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High maternal mortality and morbidity rates continue to significantly impact the United States, with Black birthing individuals being two to three times more likely to die from pregnancy related causes compared to other races. Ongoing discussions are crucial to improving care delivery and amplifying the experiences and needs of marginalized survivors of pregnancy-related psychological harm. Thus, this commentary leverages current literature and vignettes to deliver recommendations on authentically engaging patients in the cross-sectoral process of dismantling harmful clinical and research practices, thus building a safe, equitable future for maternal health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Sutton, Wyand, Char and McCullers.)

Objective: We sought to understand the lived experiences of Black women diagnosed with severe maternal morbidity (SMM) in communities with high maternal mortality to inform practices that reduce obstetric racism and improve patient outcomes., Methods: From August 2022 through December 2022, we conducted a phenomenological, qualitative study among Black women who experienced SMM. Participants were recruited via social media and met inclusion criteria if they self-identified as Black cisgender women, were 18-40 years old, had SMM diagnosed, and lived within zip codes in the United States that have the top-five highest maternal mortality rates. Family members participated on behalf of women who were deceased but otherwise met all other criteria. We conducted in-depth interviews (IDIs), and transcripts were analyzed using inductive and deductive methods to explore birth story experiences., Results: Overall, 12 participants completed IDIs; 10 were women who experienced SMM and 2 were mothers of women who died due to SMM. The mean age for women who experienced SMM was 31 years (range 26-36 years) at the time of the IDI or death. Most participants had graduate-level education, and the average annual household income was 123,750 USD. Women were especially interested in study participation because of their high-income status as they did not fit the stereotypical profile of Black women who experience racial discrimination. The average time since SMM diagnosis was 2 years. Participants highlighted concrete examples of communication failures, stereotyping by providers, differential treatment, and medical errors which patients experienced as manifestations of racism. Medical personnel dismissing and ignoring concerns during emergent situations, even when raised through strong self-advocacy, was a key factor in racism experienced during childbirth., Conclusions: Future interventions to reduce racism and improve maternal health outcomes should center on the experiences of Black women and focus on improving patient-provider communication, as well as the quality and effectiveness of responses during emergent situations. Précis statement: This study underscores the need to center Black women's experiences, enhance patient-provider communication, and address emergent concerns to mitigate obstetric racism and enhance maternal health outcomes., (© 2024 The Authors. Birth published by Wiley Periodicals LLC.)

We describe the successful management of Ancaliia Algerae microsporidial keratitis in an immunosuppressed 54-year-old woman with refractory linear IgA disease. The case highlights the challenges in diagnosis and management of this infection in immunocompromised individuals and emphasizes the usefulness of in vivo confocal microscopy as a novel, noninvasive tool to aid in the diagnosis and monitoring of microsporidial keratitis. We also discuss the possible mode of acquisition of this rare infection.

