Do Substance P and Neurokinin A Play Important Roles in the Control of LH Secretion in Ewes?

There is now general agreement that neurokinin B (NKB) acts via neurokinin-3-receptor (NK3R) to stimulate secretion of GnRH and LH in several species, including rats, mice, sheep, and humans. However, the roles of two other tachykinins, substance P (SP) and neurokinin A, which act primarily via NK1R and NK2R, respectively, are less clear. In rodents, these signaling pathways can stimulate LH release and substitute for NKB signaling; in humans, SP is colocalized with kisspeptin and NKB in the mediobasal hypothalamus. In this study, we examined the possible role of these tachykinins in control of the reproductive axis in sheep. Immunohistochemistry was used to describe the expression of SP and NK1R in the ovine diencephalon and determine whether these proteins are colocalized in kisspeptin or GnRH neurons. SP-containing cell bodies were largely confined to the arcuate nucleus, but NK1R-immunoreactivity was more widespread. However, there was very low coexpression of SP or NK1R in kisspeptin cells and none in GnRH neurons. We next determined the minimal effective dose of these three tachykinins that would stimulate LH secretion when administered into the third ventricle of ovary-intact anestrous sheep. A much lower dose of NKB (0.2 nmol) than of neurokinin A (2 nmol) or SP (10 nmol) consistently stimulated LH secretion. Moreover, the relative potency of these three neuropeptides parallels the relative selectivity of NK3R. Based on these anatomical and pharmacological data, we conclude that NKB-NK3R signaling is the primary pathway for the control of GnRH secretion by tachykinins in ewes

Emergence and Persistence of Minor Drug-Resistant HIV-1 Variants in Ugandan Women after Nevirapine Single-Dose Prophylaxis

BACKGROUND: Nevirapine (NVP) single-dose is still a widely used antiretroviral prophylaxis for the prevention of vertical HIV-1 transmission in resource-limited settings. However, the main disadvantage of the Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) NVP is the rapid selection of NVP-resistant virus with negative implications for subsequent NNRTI-based long-term antiretroviral therapy (ART). Here, we analysed the emergence of drug-resistant HIV-1 including minor variants in the early phase after NVP single-dose prophylaxis and the persistence of drug-resistant virus over time. METHODS AND FINDINGS: NVP-resistant HIV-1 harbouring the K103N and/or Y181C resistance mutations in the HIV-1 reverse transcriptase gene was measured from 1 week up to 18 months after NVP single-dose prophylaxis in 29 Ugandan women using allele-specific PCR assays capable of detecting drug-resistant variants representing less than 1% of the whole viral population. In total, drug-resistant HIV-1 was identified in 18/29 (62%) women; rates increased from 18% to 38% and 44% at week 1, 2, 6, respectively, and decreased to 18%, 25%, 13% and 4% at month 3, 6, 12 and 18, respectively. The proportion of NVP-resistant virus of the total viral population was significantly higher in women infected with subtype D (median 40.5%) as compared to subtype A (median 1.3%; p = 0.032, Mann-Whitney U test). 33% of resistant virus was not detectable at week 2 but was for the first time measurable 6-12 weeks after NVP single-dose prophylaxis. Three (10%) women harboured resistant virus in proportions >10% still at month 6. CONCLUSIONS: Current WHO guidelines recommend an additional postnatal intake of AZT and 3TC for one week to avoid NVP resistance formation. Our findings indicate that a 1-week medication might be too short to impede the emergence of NVP resistance in a substantial proportion of women. Furthermore, subsequent NNRTI-based ART should not be started earlier than 12 months after NVP single-dose prophylaxis

Temperature, recreational fishing and diapause egg connections : dispersal of spiny water fleas (Bythotrephes longimanus)

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Biological Invasions 13 (2011): 2513-2531, doi:10.1007/s10530-011-0078-8.The spiny water flea (Bythotrephes longimanus) is spreading from Great Lakes coastal waters into northern inland lakes within a northern temperature-defined latitudinal band. Colonization of Great Lakes coastal embayments is assisted by winds and seiche surges, yet rapid inland expansion across the northern states comes through an overland process. The lack of invasions at Isle Royale National Park contrasts with rapid expansion on the nearby Keweenaw Peninsula. Both regions have comparable geology, lake density, and fauna, but differ in recreational fishing boat access, visitation, and containment measures. Tail spines protect Bythotrephes against young of the year, but not larger fish, yet the unusual thick-shelled diapausing eggs can pass through fish guts in viable condition. Sediment traps illustrate how fish spread diapausing eggs across lakes in fecal pellets. Trillions of diapausing eggs are produced per year in Lake Michigan and billions per year in Lake Michigamme, a large inland lake. Dispersal by recreational fishing is linked to use of baitfish, diapausing eggs defecated into live wells and bait buckets, and Bythothephes snagged on fishing line, anchor ropes, and minnow seines. Relatively simple measures, such as on-site rinsing of live wells, restricting transfer of certain baitfish species, or holding baitfish for 24 h (defecation period), should greatly reduce dispersal.Study of Lakes Superior and Michigan was funded from NSF OCE-9726680 and OCE-9712872 to W.C.K., OCE-9712889 to J. Churchill. Geographic survey sampling and Park studies in the national parks during 2008-2010 were funded by a grant from the National Park Service Natural Resource Preservation Program GLNF CESU Task Agreement No. J6067080012

