Ultrastructural study of Rift Valley fever virus in the mouse model

AbstractDetailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed in the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV–host interactions and further characterize the mouse model of RVF

Father-daughter Incest: Comparison of Treated Cases to Untreated Control Subjects

Treatment of father daughter incest (FDI) survivors using the victim advocacy/child welfare approach to FDI that predominates today in the US has never been compared to results in untreated control subjects in any published report. In the present study, thirty-two survivors of FDI who received treatment based on the victim advocacy/child welfare approach to FDI were compared to 32 control subjects who did not receive treatment. No significant differences were found using analysis of variance on 21 scales and subscales. Statistical analysis of the data from all 64 of the FDI survivors showed that items reflecting a poor self-image and a history of maternal depression predicted more problematic scores on the depression scale. Those who scored higher on religiosity were less likely to be depressed. Redesigned therapy for FDI aimed, first and foremost, at healing the survivors and validated by prospective randomized trials is needed

Pathogenesis of aerosolized Eastern Equine Encephalitis virus infection in guinea pigs

Mice and guinea pigs were experimentally exposed to aerosols containing regionally-distinct strains (NJ1959 or ArgM) of eastern equine encephalitis virus (EEEV) at two exclusive particle size distributions. Mice were more susceptible to either strain of aerosolized EEEV than were guinea pigs; however, clinical signs indicating encephalitis were more readily observed in the guinea pigs. Lower lethality was observed in both species when EEEV was presented at the larger aerosol distribution (> 6 μm), although the differences in the median lethal dose (LD50) were not significant. Virus isolation and immunohistochemistry indicated that virus invaded the brains of guinea pigs within one day postexposure, regardless of viral strain or particle size distribution. Immunohistochemistry further demonstrated that neuroinvasion occurred through the olfactory system, followed by transneuronal spread to all regions of the brain. Olfactory bipolar neurons and neurons throughout the brain were the key viral targets. The main microscopic lesions in infected guinea pigs were neuronal necrosis, inflammation of the meninges and neuropil of the brain, and vasculitis in the brain. These results indicate that guinea pigs experimentally infected by aerosolized EEEV recapitulate several key features of fatal human infection and thus should serve as a suitable animal model for aerosol exposure to EEEV

Effects of the sex of the perpetrator on victims’ subsequent sexual behaviors and adulthood sexual orientations

Data from 2,828 female and 1,556 male adult participants from a general population convenience sample were used to measure the effect of the sex of the perpetrator on the adult sexual orientation of the victims of child sexual abuse (CSA) by adult male or female perpetrators and early incest with parents or early incest with siblings. Sexual behaviors with female perpetrators tended to promote an orientation toward sex with females and analogous behaviors with male perpetrators tended to promote an orientation toward sex with males in victims of both sexes. Many forms of incest or CSA increased the likelihood the victims would subsequently engage in behaviors with other partners or begin masturbating using adult male or female images. The subsequent early behaviors with other partners and masturbating using images of both male and female adults significantly enhanced or attenuated the conditioning resulting from interacting with the initial perpetrator. The victims’ adult sexual orientations could be statistically predicted using regression equations that took into account the sexual behaviors with both adult and underage partners and whether or not the participant had masturbated using images of male or female adults. The results were consistent with conditioning and counter-conditioning theories

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial

Objective To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae. Design Pragmatic, parallel group, cluster randomised controlled trial. Setting 228 care homes (>10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom. Participants 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n=568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n=474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012. Intervention Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment. Main outcome measures Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points. Results 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval −0.33 to 0.70, P=0.48). Secondary outcome measures also showed no significant differences at all time points. Conclusions This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies

Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA

Diversification of U.S. medical schools via affirmative action implementation

BACKGROUND: The diversification of medical school student and faculty bodies via race-conscious affirmative action policy is a societal and legal option for the U.S. Supreme Court has recently ruled its use constitutional. This paper investigates the implications of affirmative action, particularly race-conscious compared to race-blind admissions policy; explains how alternative programs are generally impractical; and provides a brief review of the history and legality of affirmative action in the United States. DISCUSSION: Selection based solely on academic qualifications such as GPA and MCAT scores does not achieve racial and ethnic diversity in medical school, nor does it adequately predict success as practicing physicians. However, race-conscious preference yields greater practice in underserved and often minority populations, furthers our biomedical research progression, augments health care for minority patients, and fosters an exceptional medical school environment where students are better able to serve an increasingly multicultural society. SUMMARY: The implementation of race-conscious affirmative action results in diversity in medicine. Such diversity has shown increased medical practice in underserved areas, thereby providing better health care for the American people