HIV risk and pre-exposure prophylaxis interest among female bar workers in Dar es Salaam: cross-sectional survey

OBJECTIVE: Female bar workers (FBW) in East Africa often conduct sex work to supplement their incomes, and may be vulnerable to HIV acquisition. Pre-exposure prophylaxis (PrEP) offers protection against HIV acquisition. However, there is little research on FBW's sexual health. Our objective was to determine HIV risk behaviours and interest in PrEP among FBW in the largest city in East Africa. DESIGN: Cross-sectional survey covering respondents' work and personal lives, including social and behavioural risk factors for HIV. The survey aimed to determine the feasibility of working with FBW and HIV prevalence estimates. Those who did not report being HIV positive were asked about their knowledge of and interest in PrEP. All women were offered free on-site HIV testing and counselling (HTC). SETTING: Eight randomly selected workplaces, that is, bars, in Kinondoni district, Dar es Salaam (DSM). PARTICIPANTS: 66 FBW (≥18 years) selected at random from all women working in selected bars on the day of visit. RESULTS: Half of respondents reported having had sex for money: 20% with bar clients only, 15% with other men only and 15% with both. Almost all (98%) reported ≥1 non-commercial partners in the past 12 months; only 30% reported using condoms with these partners. 85% of respondents had ever been pregnant; 44% had had an unintended pregnancy. Only 5% of respondents had ever heard of PrEP. However, 54% were somewhat/very interested in daily-pill PrEP and 79% were somewhat/very interested in long-acting injectable PrEP. When asked to rank modalities, long-acting injectable PrEP was the most preferred. Seven per cent of the 56 respondents who completed HTC tested HIV positive. CONCLUSIONS: FBW in DSM have elevated risk factors for HIV acquisition, and PrEP appears highly acceptable. Studies developing PrEP delivery models and assessing PrEP initiation and adherence in FBW appear warranted

Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma : preclinical efficacy in vitro and formal toxicity study of BMTP-78 in rodents and primates

Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D (KLAKLAK)2-containing class of agents. BMTP-78 was validated in cells from patients with acute myeloid leukemia and in a panel of human leukemia and lymphoma cell lines, where it induced dose-dependent cytotoxicity in all samples tested. Based on the in vitro efficacy of BMTP-78, we performed formal good laboratory practice toxicology studies in both rodents (mice and rats) and nonhuman primates (cynomolgus and rhesus monkeys). These analyses represent required steps towards an IND application of BMTP-78 for theranostic first-in-human clinical trials.Peer reviewe

Biology and conservation of freshwater bivalves : past, present and future perspectives

Freshwater bivalves have been highly threatened by human activities, and recently their global decline has been causing conservational and social concern. In this paper, we review the most important research events in freshwater bivalve biology calling attention to the main scientific achievements. A great bias exists in the research effort, with much more information available for bivalve species belonging to the Unionida in comparison to other groups. The same is true for the origin of these studies, since the publishing pattern does not always correspond to the hotspots of biodiversity but is concentrated in the northern hemisphere mainly in North America, Europe and Russia, with regions such as Africa and Southeast Asia being quite understudied. We also summarize information about past, present and future perspectives concerning the most important research topics that include taxonomy, systematics, anatomy, physiology, ecology and conservation of freshwater bivalves. Finally, we introduce the articles published in this Hydrobiologia special issue related with the International Meeting on Biology and Conservation of Freshwater Bivalves held in 2012 in Braganc¸a, Portugal.We would like to express our gratitude to our sponsors and institutions, especially to the Polytechnic Institute of Braganca for all the logistic support. We acknowledge all keynote speakers, authors, session chairpersons and especially to all attendees whose contributions were fundamental for the success of this meeting. We would also like to thank all referees of this special issue and to Koen Martens, Editor-in-Chief of Hydrobiologia, for all the valuable comments and suggestions. The chronogram was built with the help of the expert opinion of fellow colleagues Rafael Araujo, Arthur Bogan, Kevin Cummings, Dan Graf, Wendell Haag, Karl-Otto Nagel and David Strayer to whom we are very grateful. The authors acknowledge the support provided by Portuguese Foundation for Science and Technology (FCT) and COMPETE funds-projects CONBI (Contract: PTDC/AAC-AMB/117688/2010) and ECO-IAS (Contract: PTDC/AAC-AMB/116685/2010), and by the European Regional Development Fund (ERDF) through the COMPETE, under the project "PEst-C/MAR/LA0015/2011"

