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Zika virus (ZIKV) is an arbovirus associated with neurological disorders accompanying congenital infections. With no vaccine or antiviral approved, there is an urgent need for the development of effective antiviral agents against ZIKV infection. We evaluated the anti-ZIKV and immunomodulatory activity of ouabain, a Na + /K + -ATPase inhibitor known to have immunomodulatory and antiviral activities, using human neural stem and progenitor cells (hNS/PCs) and a murine model of congenital Zika syndrome (CZS). Our data demonstrated that ouabain reduces ZIKV infection in hNS/PCs, mouse placenta, yolk sac, and the fetal head. Ouabain mitigated neurogenesis impairment triggered by ZIKV in hNS/PCs and prevented ZIKV-mediated reduction of fetus and head sizes. In addition, ouabain decreased tumor necrosis factor and interleukin-1β levels in the placenta, highlighting its immunomodulatory activity in the murine model. Our findings indicate that ouabain possesses anti-ZIKV and immunomodulatory activities, suggesting that it should be investigated further as a promising treatment for CZS., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This review aims to understand the foundations of cognitive behavioral therapy (CBT) and biofeedback, their indications for therapy, and evidence-based support., Recent Findings: Both CBT and biofeedback are noninvasive therapy options for patients who are suffering from a variety of chronic pain conditions, including chronic low back pain, headache, fibromyalgia, and temporomandibular disorder (TMD). CBT has been shown to be effective in treating multiple chronic pain conditions., Competing Interests: Declarations. Ethical Approval: This article does not contain any studies with human or animal subjects performed by any of the authors. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Chronic pain affects approximately 1.5 billion people worldwide, representing the leading cause of disability and a significant financial burden on healthcare systems. Conventional treatments, such as opioids and non-steroidal anti-inflammatory drugs, are frequently linked to adverse effects, including dependency and gastrointestinal issues, and often offer limited long-term relief. This review explores the potential of psychedelics, including psilocybin, LSD, and ketamine, as alternative therapeutic agents in chronic pain management., Recent Findings: These substances modulate pain perception through actions on serotonergic and glutamatergic systems and may promote neuroplasticity, offering novel pathways for pain relief. Specifically, the review details the pharmacologic actions of psychedelics, their effects on chronic pain syndromes such as cancer pain, migraines, and neuropathic pain, and their clinical implications. The safety profiles, patient responses, and analgesic properties of these compounds are examined, highlighting the need for further research to validate their efficacy and optimize their therapeutic use in pain management., Competing Interests: Declarations. Human and Animal Rights: All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines). Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There are persistent structural barriers that threaten inclusion and retention of underrepresented in medicine (UIM) residents and fellows (trainees) as future faculty in academic medicine. We developed the Leadership Education in Advancing Diversity (LEAD) Program at a single, academic institution, to address these barriers through a 10-month longitudinal curriculum across Graduate Medical Education for trainees to develop leadership and scholarship skills in diversity, equity, and inclusion (DEI)., Objective: Explore how participation in LEAD impacted UIM trainees' sense of belonging and professional identity formation in academic medicine as well as perceptions about pursuing a career in academic medicine and future leadership roles., Methods: Institutional Review Board-approved qualitative study in August 2020-August 2021 with individual, semi-structured interviews of UIM LEAD graduates from the first four cohorts (2017-2021). Data were analyzed by two authors using modified grounded theory., Results: Fourteen UIM trainees were interviewed; seven themes emerged. Critical aspects of the program: 1) Creation of a community of shared DEI values, 2) Mentorship, 3) Role of allies. Results of the program: 4) Deepened appreciation of personal and professional identity as UIM, 5) Fostered belonging in academic medicine, 6) Appreciation of different careers in academic medicine and how to integrate DEI interests, and 7) Inspired trainees to pursue leadership roles., Conclusions: LEAD can serve as a model for other institutions that seek to support UIM trainees' sense of belonging, professional identity formation, and perceptions about pursuing careers in academic medicine and future leadership roles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Multiple rounds of whole-genome duplication (WGD) followed by diploidization have occurred throughout the evolutionary history of angiosperms. Much work has been done to model the genomic consequences and evolutionary significance of WGD. While researchers have historically modeled polyploids as either allopolyploids or autopolyploids, the variety of natural polyploids span a continuum of differentiation across multiple parameters, such as the extent of polysomic versus disomic inheritance, and the degree of genetic differentiation between the ancestral lineages. Here we present a forward-time polyploid genome evolution simulator called SpecKS. SpecKS models polyploid speciation as originating from a 2D continuum, whose dimensions account for both the level of genetic differentiation between the ancestral parental genomes, as well the time lag between ancestral speciation and their subsequent reunion in the derived polyploid. Using extensive simulations, we demonstrate that changes in initial conditions along either dimension of the 2D continuum deterministically affect the shape of the Ks histogram. Our findings indicate that the error in the common method of estimating WGD time from the Ks histogram peak scales with the degree of allopolyploidy, and we present an alternative, accurate estimation method that is independent of the degree of allopolyploidy. Lastly, we use SpecKS to derive tests that infer both the lag time between parental divergence and WGD time, and the diversity of the ancestral species, from an input Ks histogram. We apply the latter test to transcriptomic data from over 200 species across the plant kingdom, the results of which are concordant with the prevailing theory that the majority of angiosperm lineages are derived from diverse parental genomes and may be of allopolyploid origin., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

We have successfully prototyped and tested the real-driving performance of a hydraulic hybrid heavy commercial vehicle. Hydraulic hybrid driveline technology was fitted to a Euro IV diesel truck equipped with a diesel particulate diffuser/filter and an exhaust gas recirculation system. An AVL portable emissions measurement system was fitted to the test vehicle to quantify gaseous and particle phase emissions species and an on-board diagnostic scan tool was used to obtain data from the trucks electronic control unit. Fuel consumption savings up to 17 % were accomplished in hydraulic hybrid mode when testing on a short urban driving route featuring a high intensity of stop-start activity. Average reductions in solid particle number concentration of 40 % were achieved along with increases in NOx, Hydrocarbons (THCs) and CO. Future work could target improved control system integration of the various driveline components to further reduce fuel consumption and emissions in an improved prototype design., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose of Review: Peripheral nerve stimulation (PNS) refers to the technique of utilizing electrical stimulation of peripheral nerves to inhibit the transmission of pain signals. PNS is used to treat chronic intractable pain and post-surgical or post-traumatic pain alongside a variety of other pain conditions, including headaches, facial pain, pelvic and urogenital pain, chest wall pain, residual limb or phantom limb pain, and back pain., Recent Findings: More recently, PNS has been used temporarily for periods of time less than 60 days to treat acute post-surgical pain. Peripheral nerve stimulation is believed to be effective due to its effects on both central and peripheral pathways. Centrally, it is proposed that the electrical pulses of PNS inhibit alpha-delta and C fibers, which decreases pain signaling in the higher centers of the central nervous system. Peripherally, gate theory is applied as it is theorized that PNS downregulates inflammatory mediators, endorphins, and neurotransmitters associated with pain signaling to decrease the transmission of efferent nociception and reduce pain sensations., Competing Interests: Compliance with Ethical Standards. Conflict of Interest: Authors do not have financial or non-financial interests that are directly or indirectly related to the work submitted for publication. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The indiscriminate administration of broad-spectrum antibiotics is a primary contributor to the increasing prevalence of antibiotic resistance. Unfortunately, culture, the gold standard for bacterial identification is a time intensive process. Due to this extended diagnostic period, broad-spectrum antibiotics are generally prescribed to prevent poor outcomes. To overcome the deficits of culture-based methods, we have developed a rapid universal bacterial identification system. The platform utilizes a unique universal polymerase chain reaction (PCR) primer set that targets the internal transcribed spacer (ITS) regions between conserved bacterial genes, creating a distinguishable amplicon signature for every bacterial species. Bioinformatic simulation demonstrates that at least 45 commonly isolated pathogenic species can be uniquely identified using this approach. We experimentally confirmed these predictions on a representative set of pathogenic bacterial species. We also show that the system can determine the corresponding concentration of each pathogen. Finally, we validated performance in clinical urinary tract infection samples., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Despite efforts to recruit and retain Black physicians, Black individuals continue to be underrepresented in medicine in the USA. Although numerous studies have investigated the experiences of academic physicians from racial/ethnic backgrounds underrepresented in medicine, the experience of Black academic physicians, who may face additional unique challenges, remains underinvestigated. Using a qualitative research design, we investigate barriers to and facilitators of success and well-being of Black faculty at one academic medical center through interviews of 30 Black faculty members. Overall, ten themes emerged as barriers or facilitators to faculty success and well-being. Significant barriers include continued lack of representation; devaluing of research in community health and health disparities, as well as other diversity-related activities; and both overt and implicit discrimination, which contribute to feelings of isolation and disrespect. Facilitators include having a community to maintain sense of belonging, financial support for health disparities and diversity-related contributions, and collaboration with peers. Good mentorship and sponsorship as well as an institutional culture that supports inclusion can play significant roles as facilitators, whereas the lack of these factors can present substantial barriers. Institutional policies and external socio-political factors have a major influence on both the barriers and facilitators to the success and well-being of Black faculty. Our study has put a clearer focus on barriers that are unique to or more pronounced among Black faculty and the facilitators that may serve to mitigate these barriers. These findings can inform the design of interventions to recruit and retain Black faculty in medicine., (© 2024. W. Montague Cobb-NMA Health Institute.)