Introduction: Variations in confidence for procedural skills have been demonstrated when comparing male and female medical students in surgical training. This study investigates whether differences in technical skill and self-reported confidence exist between male and female medical students applying to orthopaedic residency., Methods: All medical students (2017 to 2020) invited to interview at a single orthopaedic residency program were prospectively evaluated on their technical skills and self-reported confidence. Objective evaluation of technical skill included scores for a suturing task as evaluated by faculty graders. Self-reported confidence in technical skills was assessed before and after completing the assigned task. Scores for male and female students were compared by age, self-identified race/ethnicity, number of publications at the time of application, athletic background, and US Medical Licensing Examination Step 1 score., Results: Two hundred sixteen medical students were interviewed, of which 73% were male (n = 158). No gender differences were observed in suture task technical skill scores or mean difference in simultaneous visual task scores. The mean change from pre-task and post-task self-reported confidence scores was similar between sexes. Although female students trended toward lower post-task self-reported confidence scores compared with male students, this did not achieve statistical significance. Lower self-reported confidence was associated with a higher US Medical Licensing Examination score and with attending a private medical school., Discussion: No difference in technical skill or confidence was found between male and female applicants to a single orthopaedic surgery residency program. Female applicants trended toward self-reporting lower confidence than male applicants in post-task evaluations. Differences in confidence have been shown previously in surgical trainees, which may suggest that differences in skill and confidence may develop during residency training., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Inequities in health and health care in the United States have persisted for decades, and the impacts on equity from the COVID-19 pandemic were no exception. In addition to the disproportionate burden of the disease across various populations, the pandemic posed several challenges, which exacerbated these existing inequities. This has undoubtedly contributed to deeply rooted public mistrust in medical research and healthcare delivery, particularly among historically and structurally oppressed populations. In the summer of 2020, given the series of social injustices posed by the pandemic and highly publicized incidents of police brutality, notably the murder of George Floyd, the Association of American Medical Colleges (AAMC) enlisted the help of a national collaborative, the AAMC Collaborative for Health Equity: Act, Research, Generate Evidence (CHARGE) to establish a three-way partnership that would gather and prioritize community perspectives and lived experiences from multiple regions across the US on the role of academic medicals centers (AMCs) in advancing health and social justice. Given physical gathering constraints posed by the pandemic, virtual interviews were conducted with 30 racially and ethnically diverse community members across the country who expressed their views on how medical education, clinical care, and research could or did impact their health experiences. These interviews were framed within the context of the relationship between historically oppressed groups and the COVID-19 vaccine clinical trials underway. From the three-way partnership formed with the AAMC, AAMC CHARGE participants, and 30 community members from racially and ethnically diverse groups, qualitative methods provided lived experiences supporting other literature on the lack of trust between oppressed communities and AMCs. This led to the development of the Principles of Trustworthiness (PoT) Toolkit, which features ten principles inspired by community members' insights into how AMCs can demonstrate they are worthy of their community's trust. In the end, the three-way partnership serves as a successful model for other national medical and health organizations to establish community engaged processes that elicit and prioritize lived experiences describing relationships between AMCs and oppressed communities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chinekezi, Andress, Agonafer, Massick, Piepenbrink, Sutton, Alberti, de la Torre, Guillot-Wright and Lee.)

Chicken bone marrow-derived macrophages (BMMΦ) and dendritic cells (BMDC) are utilized as models to study the mononuclear phagocytic system (MPS). A widely used method to generate macrophages and DC in vitro is to culture bone marrow cells in the presence of colony-stimulating factor-1 (CSF1) to differentiate BMMΦ and granulocyte-macrophage-CSF (GM-CSF, CSF2) and interleukin-4 (IL-4) to differentiate BMDC, while CSF2 alone can lead to the development of granulocyte-macrophage-CSF-derived DC (GMDC). However, in chickens, the MPS cell lineages and their functions represented by these cultures are poorly understood. Here, we decipher the phenotypical, functional and transcriptional differences between chicken BMMΦ and BMDC along with examining differences in DC cultures grown in the absence of IL-4 on days 2, 4, 6 and 8 of culture. BMMΦ cultures develop into a morphologically homogenous cell population in contrast to the BMDC and GMDC cultures, which produce morphologically heterogeneous cell cultures. At a phenotypical level, all cultures contained similar cell percentages and expression levels of MHCII, CD11c and CSF1R -transgene, whilst MRC1L-B expression decreased over time in BMMΦ. All cultures were efficiently able to uptake 0.5 µm beads, but poorly phagocytosed 1 µm beads. Little difference was observed in the kinetics of phagosomal acidification across the cultures on each day of analysis. Temporal transcriptomic analysis indicated that all cultures expressed high levels of CSF3R , MERTK , SEPP1 , SPI1 and TLR4 , genes associated with macrophages in mammals. In contrast, low levels of FLT3 , XCR1 and CAMD1 , genes associated with DC, were expressed at day 2 in BMDC and GMDC after which expression levels decreased. Collectively, chicken CSF2 + IL-4- and CSF2-dependent BM cultures represent cells of the macrophage lineage rather than inducing conventional DC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Borowska, Sives, Vervelde and Sutton.)

