School of Medicine

Disparities persist throughout medicine, including among conference speakership invitations. The National Institutes of Health have highlighted the importance of diversity at academic conferences. We assessed the gender composition of speakers at the American Society for Apheresis (ASFA) annual meeting. We assessed all session chairs and speakers at the annual ASFA meeting from 2019 to 2024. Two authors independently assessed individuals genders. The primary outcome was the gender composition of all session chairs and speakers by position. Subset analyzes were performed to assess the gender composition of unique individuals (i.e., examining the total number of unique men and women, independent of the number of sessions at which they spoke) and by professional degree. 820 positions (665 speaker positions and 155 chair positions) were identified; women comprised significantly more positions than men [64.3%, 528/820 (95% CI 61.1%-67.6%) vs. 35.6% 292/820 (32.4%-38.9%); p < 0.0001]. 52.7% (432/820) of all session positions were held by physicians, with no significant difference in the gender composition [women 47.5%, 205/432 (42.8%-52.2%) vs. men 52.6%, 227/432 (47.8%-57.2%); p = 0.31]. When limited to unique physician individuals, women were significantly outnumbered by men [40.1%, 71/177 (33.2%-47.5%) vs. 59.9%, 106/177 (52.5%-66.8%); p = 0.01]. This analysis demonstrated mixed findings, with more women across all positions overall but significantly more men when limited to unique physicians. Diversity in conference positions begets a broader array of perspectives, knowledge, and expertise, and can aid in realizing greater diversity in related areas. Thus, academic conference diversity should be prioritized and thoughtfully pursued.

Pregnancys effects on the brain, behavior, and hormones provide a unique opportunity to study how the immune system integrates these adaptations and influences mental health.

BACKGROUND: Follicular variant papillary thyroid carcinoma is a distinct subtype of papillary thyroid carcinoma that can occasionally present with aggressive features, including distant metastases and extrathyroidal extension. While radioactive iodine ablation is a well-established treatment for residual disease, its post-treatment effects on tracheal and paratracheal structures remain poorly characterized. CASE PRESENTATION: A 22-year-old male individual of Taiwanese descent presented with an enlarged neck mass and was diagnosed with follicular variant papillary thyroid carcinoma. He underwent thyroidectomy, modified radical neck dissection, and postoperative radioactive iodine-131 ablation (100 mCi). A total of 1 year later, a chest computed tomography revealed a paratracheal soft tissue nodule and tracheal nodularity. Bronchoscopy with endobronchial ultrasound-guided sampling identified multiple 2-3 mm submucosal tracheal nodules containing white exudate. Cytopathologic analysis of both the paratracheal soft tissue nodule and the tracheal wall nodules revealed mucinous material without evidence of malignancy or inflammation. Microbiologic studies were negative for infection. CONCLUSION: These atypical bronchoscopic and pathologic findings likely represent post-radioactive iodine treatment changes. The patient remained without evidence of disease for 22 months, ongoing on thyroid suppression levels of thyroxine hormone replacement. The case represents successful radioactive iodine treatment of papillary thyroid carcinoma residual disease after surgical resection, with the first described pathologic findings to correlate with these post-treatment changes.

BACKGROUND: The creatine-creatine kinase-phosphocreatine (Cr-CK-PCr) system maintains intracellular ratios of ATP/ADP for support of cellular functions and has been characterized at the placental-uterine interface of rodents, primates, swine and sheep, and thus may support fetal development. This study determined effects of dietary supplementation of creatine (Cr) to gestating gilts on fetal development, the number and ratio of primary and secondary muscle fibers, and on protein expression in endometrium and fetal biceps-femoris muscle, respectively in fetal pigs on d 60 and d 90 of gestation. METHODS: Reproductively mature gilts were synchronized to estrus using Matrix, observed for estrus (d 0), and artificially inseminated 12 h and 36 h later. Gilts were individually housed and fed 0.86 kg of 14% crude protein diet twice daily that meets nutritional requirements for pregnant gilts. Gilts were assigned to either basal diet control (CON) group, or Cr supplemented group (provided 30 g Cr monohydrate daily) from d 10 to either d 60 or d 90 of gestation. Gilts were euthanized and hysterectomized on either d 60 or d 90 of gestation. These protocols were completed in two replicates, as gilts were bred in spring and euthanized in summer or bred in fall and euthanized in winter (n = 20 gilts/replicate). Litter size, crown-rump length, sex, and fetal weight was recorded. Three female and male fetuses closest to mean litter weight were selected to assess effects of treatment on weight of fetal brain, kidney, liver, spleen, and biceps-femoris muscle. Data were analyzed to determine effects of treatment, days of gestation, replicate, and sex on litter size, fetal measurements, and incidence of intrauterine growth restriction. RESULTS: Dietary Cr supplementation increased fetal brain weight to body weight ratios on d 90 of gestation (P < 0.05) and fetal kidney weight to body weight ratios on d 60 of gestation (P < 0.01), while days of gestation had significant effect on expression of mitochondrial CK isoform in gilt endometria (P < 0.05). CONCLUSIONS: Results suggest that dietary supplementation of Cr in gestating gilts enhanced development of select fetal organs and contribute to understanding roles of the Cr-CK-PCr system in pregnancy.

