internalized homonegativity, drug use, and sexual behaviors among HIV positive men who have sex with men (MSM). We analyzed data from 347 HIV positive participants from the Los Angeles site for NIDA’s Sexual Acquisition and Transmission of HIV-Cooperative Agreement Program. Participants were HIV positive MSM and MSM/W and predominantly African American (36.0%) or Latino (38.7%), and unemployed (82.8%). Results from a multivariate logistic regression suggest that, compared to HIV positive participants who correctly reported their HIV positive status, being African-American (OR: 9.81, CI: 1.2–77.9) or Latino (OR: 10.92, CI: 1.3–88.4) rather than White, MSM/W rather than MSM (OR: 3.24, CI: 1.09–9.62), and having higher homonegativity scores (OR: 1.22, CI: 1.02–1.4) is associated with unrecognized HIV infection, controlling for age, education, and homelessness. Findings provide some immediate evidence to help craft HIV prevention interventions

Window screening, ceilings and closed eaves as sustainable ways to control malaria in Dar es Salaam, Tanzania.

BACKGROUND\ud \ud Malaria transmission in Africa occurs predominantly inside houses where the primary vectors prefer to feed. Human preference and investment in blocking of specific entry points for mosquitoes into houses was evaluated and compared with known entry point preferences of the mosquitoes themselves.\ud \ud METHODS\ud \ud Cross-sectional household surveys were conducted in urban Dar es Salaam, Tanzania to estimate usage levels of available options for house proofing against mosquito entry, namely window screens, ceilings and blocking of eaves. These surveys also enabled evaluation of household expenditure on screens and ceilings and the motivation behind their installation.\ud \ud RESULTS\ud \ud Over three quarters (82.8%) of the 579 houses surveyed in Dar es Salaam had window screens, while almost half (48.9%) had ceilings. Prevention of mosquito entry was cited as a reason for installation of window screens and ceilings by 91.4% (394/431) and 55.7% (127/228) of respondents, respectively, but prevention of malaria was rarely cited (4.3%, 22/508). The median cost of window screens was between US $21-30 while that of ceilings was between US$301-400. The market value of insecticide-treated nets, window screening and ceilings currently in use in the city was estimated as 2, 5 and 42 million US$. More than three quarters of the respondents that lacked them said it was too expensive to install ceilings (82.2%) or window screens (75.5%).\ud \ud CONCLUSION\ud \ud High coverage and spending on screens and ceilings implies that these techniques are highly acceptable and excellent uptake can be achieved in urban settings like Dar es Salaam. Effective models for promotion and subsidization should be developed and evaluated, particularly for installation of ceilings that prevent entry via the eaves, which are the most important entry point for mosquitoes that cause malaria, a variety of neglected tropical diseases and the nuisance which motivates uptake

High birth weight as an important risk factor for infant leukemia

In this paper, we compared the birth weight distribution among 201 infant leukaemia (IL) cases with that of 440 noncancer controls enrolled in Brazil in 1999–2005. Compared with the general population and the stratum 2500–2999 g as reference, IL cases weighing 3000–3999 g presented an odds ratio (OR) of 1.68 (95% CI: 1.03–2.76), and those of 4000 g or more, an OR of 2.28 (95% CI: 1.08–4.75), Ptrend<0.01. Using hospital-based controls, the OR for 4000 g or more, compared to 2500–2999 g, was 1.30 (95% CI: 1.02–1.43) after adjusting for confounders (gender, income, maternal age, pesticide and hormonal exposure during pregnancy). The results suggest that high birth weight is associated with increased risk of IL

Healthcare Reform and the Next Generation: United States Medical Student Attitudes toward the Patient Protection and Affordable Care Act

