Supporting LGBTQ+ Survivors on Campus

Back by popular demand, last year\u27s Supporting LGBTQ+ Survivors on Campus has been revamped for the new state of Title IX. Historically, Title IX protections have provided a much-needed resource for addressing sexual violence on campus. However, the benefits of Title IX may not apply equally to all students in practice. This workshop will discuss how the history of Title IX raises questions about its applicability for all sexual violence, and ultimately explore strategies for addressing sexual violence in lesbian, gay, bisexual, trans, and queer (LGBTQ+) communities. How effectively does Title IX address same-sex violence? What other policy and programmatic options exist? How can we improve support for LGBTQ+ students? Attendees will learn a framework for analyzing policy changes that they can bring back to their campuses

A highly versatile fluorenone-based macrocycle for the sensitive detection of polycyclic aromatic hydrocarbons and fluoride anions

Reported herein is the high yielding synthesis of a new fluorenone-based triazolophane and its sensing capabilities for polycyclic aromatic hydrocarbons (PAHs) and fluoride anions. Fluorescence, UV/Vis and 1H NMR spectroscopy results showed the triazolophane has a high sensitivity for selected PAHs and binds the fluoride anion in a 2 : 1 stoichiometry via C–H hydrogen bonding with the triazole and fluorenone protons

Synthetic β‐Cyclodextrin Dimers for Squaraine Binding: Effect of Host Architecture on Photophysical Properties, Aggregate Formation and Chemical Reactivity

Reported herein is the synthesis and application of three novel β‐cyclodextrin dimer hosts for the complexation of near infrared (NIR) squaraine dyes in aqueous solution. A series of eight different N‐substituted N‐methyl anilino squaraine dyes with variable terminal groups are investigated, with an optimal n‐hexyl‐substituted squaraine guest demonstrating binding constants orders of magnitude higher than the other squaraine–host combinations and comparable to literature‐reported systems. Moreover, hydrophobic complexation of the squaraine dyes with the β‐cyclodextrin dimer hosts causes drastic changes in the squaraine\u27s photophysical properties, propensity for aggregation and susceptibility to hydrolytic decay

Implementation of HIV Drug Resistance Testing in Kenya

Background: Testing for HIV drug resistance prior to antiretroviral therapy (ART) is standard of care in the United States but is rarely performed in Africa due to its high cost. The prevalence of HIV drug resistance is increasing in resource-limited settings (RLS). An affordable and feasible strategy is needed in RLS to identify individuals with drug resistance and prescribe effective ART. Our group developed a low-cost oligonucleotide ligation assay (OLA) that detects mutations conferring resistance. Little data exists on implementing HIV drug resistance testing in RLS. Here, we describe the implementation of OLA in one laboratory in Kenya and discuss practical aspects of executing the OLA over two years. Methods: The OLA was transferred to a research laboratory at the Coptic Hope Center in Nairobi, Kenya, as part of a randomized trial testing use of the OLA in individuals starting first-line ART to improve virologic outcome. The Seattle Lab Manager (SLM) transported equipment needed for OLA to Nairobi, set up the laboratory, and trained two Kenyan lab technicians to perform OLA. Two additional technicians were later trained. Technicians had education either as a lab technologist or lab scientist, with limited training in molecular techniques. Results: OLA was successfully performed by Kenyan lab technicians on 565 blood samples. Each week, OLA was performed on approximately 7 samples, requiring an estimated 10 hours of technician labor, and 2 hours of remote technical support, review of test results and oversight from the SLM. Some sample results were delayed during two temporary, month-long pauses in testing of specimens, due to suboptimal performance of the OLA. This required trouble-shooting by the SLM in conjunction with lab personnel. Conclusion: OLA technology was successfully transferred to the Kenyan laboratory. However, it required time-intensive technician labor and substantial oversight by the SLM. The complexity of OLA, and a paucity of lab technicians and on-site supervisors trained in molecular techniques are potential bottlenecks for implementation of the current version of OLA at a larger population-level. Research is ongoing to develop OLA Simple, a simplified kit aimed to address these challenges and serve as a point-of-care assay

Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model

Gastrointestinal (GI) models that mimic physiological conditions in vitro are important tools for developing and optimizing biopharmaceutical formulations. Oral administration of live attenuated bacterial vaccines (LBV) can safely and effectively promote mucosal immunity but new formulations are required that provide controlled release of optimal numbers of viable bacterial cells, which must survive gastrointestinal transit overcoming various antimicrobial barriers. Here, we use a gastro-small intestine gut model of human GI conditions to study the survival and release kinetics of two oral LBV formulations: the licensed typhoid fever vaccine Vivotif comprising enteric coated capsules; and an experimental formulation of the model vaccine Salmonella Typhimurium SL3261 dried directly onto cast enteric polymer films and laminated to form a polymer film laminate (PFL). Neither formulation released significant numbers of viable cells when tested in the complete gastro-small intestine model. The poor performance in delivering viable cells could be attributed to a combination of acid and bile toxicity plus incomplete release of cells for Vivotif capsules, and to bile toxicity alone for PFL. To achieve effective protection from intestinal bile in addition to effective acid resistance, bile adsorbent resins were incorporated into the PFL to produce a new formulation, termed BR-PFL. Efficient and complete release of 4.4x107 live cells per dose was achieved from BR-PFL at distal intestinal pH, with release kinetics controlled by the composition of the enteric polymer film, and no loss in viability observed in any stage of the GI model. Use of this in vitro GI model thereby allowed rational design of an oral LBV formulation to maximize viable cell release

Generational differences in practice site selection criteria amongst primary care physicians.

Background and Objectives: Generational differences are often viewed as shaping the overall attitudes and actions of different age cohorts. It is essential to understand the motivations and generational differences in primary care physicians for efforts to recruit, retain, and educate the future physician workforce. Determining what factors most influence different generations of primary care physicians when choosing a practice site is essential to build our future primary care system. This study examined generational differences in the factors that attracted primary care physicians to their current practice. Methods: A survey instrument was mailed to all active members of the North Carolina Medical Board who listed their primary occupation as a primary care specialty. The survey consisted of 24 demographic questions regarding personal and practice variables and a list of 21 reasons for choosing a practice location measured on a 7-point Likert type scale. A total of 975 surveys were returned and usable for the final analysis, for a return rate of 34.5%. Data were analyzed using regression and correlation procedures to determine attitudes of each generation and factors that significantly influenced responses. Results: While slight differences between generations did exist, the overall choices for choosing a site remained stable across generations. Personality of the practice, on-call responsibilities, ability to practice comprehensive care, and location were deemed the most important factors for all generations. Differences between various demographic groups and Family Medicine versus other primary care specialties were minor with very little alteration of the top ten items being seen between groups. Conclusion: This study indicated that there were few differences between generations regarding primary reasons for choosing a practice site. In addition, factors remained remarkably similar across different specialties, family situations, genders, and ethnic groups. Several of the top reasons that primary care physicians indicate are the most important for site selection were also potentially modifiable, such as on-call responsibilities, practice personality, and ability to practice comprehensive care. Managers, clinicians, and educators can potentially utilize this information to better prepare and recruit current and future generations of primary care physicians.ECU Open Access Publishing Fun

Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya

Background: Pre-treatment HIV-drug-resistance (PDR) to WHO-recommended 1st-line non-nucleoside reverse transcriptase inhibitors (NNRTI)-based antiretroviral treatment (ART) is increasing in low-resource communities. We evaluated the risk of PDR on treatment failure if detected at single or multiple codons, at minority (2–9%) or higher (≥10%) frequencies during efavirenz- vs. nevirapine-ART. Methods: We conducted a pooled analysis across three cohorts of Kenyans initiating 1st-line NNRTI-ART between 2006 and 2014. Mutations K103N, Y181C, G190A, M184V and K65R were detected by an oligonucleotide ligation assay (OLA) and confirmed by Sanger and next-generation sequencing (NGS). PDR was defined as detection of any mutation by OLA when confirmed by NGS. Treatment failure, defined as plasma HIV RNA ≥400 copies/mL at month-12 of ART, was compared by PDR genotypes. Findings: PDR was detected in 59/1231 (4·8%) participants. Compared to wild-type genotypes, PDR in participants prescribed nevirapine-ART was associated with increased treatment failure [PDR 69·2% (27/39) vs. wild-type 10·4% (70/674); p = 0·0001], whether detected as minority [66·7% (4/6)] or higher [69·7% (23/33)] frequencies in an individual\u27s HIV quasispecies (p = 0·002 and p \u3c 0·0001, respectively), or mutations at single [50·0% (12/24)] or multiple [100·0% (15/15)] codons (p \u3c 0·0001). During efavirenz-ART, PDR was also associated with increased virologic failure [PDR 25·0% (5/20) vs. wild-type 5·0% (25/498); p = 0·005], but only if detected at multiple drug-resistant codons [50·0% (3/6); p = 0·003] or high frequencies PDR [33·3% (5/15); p = 0·001]. Interpretation: The risk that PDR confers for treatment failure varies by number of mutant codons and their frequency in the quasispecies, with a lower risk for efavirenz- compared to nevirapine-based regimens. PDR detection and management could extend the effective use of efavirenz-ART in low-resource settings. Funding: NIH, PEPFAR

