Discovery of short-course antiwolbachial quinazolines for elimination of filarial worm infections.

Parasitic filarial nematodes cause debilitating infections in people in resource-limited countries. A clinically validated approach to eliminating worms uses a 4- to 6-week course of doxycycline that targets , a bacterial endosymbiont required for worm viability and reproduction. However, the prolonged length of therapy and contraindication in children and pregnant women have slowed adoption of this treatment.

Wolbachia and host germline components compete for kinesin-mediated transport to the posterior pole of the Drosophila oocyte.

Widespread success of the intracellular bacterium Wolbachia across insects and nematodes is due to efficient vertical transmission and reproductive manipulations. Many strains, including wMel from Drosophila melanogaster, exhibit a specific concentration to the germplasm at the posterior pole of the mature oocyte, thereby ensuring high fidelity of parent-offspring transmission. Transport of Wolbachia to the pole relies on microtubules and the plus-end directed motor kinesin heavy chain (KHC).

Commercialization, Altruism, Clinical Practice: Seeking Explanation for Similarities and Differences in Californian and Canadian Gestational Surrogacy Outcomes.

Background: Surrogacy is growing worldwide. Although recently some countries have sought to ban it, between 2010 and 2014 the number of babies born to gestational surrogates having in vitro fertilization treatment in California doubled, and in Canada it grew by 35%. This work seeks to fill identified knowledge gaps about the similarities and differences in the practices and outcomes of gestational surrogacy, which in California operates on a commercial basis, whereas in Canada it is illegal to pay a surrogate.

"One for Sorrow, Two for Joy?": American embryo transfer guideline recommendations, practices, and outcomes for gestational surrogate patients.

In January 2016, Melissa Cook, a California gestational surrogate experiencing a multiple-birth pregnancy following the in vitro fertilization (IVF) transfer of three embryos comprised of donor eggs and sperm provided by the intended father, went to the media when the intended father requested that she undergo a fetal reduction because twins were less expensive to raise than triplets. Much of the legal interest in this case to date has centered on the enforceability of surrogacy contracts. However, the Cook case also raises troubling issues about fertility treatment practices involving gestational surrogates, twin preference, and third-party reproduction medical decision-making.

Reliance of on High Rates of Host Proteolysis Revealed by a Genome-Wide RNAi Screen of Cells.

are gram-negative, obligate, intracellular bacteria carried by a majority of insect species worldwide. Here we use a -infected cell line and genome-wide RNA interference (RNAi) screening to identify host factors that influence titer. By screening an RNAi library targeting 15,699 transcribed host genes, we identified 36 candidate genes that dramatically reduced titer and 41 that increased titer.

Mechanisms of Horizontal Cell-to-Cell Transfer of Wolbachia spp. in Drosophila melanogaster.

is an intracellular endosymbiont present in most arthropod and filarial nematode species. Transmission between hosts is primarily vertical, taking place exclusively through the female germ line, although horizontal transmission has also been documented. The results of several studies indicate that spp.

Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction.

Background: Pulmonary hypertension (PH) is associated with poor outcomes, yet specific treatments only exist for a small subset of patients. The most common form of PH is that associated with left heart disease (Group 2), for which there is no approved therapy. Nitrite has shown efficacy in preclinical animal models of Group 1 and 2 PH, as well as in patients with left heart failure with preserved ejection fraction (HFpEF).

Hidden from view: Canadian gestational surrogacy practices and outcomes, 2001-2012.

This paper raises some troubling questions about the fertility treatments provided to Canadian gestational surrogates, women not genetically related to the child that they carry. Using information published between 2003 and 2012 by Canada's Assisted Reproduction Registry, the paper traces the growing incidence of births to gestational surrogates. The transfer of more than one embryo increases the chance of pregnancy and the incidence of multiple births, and while the incidence of multiple births has declined overall since 2010, gestational surrogates consistently experience a higher proportion of multiple births and experienced higher levels of multiple embryo transfers.

The impact of host diet on Wolbachia titer in Drosophila.

While a number of studies have identified host factors that influence endosymbiont titer, little is known concerning environmental influences on titer. Here we examined nutrient impact on maternally transmitted Wolbachia endosymbionts in Drosophila. We demonstrate that Drosophila reared on sucrose- and yeast-enriched diets exhibit increased and reduced Wolbachia titers in oogenesis, respectively.

Clinical vignettes improve performance in anatomy practical assessment.

Although medical curricula now adopt an integrated teaching approach, this is not adequately reflected in assessment of anatomy knowledge and skills. In this study, we aimed to explore the impact of the addition of clinical vignette to item stems on students' performance in anatomy practical examinations. In this study, 129 undergraduate medical students of Durham University took part in a 30-item anatomy practical test consisting of those with and without clinical stem, in a crossover design.

A cell-based screen reveals that the albendazole metabolite, albendazole sulfone, targets Wolbachia.

Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules.

The impact of color and role on retention of knowledge: a body-painting study within undergraduate medicine.

Body painting as a tool for teaching anatomy is becoming increasingly popular as it is fun and diffuses the formal academic context. Students claim bright color plays a significant role in retention of knowledge from painting sessions. Medical students (n = 117) were divided into two conditions: block color (CLR) and black outlines (BLK).