The Importance of Discussing the History of Racism in Medical Student Education.

Racial health disparities are tightly linked to the longstanding and pervasive institution of racism. Efforts to reverse disparities begin with awareness and accountability through education. The health care workforce must be formally educated about racist practices, tools, and ideologies that perpetuate poor health outcomes. This article explores prior efforts to integrate race didactics into medical school education, addresses current legislation, and illuminates lessons learned from a single institution pilot curriculum exploring the history of racism in the field of obstetrics and gynecology. Educating medical school students about the history of racism is an important and necessary tool for positive change.

A model for accurate quantification of CRISPR effects in pooled FACS screens.

CRISPR screens are powerful tools to identify key genes that underlie biological processes. One important type of screen uses fluorescence activated cell sorting (FACS) to sort perturbed cells into bins based on the expression level of marker genes, followed by guide RNA (gRNA) sequencing. Analysis of these data presents several statistical challenges due to multiple factors including the discrete nature of the bins and typically small numbers of replicate experiments. To address these challenges, we developed a robust and powerful Bayesian random effects model and software package called Waterbear. Furthermore, we used Waterbear to explore how various experimental design parameters affect statistical power to establish principled guidelines for future screens. Finally, we experimentally validated our experimental design model findings that, when using Waterbear for analysis, high power is maintained even at low cell coverage and a high multiplicity of infection. We anticipate that Waterbear will be of broad utility for analyzing FACS-based CRISPR screens.

Tofacitinib Regulates Endostatin via Effects on CD147 and Cathepsin S.

Angiogenesis is critical for rheumatoid arthritis (RA) progression. The effects of tofacitinib, a JAK-STAT inhibitor used for RA treatment, on angiogenesis in RA are unclear. We, therefore, evaluated the levels of angiogenic factors in two systems of a human co-culture of fibroblast (HT1080) and monocytic (U937) cell lines treated with tofacitinib and in serum samples from RA patients before and after six months of tofacitinib treatment. Tofacitinib reduced CD147 levels, matrix metalloproteinase-9 (MMP-9) activity, and angiogenic potential but increased endostatin levels and secreted proteasome 20S activity. In vitro, tofacitinib did not change CD147 mRNA but increased miR-146a-5p expression and reduced STAT3 phosphorylation. We recently showed that CD147 regulates the ability of MMP-9 and secreted proteasome 20S to cleave collagen XVIIIA into endostatin. We show here that tofacitinib-enhanced endostatin levels are mediated by CD147, as CD147-siRNA or an anti-CD147 antibody blocked proteasome 20S activity. The correlation between CD147 and different disease severity scores supported this role. Lastly, tofacitinib reduced endostatin' s degradation by inhibiting cathepsin S activity and recombinant cathepsin S reversed this in both systems. Thus, tofacitinib inhibits angiogenesis by reducing pro-angiogenic factors and enhancing the anti-angiogenic factor endostatin in a dual effect mediated partly through CD147 and partly through cathepsin S.

Corticosteroids for improving patient-relevant outcomes in HELLP syndrome: a systematic review and meta-analysis.