In this work, we extend vcfdist to be the first variant call benchmarking tool to jointly evaluate phased single-nucleotide polymorphisms (SNPs), small insertions/deletions (INDELs), and structural variants (SVs) for the whole genome. First, we find that a joint evaluation of small and structural variants uniformly reduces measured errors for SNPs (- 28.9%), INDELs (- 19.3%), and SVs (- 52.4%) across three datasets. vcfdist also corrects a common flaw in phasing evaluations, reducing measured flip errors by over 50%. Lastly, we show that vcfdist is more accurate than previously published works and on par with the newest approaches while providing improved result interpretability., (© 2024. The Author(s).)

Spinal cord injury (SCI) results in acute damage and triggers secondary injury responses with sustained neuronal loss and dysfunction. However, the underlying mechanisms for these delayed neuronal pathologies are not entirely understood. SCI results in the swelling of spinal neurons, but the contribution of cell swelling to neuronal loss and functional deficits after SCI has not been systematically characterized. In this study, we devised a three-dimensional image analysis pipeline to evaluate spinal neurons, examining their types, quantities, volumes, and spatial distribution in a double-lateral hemisection SCI mouse model. We found that both excitatory and inhibitory neurons swell and are lost, albeit with distinct temporal patterns. Inhibitory neurons demonstrated marked swelling and decline in number on day 2 after SCI, which resolved by day 14. In contrast, excitatory neurons maintained persistent swelling and continued cell loss for at least 35 days after SCI in mice. Excitatory neurons exhibited sustained expression of the Na + -K + -Cl - cotransporter 1 (NKCC1), whereas inhibitory neurons down-regulated the protein by day 14 after SCI. Treatment with a Food and Drug Administration-approved NKCC1 inhibitor, bumetanide, mitigated swelling of excitatory neurons and reduced their loss in the secondary injury phase after SCI. The administration of bumetanide after SCI in mouse improved locomotor recovery, with functional benefits persisting for at least 4 weeks after treatment cessation. This study advances our understanding of SCI-related pathology and introduces bumetanide as a potential treatment to mitigate sustained neuronal swelling and enhance recovery after SCI.

Background: The field of pancreas transplantation has undergone transformative phases, progressing from its promising inception in 1966 to becoming a standard treatment for patients with insulin-dependent diabetes. This bibliometric analysis explores the progression of pancreas transplantation research over a period of four decades, mapping milestones, contributors, and emerging trends. Methods: Our bibliometric analysis utilizes the comprehensive Scopus database, which includes publication titles, author information, affiliations, abstracts, keywords, and journal details. The search strategy was centered on research related to pancreas and pancreas-kidney transplantation. The analysis encompasses the time frame spanning from 1983 to 2023, with the data extraction taking place on October 7th, 2023. Results: The analysis of 4,897 articles uncovered unique trends in the field of pancreas transplantation research. The years 1989, 1996, and 2021 saw significant increases in the number of publications, which corresponded to the responses to clinical challenges and advancements. Contributions by authors from the United States of America were the most numerous, with 1,905 publications and 49,949 citations. The research topics were highlighted by keywords such as "graft survival," "graft rejection," and" Immunosuppressive treatment." Conclusion: The fluctuations in publication trends that have been identified indicate dynamic reactions to changing priorities and challenges. Although it has limitations, this analysis provides valuable insights for researchers, clinicians, and policymakers who are dealing with the complex field of pancreas transplantation literature. Further bibliometric research may advance our knowledge and direct future initiatives in this developing field., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Review: Persistent spinal pain syndromes are pervasive and lead to functional impairment, increased healthcare utilization, potential disability, and high societal costs. Spinal (cervical, thoracic, lumbar, and sacroiliac joint) pain includes mechanical, degenerative, inflammatory, oncologic, and infectious etiologies. Regenerative medicine is a novel biotechnology targeting mechanical, degenerative, and inflammatory conditions believed to cause pain. Preparations including platelet-rich plasma, mesenchymal stem cells (adipose tissue and bone marrow aspirate concentrates), and growth factors are derived from an autologous donor. The goal of intervention through guided injection of the regenerative media is to reduce inflammation and reverse the degenerative cascade in hopes of restoring normal cellular composition (physiologic homeostasis) and anatomical function to improve pain and function. The authors review limited research supporting the use of platelet-rich plasma injections for facet joint arthropathy and sacroiliac joint pain compared to traditional steroid treatments, as well as the use of platelet rich plasma or mesenchymal stem cells for lumbar discogenic and radicular pain., Recent Findings: Current evidence to support regenerative medicine for spine-related pain is limited. Although several studies demonstrated a reduction in pain, many of these studies had a small number of participants and were case series or prospective trials. Regenerative medicine treatments lack evidence for the treatment of spine-related pain. Large randomized controlled trials are needed with consistent study protocols to make further recommendations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Radiofrequency ablation (RFA) is a minimally invasive treatment modality that utilizes high-frequency alternating current to destroy targeted tissues through thermal ablation. This manuscript provides an overview of the advancements in RFA, focusing on its mechanism of action and technological innovations. RFA technology was first introduced in the early 1900's, and its use has expanded and evolved, especially in its current utility in the treatment of painful conditions. As the technology has evolved, new techniques, applications and modalities have expanded its use and improved its efficacy. RFA works by applying radiofrequency energy through specialized electrodes, leading to resistive heating and coagulation necrosis. Its advantages include precise tissue targeting, minimal invasiveness, reduced complications, and faster recovery compared to traditional surgical interventions. Technological advancements in RFA have led to improved treatment outcomes. Multi-electrode systems allow for larger ablation zones. Image-guided RFA improves treatment planning and minimizes damage to healthy tissues. Cooled-tip and perfusion electrodes address limitations such as heat sink effects, enhancing RFA's efficacy in challenging anatomical regions. These developments have expanded RFA's applications to liver tumors, lung tumors, renal tumors, cardiac arrhythmias, and chronic pain syndromes. In conclusion, RFA has emerged as a safe and effective thermal ablation technique. Understanding its mechanism of action and integrating advanced technologies have significantly enhanced treatment outcomes. Continued research and innovation in RFA hold immense potential for further improving patient care and outcomes.

