Postsurgical Pyoderma Gangrenosum After Penile Inversion Vaginoplasty: Case With Review of Diagnostic and Management Strategies.

Background: Postsurgical pyoderma gangrenosum (PSPG) is a highly uncommon and unpredictable wound healing complication. Rapid progression of ulcers at incisions can cause unfettered dehiscence. Most commonly, PSPG involves breast procedures; however, in this work, we detail a case of a patient who developed PSPG 10 days postoperatively after penile inversion vaginoplasty. Methods: The patient in this case underwent a penile inversion vaginoplasty with orchiectomy in the standard fashion. She had no risk factors for PSPG. Following an uncomplicated hospital stay, the patient developed difficulty with pain control and increasing serous drainage on the 10th postoperative day. On readmission, the patient was found to have developed large, mildly purulent ulcers throughout the perineal wound edges. On exam under anesthesia, the neovaginal canal was found to be patent and intact. The dehisced portions of the incisions were left open and redressed with occlusive bismuth-petrolatum dressing. Dermatology was promptly consulted with suspicion for PSPG. The patient was started on an 18-day prednisone taper with cyclosporine, along with doxycycline and ciprofloxacin. Results: After 5 days of immunosuppressive treatment, the ulcers visibly converted to healthy granulation tissue and were no longer actively purulent. Following another washout, the dehisced wound edges were reapproximated. At follow-up, the patient had no evidence of PSPG recurrence and continued dilating on schedule. Our patient recovered from PSPG without further complications and a satisfactory aesthetic result. Conclusions: This unique case highlights the importance of prompt dermatological consultation, immunosuppression, and avoidance of further pathergy in the setting of suspicion for PSPG.

Social Justice Education in CAATE-Accredited Post-Baccalaureate Athletic Training Programs.

Social justice education (SJE) prepares clinicians to provide patient-centered care. Our purpose was to assess SJE in CAATE-accredited, post-baccalaureate professional athletic training programs. We used a cross-sectional, online survey. Individuals (n=215) in their last year of post-baccalaureate professional education or those who were within 6 months post-graduation participated. The survey included closed and open-ended questions regarding types of education, topics of education, perceived confidence, and levels of agreement regarding identifying, addressing, and applying social justice concepts. Students from different cultural ethnicities reported having different educational experiences relative to their formal and informal instruction. Significant differences were identified between cultural ethnicity groups on perceptions of professors' knowledge (p<0.001), preceptors' knowledge (p<0.001), and agreement their program prepared them to address social justice issues (p<0.001). Two domains emerged from the open-ended responses: 1) social justice defined and 2) educational needs. Participants described social justice as equality, equity, and justice for minoritized people. Participants described SJE as not occurring or limited, and they expressed a desire for active practical experiences from heterogeneous and unbiased sources. As programs move to incorporate CAATE standards, more frequent and varied SJE is expected from minoritized students.

WORKPLACE CLIMATE FOR SEXUAL AND GENDER MINORITIES IN ATHLETIC TRAINING.

CONTEXT: Sexual and gender minorities (SGM) are individuals with sexual orientations, gender identities and/or expressions that differ from cultural norms. SGMs often face workplace discrimination and report decreased physical and emotional well-being from discrimination. OBJECTIVE: To explore the workplace climate of SGM athletic trainers (AT). DESIGN: Sequential mixed-methods study. SETTING: Web-based survey and interviews. PATIENTS OR OTHER PARTICIPANTS: Criterion sampling of SGM ATs (117 survey participants and 12 interview participants). DATA COLLECTION AND ANALYSIS: We modified the LGBTQ Inclusion Assessment and the Organizational Self-Assessment for the survey and developed a semi-structured interview script (scale-level content validity index=0.94). We used means, standard deviations, frequencies and the consensual qualitative research tradition to characterize participant responses. Trustworthiness was established through reflexivity (researchers checking bias throughout the research process), member-checking, multi-analyst triangulation, internal and external auditing. RESULTS: Participants indicated their workplace was inclusive (24, 20.5%), somewhat inclusive (29, 24.8%), not inclusive (14, 12.0%), or did not indicate at all (50, 42.7%). Respondents most often indicated they were unsure of the stage of change their organizations and organizational units were in addressing LGBTQPIA+ issues in the workplace as well as specific actions taken for inclusion. Two domains emerged from the interview data: safety and inclusion. The safety domain represents aspects of the workplace climate that make the participants feel safe including organizational initiatives (12/12), patient-centered policies (7/12), local and federal regulations (7/12), and signaling (12/12). The inclusion domain represents how the participants felt a sense of belonging to the organization through their own experience (12/12), through the experiences of their patients (9/12), and through an infrastructure designed for inclusion (12/12). Participants expressed both the affirmative and the negative feelings of safety and inclusion throughout their responses. CONCLUSIONS: Organizations must take both structural and cultural actions to address the issues of exclusion and lack of safety.

