Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Contraceptive use among HIV-infected women and men receiving antiretroviral therapy in Lusaka, Zambia: a cross-sectional survey

Abstract Background Family planning (FP) is an essential health service and an important part of comprehensive HIV care. However, there is limited information about the contraceptive needs of people living with HIV in sub-Saharan Africa, which in turn has hampered efforts to expand and integrate FP services into existing HIV programs. Methods We performed a cross-sectional survey to determine FP prevalence and predictors among HIV-positive women and men attending 18 public antiretroviral therapy (ART) clinics in Lusaka, Zambia. Trained peer counselors administered the 10-question survey to those seeking care for five days at each of the target sites. Results From February to April 2014, we surveyed 7,046 HIV-infected patients receiving routine HIV services. Use of modern contraception was reported by 69 % of female ART patients and 79 % of male ART patients. However, highly effective contraceptive use and dual method use were low among women (38 and 25 %, respectively) and men (19 and 14 %, respectively). HIV disclosure status (adjusted odds ratio (AOR) = 4.91, 95 % confidence interval (CI) = 3.32–7.24 for women, AOR = 3.58, 95 % CI = 2.39–5.38 for men) and sexual activity in the last 6 months (AOR = 5.80, 95 % CI = 4.51–7.47 for women, AOR = 6.24, 95 % CI = 3.51–11.08 for men) were associated with modern contraceptive use in multivariable regression. Most respondents said they would access FP services if made available within ART clinic. Conclusions While FP-ART integration may be a promising strategy for increasing FP service uptake, such services must focus on assessing sexual activity and advocating for dual method use to increase effective contraceptive use and prevent unintended pregnancies

GENDER ROLE DISTRIBUTION IN RESIDENTIAL REAL ESTATE FAMILY DECISION MAKING

Purchase and consumption behavioral patterns of various family formations in different social and cultural contexts have been subject to intensive investigation over the recent years. Residential real estate as a product category represents one of the most complex household purchases incorporating a wide diversity of attributes to be considered in order to match family members’ needs within available resources. The purpose of this paper is to add some insights into spousal perceptions of gender role specialization throughout a residential real estate purchase family decision-making process. The distribution of influence between husbands and wives across three decision-making stages, three sub-decisions and twelve housing attribute choices and the relative importance of twelve residential real estate characteristics are examined using a convenience sample of both spouses in 127 Bulgarian heterosexual married and cohabiting couples

SPECTRAL MODELS FOR CROP STATE ASSESSMENT CONSIDERING SOIL AND ANTHROPOGENIC IMPACTS

Abstract: In the contemporary world aerospace information gathered by different sensors and numerous observation missions has become a genuine necessity in various investigation and application fields. Remote sensing technologies are used for natural resources management, ecosystem change detection, environment preservation and in many other world significant problems. Vegetation monitoring is among the priorities of remote sensing being associated with plant growth assessment, stress detection, yield forecasting. This paper is devoted to the relationship between agricultural vegetation spectral and biophysical features with consideration of plant growth conditions. The influence of soil properties and anthropogenic factors (fertilization, heavy metal pollution) on crop spectral response has been examined in relation to the applicability of spectral models to estimate plant variables and assess crop state

Clastogenic effects of cigarette smoke and urethane and their modulation by olive oil, curcumin and carotenoids in adult mice and foetuses

In spite of the overwhelming epidemiological evidence for cigarette smoke (CS) carcinogenicity, less attention has been paid to the effects of CS as a complex mixture. As assessed in a series of experiments in murine models, the whole-body exposure to mainstream CS induced significant increases of micronucleated cells in the respiratory tract, bone marrow and peripheral blood of adult mice as well as in the liver and peripheral blood of foetuses whose mothers had been exposed throughout pregnancy. Urethane was potently clastogenic in the same cells when injected intraperitoneally. The daily administration of extra-virgin olive oil by gavage produced evident and consistent protective effects in all monitored experimental systems. In contrast, sunflower oil exhibited some adverse effects. Curcumin did not produce any significant effect in the bone marrow of both CS-exposed adults and foetuses but it elicited a dose-dependent protective effect traceable in blood erythrocytes. However, the higher curcumin dose further increased the frequency of micronucleated pulmonary alveolar macrophages. The apparent protective effects produced by lycopene and by a carotenoid mix were overwhelmed by those produced by olive oil, and lycopene even exhibited a worsening effect on the frequency of micronucleated erythroblasts in the bone marrow of urethane-treated adult mice

"I have grown up controlling myself a lot." Fear and misconceptions about sex among adolescents vertically-infected with HIV in Tanzania.

With increased access to HIV treatment throughout Africa, a generation of HIV positive children is now transitioning to adulthood while living with a chronic condition requiring lifelong medication, which can amplify the anxieties of adolescence. This qualitative study explored how adolescents in Tanzania with HIV experience their nascent sexuality, as part of an evaluation of a home-based care programme. We interviewed 14 adolescents aged 15-19 who had acquired HIV perinatally, 10 of their parents or other primary caregivers, and 12 volunteer home-based care providers who provided support, practical advice, and referrals to clinical services. Adolescents expressed unease about their sexuality, fearing that sex and relationships were inappropriate and hazardous, given their HIV status. They worried about having to disclose their status to partners, the risks of infecting others and for their own health. Thus, many anticipated postponing or avoiding sex indefinitely. Caregivers and home-based care providers reinforced negative views of sexual activity, partly due to prevailing misconceptions about the harmful effects of sex with HIV. The adolescents had restricted access to accurate information, appropriate guidance, or comprehensive reproductive health services and were likely to experience significant unmet need as they initiated sexual relationships. Care programmes could help to reduce this gap by facilitating open communication about sexuality between adolescents and their caregivers, providers, and HIV-positive peers