Purpose of Review: Cervical spine pain with or without radicular symptoms is a common condition leading to high utilization of the healthcare system with over 10 million medical visits per year. Many patients undergo surgical interventions and unfortunately are still left with neck and upper extremity pain, sometimes referred to as "Failed Neck Surgery Syndrome." When these options fail, cervical spinal cord stimulation can be a useful tool to decrease pain and suffering as well as reduce prescription medication use., Recent Findings: Spinal cord stimulation is a well-established therapy for chronic back and leg pain and is becoming more popular for neck and upper extremity pain. Recent studies have explored cervical spinal cord stimulation with successful outcomes regarding improved pain scores, functional outcomes, and reduction of prescription medication use. Continued research into cervical spinal cord stimulation is essential for maximizing its therapeutic potential for patients with chronic neck and upper extremity pain. This review highlights the importance of cervical spinal cord stimulation as an option for patients with failed neck surgery syndrome., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background. Performance-based outcome measures (PBOMs) are objective measures that assess physical capacity or performance in specific tasks or movements. Purpose. 1) to identify which PBOMs are most frequently reported to evaluate upper extremity (UE) function in pediatric rehabilitation 2) to determine the link between constructs of the ICF and meaningful concepts extracted from each identified PBOM. Methods. Pediatric UE PBOMs were searched in four databases. The selection of outcome measures included an initial title and abstract screening, followed by full-text review of the articles to be included based on identified selection criteria. Two reviewers were appointed to link the meaningful concepts identified in the outcome measures independently and a third reviewer was consulted in case of ambiguity to make a final decision. Findings. After the initial screening, 1786 full-text articles were reviewed, 1191 met the inclusion criteria, in which 77 outcome measures were identified and 32 were included in the linking process. From the included 32 outcome measures, 538 items were extracted and linked to the ICF. The most commonly cited measures included Assisting Hand Assessment, Jebsen-Taylor Hand Function Test, Melbourne Assessment of Unilateral Upper Limb. The Activity and Participation domain represented 364 codes followed by the Body Functions domain domain which represented 174 codes. Implications. A majority of the outcome measures identified were linked with the Mobility, Fine Hand Use of the ICF. Therefore, when selecting a PBOM, careful considerations need to be made regarding which concept of health is to be assessed.

Background: Goal attainment scaling (GAS), an established individualized, patient-centred outcome measure, is used to capture the patient's voice. Although first introduced ~60 years ago, there are few published guidelines for implementing GAS, and almost none for its use when caregivers GAS is implemented with caregiver input. We conducted a systematic review of studies that implemented GAS with caregiver input; and examined variations in GAS implementation, analysis, and reporting., Methods: Literature was retrieved from Medline, Embase, Cochrane, PsycInfo and CINAHL databases. We included randomized controlled trials (published between 1968 and November 2022) that used GAS as an outcome measure and involved caregiver input during goal setting., Results: Of the 2610 studies imported for screening, 21 met the inclusion criteria. Most studies employed GAS as a primary outcome. The majority (76%) had children as study participants. The most common disorders represented were cerebral palsy, developmental disorders, and dementia/Alzheimer's disease. The traditional five-point GAS scale, with levels from -2 to +2, was most often implemented, with -1 level typically being the baseline. However, most studies omitted essential GAS details from their reports including the number of goals set, number of attainment levels and whether any training was given to GAS facilitators., Conclusions: GAS with caregiver input has been used in a limited number of randomized controlled trials, primarily in pediatric patients and adults with dementia. There is a variability in GAS implementation and many crucial details related to the specifics of GAS implementation are omitted from reports, which may limit reproducibility. Here we propose catalog that may be utilized when reporting research results pertaining to GAS with caregivers to enhance the application of this patient-centered outcome measure., (© 2024. The Author(s).)

Introduction: Identify non-glycemic factors affecting the relationship between fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c), in order to refine diabetes diagnostic criteria., Research Design and Methods: Relationship between FPG-HbA1c was assessed in 12 531 individuals from 2001 to 2018 US National Health and Nutrition Examination Survey. Using a recently described method, FPG and HbA1c were used to calculate apparent glycation ratio (AGR) of red blood cells for different subgroups based on age, race, and gender., Results: At an FPG of 7 mmol/L, black individuals had a higher HbA1c (p<0.001, mean: 50.2 mmol/mol, 95% CI (49.8 to 50.4)) compared with white individuals (47.4 mmol/mol (47.2 to 47.5)). This corresponds to NGSP (National Glycohemoglobin Standardization Program) units of 6.7% and 6.5% for black versus white individuals, respectively. Similarly, individuals under 21 years had lower HbA1c (p<0.001, 47.9 mmol/mol (47.7 to 48.1), 6.5%) compared with those over 50 years (48.3 mmol/mol (48.2 to 48.5), 6.6%). Differences were also observed between women (p<0.001, 49.2 mmol/mol (49.1 to 49.3), 6.7%) and men (47.0 mmol/mol (46.8 to 47.1), 6.5%). Of note, the difference in HbA1c at FPG of 7 mmol/L in black females over 50 and white males under 21 years was 5 mmol/mol (0.46%). AGR differences according to race (p<0.001), age (p<0.001), and gender (p<0.001) explained altered glucose-HbA1c relationship in the analyzed groups., Conclusions: FPG-HbA1c relationship is affected by non-glycemic factors leading to incorrect diagnosis of diabetes in some individuals and ethnic groups. Assessment of AGR helps understand individual-specific relationship between glucose levels and HbA1c, which has the potential to more accurately diagnose and manage diabetes., Competing Interests: Competing interests: YR, YX, AC, and TD are employees of Abbott Diabetes Care. RAA received other research support and Honoraria from Abbott Diabetes Care., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The complexity of aortic arch reconstruction due to diverse 3-dimensional geometrical abnormalities is a major challenge. This study introduces 3-dimensional printed tissue-engineered vascular grafts, which can fit patient-specific dimensions, optimize hemodynamics, exhibit antithrombotic and anti-infective properties, and accommodate growth., Methods: We procured cardiac magnetic resonance imaging with 4-dimensional flow for native porcine anatomy (n = 10), from which we designed tissue-engineered vascular grafts for the distal aortic arch, 4 weeks before surgery. An optimal shape of the curved vascular graft was designed using computer-aided design informed by computational fluid dynamics analysis. Grafts were manufactured and implanted into the distal aortic arch of porcine models, and postoperative cardiac magnetic resonance imaging data were collected. Pre- and postimplant hemodynamic data and histology were analyzed., Results: Postoperative magnetic resonance imaging of all pigs with 1:1 ratio of polycaprolactone and poly-L-lactide-co-ε-caprolactone demonstrated no specific dilatation or stenosis of the graft, revealing a positive growth trend in the graft area from the day after surgery to 3 months later, with maintaining a similar shape. The peak wall shear stress of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft portion did not change significantly between the day after surgery and 3 months later. Immunohistochemistry showed endothelization and smooth muscle layer formation without calcification of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft., Conclusions: Our patient-specific polycaprolactone/poly-L-lactide-co-ε-caprolactone tissue-engineered vascular grafts demonstrated optimal anatomical fit maintaining ideal hemodynamics and neotissue formation in a porcine model. This study provides a proof of concept of patient-specific tissue-engineered vascular grafts for aortic arch reconstruction., Competing Interests: Drs Johnson, Krieger, and Hibino are inventors listed on international patent WO/2017/035500Al (Patient-Specific Tissue Engineered Vascular Graft Utilizing Electrospinning). Dr Johnson is an equity holder in Nanofiber Solutions. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