BACKGROUND: We conducted this updated systematic review to assess the effects of corticosteroids vs. placebo or no treatment for improving patient-relevant outcomes in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. METHODS: CENTRAL, MEDLINE/PubMed, Web of Science, and Scopus, from the date of inception of the databases to February 3, 2024 were searched. Reference lists of included studies and systematic reviews were thoroughly searched. We included RCTs that enrolled women with HELLP syndrome, whether antepartum or postpartum, to receive any corticosteroid versus placebo or no treatment. No language or publication date restrictions were made. We used a dual independent approach for screening titles and abstracts, full text screening, and data extraction. Risk of bias was assessed in the included studies using Cochrane's RoB 2 tool. Pairwise meta-analyses were conducted, where two or more studies met methodological criteria for inclusion. GRADE approach was used to assess certainty of evidence for the pre-specified outcomes. RESULTS: Fifteen trials (821 women) compared corticosteroids with placebo or no treatment. The effect of corticosteroids is uncertain for the primary outcome i.e., maternal death (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.25 to 2.38, very low certainty evidence). Out of 6 studies reporting maternal death, 5 were judged overall to have "low risk" of bias. The effect of corticosteroids is also uncertain for other important outcomes including pulmonary edema (RR 0.70, 95% CI 0.23 to 2.09), dialysis (RR 3, 95% CI 0.13 to 70.78), liver morbidity (hematoma, rupture, and failure; RR 0.22, 95% CI 0.03 to 1.83), or perinatal death (0.64, 95% CI 0.21 to 1.97) because of very low certainty evidence. Low certainty evidence suggests that corticosteroids have little or no effect on the need for platelet transfusion (RR 0.98, 95% CI 0.60 to 1.60) and may result in a slight reduction in acute renal failure (RR 0.67, 95% CI 0.40 to 1.12). Subgroup and sensitivity analyses showed results that were similar to the primary synthesis. CONCLUSIONS: In women with HELLP syndrome, the effect of corticosteroids vs. placebo or no treatment is uncertain for patient-relevant outcomes including maternal death, maternal morbidity, and perinatal death. These uncertainties regarding this critical question should be addressed by adequately powered rigorous trials. SYSTEMATIC REVIEW REGISTRATION: Center for Open Science, osf.io/yzku5.

The potential liver injury induced by metronidazole-provoked disturbance of gut microbiota: modulatory effect of turmeric supplementation.

It has been reported that the gut-liver axis and intestinal microbiome contribute crucially to different liver diseases. So, targeting this hepato-intestinal connection may provide a novel treatment modality for hepatic disorders such as drug-induced liver injury (DILI). The present study thought to investigate the protective effect of turmeric (TUR) on metronidazole (MNZ)-induced liver damage and the possible association of the gut-liver axis and gut microbiota as a suggested underlying mechanism. In the first experiment, a MNZ-induced liver injury rat model was reproduced after 130 mg/kg oral MNZ administration for 30 days. Meanwhile, the treatment group was orally treated with 100 mg/kg turmeric daily. In the second experiment, fecal microbiome transplantation (FMT) was conducted, in which the fecal microbiome of each group in the first experiment was transplanted to a healthy corresponding group in the second experiment. The liver enzymes (aminotransferase (ALT) and aspartate aminotransferase (AST)) and histopathological examination were estimated to assess liver function. Inflammatory cytokines and oxidative markers were evaluated in the liver tissues. Histological analysis, intestinal barrier markers, and expression of tight junction proteins were measured for assessment of the intestinal injury. Changes in the gut microbial community and possible hepatic bacterial transmission were analyzed using 16S rRNA sequencing. MNZ induced intestinal and liver injuries which were significantly improved by turmeric. Increased firmicutes/bacteroidetes ratio and bacterial transmission due to gut barrier disruption were suggested. Moreover, TUR has maintained the gut microbial community by rebalancing and restoring bacterial proportions and abundance, thereby repairing the gut mucosal barrier and suppressing bacterial translocation. TUR protected against MNZ-induced gut barrier disruption. Reshaping of the intestinal bacterial composition and prohibition of the hepatic microbial translocation were suggested turmeric effects, potentially mitigating MNZ-related liver toxicity.

Gain-of-function variants in CLCN7 cause hypopigmentation and lysosomal storage disease.