Three-dimensional (3D) intestinal enteroids are powerful in vitro models for studying intestinal biology. However, due to their closed structure direct access to the apical surface is impeded, limiting high-throughput applications of exogenous compounds and pathogens. In this study, we describe a method for generating confluent 2D enteroids from single-cell suspensions of enzymatically-dissociated ileum-derived bovine 3D enteroids. Confluent monolayers were first achieved using IntestiCult media but to establish a defined, cost-effective culture media, we also developed a bovine enteroid monolayer (BEM) medium. The monolayers cultured in BEM media proliferated extensively and formed confluent cell layers on both Matrigel-coated plastic plates and transwell inserts by day 3 of culture. The 2D enteroids maintained the epithelial cell lineages found in 3D enteroids and ileum tissue. In addition, the monolayers formed a functional epithelial barrier based on the presence of the adherens and tight junction proteins, E-cadherin and ZO-1, and electrical resistance across the monolayer was measured from day 3 and maintained for up to 7 days in culture. The method described here will provide a useful model to study bovine epithelial cell biology with ease of access to the apical surface of epithelial cells and has potential to investigate host-pathogen interactions and screen bioactive compounds., (© 2022. The Author(s).)

Atypical porcine pestivirus (APPV), an RNA virus member of the Flaviviridae family, has been associated with congenital tremor in newborn piglets. Previously reported quantitative polymerase chain reaction (qPCR)-based assays were unable to detect APPV in novel cases of congenital tremor originated from multiple farms from U.S. Midwest (MW). These assays targeted the viral polyprotein coding genes, which were shown to display substantial variation, with sequence identity ranging from 58.2% to 70.7% among 15 global APPV strains. In contrast, the 5'-untranslated region (5' UTR) was found to have a much higher degree of sequence conservation. In order to obtain the complete 5' UTR of the APPV strains originated from MW, the 5' end of the viral cDNA was obtained by using template switching approach followed by amplification and dideoxy sequencing. Eighty one percent of the 5' UTR was identical across 14 global and 5 MW strains with complete or relatively complete 5' UTR. Notably, some of the most highly conserved 5' UTR segments overlapped with potentially important regions of an internal ribosome entry site (IRES), suggesting their functional role in viral protein translation. A newly designed single qPCR assay, targeting 100% conserved 5' UTR regions across 19 strains, was able to detect APPV in samples of well documented cases of congenital tremor which originated from five MW farm sites (1-18 samples/site). As these fully conserved 5' UTR sequences may have functional importance, we expect that assays targeting this region would broadly detect APPV strains that are diverse in space and time., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Selected Issues in Sport-Related Concussion (SRC|Mild Traumatic Brain Injury) for the Team Physician: A Consensus Statement is title 22 in a series of annual consensus documents written for the practicing team physician. This document provides an overview of selected medical issues important to team physicians who are responsible for athletes with sports-related concussion (SRC). This statement was developed by the Team Physician Consensus Conference (TPCC), an annual project-based alliance of six major professional associations. The goal of this TPCC statement is to assist the team physician in providing optimal medical care for the athlete with SRC., Competing Interests: Competing interests: SH, MP, JJL and GS are members of the Concussion in Sport Group Expert Panel. SH and MP serve on the Center for Disease Control and Prevention and National Center for Injury Prevention and Control Board Pediatric Mild Traumatic Brain Injury Guideline Workgroup. SH serves on the NCAA Concussion Safety Advisory Group, is cofounder and Senior Medical Advisor for the Sports Institute at UW Medicine, and owns stock or stock options with Vicis. MP is a senior advisor to the NFL Head, Neck and Spine Committee, serves as the Chief Medical Officer for Major League Soccer, has received royalties from Up-To-Date and serves on the medical advisory board for US Soccer. GSS is Senior Medical Advisor for the NFL. KD has received grant funding from Children’s Hospital Foundation, and royalties from Up-To-Date. CRL has received grant funding from NOCSAE and received royalties from the AAP, and serves on medical advisory boards for Pop Warner Football, Illinois HS Association and US Soccer. JJL has received grant funding from the AMSSM, DoD and NIH, consulting fees from Neurolign and Stage 2 Contracting Engineering, participates on a Data Safety Monitoring Board or Advisory Board (Neuronasal) and has stock or stock options in Highmark Innovations. KMS is a consultant for Johnson & Johnson., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Abstract: Selected Issues in Sport-Related Concussion (SRC | Mild Traumatic Brain Injury) for the Team Physician: A Consensus Statement is title 22 in a series of annual consensus articles written for the practicing team physician. This document provides an overview of select medical issues important to team physicians who are responsible for athletes with sports-related concussion (SRC). This statement was developed by the Team Physician Consensus Conference (TPCC), an annual project-based alliance of six major professional associations. The goal of this TPCC statement is to assist the team physician in providing optimal medical care for the athlete with SRC., (Copyright © 2021 by the American College of Sports Medicine.)