Quantitative Microscopy Reveals Centromeric Chromatin Stability, Size, and Cell Cycle Mechanisms to Maintain Centromere Homeostasis

The deposited item is a book chapter and is part of the series "Centromeres and Kinetochores" published by the publisher Springer Verlag. The deposited book chapter is a post-print version and has been submitted to peer reviewing. There is no public supplementary material available for this publication. This publication hasn't any creative commons license associated.Centromeres are chromatin domains specified by nucleosomes containing the histone H3 variant, CENP-A. This unique centromeric structure is at the heart of a strong self-templating epigenetic mechanism that renders centromeres heritable. We review how specific quantitative microscopy approaches have contributed to the determination of the copy number, architecture, size, and dynamics of centromeric chromatin and its associated centromere complex and kinetochore. These efforts revealed that the key to long-term centromere maintenance is the slow turnover of CENP-A nucleosomes, a critical size of the chromatin domain and its cell cycle-coupled replication. These features come together to maintain homeostasis of a chromatin locus that directs its own epigenetic inheritance and facilitates the assembly of the mitotic kinetochore.There are no funders and sponsors indicated explicitly in the document.info:eu-repo/semantics/publishedVersio

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Nanotechnology advances towards development of targeted-treatment for obesity

Obesity through its association with type 2 diabetes (T2D), cancer and cardiovascular diseases (CVDs), poses a serious health threat, as these diseases contribute to high mortality rates. Pharmacotherapy alone or in combination with either lifestyle modifcation or surgery, is reliable in maintaining a healthy body weight, and preventing progression to obesity-induced diseases. However, the anti-obesity drugs are limited by non-specifcity and unsustainable weight loss efects. As such, novel and improved approaches for treatment of obesity are urgently needed. Nanotechnology-based therapies are investigated as an alternative strategy that can treat obesity and be able to overcome the drawbacks associated with conventional therapies. The review presents three nanotechnology-based anti-obesity strategies that target the white adipose tissues (WATs) and its vasculature for the reversal of obesity. These include inhibition of angiogenesis in the WATs, transformation of WATs to brown adipose tissues (BATs), and photothermal lipolysis of WATs. Compared to conventional therapy, the targeted-nanosystems have high tolerability, reduced side efects, and enhanced efcacy. These efects are reproducible using various nanocarriers (liposomes, polymeric and gold nanoparticles), thus providing a proof of concept that targeted nanotherapy can be a feasible strategy that can combat obesity and prevent its comorbiditie

Structural, interpersonal, psychosocial, and behavioral risk factors for HIV acquisition among female bar workers in Dar es Salaam, Tanzania

In sub-Saharan Africa, female bar workers (FBWs) often serve as informal sex workers. Little is known about the prevalence of HIV and HIV-related risk factors among FBWs in Dar es Salaam (DSM), Tanzania. Using an adapted Structural HIV Determinants Framework, we identified structural, interpersonal, psychosocial, and behavioral risk factors for HIV acquisition. We compared the prevalence of HIV and HIV-related risk factors among a random sample of 66 FBWs from DSM to an age-standardized, representative sample of female DSM-residents from the 2016 Demographic and Health and 2011–2012 AIDS Indicator Surveys. Compared to other women in DSM, FBWs had elevated prevalence of all four groups of risk factors. Key risk factors included gender and economic inequalities (structural); sexual violence and challenges negotiating condom use (interpersonal); depression, post-traumatic stress disorder, and low social support (psychosocial); and history of unprotected sex, multiple sex partners, and high alcohol consumption (behavioral). HIV prevalence did not differ between FBWs (7.1%, 95% CI 3.7-13.3%) and survey respondents (7.7%, 95% CI: 5.3-11.1%), perhaps due to FBWs’ higher – though sub-optimal – engagement with HIV prevention strategies. Elevated exposure to HIV-related risk factors but low HIV prevalence suggests economic, psychosocial, and biomedical interventions may prevent HIV among FBWs in DSM