Women in Microsurgery Fellowships: Trends and Impact on Future Practice Patterns.

BACKGROUND: While the number of female plastic surgeons has continued to increase over time, plastic surgery has historically been a male-dominated profession with only 15% of practicing plastic surgeons being female. Microsurgery, as a subspecialty, has been long perceived as an even more male-centric career path. The objective of this study was to determine the representation of females in the subspecialty field of microsurgery and the impact of microsurgical fellowship training. METHODS: A review of all microsurgery fellowship programs participating in the microsurgery fellowship match from 2010 to 2019 were analyzed. Fellows were identified through fellowship Web site pages or direct contact with fellowship program coordinators and directors. The current type of practice and performance of microsurgery were also identified through a Web search and direct contact with fellowship program coordinators and directors. RESULTS: A total of 21 programs and 317 fellows over a 10-year period were analyzed. Over this 10-year period, there was a total of 100 (31.5%) female microsurgery fellows and 217 (68.5%) male microsurgery fellows. There was a small, statistically insignificant increase in the yearly percentage of female microsurgery fellows over this 10-year period with an average yearly increase of 2.7% (p = 0.60; 95% confidence interval: -6.9 to 13.2%). There were significantly fewer females who continued to practice microsurgery compared to males (75 [75.0%] vs. 186 [85.7%], p = 0.02). There was no significant difference in the current practice types (academic, private, and nonacademic hospital) between females and males (p = 0.29). CONCLUSION: Women are underrepresented in the field of microsurgery to a similar extent as they are underrepresented in overall plastic surgery. While there is a small insignificant increase in the number of female microsurgery fellows every year, a significantly smaller proportion of females continue to practice microsurgery compared to males.

Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis.

Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.

Epidithiodiketopiperazines (ETPs) exhibit in vitro antiangiogenic and in vivo antitumor activity by disrupting the HIF-1α/p300 complex in a preclinical model of prostate cancer.

The downstream targets of hypoxia inducible factor-1 alpha (HIF-1α) play an important role in tumor progression and angiogenesis. Therefore, inhibition of HIF-mediated transcription has potential in the treatment of cancer. One attractive strategy for inhibiting HIF activity is the disruption of the HIF-1α/p300 complex, as p300 is a crucial coactivator of hypoxia-inducible transcription. Several members of the epidithiodiketopiperazine (ETP) family of natural products have been shown to disrupt the HIF-1α/p300 complex in vitro; namely, gliotoxin, chaetocin, and chetomin. Here, we further characterized the molecular mechanisms underlying the antiangiogenic and antitumor effects of these ETPs using a preclinical model of prostate cancer. In the rat aortic ring angiogenesis assay, gliotoxin, chaetocin, and chetomin significantly inhibited microvessel outgrowth at a GI50 of 151, 8, and 20 nM, respectively. In vitro co-immunoprecipitation studies in prostate cancer cell extracts demonstrated that these compounds disrupted the HIF-1α/p300 complex. The downstream effects of inhibiting the HIF-1α/p300 interaction were evaluated by determining HIF-1α target gene expression at the mRNA and protein levels. Dose-dependent decreases in levels of secreted VEGF were detected by ELISA in the culture media of treated cells, and the subsequent downregulation of VEGFA, LDHA, and ENO1 HIF-1α target genes were confirmed by semi-quantitative real-time PCR. Finally, treatment with ETPs in mice bearing prostate tumor xenografts resulted in significant inhibition of tumor growth. These results suggest that directly targeting the HIF-1α/p300 complex with ETPs may be an effective approach for inhibiting angiogenesis and tumor growth.

Operative Management of Abdominal Wound Dehiscence: Outcomes and Factors Influencing Time to Healing in Patients Undergoing Surgical Debridement With Primary Closure.