Background and Purpose: Individuals after stroke often have multiple chronic conditions, such as hypertension, diabetes, dyslipidemia, obesity, and tobacco use. These comorbidities not only are commonly found in individuals with stroke, but also negatively affect functional outcomes and increase risk for hospital readmission and overall mortality. It is important for physical therapists to address the whole person during treatment after stroke, including comorbidities, not just the problems resulting from the stroke itself. However, it is unclear how common it is for physical therapists to address multiple diagnoses at once using a wellness model. Therefore, the purpose of this scoping review was to examine current evidence regarding the role of physical therapy in addressing modifiable risk factors for individuals after stroke, to identify gaps in research associated with physical therapy management of related comorbid diagnoses during treatment for stroke., Methods: A scoping review methodology was utilized searching PubMed and CINAHL databases to identify interventional research studies specifically addressing multiple modifiable risk factors utilizing physical therapy for individuals after stroke., Results: The initial search yielded 5358 articles and 12 articles met full inclusion criteria. Only 2 studies included participants with significant mobility impairments, and none included individuals with communication impairments. Only 4 of the 12 studies provided education in their design. Eight studies did not include any patient-reported outcome measures. Only 3 studies included long-term follow-up assessments., Discussion: Secondary stroke risk factors can be positively addressed using physical therapy interventions; however, more research is needed regarding individuals with moderate to severe mobility or communication deficits. Opportunities for physical therapy research to address stroke risk factors in this complex population include expanding follow-up periods, improving educational interventions, and including caregivers in study design., Conclusions: This review highlights the need for better integration of clinical considerations into stroke rehabilitation research as a whole, along with the need for additional research regarding the role physical therapy can play in addressing multimorbidity in individuals with stroke., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 APTA Geriatrics, An Academy of the American Physical Therapy Association.)

Background: Limited data exist on injuries in men's lacrosse at the international level. As lacrosse's popularity grows rapidly across the globe, health care providers must understand how to treat lacrosse athletes., Purpose: To analyze injury data from the 2018 Men's World Lacrosse Championship., Study Design: Descriptive epidemiology study., Methods: This study prospectively observed injuries that occurred during the 2018 Men's World Lacrosse Championship. The medical staff of each team completed injury report forms, and data were categorized into body part injury, type, mechanism, time, and location of injury., Results: Over 11 days, 1019 athletes competed in 170 games, resulting in a total of 7147 athlete-exposures (AEs). A total of 140   injuries were recorded during the tournament for an injury rate of 19.6 per 1000 AEs (95% CI, 16.4-22.7). Overall, there were more contact injuries (n = 99; 70.7%) than noncontact injuries (n = 41; 29.3%) ( P < .0001). Contact injuries most commonly affected the upper extremity, while noncontact injuries most commonly affected the lower extremity. Contusions were the most commonly reported injury type in the tournament (n = 41; 29.3%), followed by ligament sprains (n = 32; 22.9%) and muscle strains (n = 21; 15.0%). Although there was no difference between the first and second half of gameplay, the injury rate increased in the latter portion of each half (the first and third quarters vs the second and fourth quarters) ( P < .0001). A total of 4 injuries required trips to the hospital., Conclusion: Lacrosse has a unique injury profile, as it includes both overhead and collision activity as well as multidirectional, cutting movements. Understanding common injury patterns may help with treatment and prevention. Fatigue may play a role in injury rate, and future research of within-game and within-tournament fatigue should explore this relationship., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: K.B.T. has received education payments from Supreme Orthopedic Systems and hospitality payments from Smith & Nephew and Stryker. K.M.S. has received education payments from Arthrex and Gotham Surgical and consulting fees from DePuy and Medical Device Business Services. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2021.)

