Surgically correctable congenital anomalies cause a substantial burden of global morbidity and mortality. These anomalies disproportionately affect children in low- and middle-income countries (LMICs) due to sociocultural, economic, and structural factors that limit the accessibility and quality of pediatric surgery. While data from LMICs are sparse, available evidence suggests that the true human and financial cost of congenital anomalies is grossly underestimated and that pediatric surgery is a cost-effective intervention with the potential to avert significant premature mortality and lifelong disability.

Myelomeningocele (MMC)-commonly known as spina bifida-is a congenital birth defect that causes lifelong paralysis, incontinence, musculoskeletal deformities, and severe cognitive disabilities. The recent landmark Management of Myelomeningocele Study (MOMS) demonstrated for the first time in humans that in utero surgical repair of the MMC defect improves lower limb motor function, suggesting a capacity for improved neurologic outcomes in this disorder. However, functional recovery was incomplete, and 58% of the treated children were unable to walk independently at 30 months of age. In the present study, we demonstrate that using early gestation human placenta-derived mesenchymal stromal cells (PMSCs) to augment in utero repair of MMC results in significant and consistent improvement in neurologic function at birth in the rigorous fetal ovine model of MMC. In vitro, human PMSCs express characteristic MSC markers and trilineage differentiation potential. Protein array assays and enzyme-linked immunosorbent assay show that PMSCs secrete a variety of immunomodulatory and angiogenic cytokines. Compared with adult bone marrow MSCs, PMSCs secrete significantly higher levels of brain-derived neurotrophic factor and hepatocyte growth factor, both of which have known neuroprotective capabilities. In vivo, functional and histopathologic analysis demonstrated that human PMSCs mediate a significant, clinically relevant improvement in motor function in MMC lambs and increase the preservation of large neurons within the spinal cord. These preclinical results in the well-established fetal ovine model of MMC provide promising early support for translating in utero stem cell therapy for MMC into clinical application for patients. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:659-669 SIGNIFICANCEThis study presents placenta-derived mesenchymal stromal cell (PMSC) treatment as a potential therapy for myelomeningocele (MMC). Application of PMSCs can augment current in utero surgical repair in the well-established and rigorously applied fetal lamb model of MMC. Treatment with human PMSCs significantly and dramatically improved neurologic function and preserved spinal cord neuron density in experimental animals. Sixty-seven percent of the PMSC-treated lambs were able to ambulate independently, with two exhibiting no motor deficits whatsoever. In contrast, none of the lambs treated with the vehicle alone were capable of ambulation. The locomotor rescue demonstrated in PMSC-treated lambs indicates great promise for future clinical trials to improve paralysis in children afflicted with MMC.

Purpose: Sexual and gender minorities (SGMs) in medicine experience unique stressors in training. However, little is known about SGM specialty choice. This study examined predictors of SGM specialty choice, associations between specialty prestige and perceived SGM inclusion, and self-reported influences on specialty choice. Methods: Medical trainees and practitioners (358 SGM, 1528 non-SGM) were surveyed online. We operationalized specialty choice at the individual level as respondents' specialty of practice; at the specialty level, as a percentage of SGM respondents in each specialty. We examined specialty prestige, perceived SGM inclusivity, and medical school climate as predictors of SGM specialty choice, and we compared additional influences on specialty choice between SGM and non-SGM. Results: The percentage of SGM in each specialty was inversely related to specialty prestige (P = 0.001) and positively related to perceived SGM inclusivity (P = 0.01). Prestigious specialties were perceived as less SGM inclusive (P < 0.001). Medical school climate did not predict specialty prestige (P = 0.82). SGM were more likely than non-SGM to indicate that sexual and gender identity strongly influenced specialty choice (P < 0.01). SGM most frequently rated personality fit, specialty content, role models, and work-life balance as strong influences on specialty choice. Exposure as a medical student to SGM faculty did not predict specialty prestige among SGM. Conclusion: Specialty prestige and perceived inclusivity predict SGM specialty choice. SGM diversity initiatives in prestigious specialties may be particularly effective by addressing SGM inclusion directly. Further research is needed to inform effective mentorship for SGM medical students. Exposure to SGM in medical training reduces anti-SGM bias among medical professionals, and SGM in medicine often assume leadership roles in clinical care, education, and research regarding SGM health. Supporting and promoting SGM diversity across the spectrum of medical specialties, therefore, represents a critical avenue to improve the care delivered to SGM populations and addresses the role of providers in the health disparities experienced by SGM.

There is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. The causes for such sex disparity is the focus of this Blue Conference Perspective review, which explores basic cellular and molecular mechanisms, life stages, and clinical outcomes based on environmental, sociocultural, occupational, and infectious scenarios, as well as medical health beliefs. Owing to the breadth of issues related to women and lung disease, we present examples of both basic and clinical concepts that may be the cause for pulmonary disease disparity in women. These examples include those diseases that predominantly affect women, as well as the rising incidence among women for diseases traditionally occurring in men, such as chronic obstructive pulmonary disease. Sociocultural implications of pulmonary disease attributable to biomass burning and infectious diseases among women in low-to middle-income countries are reviewed, as are disparities in respiratory health among sexual minority women in high-income countries. The implications of the use of complementary and alternative medicine by women to influence respiratory disease are examined, and future directions for research on women and respiratory health are provided.

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