Together with its ß-subunit OSTM1, ClC-7 performs 2Cl-/H+ exchange across lysosomal membranes. Pathogenic variants in either gene cause lysosome-related pathologies, including osteopetrosis and lysosomal storage. CLCN7 variants can cause recessive or dominant disease. Different variants entail different sets of symptoms. Loss of ClC-7 causes osteopetrosis and mostly neuronal lysosomal storage. A recently reported de novo CLCN7 mutation (p.Tyr715Cys) causes widespread severe lysosome pathology (hypopigmentation, organomegaly, and delayed myelination and development, "HOD syndrome"), but no osteopetrosis. We now describe two additional HOD individuals with the previously described p.Tyr715Cys and a novel p.Lys285Thr mutation, respectively. Both mutations decreased ClC-7 inhibition by PI(3,5)P2 and affected residues lining its binding pocket, and shifted voltage-dependent gating to less positive potentials, an effect partially conferred to WT subunits in WT/mutant heteromers. This shift predicts augmented pH gradient-driven Cl- uptake into vesicles. Overexpressing either mutant induced large lysosome-related vacuoles. This effect depended on Cl-/H+-exchange, as shown using mutants carrying uncoupling mutations. Fibroblasts from the p.Y715C patient also displayed giant vacuoles. This was not observed with p.K285T fibroblasts probably due to residual PI(3,5)P2 sensitivity. The gain of function caused by the shifted voltage-dependence of either mutant likely is the main pathogenic factor. Loss of PI(3,5)P2 inhibition will further increase current amplitudes, but may not be a general feature of HOD. Overactivity of ClC-7 induces pathologically enlarged vacuoles in many tissues, which is distinct from lysosomal storage observed with the loss of ClC-7 function. Osteopetrosis results from a loss of ClC-7, but osteoclasts remain resilient to increased ClC-7 activity.

Redesigning Continuous Professional Development: Aligning Learning Needs With Clinical Practice.

Continuous professional development (CPD) in health care refers to the process of lifelong learning including the acquisition of new competencies, knowledge, and professional growth throughout the career of a health care professional. Since implementation, there has seen little change or innovation in CPD. This perspective will review the current state of CPD, including the challenges in traditional CPD models, foundations and strategies for redesign to meet the needs of current and future physicians, and suggestions for changes to modernize CPD. Precision education and the use of technology, including artificial intelligence, and their application to CPD will be discussed.

Risk Factors for Trochanteric Bursitis Following Total Hip Arthroplasty: A Radiographic Analysis.

BACKGROUND: Trochanteric bursitis (TB) is a prevalent complication following total hip arthroplasty (THA), with increased offset hypothesized as a potential risk factor. This study investigated potential TB predictors in THA patients, including radiographic measurements of offset and leg length, comorbidities, and patient characteristics. METHODS: In this retrospective cohort study, all THA patients from a single academic tertiary care center between 2005 and 2021 were reviewed. Exclusion criteria included less than one-year follow-up, osteonecrosis, or fracture. Manual radiographic measurements of offset (acetabular, femoral, and total) and leg length from preoperative and postoperative antero-posterior pelvis X-rays were taken, with scaling using femoral cortical diameter. Univariable and multivariable Cox proportional hazard models were employed to estimate TB risk. RESULTS: Of 1,094 patients, 103 (9.4%) developed TB, with a median (Q1, Q3) time to presentation of 41.8 weeks (25.5, 66.9). In univariable models, only sex was associated with increased TB risk, with women exhibiting a 1.79 times increased risk (hazard ratio: 1.79 (1.16, 2.76), P = .009). Changes in acetabular offset, femoral offset, total offset, and leg length between preoperative and postoperative radiographs were not associated with an increased risk of developing TB in the univariate or multivariate models. Furthermore, various offset thresholds were evaluated, with no amount of increased offset showing increased TB risk. CONCLUSIONS: This study found no relationship between femoral, acetabular, or total offset and TB following THA. These findings suggest that surgeons may consider adding offset for increased prosthetic stability in high-risk cases. However, given that this is a retrospective study, the authors are not advocating for the routine use of increased offset. The study identified women as a risk factor with a 1.79 times higher TB risk, highlighting the importance of counseling women patients on this heightened risk.

Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells.

Cis-regulatory elements (CREs) interact with trans regulators to orchestrate gene expression, but how transcriptional regulation is coordinated in multi-gene loci has not been experimentally defined. We sought to characterize the CREs controlling dynamic expression of the adjacent costimulatory genes CD28, CTLA4 and ICOS, encoding regulators of T cell-mediated immunity. Tiling CRISPR interference (CRISPRi) screens in primary human T cells, both conventional and regulatory subsets, uncovered gene-, cell subset- and stimulation-specific CREs. Integration with CRISPR knockout screens and assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling identified trans regulators influencing chromatin states at specific CRISPRi-responsive elements to control costimulatory gene expression. We then discovered a critical CCCTC-binding factor (CTCF) boundary that reinforces CRE interaction with CTLA4 while also preventing promiscuous activation of CD28. By systematically mapping CREs and associated trans regulators directly in primary human T cell subsets, this work overcomes longstanding experimental limitations to decode context-dependent gene regulatory programs in a complex, multi-gene locus critical to immune homeostasis.

