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Background: In 2014, students from the University of Texas Health San Antonio Long School of Medicine conducted a community assessment of lesbian, gay, bisexual, transgender, and queer (LGBTQ+) healthcare needs. Participants reported low levels of sexually-transmitted infection (STI) screening, incomplete reporting of sexual history, and a desire for LGBTQ+-friendly physicians. As a result, a student-run free clinic, the Pride Community Clinic (PCC), was established. The PCC provides STI testing, mental health counseling, hormone replacement therapy (HRT), discounted medications, pre-exposure prophylaxis, human immunodeficiency (HIV) testing, and Pap smears. The purpose of this study is to analyze the demographics of the population treated at the PCC and the resources used to inform future developments within the clinic. Methods: PCC patient records were analyzed, and quantitative analysis was conducted with Microsoft Excel. The qualitative analysis was performed using notes written by medical students, attending physicians, and mental health providers. Results: The average age of patients (n=44) was 22 years, with a standard deviation of 10 years. Of the patients, 52% were racial minorities, and 50% lived below the poverty line. 84% identified as transgender and 68% a sexual minority. Additionally, 84% did not have a primary care provider, and 89% did not have insurance. HIV, gonorrhea, chlamydia, hepatitis C, and syphilis education were the most common screenings done. A review of medical notes found themes of transgender exploration, problems with healthcare access, and the utilization of counseling and preventative care. Conclusions: The PCC offers low-cost care for the underserved LGBTQ+ population in San Antonio. HRT is a common reason for visits, but patients also utilize STI testing and mental health services. The clinic has provided a valuable opportunity for students not only to gain general clinical experience but also to learn about the unique needs of LGBTQ+ patients.

A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.

Few treatments for obesity exist and, whereas efficacious therapeutics for hyperlipidemia are available, further improvements are desirable. Thyroid hormone receptors (TRs) regulate both body weight and cholesterol levels. However, thyroid hormones also have deleterious effects, particularly on the heart. The TRβ subtype is involved in cholesterol lowering and possibly elevating metabolic rate, whereas TRα appears to be more important for control of heart rate (HR). In the current studies, we examined the effect of TRβ activation on metabolic rate and HR with either TR α 1 – / – mice or the selective TRβ agonist KB-141 in mice, rats, and monkeys. 3,5,3′-triiodi- l -thyronine (T 3 ) had a greater effect on increasing HR in WT than in TR α – / – mice (ED 15 values of 34 and 469 nmol/kg/day, respectively). T 3 increased metabolic rate [whole body oxygen consumption (MV O 2 )] in both WT and TR α – / – mice, but the effect in the TR α 1 – / – mice at the highest dose was half that of the WT mice. Thus, stimulation of MV O 2 is likely due to both TRα and -β. T 3 had equivalent potency for cholesterol reduction in WT and TR α – / – mice. KB-141 increased MV O 2 with selectivities of 16.5- and 11.2-fold vs. HR in WT and TR α 1 – / – mice, respectively. KB-141 also increased MV O 2 with a 10-fold selectivity and lowered cholesterol with a 27-fold selectivity vs. HR in rats. In primates, KB-141 caused significant cholesterol, lipoprotein (a), and body-weight reduction (up to 7% after 1 wk) with no effect on HR. TRβ-selective agonists may constitute a previously uncharacterized class of drugs to treat obesity, hypercholesterolemia, and elevated lipoprotein (a).

We analyzed clinical data on 22,739 contact lens wearers who were studied and whose lenses were approved under 48 manufacturer-sponsored studies for the Food and Drug Administration between 1980 and 1988. The incidence of corneal ulcers was low in the cosmetic (nontherapeutic) daily-wear soft and rigid gas-permeable lens wearers (1/1,923 and 1/1,471 patient-years, respectively). Corneal ulcers and severe adverse reactions occurred two to four times more frequently in extended-wear cosmetic soft and rigid gas-permeable lens wearers than in cosmetic daily-wear lens wearers. Aphakic extended-wear soft lens users were nine times more likely to develop a corneal ulcer when compared to the soft daily-wear cosmetic group. Corneal abrasions and keratitis accounted for 81 of 159 severe adverse reactions, whereas corneal ulcers accounted for 28 of 159 adverse reactions. The data indicate that overnight extended wear of contact lenses is associated with a greater risk of serious, sight-threatening complications than daily wear.

