Functional Genomics of the Insect-Vector Symbiont, Sodalis glossinidius

Animal- (AAT) and human African trypanosomiasis (HAT) is endemic within sub-Saharan Africa and is caused by Trypanosoma spp. parasites vectored by biting tsetse flies. The facultative secondary symbiont, Sodalis glossinidius, has been controversially implemented in increased parasite establishment in tsetse. As the role of S. glossinidius in tsetse is not fully understood within the literature, the research presented here aimed to utilise a functional genomics approach to elucidate S. glossinidius functionality from a genetic context. Initial phenotypic-level in vitro media screening experiments confirmed S. glossinidius heterotrophy and revealed higher growth levels in the presence of glucose: S. glossinidius was unable to grow in a minimal salts medium (M9) devoid of a sufficient organic carbon source, and showed higher growth values in glucose-positive M9 variations compared to equivalent glucose-negative counterparts. This glucose utilisation was also observed with better growth between a complex medium rich in glucose (Mitsuhashi and Maramorosch Insect Medium) versus one with lower concentrations (Schneider’s Insect Medium). Subsequent genotypic-level transposon-directed insertion site sequencing (TraDIS) library selection experiments supported S. glossinidius glucose utilisation with essential gene candidacy in glycolysis, gluconeogenesis and the pentose phosphate pathway. These results, in combination within essentiality in the citric acid cycle, a wide range of carbon source metabolism pathways, and virulence-associated genes (Omp porins, flagellar components and type III secretion system constituents), experimentally confirm the sequence-inferred literature consensus that S. glossinidius has retained a functional repertoire more aligned with free-living organisms. Many of the essential gene candidates were pseudogenes, which when considered with the literature evidence that S. glossinidius is actively maintaining a core pseudogene set across lineages, experimentally supports the theory that symbionts in early stages of genome degradation associated with the free-living to symbiont lifestyle switch preference pseudogene retention. The novel TraDIS library presented here provides the currently missing tool for subsequent targeted functionality in vivo experiments, aimed at fully understanding the S. glossinidius role in the tsetse system

Similar Adverse Events from Two Disparate Agents Implicate Lipid Inflammatory Mediators for a Role in Anxiety States

We recently reported a case in which a 54-year-old male experienced maintenance insomnia, generalized anxiety and panic symptoms associated with consumption of a fish oil supplement enriched in eicosapentaenoic acid (EPA). We report here that the same patient has experienced identical but more severe symptoms in response to the use of the leukotriene receptor antagonist montelukast, in accordance with other cases reported to the Food and Drug Administration. Since omega-3 fatty acids like EPA are precursors for the biosynthesis of eicosanoids including leukotrienes, a common factor to these psychiatric adverse events may be perturbations in this highly complex system of lipid inflammatory mediators

Introduction: Issues of Reproductive Rights: Life, Liberty & the Pursuit of Policy

On March 7, 2014, the Journal of Law and Health of Cleveland-Marshall College of Law hosted a symposium entitled “Issues of Reproductive Rights: Life, Liberty, and the Pursuit of Policy” in response to recent developments in the regulation of women’s reproductive rights. The discussion about women’s reproductive rights has expanded far beyond the morality of abortion and right to privacy, established by the United States Supreme Court in Roe v. Wade, and has been complicated by new technology, statutory developments, and case law discussing the nature of a corporation. The symposium presenters addressed key legal developments in each stage of reproductive health: contraceptive rights, decision-making during gestation, and legal consequences during pregnancy after a pregnancy has been terminated

Introduction: Issues of Reproductive Rights: Life, Liberty & the Pursuit of Policy

On March 7, 2014, the Journal of Law and Health of Cleveland-Marshall College of Law hosted a symposium entitled “Issues of Reproductive Rights: Life, Liberty, and the Pursuit of Policy” in response to recent developments in the regulation of women’s reproductive rights. The discussion about women’s reproductive rights has expanded far beyond the morality of abortion and right to privacy, established by the United States Supreme Court in Roe v. Wade, and has been complicated by new technology, statutory developments, and case law discussing the nature of a corporation. The symposium presenters addressed key legal developments in each stage of reproductive health: contraceptive rights, decision-making during gestation, and legal consequences during pregnancy after a pregnancy has been terminated

Insomnia and Exacerbation of Anxiety Associated with High-EPA Fish Oil Supplements after Successful Treatment of Depression

A 54-year-old male consulted his general practitioner for increasing general anxiety and mild panic attacks despite effective treatment for recurrent major depressive disorder, which included a fish oil supplement enriched in eicosapentaenoic acid (EPA). The patient would awaken suddenly at night with shortness of breath and overwhelming worry. During the daytime, he felt a general, nonspecific anxiety and frequently experienced sympathetic activation upon confronting routine challenges. He also experienced dyspnea-induced feelings of panic. He reported that he stopped taking the fish oil supplements after several more months of symptoms, and his anxiety and insomnia then largely disappeared. Several weeks later, he resumed consumption of high-EPA fish oil at the prior dosage for 2 days. On both nights, the patient reported nighttime awakening similar to the previous episodes, followed by daytime agitation. Since halting the fish oil supplements, the anxiety and insomnia have not returned and his depression remains in remission

How to be SSB-free: Assessing the attitudes and readiness for a sugar sweetened beverage-free healthcare center in the Bronx, NY

In recent years, communities and institutions have sought new interventions intended to reduce sugar sweetened beverage (SSB) consumption among children. Among these interventions are “SSB-free zones,” where such beverages are not permitted to be consumed on the premises. Insufficient knowledge still exists, however, about the readiness for such restrictive SSB policies within health care institutions. Understanding attitudes toward SSB consumption among adults is necessary to guide an institution-wide policy, where staff and patients serve as role models for parents and their children. We conducted focus groups with health center patients and staff to determine perceptions surrounding health and SSB consumption and to better understand the support and readiness (or lack thereof) for an SSB-free zone intervention prior to its implementation. We found that contextual practices present challenges to breaking personal consumption habits, even if beverages are banned from the worksite. Nevertheless, participants expressed support for SSB-free zones, and recommended more education about the harmful effects of soda and energy drink consumption to help improve acceptability for the policy. We conclude that policies restricting onsite SSB consumption may be more effective when combined with educational information and expressions of understanding that this specific behavior change can be difficult

Can hate be diluted?