Local Structural Features Elucidate Crystallization of Complex Structures.

Complex crystal structures are composed of multiple local environments, and how this type of order emerges spontaneously during crystal growth has yet to be fully understood. We study crystal growth across various structures and along different crystallization pathways, using self-assembly simulations of identical particles that interact via multiwell isotropic pair potentials. We apply an unsupervised machine learning method to features from bond-orientational order metrics to identify different local motifs present during a given structure's crystallization process. In this manner, we distinguish different crystallographic sites in highly complex structures. Tailoring this order parameter to structures of varying complexity and coordination number, we study the emergence of local order along a multistep crystal growth pathway─from a low-density fluid to a high-density, supercooled amorphous liquid droplet and to a bulk crystal. We find a consistent under-coordination of the liquid relative to the average coordination number in the bulk crystal. We use our order parameter to analyze the geometrically frustrated growth of a Frank-Kasper phase and discover how structural defects compete with the formation of crystallographic sites that are more high-coordinated than the liquid environments. The method presented here for classifying order on a particle-by-particle level has broad applicability to future studies of structural self-assembly and crystal growth, and they can aid in the design of building blocks and for targeting pathways of formation of soft-matter structures.

Inequities at the Transition to Obstetrics and Gynecology Residency.

OBJECTIVE: Although approximately one-fifth of obstetrics and gynecology (OBGYN) residents matriculate from osteopathic or international medical schools, most literature regarding the transition to residency focuses on allopathic medical school graduates. To create comprehensive interventions for this educational transition, we must understand the needs of all incoming residents. Our objective was to examine OBGYN residents' perceptions of their transition to residency, and to understand how residents' background and medical school environment influence their perceived sense of readiness. DESIGN: A 16-item survey asked questions about demographics, the transition to residency, resident well-being, burnout, and the transition to fellowship. Perception of preparedness was assessed with the question "I felt that I was well-prepared for the first year of residency" (1=strongly agree, 5=strongly disagree). Chi-squared and Fisher's exact tests and logistic regression explored association of perceived preparedness with residents' backgrounds. SETTING: Survey administered at time of the in-training examination in 2022. PARTICIPANTS: All OBGYN residents. RESULTS: Of 5761 eligible participants, 3741 (64.9%) provided consent and completed the survey. Of the 3687 participants who answered the question, 2441 (66.2%) either agreed or strongly agreed that they felt well-prepared. Fewer osteopathic graduates reported feeling prepared compared to allopathic graduates (379/610, 62.1% vs 1,924/2,766, 69.6%) (OR 0.72, 95%CI 0.60-0.86, p < 0.01). International medical school graduates were seven times less likely to report feeling prepared compared to those from allopathic institutions (137/304, 45.1% vs 1924/2776, 69.6%) (OR 0.60, 95%CI 0.53-0.68, p < 0.01). Respondents from underrepresented racial and ethnic backgrounds were less likely to report feeling prepared compared to White respondents (276/535, 51.6% vs 1738/2387, 72.8%) (OR 0.39, 95%CI 0.33-0.48, p < 0.01). CONCLUSIONS: Differences in residents' perceptions of their transition to residency highlight the need to begin offsetting pervasive inequities with comprehensive and accessible resources.

Structural Racism, Residential Segregation, and Exposure to Trauma: The Persistent Impact of Redlining.