We examined associations between prejudice toward transgender people, aggression proneness, history of family violence, contact and closeness with transgender people, and education about issues that impact transgender individuals. We also examined the moderating effects of contact, education, and closeness on the relations between aggression and history of family violence with prejudice. There were 360 participants ( M age = 31.34, SD  = 12.47, range 18-75) who completed the survey online. Participants were recruited through social media, websites, and MTurk. Higher levels of aggression proneness were related to higher levels of prejudice. Higher levels of education about issues that impact transgender people and prior contact with a transgender person were associated with less prejudice. In a multiple regression analysis, the strongest predictor of prejudice was education about transgender people and topics. Moderation analyses revealed that prior contact may buffer the effects of aggression proneness on prejudiced beliefs.

Background: Amyotrophic lateral sclerosis (ALS) leads to paralysis and death by progressive degeneration of motor neurons. Recently, specific gain-of-function mutations in SPTLC1 were identified in patients with juvenile form of ALS . SPTLC2 encodes the second catalytic subunit of the serine-palmitoyltransferase (SPT) complex., Methods: We used the GENESIS platform to screen 700 ALS whole-genome and whole-exome data sets for variants in SPTLC2 . The de-novo status was confirmed by Sanger sequencing. Sphingolipidomics was performed using liquid chromatography and high-resolution mass spectrometry., Results: Two unrelated patients presented with early-onset progressive proximal and distal muscle weakness, oral fasciculations, and pyramidal signs. Both patients carried the novel de-novo SPTLC2 mutation, c.203T>G, p.Met68Arg. This variant lies within a single short transmembrane domain of SPTLC2, suggesting that the mutation renders the SPT complex irresponsive to regulation through ORMDL3. Confirming this hypothesis, ceramide and complex sphingolipid levels were significantly increased in patient plasma. Accordingly, excessive sphingolipid production was shown in mutant-expressing human embryonic kindney (HEK) cells., Conclusions: Specific gain-of-function mutations in both core subunits affect the homoeostatic control of SPT. SPTLC2 represents a new Mendelian ALS gene, highlighting a key role of dysregulated sphingolipid synthesis in the pathogenesis of juvenile ALS. Given the direct interaction of SPTLC1 and SPTLC2, this knowledge might open new therapeutic avenues for motor neuron diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Accurately benchmarking small variant calling accuracy is critical for the continued improvement of human whole genome sequencing. In this work, we show that current variant calling evaluations are biased towards certain variant representations and may misrepresent the relative performance of different variant calling pipelines. We propose solutions, first exploring the affine gap parameter design space for complex variant representation and suggesting a standard. Next, we present our tool vcfdist and demonstrate the importance of enforcing local phasing for evaluation accuracy. We then introduce the notion of partial credit for mostly-correct calls and present an algorithm for clustering dependent variants. Lastly, we motivate using alignment distance metrics to supplement precision-recall curves for understanding variant calling performance. We evaluate the performance of 64 phased Truth Challenge V2 submissions and show that vcfdist improves measured insertion and deletion performance consistency across variant representations from R 2  = 0.97243 for baseline vcfeval to 0.99996 for vcfdist., (© 2023. The Author(s).)

Excited delirium syndrome (ExDS) is a controversial and disputed diagnosis involving altered mentation, agitation, and, frequently, substance abuse. Recently, it has become a common pre-hospital diagnosis, serving as justification for use of force, restraint, and/or medication administration. To conduct a scoping review across three databases to describe the most frequently reported diagnostic criteria for ExDS, as well as to explore its use as a diagnosis for deaths of individuals in the custody of law enforcement. In 2021, three literature databases were searched: Ovid Medline, PsycInfo, and Scopus. Studies were included if they were peer-reviewed, English articles describing (1) ExDS symptoms, (2) substance intoxication with at least 2 ExDS symptoms present, or (3) centering on deaths occurring in the custody of law enforcement and attributed to ExDS. Key study data were extracted and the current literature was described qualitatively. Analysis took place between March and December 2021. A total of 97 studies were identified through initial abstract and secondary full-text review, with noted discrepancies in the definition of ExDS itself. After review, differences in ExDS diagnosis among organizations were explored, along with subsequent clinical impact, particularly in the pre-hospital setting. Resulting impact on patients, particularly those of minoritized ethnic and racial groups, was also noted. Prone aggressive restraint, in particular, is noted as an established risk factor for fatalities in ExDS cases. At this time, ExDS should not be utilized as a diagnosis; major medical organizations have an urgent responsibility to convene to formalize consensus-based diagnostic criteria or to propose alternate management guidelines for agitated and altered persons., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Endometriosis is linked to increased infertility and pregnancy complications due to defective endometrial decidualization. We hypothesized that identification of altered signaling pathways during decidualization could identify the underlying cause of infertility and pregnancy complications. Our study reveals that transforming growth factor β (TGFβ) pathways are impaired in the endometrium of individuals with endometriosis, leading to defective decidualization. Through detailed transcriptomic analyses, we discovered abnormalities in TGFβ signaling pathways and key regulators, such as SMAD4, in the endometrium of affected individuals. We also observed compromised activity of bone morphogenetic proteins (BMP), a subset of the TGFβ family, that control endometrial receptivity. Using 3-dimensional models of endometrial stromal and epithelial assembloids, we showed that exogenous BMP2 improved decidual marker expression in individuals with endometriosis. Our findings unveil a previously unidentified dysfunction in BMP/SMAD signaling in the endometrium of individuals with endometriosis, explaining decidualization defects and subsequent pregnancy complications in these individuals., Competing Interests: COMPETING INTERESTS. There are no competing interests to declare.