Precisely timed immune adaptations, observed in the maternal circulation, underpin the notion of an immune clock of human pregnancy that supports its successful progression and completion at delivery. This immune clock is divided into three immunological phases, with the first phase starting at the time of conception and implantation, shifting into the second phase that supports homeostasis and tolerance throughout pregnancy, and culminating in the last phase of labor and parturition. Disruptions of this immune clock are reported in pregnancy complications such as spontaneous preterm birth. However, our understanding of the immune clock preceding spontaneous preterm birth remains scattered. In this review, we describe the chronology of maternal immune cell adaptations during healthy pregnancies and highlight its disruption in spontaneous preterm birth. With a focus on single-cell cytometric, proteomic and transcriptomic approaches, we review recent studies of term and spontaneous preterm pregnancies and discuss the need for future prospective studies aimed at tracking pregnancies longitudinally on a multi-omic scale. Such studies will be critical in determining whether spontaneous preterm pregnancies progress at an accelerated pace or follow a preterm-intrinsic pattern when compared to those delivered at term.

Methamphetamine (METH) use is frequent among people with HIV (PWH) and appears to increase the risk of neuronal injury and neurocognitive impairment (NCI). This study explored in vivo the effects of a 12 week (long-term), low-dose METH regimen in a transgenic animal model of neuroHIV with inducible expression of HIV-1 transactivator of transcription (Tat). Seven months after transient Tat induction and five months after METH exposure ended, we detected behavioral changes in the Barnes maze (BM) spatial memory task in the Tat and METH groups but not the combined Tat + METH group. The novel object recognition (NOR) task revealed that Tat extinguished discrimination in female animals with and without METH, although METH alone slightly improved NOR. In contrast, in males, Tat, METH, and Tat + METH all compromised NOR. Neuropathological examination detected sex-dependent and brain region-specific changes of pre-synaptic terminals, neurites, and activation of astrocytes and microglia. RNA-sequencing and quantitative reverse transcription polymerase chain reaction indicated that METH and Tat significantly altered gene expression, including factors linked to Alzheimer's disease-like NCI. In summary, chronic low-dose METH exerts long-term effects on behavioral function, neuropathology, and mRNA expression, and modulates the effects of Tat, suggesting sex-dependent and -independent mechanisms may converge in HIV brain injury and NCI.

The high-temperature requirement A1 (HTRA1), a serine protease, has been demonstrated to play a pivotal role in the extracellular matrix (ECM) and has been reported to be associated with the pathogenesis of age-related macular degeneration (AMD). To delineate its role in the retina, the phenotype of homozygous Htra1-KO (Htra1-/-) mice was characterized to examine the effect of Htra1 loss on the retina and retinal pigment epithelium (RPE) with age. The ablation of Htra1 led to a significant reduction in rod and cone photoreceptor function, primary cone abnormalities followed by rods, and atrophy in the RPE compared with WT mice. Ultrastructural analysis of Htra1-/- mice revealed RPE and Bruch's membrane (BM) abnormalities, including the presence of sub-RPE deposits at 5 months (m) that progressed with age accompanied by increased severity of pathology. Htra1-/- mice also displayed alterations in key markers for inflammation, autophagy, and lipid metabolism in the retina. These results highlight the crucial role of HTRA1 in the retina and RPE. Furthermore, this study allows for the Htra1-/- mouse model to be utilized for deciphering mechanisms that lead to sub-RPE deposit phenotypes including AMD.

Smoking plays an underappreciated role in breast cancer progression, increasing recurrence and mortality in patients. Here, we show that S100A8/A9 innate immune signaling is a molecular mechanism that identifies smoking-related breast cancers and underlies their enhanced malignancy. In contrast to acute exposure, chronic nicotine increased tumorigenicity and reprogrammed breast cancer cells to express innate immune response genes. This required the α7 nicotinic acetylcholine receptor, which elicited dynamic changes in cell differentiation, proliferation, and expression of secreted cytokines, such as S100A8 and S100A9, as assessed by unbiased scRNA-seq. Indeed, pharmacologic or genetic inhibition of S100A8/A9-RAGE receptor signaling blocked nicotine's tumor-promoting effects. We also discovered Syntaphilin (SNPH) as an S100A8/A9-dependent gene enriched specifically in estrogen receptor-negative (ER^-) cancers from former smokers, linking this response to patient disease. Together, our findings describe a new α7 nAChR-S100A8/A9-Syntaphilin immune signaling module that drives nicotine-induced tumor progression and distinguishes smoking-related patient disease as a distinct subset of aggressive breast cancers.

Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used an engineered angiotensin-converting enzyme 2 to capture intact virus from plasma and other complex biofluids. Our device leverages a staggered herringbone pattern, nanoparticle surface coating, and processing conditions to achieve detection of as few as 3 viral copies per milliliter. We further validated our microfluidic assay on 103 plasma, 36 saliva, and 29 stool samples collected from unique patients with COVID-19, showing SARS-CoV-2 detection in 72% of plasma samples. Longitudinal monitoring in the plasma revealed our device's capacity for ultrasensitive detection of active viral infections over time. Our technology can be adapted to target other viruses using relevant cell entry molecules for affinity capture. This versatility underscores the potential for widespread application in viral load monitoring and disease management.

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