INTRODUCTION: As part of New Deal era federal housing policy, the Home Owners Loan Corporation (HOLC) developed maps grading US neighborhoods by perceived financial security. Neighborhoods with high concentrations of racial and ethnic minorities were deemed financially unstable and denied federal investment, a practice colloquially known as redlining. The aim of this study was to assess the association of historical redlining within Austin, Texas to spatial patterns of penetrating traumatic injury. METHODS: Retrospective cross sectional study utilizing data from violent penetrating trauma admissions between January 1, 2014 - December 31, 2021, at the single Level 1 trauma center in Austin, Texas. Using ArcGIS, addresses where the injury took place were geocoded and spatial joining was used to match them to their corresponding census tract, for which 1935 HOLC financial designations are classified as: "Hazardous", "Definitely Declining", "Still Desirable", "Best", or "Non HOLC Graded". Tracts with designations of "Hazardous" and "Definitely Declining" were categorized as Redlined. The adjusted incidence rate ratio comparing rates of penetrating trauma among historically Redlined vs. Not Redlined and Not Graded census tracts was calculated. RESULTS: 1,404 violent penetrating trauma admissions were identified for the study period, of which 920 occurred within the county of interest. Among these, 5% occurred in census tracts that were Not Redlined, 13% occurred in Redlined tracts, and 82% occurred in non HOLC graded tracts. When adjusting for differences in current census tract demographics and social vulnerability, historically Redlined areas experienced a higher rate of penetrating traumatic injury (Not Redlined IRR = 0.42, 95% CI 0.19-0.94, p = 0.03; Not Graded IRR = 0.15, 95% CI 0.07-0.29, p < 0.001). CONCLUSIONS: Neighborhoods unfavorably classified by HOLC in 1935 continue to experience a higher incidence rate of violent penetrating trauma today. These results underscore the persistent impacts of structural racism and of historical residential segregation policies on exposure to trauma. LEVEL OF EVIDENCE: Level IV, Prognostic and Epidemiological.

Conversion of sleeve gastrectomy to Roux-en-Y gastric bypass: impact on reflux and weight loss.

BACKGROUND: Sleeve gastrectomy (SG) is the most commonly performed weight loss operation, and its 2 most common complications are postoperative reflux and weight recurrence. There is limited evidence to guide decision-making in treating these conditions. OBJECTIVES: To determine the efficacy of conversion of SG to Roux-en-Y gastric bypass (RYGB) for GERD management and weight loss. SETTING: Forty-one hospitals in Michigan. METHODS: We conducted a retrospective cohort study examining patients who underwent conversion of SG to RYGB from 2014 to 2022. The primary outcomes were changes in GERD-HRQL scores, anti-reflux medication use, and weight from baseline to 1 year after conversion. Secondary outcomes included 30-day postoperative complications and resource utilization. RESULTS: Among 2133 patients undergoing conversion, 279 (13%) patients had baseline and 1-year GERD-HRQL survey data and anti-reflux medication data. GERD-HRQL scores decreased significantly from 24.6 to 6.6 (P < .01). Among these, 207 patients (74%) required anti-reflux medication at baseline, with only 76 patients (27%) requiring anti-reflux medication at 1 year postoperatively (P < .01). Of the 380 patients (18%) with weight loss data, mean weight decreased by 68.4lbs, with a 24.3% decline in total body weight and 51.5% decline in excess body weight. In terms of 30-day complications, 308 (14%) patients experienced any complication and 89 (4%) experienced a serious complication, but there were no leaks, perforations, or deaths. Three-hundred and fifty-five (17%) patients presented to the emergency department and 64 (3%) patients underwent reoperation. CONCLUSIONS: This study represents the largest reported experience with conversion from SG to RYGB. We found that conversion to RYGB is associated with significant improvement in GERD symptoms, reduction in anti-reflux medication use, and significant weight loss and is therefore an effective treatment for GERD and weight regain after SG. However, the risks and benefits of conversion surgery should be carefully considered, especially in patients with significant comorbidity burden.

Incorporation of Resveratrol-Hydroxypropyl-ß-Cyclodextrin Complexes into Hydrogel Formulation for Wound Treatment.