Unique biologic and biomechanical aspects of the female body make women more prone to certain orthopedic injuries. Sex differences are well understood with regard to certain orthopedic pathologies such as anterior cruciate ligament injury, hallux valgus, carpal tunnel, and carpometacarpal joint arthritis; however, sex differences are less commonly discussed with regard to shoulder and elbow pathology. The purpose of this review is to elucidate sex differences specific to sports-related shoulder and elbow injuries in the female athlete population., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

The outbreak of the novel coronavirus (COVID-19) has resulted in upward of 14 million confirmed cases and >597,000 deaths worldwide as of July 19, 2020. The current disruption in sports activities caused by COVID-19 presents a challenge to physicians, coaches, and trainers in discerning best practices for a safe return to sport. There is a distinct need to develop and adopt consistent measures for resumption of sports activities, including training and competition, in a way that places the health and well-being of athletes at the forefront while also protecting coaches, allied staff, and spectators. This article provides an overview of the effects of COVID-19 in the athletic population and presents considerations for training during the pandemic, as well as guidelines for return to sports as restrictions are lifted.

Competing Interests: Conflict of InterestAngela Mercurio, BS, and Arianna L. Gianakos, DO, declare that they have no conflict of interest. Mary K. Mulcahey reports being a paid consultant, presenter, or speaker to Arthrex, Inc., and Arthroscopy Association of North America, and a board or committee member at AAOS, ACSM Translational Journal, American Orthopaedic Society for Sports Medicine, Ortho Info, Ruth Jackson Orthopaedic Society, and The Forum. Karen Sutton, MD, reports being paid a consultant, presenter, or speaker to Johnson and Johnson; an unpaid consultant to ESPN-W and SportsMD; and a board or committee member at AAOS, American Orthopaedic Society for Sports Medicine, Bassett Society, Ruth Jackson Orthopaedic Society, The Forum, US Lacrosse, and World Lacrosse.

The COVID-19 pandemic has resulted in significant morbidity and mortality around the world. The spectrum of COVID-19 is broad, from clinical disease requiring intensive medical care to less severe symptoms that are treated with supportive care. The majority of COVID-19 cases fall into the mild-to-moderate category, with symptoms lasting less than 6 weeks. Nevertheless, the morbidity from COVID-19 is significant and can affect multiple body systems, most frequently the cardiac, pulmonary, hematologic, musculoskeletal, and gastrointestinal systems. For patients who wish to return to exercise after mild-to-moderate COVID-19, the wide range of disease expression presents a challenge for clinicians seeking to offer counsel. This literature review on return to activity following mild to moderate COVID-19 in the recreational athlete includes evidence-based considerations and recommendations for clinicians in guiding the safest return to activity., Competing Interests: Conflict of InterestJordan D. Metzl, MD, Kathryn McElheny, MD, James N. Robinson, MD, and Daphne A. Scott, MD, declare that they have no conflicts of interest. Karen M. Sutton, MD, reports support from Johnson & Johnson and from ESPN, outside the submitted work. Brett G. Toresdahl, MD, reports grants from GE Healthcare, outside the submitted work., (© The Author(s) 2020.)