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis

Challenging Masculinity in CSR Disclosures: Silencing of Women’s Voices in Tanzania’s Mining Industry

This paper presents a feminist analysis of corporate social responsibility (CSR) in a male-dominated industry within a developing country context. It seeks to raise awareness of the silencing of women’s voices in CSR reports produced by mining companies in Tanzania. Tanzania is one of the poorest countries in Africa, and women are often marginalised in employment and social policy considerations. Drawing on work by Hélène Cixous, a post-structuralist/radical feminist scholar, the paper challenges the masculinity of CSR discourses that have repeatedly masked the voices and concerns of ‘other’ marginalised social groups, notably women. Using interpretative ethnographic case studies, the paper provides much-needed empirical evidence to show how gender imbalances remain prevalent in the Tanzanian mining sector. This evidence draws attention to the dynamics faced by many women working in or living around mining areas in Tanzania. The paper argues that CSR, a discourse enmeshed with the patriarchal logic of the contemporary capitalist system, is entangled with tensions, class conflicts and struggles which need to be unpacked and acknowledged. The paper considers the possibility of policy reforms in order to promote gender balance in the Tanzanian mining sector and create a platform for women’s concerns to be voiced

Costs of treating patients with schizophrenia who have illness-related crisis events

<p>Abstract</p> <p>Background</p> <p>Relatively little is known about the relationship between psychosocial crises and treatment costs for persons with schizophrenia. This naturalistic prospective study assessed the association of recent crises with mental health treatment costs among persons receiving treatment for schizophrenia.</p> <p>Methods</p> <p>Data were drawn from a large multi-site, non-interventional study of schizophrenia patients in the United States, conducted between 1997 and 2003. Participants were treated at mental health treatment systems, including the Department of Veterans Affairs (VA) hospitals, community mental health centers, community and state hospitals, and university health care service systems. Total costs over a 1-year period for mental health services and component costs (psychiatric hospitalizations, antipsychotic medications, other psychotropic medications, day treatment, emergency psychiatric services, psychosocial/rehabilitation group therapy, individual therapy, medication management, and case management) were calculated for 1557 patients with complete medical information. Direct mental health treatment costs for patients who had experienced 1 or more of 5 recent crisis events were compared to propensity-matched samples of persons who had not experienced a crisis event. The 5 non-mutually exclusive crisis event subgroups were: suicide attempt in the past 4 weeks (n = 18), psychiatric hospitalization in the past 6 months (n = 240), arrest in the past 6 months (n = 56), violent behaviors in the past 4 weeks (n = 62), and diagnosis of a co-occurring substance use disorder (n = 413).</p> <p>Results</p> <p>Across all 5 categories of crisis events, patients who had a recent crisis had higher average annual mental health treatment costs than patients in propensity-score matched comparison samples. Average annual mental health treatment costs were significantly higher for persons who attempted suicide ($46,024), followed by persons with psychiatric hospitalization in the past 6 months ($37,329), persons with prior arrests ($31,081), and persons with violent behaviors ($18,778). Total cost was not significantly higher for those with co-occurring substance use disorder ($19,034).</p> <p>Conclusion</p> <p>Recent crises, particularly suicide attempts, psychiatric hospitalizations, and criminal arrests, are predictive of higher mental health treatment costs in schizophrenia patients.</p

Predictors of switching antipsychotic medications in the treatment of schizophrenia

