Examining How Black Women Medical Students Rate Their Experiences with Medical School Mistreatment on the Aamc Graduate Questionnaire.

Introduction: Few researchers have examined how medical student mistreatment varies by race/ethnicity and gender, specifically highlighting Black women's experiences. Moreover, researchers often fail to use theoretical frameworks when examining the experiences of minoritized populations. The purpose of this study was to examine the frequency of mistreatment US Black women medical students experience and how this compared to other students underrepresented in medicine (URiM) using intersectionality as a theoretical framework. Methods: We used the Association of American Medical Colleges Graduate Questionnaire (GQ) as the data source for examining descriptive statistics and frequencies. We examined differences between US Black women (N = 2,537) and other URiM students (N = 7,863) with Mann-Whitney U tests. Results: The results from this study highlighted that most Black women medical students did not experience mistreatment, yet a higher proportion of these trainees reported experiencing gendered (χ2(1) = 28.59, p < .01) and racially/ethnically (χ2(1) = 2935.15, p < .01) offensive remarks at higher frequency than their URiM counterparts. We also found US Black women medical students infrequently (27.3%) reported mistreatment from a lack of confidence for advocacy on their behalf, fear of reprisal, and seeing the incident as insignificant. Discussion: A paucity of research exists on Black women medical students and even less using relevant theoretical frameworks such as intersectionality. Failure to extract Black women's experiences exacerbates alienation, invisibility, and inappropriate attention to their mistreatment.

Effectiveness of Thromboprophylaxis Agents Following Hip Fracture: A Systematic Review and Network Meta-Analysis.

Background: Multiple studies have compared different pharmacologic thromboprophylaxis agents after hip fracture surgery, including aspirin, unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOAC), and warfarin, resulting in variability in clinical practice. To guide clinical management, a systematic review and network meta-analysis (NMA), which enables the simultaneous assessment of the effects of multiple interventions for the same patient population, was performed. This study aimed to determine the comparative effectiveness of thromboprophylaxis in reducing venous thromboembolism (VTE) in patients with surgically treated hip fractures. Methods: The primary outcome was the effect of the treatment on the VTE rate, and the secondary outcome was the treatment effect on the bleeding rate. Relevant studies were identified by a systematic search of Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 2000 to February 2022. Title, abstract, and full-text screening; data extraction; and risk-of-bias assessment were performed. All studies examining thromboprophylaxis interventions (DOAC, LMWH, UFH, aspirin, and warfarin) in patients with a surgically treated hip fracture were included. Bayesian NMA was performed, and dichotomous outcome data were pooled using the odds ratio. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) for each outcome. Results: A total of 19 studies were included after the screening of 466 citations and 77 full-text articles. Of the included studies, 15 studies had a high overall risk of bias. The NMA of the VTE outcome included 19 studies, 49,409 participants, and 6 thromboprophylaxis interventions. The NMA of the bleeding outcome included 3 studies, 18,163 participants, and 3 interventions. The mean age ranged from 43.5 to 86.2 years among the included studies. No thromboprophylaxis intervention was statistically different from any other intervention in its effect on the VTE or bleeding rate in hip fracture patients. Conclusions: This NMA demonstrated that there was no difference between the thromboprophylaxis interventions in reducing VTE or bleeding rates in hip fracture patients. More robust randomized controlled trials are needed to determine the most effective thromboprophylaxis interventions for patients with hip fractures. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Tolfenpyrad displays Francisella-targeted antibiotic activity that requires an oxidative stress response regulator for sensitivity.

IMPORTANCE: Francisella species are highly pathogenic bacteria that pose a threat to global health security. These bacteria can be made resistant to antibiotics through facile methods, and we lack a safe and protective vaccine. Given their history of development as bioweapons, new treatment options must be developed to bolster public health preparedness. Here, we report that tolfenpyrad, a pesticide that is currently in use worldwide, effectively inhibits the growth of Francisella. This drug has an extensive history of use and a plethora of safety and toxicity data, making it a good candidate for development as an antibiotic. We identified mutations in Francisella novicida that confer resistance to tolfenpyrad and characterized a transcriptional regulator that is required for sensitivity to both tolfenpyrad and reactive oxygen species.

A Case of Myxedema Coma and Respiratory Failure.

Myxedema coma is a rare, but potentially fatal condition due to severe hypothyroidism, and most commonly seen in patients with long standing, untreated hypothyroidism. Here, I report a case of a 75-year-old male who presented to the emergency department with acute respiratory failure and altered mental status. Interestingly, this case led to a new diagnosis of hypothyroidism presenting in its most severe form - myxedema coma. This case highlights the diagnostic challenges in identifying patients with myxedema coma and recognizing its potential role as a cause of respiratory failure.

Extracellular Lactate: A Novel Measure of T Cell Proliferation.