It's Hip to Go Home: An Evaluation of Outpatient Alveolar Bone Grafting in Patients With Cleft Palate.

INTRODUCTION: Secondary alveolar bone grafting (ABG) is a common procedure performed at cleft care centers used to fill the alveolar cleft. The advent of techniques such as minimally invasive trephine drill harvest and placement of continuous-infusion pain pumps at the donor site has made outpatient ABG an increasingly feasible and cost-effective procedure. However, enhanced recovery after surgery protocols to maximize pain control and recovery times for this patient population have not been well established. METHODS: A retrospective single-institution review was conducted of pediatric patients with cleft palate who underwent iliac crest bone graft ABG at a large urban academic children's hospital from 2017 to 2022. Patient age, alveolar cleft repair laterality, pain scores, surgery duration, hospital LOS, readmissions, and re-operations within 30 days were examined. RESULTS: Fifty-four patients met our inclusion criteria. Fifty patients (92.6%) received a pain pump during the operation. The median duration of surgery and LOS in the post-anesthesia care unit were 1.28 and 1.75 hours, respectively. Fifty-two patients (96.3%) were discharged on the same day as their surgery whereas 2 patients (3.7%) stayed in the hospital overnight. The median pain score at the time of discharge was 0 (interquartile range 0, 0). There were 6 (11.1%) minor complications including 5 pain pump malfunctions and 1 recipient site wound breakdown. There was 1 readmission (1.9%) for development of a surgical site infection at the hip and no re-operations within 30 days of surgery. CONCLUSION: The described outpatient ABG protocol demonstrates effective postoperative pain control, short hospital LOS, and few complications requiring hospital readmission or reoperation.

Multiplexing the Quantitation of MAP Kinase Activities Using Differential Sensing.

Protein kinases are therapeutic targets for many human diseases, but the lack of user-friendly quantitative assays limits the ability to follow the activities of numerous kinases at once (multiplexing). To develop such an assay, we report an array of sulfonamido-oxine (SOX)-labeled peptides showing cross-reactivity to different mitogen-activated protein kinases (MAPKs) for use in a differential sensing scheme. We first verified using linear discriminant analysis that the array could differentiate MAPK isoforms. Then, using principal component analysis, the array was optimized based on the discrimination imparted by each SOX-peptide. Next, the activity of individual MAPK families in ternary mixtures was quantified by support vector machine regression. Finally, we multiplexed the quantification of three MAPK families using partial least squares regression in A549 cell lysates, which has possible interference from other kinase classes. Thus, our method simultaneously quantifies the activity of multiple kinases. The technique could be applied to other protein kinase families and the monitoring of diseases.

Chromosome X-wide Analysis of Positive Selection in Human Populations: Common and Private Signals of Selection and its Impact on Inactivated Genes and Enhancers.

The ability of detecting adaptive (positive) selection in the genome has opened the possibility of understanding the genetic basis of population-specific adaptations genome-wide. Here, we present the analysis of recent selective sweeps, specifically in the X chromosome, in human populations from the third phase of the 1,000 Genomes Project using three different haplotype-based statistics. We describe instances of recent positive selection that fit the criteria of hard or soft sweeps, and detect a higher number of events among sub-Saharan Africans than non-Africans (Europe and East Asia). A global enrichment of neural-related processes is observed and numerous genes related to fertility appear among the top candidates, reflecting the importance of reproduction in human evolution. Commonalities with previously reported genes under positive selection are found, while particularly strong new signals are reported in specific populations or shared across different continental groups. We report an enrichment of signals in genes that escape X chromosome inactivation, which may contribute to the differentiation between sexes. We also provide evidence of a widespread presence of soft-sweep-like signatures across the chromosome and a global enrichment of highly scoring regions that overlap potential regulatory elements. Among these, enhancers-like signatures seem to present putative signals of positive selection which might be in concordance with selection in their target genes. Also, particularly strong signals appear in regulatory regions that show differential activities, which might point to population-specific regulatory adaptations.

Estimating Conformational Traits in Dairy Cattle With DeepAPS: A Two-Step Deep Learning Automated Phenotyping and Segmentation Approach.

Assessing conformation features in an accurate and rapid manner remains a challenge in the dairy industry. While recent developments in computer vision has greatly improved automated background removal, these methods have not been fully translated to biological studies. Here, we present a composite method (DeepAPS) that combines two readily available algorithms in order to create a precise mask for an animal image. This method performs accurately when compared with manual classification of proportion of coat color with an adjusted R 2 = 0.926. Using the output mask, we are able to automatically extract useful phenotypic information for 14 additional morphological features. Using pedigree and image information from a web catalog (www.semex.com), we estimated high heritabilities (ranging from h 2 = 0.18-0.82), indicating that meaningful biological information has been extracted automatically from imaging data. This method can be applied to other datasets and requires only a minimal number of image annotations (∼50) to train this partially supervised machine-learning approach. DeepAPS allows for the rapid and accurate quantification of multiple phenotypic measurements while minimizing study cost. The pipeline is available at https://github.com/lauzingaretti/deepaps.