Resveratrol could be applied in wound healing therapies because of its antioxidant, anti-inflammatory and antibacterial effects. However, the main limitation of resveratrol is its low aqueous solubility. In this study, resveratrol was included in hydroxypropyl-ß-cyclodextrin complexes and further formulated in Pluronic F-127 hydrogels for wound treatment therapy. IR-spectroscopy and XRD analysis confirmed the successful incorporation of resveratrol into complexes. The wound-healing ability of these complexes was estimated by a scratch assay on fibroblasts, which showed a tendency for improvement of the effect of resveratrol after complexation. The antimicrobial activity of resveratrol in aqueous dispersion and in the complexes was evaluated on methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans strains. The results revealed a twofold decrease in the MIC and stronger inhibition of the metabolic activity of MRSA after treatment with resveratrol in the complexes compared to the suspended drug. Furthermore, the complexes were included in Pluronic hydrogel, which provided efficient drug release and appropriate viscoelastic properties. The formulated hydrogel showed excellent biocompatibility which was confirmed via skin irritation test on rabbits. In conclusion, Pluronic hydrogel containing resveratrol included in hydroxypropyl-ß-cyclodextrin complexes is a promising topical formulation for further studies directed at wound therapy.

Falsely low glycosylated haemoglobin levels probably secondary to hypersplenism in a patient with diabetes mellitus.

A man in his 70s presented with a history of low glycated haemoglobin (HbA1c) values despite a diagnosis of type 2 diabetes. His blood glucose readings ranged between 8 and 15 mmol/L, but his HbA1c values were below 27 mmol/mol. Initial investigations demonstrated evidence of reduced red blood cell lifespan as a cause of misleadingly low HbA1c values. Further investigation revealed chronic liver disease and splenomegaly, with hypersplenism being the probable cause of increased red blood cell turnover. HbA1c estimation was no longer reliable, so ongoing diabetic care was guided by home capillary blood glucose monitoring. Healthcare providers and clinical laboratorians need to be aware of the possible clinical implications of very low HbA1c values in patients with type 2 diabetes.

Insight into the influence of natural deep eutectic solvents on the extraction of phenolic compounds from poplar type propolis: Composition and in vitro biological activity.

Natural deep eutectic solvents (NADESs) have been considered promising to replace traditional volatile and toxic organic solvents for the extraction of biologically active substances from natural sources. This work applied an efficient and ethanol-exclusion strategy for extraction of phenolic compounds from poplar type propolis using five known NADESs (lactic acid:1,2-propanediol 1:1, lactic acid:fructose 5:1, choline chloride:1,2-propanediol 1:3, choline chloride:1,2-propanediol:water 1:1:1 and betaine:malic acid:water 1:1:6). The selected NADESs' extractability was evaluated by measuring the concentrations of total phenolics and total flavones and flavonols in the propolis extracts obtained, which qualitative chemical composition was further determined in detail by gas chromatography-mass spectrometry (GC-MS) analysis. It demonstrated that the chemical profiles of NADES and 70% ethanolic propolis extracts are similar. To expand the knowledge about the role of the applied solvents in the poplar propolis extraction process, the in vitro antimicrobial, cytotoxic and genotoxic activity of both NADESs and liquid NADES extracts were evaluated. The results revealed that the use of the selected NADESs as an extraction media for phenolic compounds from poplar propolis not only delivered a good extraction yield in some cases, but generally led to the preservation of propolis extracts' biological activity and even to the enhancement of their antimicrobial effect in comparison with the hydroethanolic one. Besides, the tested NADESs except for lactic acid:fructose and betaine:malic acid:water exerted low to negligible toxicity against normal cells treated and apart from lactic acid:fructose the remaining solvents demonstrated concentration-dependent moderate to subtle genotoxicity. There is a probability that not the supramolecular structure of the NADESs, but their components, played a key role for the observed biological effects. The present study has demonstrated an alternative approach for extracting the biologically active complex from poplar type propolis using NADESs, which could be useful for further pharmaceutical and cosmeceutical applications.

The Association of Master Adaptive Learning With Less Burnout and More Resilience in Obstetrics and Gynecology Residents.