INTRODUCTION: Plastic surgeons are often consulted by other surgical teams for management of wound dehiscence following abdominopelvic surgery. OBJECTIVE: The purpose of this study is to determine whether operative debridement and primary closure of abdominopelvic wounds are safe and expeditious for patients. MATERIALS AND METHODS: A retrospective analysis was conducted on a database of patients who underwent operative debridement and closure at a single institution between January 2011 and December 2015 for dehisced abdominal or pelvic wounds acquired from prior obstetric, gynecologic, transplant, plastic, or general surgery procedures. RESULTS: Of the 163 patient records identified, 43 patients met inclusion criteria. The median time from final debridement and primary surgical closure to complete wound healing was 27 days. Time to healing differed significantly by index procedure type (P = .004), with obstetric procedures requiring the shortest median time (12.0 days) and general surgery procedures requiring the longest (39.5 days). Wound healing took 3.6 times longer for patients with diabetes (P = .046) and 11.4 times longer for patients who experienced delayed superficial wound healing or redehiscence (P = .003). Nevertheless, with the exception of 4 patients who died of other causes, all wounds (39/39; 100%) achieved complete wound closure. CONCLUSIONS: Operative debridement and closure of abdominopelvic wound dehiscence through a multidisciplinary team approach with plastic surgery results in expeditious wound healing with minimal complications, and it may be safer and more cost effective than healing by secondary intention.

Dihydrotestosterone synthesis from adrenal precursors does not involve testosterone in castration-resistant prostate cancer.

Androgen deprivation therapy is the frontline treatment for metastatic prostate cancer; however, because the majority of cases of advanced prostate cancer progress to castration-resistant prostate cancer (CRPC), there is a considerable need to better understand the synthesis of intratumoral concentrations of the androgen receptor (AR) agonist, 5α-dihydrotestosterone (DHT) in CRPC. In a recent article in the Proceedings of the National Academy of Sciences, Chang et al. show that, contrary to widely held assumptions, the dominant pathway to DHT synthesis does not involve testosterone as a precursor to DHT, but instead involves the conversion of Δ ( 4) -androstenedione (AD) to 5α-dione (AD→5α-dione→DHT) by the steroid-5α-reductase isoenzyme 1 (SRD5A1). The authors show that it is this alternative pathway that drives the progression of CRPC, and they confirm these findings in six established human prostate cancer cell lines as well as in the metastatic tumors from two patients with CRPC. Such findings open the door to new areas of research and to the development of new therapeutic targets in CRPC.

Transporter pharmacogenetics: transporter polymorphisms affect normal physiology, diseases, and pharmacotherapy.

Drug transporters mediate the movement of endobiotics and xenobiotics across biological membranes in multiple organs and in most tissues. As such, they are involved in physiology, development of disease, drug pharmacokinetics, and ultimately the clinical response to a myriad of medications. Genetic variants in transporters cause population-specific differences in drug transport and are responsible for considerable inter-individual variation in physiology and pharmacotherapy. The purpose of this review is to provide a broad overview of how inherited variants in transporters are associated with disease etiology, disease state, and the pharmacological treatment of diseases. Given that there are thousands of published papers related to the interplay between transporter genetics and medicine, this review will provide examples that exemplify the broader focus of the literature.

A novel predicted bromodomain-related protein affects coordination between meiosis and spermiogenesis in Drosophila and is required for male meiotic cytokinesis.

Temporal coordination of meiosis with spermatid morphogenesis is crucial for successful generation of mature sperm cells. We identified a recessive male sterile Drosophila melanogaster mutant, mitoshell, in which events of spermatid morphogenesis are initiated too early, before meiotic onset. Premature mitochondrial aggregation and fusion lead to an aberrant mitochondrial shell around premeiotic nuclei. Despite successful meiotic karyokinesis, improper mitochondrial localization in mitoshell testes is associated with defective astral central spindles and a lack of contractile rings, leading to meiotic cytokinesis failure. We mapped and cloned the mitoshell gene and found that it encodes a novel protein with a bromodomain-related region. It is conserved in some insect lineages. Bromodomains typically bind to histone acetyl-lysine residues and therefore are often associated with chromatin. The Mitoshell bromodomain-related region is predicted to have an alpha helical structure similar to that of bromodomains, but not all the crucial residues in the ligand-binding loops are conserved. We speculate that Mitoshell may participate in transcriptional regulation of spermatogenesis-specific genes, though perhaps with different ligand specificity compared to traditional bromodomains.