CONTEXT: Over one year after passage of the Patient Protection and Affordable Care Act (PPACA), legislators, healthcare experts, physicians, and the general public continue to debate the implications of the law and its repeal. The PPACA will have a significant impact on future physicians, yet medical student perspectives on the legislation have not been well documented. OBJECTIVE: To evaluate medical students' understanding of and attitudes toward healthcare reform and the PPACA including issues of quality, access and cost. DESIGN, SETTING, AND PARTICIPANTS: An anonymous electronic survey was sent to medical students at 10 medical schools (total of 6982 students) between October-December 2010, with 1232 students responding and a response rate of 18%. MAIN OUTCOME MEASURES: Medical students' views and attitudes regarding the PPACA and related topics, measured with Likert scale and open response items. RESULTS: Of medical students surveyed, 94.8% agreed that the existing United States healthcare system needs to be reformed, 31.4% believed the PPACA will improve healthcare quality, while 20.9% disagreed and almost half (47.7%) were unsure if quality will be improved. Two thirds (67.6%) believed that the PPACA will increase access, 6.5% disagreed and the remaining 25.9% were unsure. With regard to containing healthcare costs, 45.4% of participants indicated that they are unsure if the provisions of the PPACA will do so. Overall, 80.1% of respondents indicated that they support the PPACA, and 78.3% also indicated that they did not feel that reform efforts had gone far enough. A majority of respondents (58.8%) opposed repeal of the PPACA, while 15.0% supported repeal, and 26.1% were undecided. CONCLUSION: The overwhelming majority of medical students recognized healthcare reform is needed and expressed support for the PPACA but echoed concerns about whether it will address issues of quality or cost containment

Effect of gamified perceptual learning on visual detection and discrimination skills in equine gait assessment

Background Visual assessment of equine lameness is an everyday veterinary task suffering from poor diagnostic accuracy. The aim of this study was to quantify the impact of the perceptual learning game ‘LamenessTrainer’ on skill development. Methods Thirty‐six undergraduate veterinary students engaged in four game modules teaching the assessment of fore‐ and hindlimb lameness. Computer animations of horses in this game displayed 0% (sound) to 70% (moderately lame) vertical movement asymmetry of head and pelvis. Performance, learning effects, diagnostic accuracy, detection thresholds and survey responses were analysed. Results Following staircase learning, more than 80% of students reliably classified horses with ≥20% asymmetry for forelimb lameness, ≥40% asymmetry for simplified hindlimb lameness and ≥50% asymmetry for realistic hindlimb lameness. During random presentation, on average 82% of sound and 65% of lame horses were assessed correctly during forelimb lameness evaluation, dropping to 39% of sound and 56% of lame horses for hindlimb lameness. Conclusion In less than two hours, systematic perceptual learning through deliberate practice can develop visual assessment skills to an accuracy level comparable to expert assessors scoring the same animations. Skills should be developed further to improve misclassifications of sound and mildly lame horses, especially for hindlimb lameness evaluation

Primary source of income is associated with differences in HIV risk behaviors in street-recruited samples

BACKGROUND: The relationship between primary source of income and HIV risk behaviors and the racial/ethnic differences in risk behavior profiles among disadvantaged populations have not been fully explored. This is unusual given that the phenomenon of higher risk in more disadvantaged populations is well-known but the mechanisms remain unclear. We examined the relationship between primary source of income and differences in HIV risk behaviors among four racial/ethnic groups in the southern United States. METHODS: Self-reported data on primary source of income and HIV risk behaviors were collected from 1494 African American, Hispanic, Asian, and White men and women in places of public congregation in Houston, Texas. Data were analyzed using calculation of percentages and by chi-square tests with Yates correction for discontinuity where appropriate. RESULTS: Data revealed that a higher proportion of whites were involved in sex for money exchanges compared to the other racial groups in this sample. The data suggest that similar street sampling approaches are likely to recruit different proportions of people by primary income source and by ethnicity. It may be that the study locations sampled are likely to preferentially attract those involved in illegal activities, specifically the white population involved in sex for drug or money exchanges. Research evidence has shown that people construct highly evolved sexual marketplaces that are localized and most unlikely to cross racial, ethnic, and socioeconomic or geographical boundaries. Thus, the areas that we sampled may have straddled a white sexual marketplace more than that of the other groups, leading to an over-representation of sex exchange in this group. Drug use was highest among those with illegal primary sources of income (sex exchange and drug dealing and theft), and they were also those most likely to have injected drugs rather than administered them by any other route (p < 0.001). In addition, bisexual or homosexual identification was reported by more respondents in the sex exchange as primary source of income category. The number of sexual partners in the last three months followed a similar pattern, with those whose primary source of income was drug dealing or theft reporting relatively high partner numbers. CONCLUSIONS: These data suggest that social disadvantage is associated with HIV risk in part by its association with drug and sex work for survival, and offers one variable that may be associated with the concentration of disease among those at greatest disadvantage by having an illegal and unstable primary income source