Purpose: Clinicians assessing patients with deliberate self-inflicted amputations face a problem of whether or not to replant. The objective of this study was to summarize the literature on this topic and provide recommendations regarding the acute management of patients following self-inflicted amputations in the upper extremity., Methods: Two reviewers searched four databases using the keywords "Upper extremity," "Amputation," and "Self-Inflicted." The reviewers systematically screened and collected data on publications reporting cases of self-inflicted upper-extremity amputations. The findings then were summarized in a narrative fashion., Results: Twenty-four studies were included. Twenty-nine cases of self-inflicted upper-extremity amputations were reported. There were 25 unilateral and four bilateral extremity amputations. Amputations were most commonly at the hand/wrist (18 patients) and forearm level (6 patients). The amputations were most commonly performed with a saw (9 patients) or a knife (8 patients). Reasons for amputation included psychosis (10 cases), suicide attempt (7 cases), depression (5 cases), and body integrity identity disorder (four cases). Fifteen replantations were performed; all were successful. Reasons for not pursuing replantation were related to injury factors (ie, multilevel injury, prolonged ischemia, damaged part) rather than patient-level factors. Two patients with replantable extremities declined replantation, both of whom had body integrity identity disorder. Of the patients who underwent replantation, none expressed regret., Conclusions: The literature shows that patients experiencing psychosis or depression committed self-harm during an acute psychiatric decompensation, and once medically and psychiatrically stabilized, expressed satisfaction with their replanted limb. Surgeons should not consider psychiatric decompensation a contraindication to replantation and should be aware of patients with body integrity identity disorder who consciously may elect to undergo revision amputation. When presented with patients experiencing psychiatric decompensation who refuse replantation/are not competent, surgeons should seek emergency assistance from the psychiatry team to determine the best management of a self-inflicted amputation., Type of Study/level of Evidence: Therapy/Prevention/Etiology/Harm V., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Exposures to ambient air pollutants may prime the lung enhancing risk of acute respiratory distress syndrome (ARDS) in sepsis. Our objective was to determine the association of short-, medium-, and long-term pollutant exposures and ARDS risk in critically ill sepsis patients., Methods: We analyzed a prospective cohort of 1858 critically ill patients with sepsis, and estimated short- (3 days), medium- (6 weeks), and long- (5 years) term exposures to ozone, nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), carbon monoxide (CO), particulate matter < 2.5 μm (PM 2.5 ), and PM < 10 μm (PM 10 ) using weighted averages of daily levels from monitors within 50 km of subjects' residences. Subjects were followed for 6 days for ARDS by the Berlin Criteria. The association between each pollutant and ARDS was determined using multivariable logistic regression adjusting for preselected confounders. In 764 subjects, we measured plasma concentrations of inflammatory proteins at presentation and tested for an association between pollutant exposure and protein concentration via linear regression., Results: ARDS developed in 754 (41%) subjects. Short- and long-term exposures to SO 2 , NO 2 , and PM 2.5 were associated with ARDS risk (SO 2 : odds ratio (OR) for the comparison of the 75-25th long-term exposure percentile 1.43 (95% confidence interval (CI) 1.16, 1.77); p < 0.01; NO 2 : 1.36 (1.06, 1.74); p = 0.04, PM 2.5 : 1.21 (1.04, 1.41); p = 0.03). Long-term exposures to these three pollutants were also associated with plasma interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor-1 concentrations., Conclusion: Short and long-term exposures to ambient SO 2 , PM 2.5 , and NO 2 are associated with increased ARDS risk in sepsis, representing potentially modifiable environmental risk factors for sepsis-associated ARDS., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cotard's Syndrome (CS) is a rare clinical entity where patients can report nihilistic, delusional beliefs that they are already dead. Curiously, while weight loss, dehydration, and metabolic derangements have been described as discussed above, a review of the literature revealed neither a single case of a severely underweight patient nor a serious metabolic complication such as Diabetic Ketoacidosis. Further, a search on PubMed revealed no articles discussing the co-occurrence of Cotard's Delusion and eating disorders or comorbid metabolic illnesses such as diabetes mellitus. In order to better examine the association between Cotard's Delusion and comorbid eating disorders and metabolic illness, we will present and discuss a case where Cotard's delusion led to a severe metabolic outcome of DKA and a BMI of 15., Case Presentation: Mr. B is a 19 year old transgender man admitted to the hospital due to diabetic ketoacidosis secondary to Type 1 Diabetes Mellitus. Mr. B had a history of Obsessive-Compulsive Disorder, Major Depressive Disorder, and Post-Traumatic Stress Disorder. The primary pediatric team discovered that Mr. B had not been using his insulin appropriately and was severely underweight, and they believed this could be due to his underlying mental illness. The psychiatric consultation/liaison service found that Mr. B was suffering from Cotard's delusion leading him to be noncompliant with his insulin due to a belief that he was already dead. Cotard's delusion had in this case led to a severe metabolic outcome of DKA and a BMI of 15., Conclusions: This case provides clinical insight into the interactions of eating disorders and Cotard's delusion as well as the potential medical complications when Cotard's delusion is co-morbid with medical conditions such as Diabetes Mellitus. We recommend that clinicians routinely screen patients for Cotard's delusion and assess whether the presence of which could exacerbate any underlying medical illness. This includes clinicians taking special care in assessing patient's caloric and fluid intake as well as their adherence to medications both psychiatric and medical. Further research could be conducted to explore the potential overlap of Cotard's delusion and eating disorder phenomenology., (© 2023. The Author(s).)

Background: Social media may be an effective tool in residency recruitment, given its ability to engage a broad audience; however, there are limited data regarding the influence of social media on applicants' evaluation of anesthesiology residency programs., Objective: This study evaluates the influence of social media on applicants' perceptions of anesthesiology residency programs during the COVID-19 pandemic to allow programs to evaluate the importance of a social media presence for residency recruitment. The study also sought to understand if there were differences in the use of social media by applicant demographic characteristics (eg, race, ethnicity, gender, and age). We hypothesized that given the COVID-19 pandemic restrictions on visiting rotations and the interview process, the social media presence of anesthesiology residency programs would have a positive impact on the recruitment process and be an effective form of communication about program characteristics., Methods: All anesthesiology residency applicants who applied to Mayo Clinic Arizona were emailed a survey in October 2020 along with statements regarding the anonymity and optional nature of the survey. The 20-item Qualtrics survey included questions regarding subinternship rotation completion, social media resource use and impact (eg, "residency-based social media accounts positively impacted my opinion of the program"), and applicant demographic characteristics. Descriptive statistics were examined, and perceptions of social media were stratified by gender, race, and ethnicity; a factor analysis was performed, and the resulting scale was regressed on race, ethnicity, age, and gender., Results: The survey was emailed to 1091 individuals who applied to the Mayo Clinic Arizona anesthesiology residency program; there were 640 unique responses recorded (response rate=58.6%). Nearly 65% of applicants reported an inability to complete 2 or more planned subinternships due to COVID-19 restrictions (n=361, 55.9%), with 25% of applicants reporting inability to do any visiting student rotations (n=167). Official program websites (91.5%), Doximity (47.6%), Instagram (38.5%), and Twitter (19.4%) were reported as the most used resources by applicants. The majority of applicants (n=385, 67.3%) agreed that social media was an effective means to inform applicants, and 57.5% (n=328) of them indicated that social media positively impacted their perception of the program. An 8-item scale with good reliability was created, representing the importance of social media (Cronbach α=.838). There was a positive and statistically significant relationship such that male applicants (standardized β=.151; P=.002) and older applicants (β=.159; P<.001) had less trust and reliance in social media for information regarding anesthesiology residency programs. The applicants' race and ethnicity were not associated with the social media scale (β=-.089; P=.08)., Conclusions: Social media was an effective means to inform applicants, and generally positively impacted applicants' perception of programs. Thus, residency programs should consider investing time and resources toward building a social media presence to improve resident recruitment., (©Tyler Dunn, Shyam Patel, Adam J Milam, Joseph Brinkman, Andrew Gorlin, Monica W Harbell. Originally published in JMIR Medical Education (https://mededu.jmir.org), 29.06.2023.)