Avian pathogenic Escherichia coli (APEC) cause severe respiratory and systemic disease in chickens, commonly termed colibacillosis. Early immune responses after initial infection are highly important for the outcome of the infection. In this study, the early interactions between GFP -expressing APEC strains of serotypes O1:K1:H7 and O2:K1:H5 and phagocytic cells in the lung of CSF1R -reporter transgenic chickens were investigated. CSF1R -reporter transgenic chickens express fluorescent protein under the control of elements of the CSF1R promoter and enhancer, such that cells of the myeloid lineage can be visualized in situ and sorted. Chickens were separately inoculated with APEC strains expressing GFP and culled 6 h post-infection. Flow cytometric analysis was performed to phenotype and sort the cells that harbored bacteria in the lung, and the response of the sorted cells was defined by transcriptomic analysis. Both APEC strains were mainly detected in CSF1R -transgene neg ( CSF1R -tg neg ) and CSF1R -tg low MHC II neg MRC1L-B neg cells and low numbers of APEC were detected in CSF1R -tg high MHC II pos MRC1L-B pos cells. Transcriptomic and flow cytometric analysis identified the APEC pos CSF1R -tg neg and CSF1R -tg low cells as heterophils and the APEC pos CSF1R -tg high cells as macrophages and dendritic cells. Both APEC strains induced strong inflammatory responses, however in both CSF1R -tg neg/low and CSF1R -tg high cells, many immune related pathways were repressed to a greater extent or less activated in birds inoculated with APEC O2- GFP compared to APEC O1- GFP inoculated birds. Comparison of the immune pathways revealed the aryl hydrocarbon receptor ( AhR ) pathway, IL17 and STAT3 signaling, heterophil recruitment pathways and the acute phase response, are modulated particularly post-APEC O2- GFP inoculation. In contrast to in vivo data, APEC O2- GFP was more invasive in CSF1R -tg high cells in vitro than APEC O1- GFP and had higher survival rates for up to 6 h post-infection. Our data indicate significant differences in the responses induced by APEC strains of prevalent serotypes, with important implications for the design and interpretation of future studies. Moreover, we show that bacterial invasion and survival in phagocyte populations in vitro is not predictive of events in the chicken lung., (Copyright © 2020 Alber, Morris, Bryson, Sutton, Monson, Chintoan-Uta, Borowska, Lamont, Schouler, Kaiser, Stevens and Vervelde.)