A fully integrated machine learning scan of selection in the chimpanzee genome.

After diverging, each chimpanzee subspecies has been the target of unique selective pressures. Here, we employ a machine learning approach to classify regions as under positive selection or neutrality genome-wide. The regions determined to be under selection reflect the unique demographic and adaptive history of each subspecies. The results indicate that effective population size is important for determining the proportion of the genome under positive selection. The chimpanzee subspecies share signals of selection in genes associated with immunity and gene regulation. With these results, we have created a selection map for each population that can be displayed in a genome browser (www.hsb.upf.edu/chimp_browser). This study is the first to use a detailed demographic history and machine learning to map selection genome-wide in chimpanzee. The chimpanzee selection map will improve our understanding of the impact of selection on closely related subspecies and will empower future studies of chimpanzee.

Quantification of ERK Kinase Activity in Biological Samples Using Differential Sensing.

The understanding of complex biological systems requires an ability to evaluate interacting networks of genes, proteins, and cellular reactions. Enabling technologies that support the rapid quantification of these networks will facilitate the development of biological models and help to identify treatment targets and to assess treatment plans. The biochemical process of protein phosphorylation, which underlies almost all aspects of cell signaling, is typically evaluated by immunoblotting procedures (Western blot) or more recently proteomics procedures, which provide qualitative estimates of the concentration of proteins and their modifications in cells. However, protein modifications are difficult to correlate with activity, and while immunoblotting and proteomics approaches have the potential to be quantitative, they require a complex series of steps that diminish reproducibility. Here, a complementary approach is presented that allows for the rapid quantification of a protein kinase activity in cell lysates and tumor samples. Using the activity of cellular ERK (extracellular signal-regulated kinase) as a test case, an array sensing approach that utilizes a library of differential peptide-based biosensors and chemometric tools was used to rapidly quantify nanograms of active ERK in micrograms of unfractionated cell lysates and tumor extracts. This approach has the potential both for high-throughput and for quantifying the activities of multiple protein kinases in a single biological sample. The critical advantages of this differential sensing approach over others are that it removes the need for the addition of exogenous inhibitors to suppress the activities of major off-target kinases and allows us to quantitate the amount of active kinase in tested samples rather than measuring the changes in its activity upon induction or inhibition.

A Multivariate Genome-Wide Association Study of Wing Shape in Drosophila melanogaster.

Due to the complexity of genotype-phenotype relationships, simultaneous analyses of genomic associations with multiple traits will be more powerful and informative than a series of univariate analyses. However, in most cases, studies of genotype-phenotype relationships have been analyzed only one trait at a time. Here, we report the results of a fully integrated multivariate genome-wide association analysis of the shape of the Drosophila melanogaster wing in the Drosophila Genetic Reference Panel. Genotypic effects on wing shape were highly correlated between two different laboratories. We found 2396 significant SNPs using a 5% false discovery rate cutoff in the multivariate analyses, but just four significant SNPs in univariate analyses of scores on the first 20 principal component axes. One quarter of these initially significant SNPs retain their effects in regularized models that take into account population structure and linkage disequilibrium. A key advantage of multivariate analysis is that the direction of the estimated phenotypic effect is much more informative than a univariate one. We exploit this fact to show that the effects of knockdowns of genes implicated in the initial screen were on average more similar than expected under a null model. A subset of SNP effects were replicable in an unrelated panel of inbred lines. Association studies that take a phenomic approach, considering many traits simultaneously, are an important complement to the power of genomics.

Selection in the Introgressed Regions of the Chimpanzee Genome.

During the demographic history of the Pan clade, there has been gene-flow between species, likely >200,000 years ago. Bonobo haplotypes in three subspecies of chimpanzee have been identified to be segregating in modern-day chimpanzee populations, suggesting that these haplotypes, with increased differentiation, may be a target of natural selection. Here, we investigate signatures of adaptive introgression within the bonobo-like haplotypes in chimpanzees using site frequency spectrum-based tests. We find evidence for subspecies-specific adaptations in introgressed regions involved with male reproduction in central chimpanzees, the immune system in eastern chimpanzees, female reproduction and the nervous system in Nigeria-Cameroon chimpanzees. Furthermore, our results indicate signatures of balancing selection in some of the putatively introgressed regions. This might be the product of long-term balancing selection resulting in a similar genomic signature as introgression, or possibly balancing selection acting on alleles reintroduced through gene flow.