The Safety Benefits of Remote Operations Centres The rig site is historically an environment that has both a significant range and number of hazards associated with the operations that occur at it, as well as with travel to and from it. To undertake an effective risk avoidance strategy as well as being able to deal with the practical limitations of accommodation at the rig site means that minimization of risk exposure is the ideal approach. The question is whether this is viable or possible. A remote operations centre has now been developed and used that allows support to rig sites and even some aspects of remote management of operations. While there are always attempts to utilize new technology to reduce the number of people at the rig, this process maintains or even improves the competency available to support such remote operations. Communications infrastructure now allows delivery of this support to multiple rig sites simultaneously and even facilitates remote control of rig site PC’s. Additionally, full time Applications Engineering in the centre improve Drilling Optimisation and Geoscience deliverables on a 24/7 basis 365 days a year. These centres therefore allow safety benefits as well as efficiencies in resources with several wells being managed at the same time, in addition to providing depths of expertise that hitherto was unimaginable. Although these centres of expertise reduce risk significantly, it was recognized that there remained other hazards that needed to be effectively managed and addressed at the planning stage. These include risks to the centre based staff as well as those that potentially could increase risks at the rig site. This paper seeks to share some of the problems, the hazards and risks as well as the good practices that can be applied in developing such a remote engineering centre. Using this technology, safe and efficient remote working can be achieved making the concept of the remote operations centre a truly low risk environment.

There are two major defects in type 2 diabetes: 1) insulin resistance and 2) insulin deficiency due to loss of beta-cell function. Here we demonstrated that treatment with muraglitazar (a dual peroxisome proliferator-activated receptor alpha/gamma activator), when initiated before or after the onset of diabetes in mice, is effective against both defects. In study 1, prediabetic db/db mice were treated for 12 weeks. The control mice developed diabetes, as evidenced by hyperglycemia, hyperinsulinemia, reduced insulin levels in the pancreas, blunted insulin response to glucose, and impaired glucose tolerance. The muraglitazar-treated mice had normal plasma glucose, and insulin levels, equivalent or higher pancreatic insulin content than normal mice, showed a robust insulin response to glucose and exhibited greater glucose tolerance. In study 2, diabetic db/db mice were treated for 4 weeks. The control mice displayed increased glucose levels, severe loss of islets, and their isolated islets secreted reduced amounts of insulin in response to glucose and exendin-4 compared with baseline. In muraglitazar-treated mice, glucose levels were reduced to normal. These mice showed reduced loss of islets, and their isolated islets secreted insulin at levels comparable to baseline. Thus, muraglitazar treatment decreased both insulin resistance and preserved beta-cell function. As a result, muraglitazar treatment, when initiated before the onset of diabetes, prevented development of diabetes and, when initiated after the onset of diabetes, prevented worsening of diabetes in db/db mice.

Efforts to further elucidate structure-activity relationships (SAR) within our previously disclosed series of beta-quaternary amino acid linked l-cis-4,5-methanoprolinenitrile dipeptidyl peptidase IV (DPP-IV) inhibitors led to the investigation of vinyl substitution at the beta-position of alpha-cycloalkyl-substituted glycines. Despite poor systemic exposure, vinyl-substituted compounds showed extended duration of action in acute rat ex vivo plasma DPP-IV inhibition models. Oxygenated putative metabolites were prepared and were shown to exhibit the potency and extended duration of action of their precursors in efficacy models measuring glucose clearance in Zucker(fa/fa) rats. Extension of this approach to adamantylglycine-derived inhibitors led to the discovery of highly potent inhibitors, including hydroxyadamantyl compound BMS-477118 (saxagliptin), a highly efficacious, stable, and long-acting DPP-IV inhibitor, which is currently undergoing clinical trials for treatment of type 2 diabetes.

Current drug therapies for obesity are ineffective, and existing treatments for lipid disorders can be further improved. Thyroid hormones affect both conditions, although currently available nonselective thyromimetics are not clinically useful for such treatment due to cardiac side effects. Recent studies suggest that thyroid hormone receptor subtype beta (TRbeta) selective agonists have a profile in which cholesterol can be reduced with minimal tachycardia. The purpose of this study was to determine whether modest (5-10%) increases in metabolic rate could also be observed with minimal tachycardia after TRbeta stimulation. For these studies, the TRbeta selective agonist, GC-1, was used to assess selectivity for lipid-lowering and metabolic rate changes relative to tachycardia. Studies in cholesterol-fed rats (7 d treatment) showed that GC-1 reduced cholesterol (ED(50) = 190 nmol/kg x d) approximately 30 times more potently than it induced tachycardia (ED(15) = 5451 nmol/kg x d). T(3) showed no potency difference between cholesterol lowering and tachycardia. GC-1 showed approximately 10-fold selectivity for increasing metabolic rate (ED(5) = 477 nmol/kg x d) relative to tachycardia compared with T(3), which showed no selectivity. In cynomolgus monkeys treated for 7 d, significant cholesterol-lowering and lipoprotein (a) reduction was noted for both T(3) and GC-1, whereas no tachycardia was observed for GC-1, unlike T(3). T(3) and GC-1 caused a significant (approximately 4%) reduction in body weight in these animals. Therefore, selective TRbeta activation may be a potentially usefully treatment for obesity and reduction of low density lipoprotein cholesterol and reduction of the atherogenic risk factor lipoprotein (a).