Generational differences in practice site selection criteria amongst primary care physicians.

ABSTRACT Background and Objectives: Generational differences are often viewed as shaping the overall attitudes and actions of different age cohorts. It is essential to understand the motivations and generational differences in primary care physicians for efforts to recruit, retain, and educate the future physician workforce. Determining what factors most influence different generations of primary care physicians when choosing a practice site is essential to build our future primary care system. This study examined generational differences in the factors that attracted primary care physicians to their current practice. Methods: A survey instrument was mailed to all active members of the North Carolina Medical Board who listed their primary occupation as a primary care specialty. The survey consisted of 24 demographic questions regarding personal and practice variables and a list of 21 reasons for choosing a practice location measured on a 7-point Likert type scale. A total of 975 surveys were returned and usable for the final analysis, for a return rate of 34.5%. Data were analyzed using regression and correlation procedures to determine attitudes of each generation and factors that significantly influenced responses. Results: While slight differences between generations did exist, the overall choices for choosing a site remained stable across generations. Personality of the practice, on-call responsibilities, ability to practice comprehensive care, and location were deemed the most important factors for all generations. Differences between various demographic groups and Family Medicine versus other primary care specialties were minor with very little alteration of the top ten items being seen between groups. Conclusion: This study indicated that there were few differences between generations regarding primary reasons for choosing a practice site. In addition, factors remained remarkably similar across different specialties, family situations, genders, and ethnic groups. Several of the top reasons that primary care physicians indicate are the most important for site selection were also potentially modifiable, such as on-call responsibilities, practice personality, and ability to practice comprehensive care. Managers, clinicians, and educators can potentially utilize this information to better prepare and recruit current and future generations of primary care physicians. Keywords: site selection, recruiting, generational differenc

Differential Susceptibility to Hypertension Is Due to Selection during the Out-of-Africa Expansion

Hypertension is a leading cause of stroke, heart disease, and kidney failure. The genetic basis of blood pressure variation is largely unknown but is likely to involve genes that influence renal salt handling and arterial vessel tone. Here we argue that susceptibility to hypertension is ancestral and that differential susceptibility to hypertension is due to differential exposure to selection pressures during the out-of-Africa expansion. The most important selection pressure was climate, which produced a latitudinal cline in heat adaptation and, therefore, hypertension susceptibility. Consistent with this hypothesis, we show that ecological variables, such as latitude, temperature, and rainfall, explain worldwide variation in heat adaptation as defined by seven functional alleles in five genes involved in blood pressure regulation. The latitudinal cline in heat adaptation is consistent worldwide and is largely unmatched by latitudinal clines in short tandem repeat markers, control single nucleotide polymorphisms, or non-functional single nucleotide polymorphisms within the five genes. In addition, we show that latitude and one of these alleles, GNB3 (G protein β3 subunit) 825T, account for a major portion of worldwide variation in blood pressure. These results suggest that the current epidemic of hypertension is due to exposures of the modern period interacting with ancestral susceptibility. Modern populations differ in susceptibility to these new exposures, however, such that those from hot environments are more susceptible to hypertension than populations from cold environments. This differential susceptibility is likely due to our history of adaptation to climate