Background: Patient-specific, 3-dimensional printed, tissue engineered vascular grafts (3DTEVGs) are manufactured to optimize hemodynamic performance and to accommodate growth. We evaluate growth outcomes of 3DTEVGs compared with standard grafts for pulmonary artery reconstruction in porcine models., Methods: Magnetic resonance imaging (MRI) with 4-dimensional flow data was acquired in porcine models (n = 8). 3DTEVGs guided in design by computational flow dynamics were implanted (n = 4), with polytetrafluorethylene grafts used as controls (n = 4). Postoperative MRI and histologic features of explanted grafts were evaluated after 10 weeks., Results: All pigs survived, with evidence of patent grafts on postoperative MRI. Graft inner diameter changes were 0.47 ± 2.31 mm in 3DTEVGs and -4.61 ± 2.15 mm in controls ( P  = .018). Mean main pulmonary artery wall shear stress was significantly lower in 3DTEVGs (7.12 ± 4.21 Pa) than in controls (18.15 ± 8.37 Pa; P  = .0396). Histologic evaluation of 3DTEVGs showed a single layer of endothelial cells, an organized smooth muscle layer, and collagen deposition with a remaining scaffold area of 21.37% ± 20.46%., Conclusions: Our patient-specific 3DTEVGs demonstrated optimal anatomic fit while maintaining ideal flow dynamics and promoting appropriate neovessel formation., (© 2023 The Authors.)

Summary: Doing more with less has been a business mantra for decades. Healthcare leaders have implemented flex scheduling and job sharing, streamlined workflows, committed to process improvement techniques such as Lean, hired retirees, gained efficiencies from remote work ... and the list goes on. Each tactic has yielded productivity improvements, yet the need to do more with less continues. Postpandemic challenges include staff recruitment and retention, labor inflation, and dwindling margins, all of which must be addressed while maintaining corporate cultures. The journey with bots described here started in this dynamic environment, and the work has not been single-threaded. The organization featured here-an integrated delivery network-has digital front-door and back-end robotic process automation (RPA) projects underway. The digital front-door initiative supports patient self-registration and automates authorizations and insurance verification processes. The back-end patient financial services RPA project replaces and enhances existing technology. Revenue cycle as a multidepartment function is leadership's poster child for RPA, and the revenue cycle team is tasked to demonstrate the value of the technology. This article covers the initial steps and lessons learned in the process., Competing Interests: The author declares no conflicts of interest., (Copyright © 2023 Foundation of the American College of Healthcare Executives.)

Despite recent improvements in nanopore basecalling accuracy, germline variant calling of small insertions and deletions (INDELs) remains poor. Although precision and recall for single nucleotide polymorphisms (SNPs) now exceeds 99.5%, INDEL recall remains below 80% for standard R9.4.1 flow cells. We show that read phasing and realignment can recover a significant portion of false negative INDELs. In particular, we extend Needleman-Wunsch affine gap alignment by introducing new gap penalties for more accurately aligning repeated n-polymer sequences such as homopolymers ([Formula: see text]) and tandem repeats ([Formula: see text]). At the same precision, haplotype phasing improves INDEL recall from 63.76 to [Formula: see text] and nPoRe realignment improves it further to [Formula: see text]., (© 2023. The Author(s).)

Background: Specialty public health training consists of 48 months of practice across the domains of health protection, healthcare public health and health improvement.With the onset of the COVID-19 pandemic, activity pivoted towards pandemic management and the response became a significant element of registrar practice.This research aimed to understand the impact of this shift in focus on registrars' role and training., Methods: Participatory action research comprising (i) a reflective survey sent to all specialty registrars in the East Midlands training region and (ii) Delphi rounds with survey respondents to generate consensus and define themes., Results: Sixteen (44%) registrars completed the survey with 12 (75%) participating in the Delphi rounds. The early pandemic response stages both challenged and re-affirmed registrars' role and identity in public health and training while providing unique and diverse learning and development. Underpinning these themes is a variability in experience depending on prior experience, placement and training stage., Conclusions: The pandemic impacted the practice, training and home-life of registrars who were required to negotiate significant challenge and uncertainty. This original work adds to a growing body of correspondence and opinion pieces articulating the experiences and challenges of medical and public health education during a pandemic., (© The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Motivation: As genome sequencing becomes cheaper and more accurate, it is becoming increasingly viable to merge this data with electronic health information to inform clinical decisions., Results: In this work, we demonstrate a full pipeline for working with both PacBio sequencing data and clinical FHIR ® data, from initial data to tertiary analysis. The electronic health records are stored in FHIR ® (Fast Healthcare Interoperability Resource) format, the current leading standard for healthcare data exchange. For the genomic data, we perform variant calling on long-read PacBio HiFi data using Cromwell on Azure. Both data formats are parsed, processed and merged in a single scalable pipeline which securely performs tertiary analyses using cloud-based Jupyter notebooks. We include three example applications: exporting patient information to a database, clustering patients and performing a simple pharmacogenomic study., Availability and Implementation: https://github.com/microsoft/genomicsnotebook/tree/main/fhirgenomics., Supplementary Information: Supplementary data are available at Bioinformatics Advances online., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Alcohol use disorder (AUD) is a highly prevalent public health problem that contributes to opioid- and benzodiazepine-related morbidity and mortality. Even though co-utilization of these substances is particularly harmful, data are sparse on opioid or benzodiazepine prescribing patterns among individuals with AUD., Objective: To estimate temporal trends and disparities in opioid, benzodiazepine, and opioid/benzodiazepine co-prescribing among individuals with AUD in New York State (NYS)., Design/participants: Serial cross-sectional study analyzing merged data from the NYS Office of Addiction Services and Supports (OASAS) and the NYS Department of Health Medicaid Data Warehouse. Subjects with a first admission to an OASAS treatment program from 2005-2018 and a primary AUD were included. A total of 148,328 subjects were identified., Measures: Annual prescribing rates of opioids, benzodiazepines, or both between the pre- (2005-2012) and post- (2013-2018) Internet System for Tracking Over-Prescribing (I-STOP) periods. I-STOP is a prescription monitoring program implemented in NYS in August 2013. Analyses were stratified based on sociodemographic factors (age, sex, race/ethnicity, and location)., Results: Opioid prescribing rates decreased between the pre- and post-I-STOP periods from 25.1% (95% CI, 24.9-25.3%) to 21.3% (95% CI, 21.2-21.4; P <.001), while benzodiazepine (pre: 9.96% [95% CI, 9.83-10.1%], post: 9.92% [95% CI, 9.83-10.0%]; P =.631) and opioid/benzodiazepine prescribing rates remained unchanged (pre: 3.01% vs. post: 3.05%; P =.403). After I-STOP implementation, there was a significant decreasing trend in opioid (change, -1.85% per year, P <.0001), benzodiazepine (-0.208% per year, P =.0184), and opioid/benzodiazepine prescribing (-0.267% per year, P <.0001). Opioid, benzodiazepine, and co-prescription rates were higher in females, White non-Hispanics, and rural regions., Conclusions: Among those with AUD, opioid prescribing decreased following NYS I-STOP program implementation. While both benzodiazepine and opioid/benzodiazepine co-prescribing rates remained high, a decreasing trend was evident after program implementation. Continuing high rates of opioid and benzodiazepine prescribing necessitate the development of innovative approaches to improve the quality of care., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Despite a steady increase in the number of organs available for transplant in the United States, over the last two decades there has been a precipitous decrease in the annual number of pancreas transplants performed. One overlooked consequence of this decline in pancreas transplant volume has been a decrease in experience in proper pancreas procurement and transplantation techniques for transplant surgeons as well as fewer trained abdominal transplant fellows entering the workforce certified for pancreas procurement and transplantation, with those achieving certification having less-developed judgment, skills, and experience. To augment current fellowship training and provide a concentrated experience in pancreas procurement and transplantation, the ASTS developed a hands-on surgical skills workshop focused on proper techniques for pancreas allograft procurement and backbench preparation., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Association for Surgical Education 2023.)