<p>Abstract</p> <p>Background</p> <p>To identify patient characteristics and early changes in patients' clinical status that best predict subsequent switching of antipsychotic agents in the long-term treatment of schizophrenia.</p> <p>Methods</p> <p>This post-hoc analysis used data from a one-year randomized, open-label, multisite study of antipsychotics in the treatment of schizophrenia. The study protocol permitted switching of antipsychotics when clinically warranted after the first eight weeks. Baseline patient characteristics were assessed using standard psychiatric measures and reviews of medical records. The prediction model included baseline sociodemographics, comorbid psychiatric and non-psychiatric conditions, body weight, clinical and functional variables, as well as change scores on standard efficacy and tolerability measures during the first two weeks of treatment. Cox proportional hazards modeling was used to identify the best predictors of switching from the initially assigned antipsychotic medication.</p> <p>Results</p> <p>About one-third of patients (29.5%, 191/648) switched antipsychotics before the end of the one-year study. There were six variables identified as the best predictors of switching: lack of antipsychotic use in the prior year, pre-existing depression, female gender, lack of substance use disorder, worsening of akathisia (as measured by the Barnes Akathisia Scale), and worsening of symptoms of depression/anxiety (subscale score on the Positive and Negative Syndrome Scale) during the first two weeks of antipsychotic therapy.</p> <p>Conclusions</p> <p>Switching antipsychotics appears to be prevalent in the naturalistic treatment of schizophrenia and can be predicted by a small and distinct set of variables. Interestingly, worsening of anxiety and depressive symptoms and of akathisia following two weeks of treatment were among the more robust predictors of subsequent switching of antipsychotics.</p

Access to housing subsidies, housing status, drug use and HIV risk among low-income U.S. urban residents

<p>Abstract</p> <p>Background</p> <p>Much research has shown an association between homelessness and unstable housing and HIV risk but most has relied on relatively narrow definitions of housing status that preclude a deeper understanding of this relationship. Fewer studies have examined access to housing subsidies and supportive housing programs among low-income populations with different personal characteristics. This paper explores personal characteristics associated with access to housing subsidies and supportive housing, the relationship between personal characteristics and housing status, and the relationship between housing status and sexual risk behaviors among low-income urban residents.</p> <p>Methods</p> <p>Surveys were conducted with 392 low-income residents from Hartford and East Harford, Connecticut through a targeted sampling plan. We measured personal characteristics (income, education, use of crack, heroin, or cocaine in the last 6 months, receipt of welfare benefits, mental illness diagnosis, arrest, criminal conviction, longest prison term served, and self-reported HIV diagnosis); access to housing subsidies or supportive housing programs; current housing status; and sexual risk behaviors. To answer the aims above, we performed univariate analyses using Chi-square or 2-sided ANOVA's. Those with significance levels above (0.10) were included in multivariate analyses. We performed 2 separate multiple regressions to determine the effects of personal characteristics on access to housing subsidies and access to supportive housing respectively. We used multinomial main effects logistic regression to determine the effects of housing status on sexual risk behavior.</p> <p>Results</p> <p>Being HIV positive or having a mental illness predicted access to housing subsidies and supportive housing, while having a criminal conviction was not related to access to either housing subsidies or supportive housing. Drug use was associated with poorer housing statuses such as living on the street or in a shelter, or temporarily doubling up with friends, acquaintances or sex partners. Living with friends, acquaintances or sex partners was associated with greater sexual risk than those living on the street or in other stable housing situations.</p> <p>Conclusions</p> <p>Results suggest that providing low-income and supportive housing may be an effective structural HIV prevention intervention, but that the availability and accessibility of these programs must be increased.</p

Loss of Cofilin 1 Disturbs Actin Dynamics, Adhesion between Enveloping and Deep Cell Layers and Cell Movements during Gastrulation in Zebrafish

During gastrulation, cohesive migration drives associated cell layers to the completion of epiboly in zebrafish. The association of different layers relies on E-cadherin based cellular junctions, whose stability can be affected by actin turnover. Here, we examined the effect of malfunctioning actin turnover on the epibolic movement by knocking down an actin depolymerizing factor, cofilin 1, using antisense morpholino oligos (MO). Knockdown of cfl1 interfered with epibolic movement of deep cell layer (DEL) but not in the enveloping layer (EVL) and the defect could be specifically rescued by overexpression of cfl1. It appeared that the uncoordinated movements of DEL and EVL were regulated by the differential expression of cfl1 in the DEL, but not EVL as shown by in situ hybridization. The dissociation of DEL and EVL was further evident by the loss of adhesion between layers by using transmission electronic and confocal microscopy analyses. cfl1 morphants also exhibited abnormal convergent extension, cellular migration and actin filaments, but not involution of hypoblast. The cfl1 MO-induced cell migration defect was found to be cell-autonomous in cell transplantation assays. These results suggest that proper actin turnover mediated by Cfl1 is essential for adhesion between DEL and EVL and cell movements during gastrulation in zebrafish