Negative social evaluation can create a negative emotional response. Extreme negative evaluations create fear or anger and reduce self-efficacy (Pekrun, 2006; Shields, 2015). These negative feelings could harm the individual and they almost certainly reduce performance. Factors that neutralize the harmful effect of negative social evaluation could have utility in any performance or work setting. One factor that should be considered is the size of the social group within which the negative evaluation occurred and the “weight” of the negative evaluation. In simple terms, perhaps several positive or neutral evaluations can offset the effect of a single negative evaluation. This test will measure whether several neutral or positive evaluation will reduce the impact of one negative evaluation. The hypothesis is that in a larger group one negative evaluation will have less of an emotional impact on an individual. About 160 student participants will be tested in a performance task. The participants will be assigned to a group of either 2 or 8. Participants will be told that multiple groups are competing in the performance task. After an initial measure of performance, the participants will be told that their scores have been distributed to everyone in their group. Participants will believe this is 1 or 7 other people. The participants will then receive fabricated performance scores from the members of their team. They will rate these performances and express whether they want the team members to remain in the team. Finally, each participant will receive fabricated feedback which indicates that one team member does not want the participant to remain on the team. These will be either 100% negative evaluation in a team of 2 or 14% negative evaluation in a team of 8. Before the initial anagram task and after reading the fabricated evaluation data the participants will complete the PANAS scale (Watson, Clark & Tellegen, 1988). The change in the PANAS score will be the dependent measure in this study. The group size, 2 versus 8, will be the independent variable. The analysis will be an ANOVA for a 2X2 mixed design. The findings could show whether positive individuals can offset the negative impact of critical individuals. In simple terms, can the presence of neutral or positive people dilute the harmful impact of one hateful individual? If this effect were confirmed it would have implications for group management in many performance settings

What hormonal contraception is most effective for obese women?

Depot medroxyprogesterone acetate (DMPA; Depo-Provera) and the combination contraceptive vaginal ring (NuvaRing) are most effective for obese women because they don't appear to be affected by body weight (strength of recommendation [SOR]: B, consistent cohort studies)

Physician Executive Leadership: Assessing a Student-Led Approach to Healthcare Leadership Education in Medical School

Poster presented at: 14th Annual AMA Research Symposium in Orlando, Fl Objective: To investigate the effectiveness of Physican Leadership, an open access, student-led healthcare leadership program at Sidney Kimmel Medical College, in preparing to face five key emerging topics in medical practice: healthcare economics, health policy, care and quality and safety, law and medicine, and patient experience. The Problem: Gaps in Medical Education Healthcare in the US continues to evolve, and topics such as health policy, health finance, and patient experience are not central to the practice of medicine. However, the sheer volume of material students are required to learn in the preclinical years makes it challenging to introduce new subjects into traditional medical school curricula. As a result, these topics in healthcare leadership are often left out. Indeed, only 40-50% of medical student report appropriate training in the practice of medicine, including subjects as medical economics, healthcare systems, and managed care.https://jdc.jefferson.edu/pel/1002/thumbnail.jp

The Broad Spectrum HDAC Inhibitor PCI-24781 Induces Caspase- and ROS-Dependent Apoptosis and is Synergistic with Bortezomib in Lymphoma

We investigated the cytotoxicity and biology of the novel broad-spectrum hydroxamic acid-based histone deacetylase inhibitor (HDACi), PCI-24781. PCI-24781 was studied alone and combined with bortezomib in Hodgkin lymphoma (L428) and non-Hodgkin's lymphoma cell lines (Ramos, HF1, SUDHL4). PCI-24781 induced dose-dependent apoptosis that was associated with prominent G0/G1 arrest, decreased S-phase, increased p21 protein expression, and production of reactive oxygen species (ROS). Furthermore, PCI-24781-induced apoptosis was shown to be ROS- and caspase-dependent. Combined PCI-24781 and bortezomib exposure resulted in strong synergistic apoptosis in all cell lines (combination indices 0.19-0.6). Furthermore, compared to either agent alone, PCI-24781/bortezomib resulted in increased caspase cleavage, mitochondrial depolarization, and histone hyperacetylation. Microarray analyses showed that PCI-24781 alone significantly downregulated several antioxidant genes, proteasome components, and NF-kappaB pathway genes, effects which were enhanced further with bortezomib. RT-PCR confirmed downregulation of NF-kappaB targets NF-kappaB1 (p105), c-Myc, and IkappaB-kinase subunits, while gel-shift showed decreased NF-kappaB DNA-binding activity. Taken together, these results suggest that increased oxidative stress and NF-kappaB inhibition, leading to caspase activation and apoptosis, are likely responsible for the activity of PCI-24781 as well as the observed synergy with bortezomib. These data indicate that PCI-24781 has potential therapeutic value in lymphoma as a single-agent and combined with bortezomib