Introduction: Social isolation and reduced access to public life in response to SARS-CoV-2 (COVID-19) challenges health and well-being for many. Marginalized communities, including transgender and gender diverse (TGD) people, have been disproportionally impacted. Experiences of TGD people should be centered in pandemic-related research to better inform policy., Methods: A diverse sample of TGD people ( N  = 158) were recruited from Michigan, Nebraska, Oregon, and Tennessee to participate in the Trans Resilience and Health Study. Participants ranged from 19 to 70 years old ( M  = 33.06; SD  = 12.88) with 27.2% identifying as trans men/men, 26% identifying as trans women/women, and remaining identifying with terms like genderqueer and nonbinary. Thirty percent identified as people of color. Participants completed a monthly COVID-19-related questionnaire April 2020-March 2021 including open-ended questions to learn what contributed to resilience during this time. Thematic analyses of responses enabled identification of salient themes., Results: Analyses revealed pandemic-related changes in social experiences of marginalization and mask-wearing. Twenty-six participants mentioned face masks as contributing to resilience while also elaborating the influence of masks on experiences of misgendering. Participants identifying as trans women reported decreased misgendering while trans men and nonbinary participants reported increased misgendering., Conclusions and Policy Implications: Mask-wearing helps reduce transmission of COVID-19. For some trans women, masks also reduce the threat of misgendering and possibly other forms of enacted stigma. However, increased risk for misgendering, as noted by trans men in our study, should be considered and increased supports should be provided., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Precisely measuring the number and somatic volume of neurons in the central nervous system at single-cell resolution is technically challenging. Here, we combine multiple techniques to address this challenge in optically cleared mouse spinal cords. We describe in vivo neuron labeling approaches, tissue-clearing technology, light sheet fluorescence microscopy, and machine learning-guided imaging analysis. This combination provides a precise determination of the cell number and somatic volume of any neuron population in the spinal cords., Competing Interests: Declaration of interests A.E. is an employee of Bitplane., (Published by Elsevier Inc.)

The presence of circulating cancer cells in the bloodstream is positively correlated with metastasis. We hypothesize that fluid shear stress (FSS) occurring during circulation alters mitochondrial function, enhancing metastatic behaviors of cancer cells. MCF7 and MDA-MB-231 human breast cancer cells subjected to FSS exponentially increased proliferation. Notably, FSS-treated cells consumed more oxygen but were resistant to uncoupler-mediated ATP loss. We found that exposure to FSS downregulated the F 1 F O ATP synthase c-subunit and overexpression of the c-subunit arrested cancer cell migration. Approaches that regulate c-subunit abundance may reduce the likelihood of breast cancer metastasis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Names are a reflection of identity and often have personal meaning. The chronic mispronunciation of names can undermine one's identity and be experienced as a microaggression. This workshop aims to provide historical context for names as well as resources for correct name pronunciation., Methods: We developed a 60-minute interactive virtual workshop with didactics, small-group sharing of personal experiences, and case discussions. We used an anonymous postworkshop survey to evaluate workshop effectiveness., Results: We presented the workshop at one local academic conference and two local educational conferences to learners of all levels from medical students to faculty. We collected postworkshop survey results from 78 participants of diverse racial and ethnic backgrounds. Participants reported learning historical context, ways to ask about correct name pronunciation, correcting name mispronunciation, documenting pronunciation, and sources for applications to practice. The main barriers to implementing workshop lessons included personal and structural factors., Discussion: This workshop effectively fills an educational gap by addressing the importance of correct name pronunciation in order to provide a more inclusive environment for clinicians and patients alike., (© 2022 Dali et al.)

Laparoscopic donor nephrectomy (LDN) offers advantages to the donor. The reported incidence of testicular pain after LDN varies in the literature ranging from 3% to 55%., Methods: A survey was sent to 322 male LDN patients who donated from February 5, 2009, to February 5, 2019. The survey assessed if the donor had testicular pain or saw an additional medical professional after donation., Results: Of the 322 surveyed, 147 (46%) responses were received. Of those who had a left nephrectomy, 39% had testicular pain; 23.8% of those patients had testicular swelling in addition. Of those who had pain, laterality of kidney donated did not impact if the patient had pain, pain onset, pain level, or pain duration. Of those who donated their right kidney, 35% had testicular pain, and 16.7% of those patients reported testicular swelling in addition. Twenty-seven symptomatic patients sought additional medical care for the testicular symptoms postdonation. Seven (25%) had hydroceles, 2 (7%) had testicular cysts, 1 had a urinary tract infection, and 16 (59%) had reassurance or no additional procedures provided., Conclusions: Our results suggest that orchialgia is not as uncommon as previously thought and may be one of the most common minor complications experienced by male donors., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Powassan virus (POWV) is a tick-borne flavivirus (TBFV) that can cause severe encephalitis in humans with a case-fatality rate as high as 11%. Patients who survive severe encephalitic disease can develop long-term neurological sequelae that can be debilitating and life-long. In this study, we have sought to characterize a primary human fetal brain neural stem cell system (hNSC), which can be differentiated into neuron and astrocyte co-cultures, to serve as a translational in vitro system for infection with POWV and a comparative mosquito-borne flavivirus (MBFV), West Nile virus (WNV). We found that both viruses are able to infect both cell types in the co-culture and that WNV elicits a strong inflammatory response characterized by increased cytokines IL-4, IL-6, IL-8, TNF-α and IL-1β and activation of apoptosis pathways. POWV infection resulted in fewer cytokine responses, as well as less detectable apoptosis, while neurons infected with POWV exhibited structural aberrations forming in the dendrites. These anomalies are consistent with previous findings in which tick-borne encephalitis virus (TBEV) infected murine primary neurons formed laminal membrane structures (LMS). Furthermore, these structural aberrations are also recapitulated in brain tissue from infected mice. Our findings indicate that POWV is capable of infecting human primary neurons and astrocytes without causing apparent widespread apoptosis, while forming punctate structures reminiscent with LMS in primary human neurons and in vivo.

Tailored public health messaging encouraging COVID-19 vaccination may help increase vaccination rates and decrease the burden of COVID-19. We conducted a three-part COVID-19 vaccine uptake public health campaign disseminated on Facebook between April and June 2021. Our first campaign focused on reaching Black and Latinx communities; our second campaign focused on addressing vaccine access and scheduling in Latinx communities; and our third campaign focused on religious communities. Overall, we reached 25 million individuals with 171 million views across the United States. ( Am J Public Health . 2022;112(9):1253-1256. https://doi.org/10.2105/AJPH.2022.306934).