Background: The majority of studies on multimorbidity have been in aging populations and there is a paucity of data on individuals following stroke., Objective: In order to better understand the overall complexity of the stroke population in rural Kentucky, we examined the prevalence of multimorbidity that impact the overall long-term health and health care for these individuals., Methods: A secondary analysis examined whether there are gender or age differences in this stroke population related to the prevalence of multimorbidity. A total of 5325 individuals, 18 years of age and older, seen at an academic medical center for the primary diagnosis of acute ischemic stroke or transient ischemic attack between the years of 2010-2017 were identified using the Kentucky Appalachian Stroke Registry. Descriptive analysis was used to report the prevalence of each comorbidity in the rural population by age group, gender, and level of multimorbidity by looking at concurrent frequencies., Results: Overall, hypertension, dyslipidemia, tobacco use, diabetes, and obesity were the comorbidities with the highest prevalence in our population irrespective of gender. Over 78% (n = 4153) of the individuals had 3 or more comorbidities while 61% (n = 3285) had at least 3 out of the top 5 comorbidities (hypertension, hyperlipidemia, tobacco, obesity, diabetes). With respect to age, 15% (n = 795) of the sample was under the age of 50, while 32% (n = 1704) were between the age of 50 and 64 and 53% (n = 2826) of the sample were 65 years or older., Conclusions: The results of this study indicate the majority of individuals affected by stroke in rural Appalachia Kentucky have multimorbidity. In addition, almost half of these individuals are having their strokes at a younger age, which will require a shift in the focus for therapeutic interventions (eg, reintegration into the workforce versus just community reintegration)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The follicle-associated epithelium (FAE) is a specialized structure that samples luminal antigens and transports them into mucosa-associated lymphoid tissues (MALT). In mammals, transcytosis of antigens across the gut epithelium is performed by a subset of FAE cells known as M cells. Here we show that colony-stimulating factor 1 receptor (CSF1R) is expressed by a subset of cells in the avian bursa of Fabricius FAE. Expression was initially detected using a CSF1R -reporter transgene that also label subsets of bursal macrophages. Immunohistochemical detection using a specific monoclonal antibody confirmed abundant expression of CSF1R on the basolateral membrane of FAE cells. CSF1R -transgene expressing bursal FAE cells were enriched for expression of markers previously reported as putative M cell markers, including annexin A10 and CD44. They were further distinguished from a population of CSF1R -transgene negative epithelial cells within FAE by high apical F-actin expression and differential staining with the lectins jacalin, PHA-L and SNA. Bursal FAE cells that express the CSF1R -reporter transgene were responsible for the bulk of FAE transcytosis of labeled microparticles in the size range 0.02-0.1 μm. Unlike mammalian M cells, they did not readily take up larger bacterial sized microparticles (0.5 μm). Their role in uptake of bacteria was tested using Salmonella , which can enter via M cells in mammals. Labeled Salmonella enterica serovar Typhimurium entered bursal tissue via the FAE. Entry was partially dependent upon Type III secretion system-1. However, the majority of invading bacteria were localized to CSF1R -negative FAE cells and in resident phagocytes that express the phosphatidylserine receptor TIM4. CSF1R -expressing FAE cells in infected follicles showed evidence of cell death and shedding into the bursal lumen. In mammals, CSF1R expression in the gut is restricted to macrophages which only indirectly control M cell differentiation. The novel expression of CSF1R in birds suggests that these functional equivalents to mammalian M cells may have different ontological origins and their development and function are likely to be regulated by different growth factors., (Copyright © 2019 Balic, Chintoan-Uta, Vohra, Sutton, Cassady-Cain, Hu, Donaldson, Stevens, Mabbott, Hume, Sang and Vervelde.)

Recently, piglets from a high-health status farm began exhibiting congenital tremors, high preweaning mortality and incidence of splayed legs. Postmortem histological examination identified a small number of scattered white matter vacuoles in the cerebellum and underlying brainstem of affected piglets. Presence of potential viral sources associated with this neurologic condition was initially infirmed using quantitative PCR for atypical porcine pestivirus (APPV), porcine teschovirus, and porcine sapelovirus. Using metagenomic analysis, APPV was identified as the main microbial species in serum obtained from piglets affected by congenital tremor. These piglets had higher preweaning mortality rates (46.4% vs. 15.3%) and incidence of splayed legs (33.0% vs. 0.8 %) compared to unaffected piglets. Piglets affected by congenital tremor had higher viral titer (P < 0.15) and larger birth weights (P < 0.05) compared to normal litter mates. Whole-genome sequencing and genome assembly of the novel APPV strain (MK728876) was carried out using Oxford Nanopore and related bioinformatics pipelines. Phylogenic analysis demonstrated that this strain along with other completely sequenced APPV strains were grouped into 2 clades, both including strains-inducing congenital tremor. Strains appear to cluster based on region but there were still significant differences within regions. Future research needs to address potential underdiagnosis due to genetic diversity but also to understand mode of transmission, variation in virulence, and the role of host genetics in APPV susceptibility., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen that continues to threaten swine industry sustainability. The complexity and high genetic diversity of PRRSV has prevented vaccines from conferring adequate protection against disease outbreaks. Genome-wide association analyses of PRRSV experimentally infected pigs representing two genetic lines (n = 174 to 176) revealed two major genomic regions accounting for ~1.2% of the genetic variation in PRRSV-specific antibody level in serum or lung. The major region for serum antibody was mapped to SSC7 near the SLAII complex, which has also been implicated in susceptibility to other swine viral pathogens. Haplotype substitution analysis uncovered potential DQB1 haplotypes associated with divergent effects. A novel major region for lung antibody was mapped to the proximal end of SSC17 with the top SNP overlapping two genes, PRAG1 and LONRF1. Sequencing LONRF1 uncovered polymorphisms within the coding region that may play a role in regulating PRRSV-specific antibody production in lung tissue following PRRSV infection. These data implicate novel host genomic regions (SSC17) that influence PRRSV-specific immune response as well as a common region (SSC7) potentially involved in susceptibility to multiple viral pathogens., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In rural communities, individuals living with neurological conditions, such as stroke, traumatic brain injury (TBI), or spinal cord injury (SCI) and their caregivers face limited resources, decreased support, and a lack of access to health information and research. Little information exists on how to engage these individuals in community-based research., Objectives: We sought to 1) determine the most effective method(s) for engaging individuals with stroke, TBI, or SCI, and their caregivers in rural communities; 2) determine the perceived value of patient-centered outcomes research (PCOR) in their health care and clinical decision making; 3) to determine their health needs and related research priorities; and 4) to establish a community-based research team to support the development of relevant questions., Methods: Targeting a population of individuals with stroke, TBI, or SCI and their caregivers, as well as health care providers, 17 in-depth interviews were conducted, followed by seven focus groups, and two half-day meetings to establish a community-based research team and develop a research agenda., Results: Recruitment through trusted community networks was found to be the most beneficial for engaging participants. Participants placed high value on health research, but reported difficulties in accessing health information and in finding the information most relevant to them. A research team was established and research priorities centered on access to care and education., Conclusions: It is imperative to involve those living with a diagnosis or in an under-resourced community to develop the solutions that will work for them in their settings.