Following activation, T cells rapidly divide and acquire effector functions. This energetically demanding process depends upon the ability of T cells to undergo metabolic remodeling from oxidative phosphorylation to aerobic glycolysis, during which glucose is converted into lactate and released extracellularly. In this article, we demonstrate that extracellular lactate can be used to dynamically assess human T cell responses in vitro. Extracellular lactate levels strongly correlated with T cell proliferation, and measuring lactate compared favorably with traditional methods for determining T cell responses (i.e., [3H]thymidine incorporation and the use of cell proliferation dyes). Furthermore, we demonstrate the usefulness of measuring lactate as a read-out in conventional suppression assays and high-throughput peptide-screening assays. Extracellular lactate was stably produced over 7 d, and results were reproducibly performed over several freeze-thaw cycles. We conclude that the use of extracellular lactate measurements can be a sensitive, safe, stable, and easy-to-implement research tool for measuring T cell responses and cellular metabolic changes in vitro.

Controlled drug release from pellets containing water-insoluble drugs dissolved in a self-emulsifying system.

The aim of the study was to provide a controlled release system, which could be used for the oral administration of highly water-insoluble drugs. Pellets have been prepared by extrusion/spheronization containing two model drugs (methyl and propyl parabens) of low water solubility. One type of pellets contained the drugs mixed with lactose and microcrystalline cellulose (MCC) and the other types of pellets contained the model drugs dissolved in a self-emulsifying system (4.8%) consisting of equal parts of mono-diglycerides and polysorbate 80 and MCC. Pellets of all types in the same size fraction (1.4-2.0 mm) were coated to different levels of weight gain, with ethylcellulose, talc and glycerol. A sample of pellets containing methyl parabens in the self-emulsifying system was pre-coated with a film of hydroxypropylmethyl cellulose from an aqueous solution and then coated as above. Dissolution experiments established that the presence of the self-emulsifying system enhanced the drug release of both model drugs and that the film coating considerably reduced the drug release from pellets made with just water, lactose and MCC. The coating reduced the drug release from the pellets containing the self-emulsifying system to a lesser extent but in relation to the quantity of coat applied to the pellets. The application of a sub-coating of hydroxypropylmethyl cellulose was able to reduce the release rate of methyl parabens self-emulsifying system ethyl cellulose coated pellets. Thus, the formulation approach offers the possibility of formulating and controlling the in vitro release of water-insoluble drugs from solid oral dosage forms.

Rat pharmacokinetics and pharmacodynamics of a sustained release formulation of the GABAA alpha5-selective compound L-655,708.

The pharmacokinetic and pharmacodynamic (i.e., receptor occupancy) properties of L-655,708, a compound with selectivity for alpha5-over alpha1-, alpha2-, and alpha3-containing GABA(A) receptors, were examined in rats with the aim of developing a formulation that would give sustained (up to 6 h) and selective occupancy of alpha5-containing GABA(A) receptors suitable for behavioral studies. Standard rat pharmacokinetic analyses showed that L-655,708 has a relatively short half-life with kinetics in the brain mirroring those in the plasma. In vivo binding experiments showed that plasma concentrations of around 100 ng/ml gave relatively selective in vivo occupancy of rat brain alpha5-versus alpha1-, alpha2-, and alpha3-containing GABA(A) receptors. Therefore, this plasma concentration was chosen as a target to achieve relatively selective occupancy of alpha5-containing receptors using s.c. implantations of L-655,708 (0.4, 1.5, or 2.0 mg) formulated into tablets of various size (20 or 60 mg) containing different amounts of L-655,708 and combinations of low and high viscosity hydroxypropyl methylcellulose (LV- and HV-HPMC). The optimum formulation, 1.5 mg of L-655,708 compressed into a 60-mg tablet with 100% HV-HPMC, resulted in relatively constant plasma concentrations being maintained for at least 6 h with very little difference between C(max) concentrations (125-150 ng/ml) and plateau concentrations (100-125 ng/ml). In vivo binding experiments confirmed the selective occupancy of rat brain alpha5-over alpha1-, alpha2-, and alpha3-containing GABA(A) receptors.

Comparative bioavailability study in dogs of a self-emulsifying formulation of progesterone presented in a pellet and liquid form compared with an aqueous suspension of progesterone.

A pellet formulation of progesterone in a self-emulsifying system (SES) was prepared by the process of extrusion/spheronization to provide a good in vitro drug release (100% within 30 min, T(50%) at 13 min). A three-way randomized crossover study was performed in six fasted male beagle dogs with these pellets and the same SES liquid formulation, both contained in a hard shell capsule, and an aqueous suspension. The same dose of progesterone (16 mg) in pellets and in the SES liquid formulation resulted in similar AUC, C(max) and T(max) values, estimated from progesterone plasma levels by (125)I radioimmunoassay. Although the maximum absorption was slightly retarded (0.5 to 1 h) by SES (pellets and liquid), AUC and C(max) were approximately seven and nine times greater then those obtained when an aqueous suspension formulation of the same dose of progesterone was administered to the same dogs. These results showed that it was possible to improve the bioavailability of the poorly soluble, poorly permeable progesterone when administered in SES. Moreover, presenting the progesterone in the form of a pellet did not prevent the release of the drug in vivo. These data demonstrate the utility of extrusion/spheronization in delivering a nonaqueous system in a novel solid dosage form.