PURPOSE: Medical education should prepare learners for complex and evolving work, and should ideally include the Master Adaptive Learner (MAL) model-meta-learning skills for continuous self-regulated learning. This study aimed to measure obstetrics and gynecology (OB/GYN) residents' MAL attributes, assess associations with burnout and resilience, and explore learning task associations with MAL. METHOD: OB/GYN residents were surveyed electronically at an in-training examination in January 2022. The survey included demographic information, the 2-item Maslach Burnout Inventory, the 2-item Connor-Davidson Resilience Scale, 4 MAL items (e.g., "I take every opportunity to learn new things"), and questions about training and learning experiences. RESULTS: Of 5,761 residents, 3,741 respondents (65%) were included. A total of 1,478 of 3,386 (39%) demonstrated burnout (responded positive for burnout on emotional exhaustion or depersonalization items). The mean (SD) Connor-Davidson Resilience Scale score was 6.4 (1.2) of a total possible score of 8. The mean (SD) MAL score was 16.3 (2.8) of a total possible score of 20. The MAL score was inversely associated with burnout, with lower MAL scores for residents with (mean [SD] MAL score, 16.5 [2.4]) vs without (mean [SD], 16.0 [2.3]) burnout (P < .001). Higher MAL scores were associated with higher resilience (R = 0.29, P < .001). Higher MAL scores were associated with the statement, "I feel that I was well prepared for my first year of residency" (R = 0.19, P < .001) and a plan to complete subspecialty training after residency (mean [SD] of 16.6 [2.4] for "yes" and 16.2 [2.4] for "no," P < .001). CONCLUSIONS: Residents who scored higher on MAL showed more resilience and less burnout. Whether less resilient, burned-out residents did not have the agency to achieve MAL status or whether MAL behaviors filled the resiliency reservoir and protected against burnout is not clear.

Functional Hydrogels for Delivery of the Proteolytic Enzyme Serratiopeptidase.

Hydrogels are superior wound dressings because they can provide protection and hydration of the wound, as well as the controlled release of therapeutic substances to aid tissue regeneration and the healing process. Hydrogels obtained from natural precursors are preferred because of their low cost, biocompatibility, and biodegradability. We describe the synthesis of novel functional hydrogels based on two natural products-citric acid (CA) and pentane-1,2,5-triol (PT, a product from lignocellulose processing) and poly(ethylene glycol) (PEG-600)-via an environment friendly approach. The hydrogels were prepared via monomer crosslinking through a polycondensation reaction at an elevated temperature in the absence of any solvent. The reagents were blended at three different compositions with molar ratios of hydroxyl (from PT and PEG) to carboxyl (from CA) groups of 1:1, 1:1.4, and 1.4:1, respectively. The effect of the composition on the physicomechanical properties of materials was investigated. All hydrogels exhibited pH-sensitive behavior, while the swelling degree and elastic modulus were dependent on the composition of the polymer network. The proteolytic enzyme serratiopeptidase (SER) was loaded into a hydrogel via physical absorption as a model drug. The release profile of SER and the effects of the enzyme on healthy skin cells were assessed. The results showed that the hydrogel carrier could provide the complete release of the loaded enzyme.

Polycarbonate-Based Copolymer Micelles as Biodegradable Carriers of Anticancer Podophyllotoxin or Juniper Extracts.

Podophyllotoxin (PPT) is used in the industrial production of efficient anticancer, antiviral and other drugs. Sinopodophyllum hexandrum or Podophyllum peltatum are natural sources of PPT, but at present they are considered as endangered species. Their PPT content is variable, depending on the growing conditions. Searching for new sources of PPT, some representatives of the genus Juniperus were found to exhibit efficient PPT biosynthesis. However, PPT is highly toxic and poorly soluble in water compound, which limits its clinical applications. In this connection, amphiphilic polymer micelles are considered to be suitable PPT carriers, aimed at increase in water solubility and decrease in toxicity. The present research deals with the evaluation of MPEG-polycarbonate block copolymer micelles loaded with PPT or juniper extracts. The active component-loaded polymer nanocarriers were characterized by dynamic and electrophoretic light scattering, as well as by transmission electron microscopy. The active component loading efficiency and loading capacity were also determined. Highly efficient antiproliferative activity of the loaded micelles was determined in a panel of cancer cell lines. The obtained amphiphilic nanocarriers, loaded with PPT-containing bioactive components, have application in future in vivo preclinical trials of their pharmacokinetics and pharmacodynamics as potential therapeutical agents in the prospective nanomedicine.