Background: Computerised Physician Order Entry (CPOE) software is increasingly used across the world to improve medication safety. However, few high-quality studies have reviewed the impact of CPOE on prescribing errors and patient harm., Objective: To investigate the effect of a hybrid CPOE-paper prescribing system on prescribing errors at a secondary hospital site., Design: An interrupted time-series study was conducted by identifying prescribing errors via prospective medical chart review before and after the implementation of CPOE across three medical wards., Participants: The medication orders of all patients admitted to the medical wards during the study period were reviewed., Intervention: Implementation of a CPOE across three medical wards., Measures: A blinded expert panel risk stratified the errors according to level of severity, preventability and potential for harm. Pearson's chi square and segmented regressions were used to determine if there were differences in prescribing errors pre- and post-CPOE implementation., Key Results: A total of 10,535 medication orders were reviewed pre-CPOE and 13,841 medication orders reviewed post-CPOE. Analysis demonstrated that after implementation of CPOE there were reductions in the proportion of orders with one or more of any error (-30.1%, 95 %CI: -36.5%, -23.7%, p < 0.001). Reductions in the proportion of orders with one or more errors were seen across the error categories of dosing errors (-20.1%, 95 %CI: -25.1%, -15%, p < 0.001), procedural/administrative errors (-18.9%, 95 %CI: -22.8%, -15%, p < 0.001), and therapeutic errors (-2.6%, 95 %CI: -4.1%, -1%, p = 0.002). Post-CPOE there were reductions in the proportion of orders with at least one non-intercepted serious error (-12.6%, 95 %CI: -16.4%, -8.8%, p < 0.001)., Conclusion: The introduction of CPOE was associated with reductions in prescribing errors. There is also evidence that this translated into a reduced risk of harm to patients post-CPOE implementation through the reduction in actual adverse drug events., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Some risk factors for severe coronavirus disease 2019 (COVID-19) have been identified, including age, race, and obesity. However, 20%-50% of severe cases occur in the absence of these factors. Cytomegalovirus (CMV) is a herpesvirus that infects about 50% of all individuals worldwide and is among the most significant nongenetic determinants of immune system. We hypothesized that latent CMV infection might influence the severity of COVID-19. Our analyses demonstrate that CMV seropositivity is associated with more than twice the risk of hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune profiling of blood and CMV DNA quantitative polymerase chain reaction in a subset of patients for whom respiratory tract samples were available revealed altered T-cell activation profiles in absence of extensive CMV replication in the upper respiratory tract. These data suggest a potential role for CMV-driven immune perturbations in affecting the outcome of SARS-CoV-2 infection and may have implications for the discrepancies in COVID-19 severity between different human populations., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: There is no standard way in which physicians teach or evaluate surgical residents intraoperatively, and residents are proving to not be fully competent at core surgical procedures upon graduating. The Surgical Autonomy Program (SAP) is a novel educational model that combines a modified version of the Zwisch scale with Vygotsky's social learning theory. The objective of this study was to establish preliminary validity evidence that SAP is a reliable measure of autonomy and a useful tool for tracking competency over time., Methods: The SAP breaks each surgical case into 4 parts, or zones of proximal development (ZPDs). Residents are evaluated on a 4-tier autonomy scale (TAGS scale) for each ZPD in every surgical case. Attendings were provided with a teaching session about SAP and identified appropriate ZPDs for surgical cases under their area of expertise. All neurosurgery residents at Duke University Hospital from July 2017 to July 2021 participated in this study. Chi-square tests and ordinal logistic regression were used for the analyses., Results: Between 2017 and 2021, there were 4885 cases logged by 27 residents. There were 30 attendings who evaluated residents using SAP. Faculty completed evaluations on 91% of cases. The ZPD of focus directly correlated with year of residency (postgraduate year) (χ2 = 1221.1, df = 15, p < 0.001). The autonomy level increased with year of residency (χ2 = 3553.5, df = 15, p < 0.001). An ordinal regression analysis showed that for every year increase in postgraduate year, the odds of operating at a higher level of independence was 2.16 times greater (95% CI 2.11-2.21, p < 0.001). The odds of residents performing with greater autonomy was lowest for the most complex portion of the case (ZPD3) (OR 0.18, 95% CI 0.17-0.20, p < 0.001). Residents have less autonomy with increased case complexity (χ2 = 160.28, df = 6, p < 0.001). Compared with average cases, residents were more likely to operate with greater autonomy on easy cases (OR 1.44, 95% CI 1.29-1.61, p < 0.001) and less likely to do so on difficult cases (OR 0.72, 95% CI 0.67-0.77, p < 0.001)., Conclusions: This study demonstrates preliminary evidence supporting the construct validity of the SAP. This tool successfully tracks resident autonomy and progress over time. The authors' smartphone application was widely used among surgical faculty and residents, supporting integration into the perioperative workflow. Wide implementation of SAP across multiple surgical centers will aid in the movement toward a competency-based residency education system.

Objective: To report 2 cases of women with vertebral defects, anal atresia, cardiac defects, tracheaesophageal fistula, renal anomalies, and/or limb anomalies (VACTERL association) and the outcomes of their in vitro fertilization (IVF) cycles., Design: A case report. We obtained informed consent from both the patients for this case report., Setting: Outpatient clinic at an academic hospital., Patients: Patient 1 was a 23-year-old woman with scoliosis, tethered spinal cord, tracheaesophageal fistula, duodenal atresia, and a common cloaca at birth. Patient 2 was a 36-year-old woman with dextrocardia, congenital heart disease, scoliosis, and an imperforate anus at birth., Interventions: Both the patients underwent IVF., Main Outcome Measures: Oocyte yield, oocyte quality, and number of embryos., Results: Patient 1 underwent 1 IVF cycle, with 16 oocytes retrieved, of which 6 were mature. However, during intracytoplasmic sperm injection, the oocytes were noted to be extremely fragile and degenerated immediately after sperm injection. No oocyte was fertilized. Patient 2 underwent 3 IVF cycles, and 2 oocyte retrievals, with a total of 7 oocytes under cryopreservation., Conclusions: Both the patients' cases presented challenges due to aberrations in pelvic anatomy and poor IVF outcomes. There is a paucity of data regarding fertility outcomes and, specifically, oocyte quality in patients with vertebral defects, anal atresia, cardiac defects, tracheaesophageal fistula, renal anomalies, and/or limb anomalies association. Their care requires a multidisciplinary assessment, an individualized approach, and continued investigation of their IVF and fertility outcomes., (© 2022 The Authors.)

Laparoscopic surgery is performed quite commonly and is known to have numerous advantages over traditional open surgery. Albeit rare, there are life-threatening complications as a result of laparoscopic surgery including those associated with the cardiopulmonary system. In our case, we present hemodynamically unstable capnothorax that occurred during robotic diaphragmatic endometriosis excision which was treated conservatively. It is critical for anesthesia providers to recognize when capnothorax occurs and to understand the implications and treatment in order to minimize unnecessary procedures and morbidity associated with such., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Tyler Dunn and Lopa Misra.)

In the ongoing search for the optimal biomaterial for tissue engineered vascular grafts (TEVGs), poly (glycerol sebacate) (PGS) has emerged as a new potential candidate. We have utilized a novel method to create unique, pore-free, extruded PGS grafts with and without a supportive exterior layer of polyglycolic acid (PGA). The 1 mm diameter by 5 mm length TEVGs were implanted in a rat model of infrarenal abdominal aorta interposition grafting. Three months after implantation, TEVGs comprised of extruded PGS with an external PGA braid demonstrated a patency rate of 9/10 (90%) with no signs of dilatation, dehiscence, or rupture. The PGS/PGA graft was remodeled into a neoartery with complete endothelialization of the neoartery lumen and formation of smooth muscle actinin multilayers as demonstrated via immunohistochemistry. Formation and maturation of extracellular matrix material were also observed, with amounts of elastin and collagen comparable to native rat aorta. No significant host inflammatory response was observed. These findings suggest the combination of an extruded PGS tube with an external reinforcing PGA braid is a promising material for small diameter TEVGs., (© 2022 John Wiley & Sons Ltd.)