Purpose: U.S. teaching hospitals that qualify as 501(c)(3) organizations (a not-for-profit designation) are required to demonstrate community benefit annually. Increases in health insurance access driven by Affordable Care Act (ACA) implementation, along with new regulations, research opportunities, and educational expectations, may be changing hospitals' allocations of community benefit dollars. This study aimed to describe changes in teaching hospitals' community benefit spending between 2012 (pre-ACA implementation) and 2015 (post-ACA implementation), and to explore differences in spending changes between hospitals in Medicaid expansion and nonexpansion states., Method: In 2017, for each teaching hospital member of the Association of American Medical Colleges' (AAMC's) Council of Teaching Hospitals and Health Systems required to submit Form 990s to the Internal Revenue Service, the authors sought community benefit spending data for 2012 and 2015 as reported on Schedule H., Results: The analysis included 169 pairs of Form 990s representing 184 AAMC member teaching hospitals (93% of 198 eligible hospitals). Compared with 2012, hospitals in 2015 spent $3.1 billion (20.14%) more on community benefit despite spending $804 million (16.17%) less on charity care. Hospitals in Medicaid expansion states increased spending on subsidized health services and Medicaid shortfalls at rates higher than hospitals in nonexpansion states. The latter increased spending at higher rates on community health improvement and cash/in-kind contributions., Conclusions: After ACA implementation, teaching hospitals increased their overall community benefit spending while their charity care spending declined. Changes in community benefit spending differed according to states' Medicaid expansion status, demonstrating hospitals' responsiveness to state and local realities.

Popliteal artery entrapment syndrome is a condition in which compression of the popliteal neurovascular structures results in symptoms of lower extremity claudication by way of a constricting anatomic structure or a hypertrophied surrounding musculature. This diagnosis is often missed or misdiagnosed because popliteal artery entrapment syndrome has a presentation similar to that of exertional compartment syndrome. Popliteal artery entrapment syndrome may result in persistent disability or unnecessary morbidity or prevent athletes' return to sport. A female collegiate athlete presented with bilateral popliteal artery entrapment syndrome. She had successful surgical treatment and returned to a high level of sport. This article describes popliteal artery entrapment syndrome, emphasizes the importance of a thorough history and physical examination to elucidate the diagnosis, and provides information that may lead to the identification of individuals who will benefit from surgical intervention. [Orthopedics. 2018; 41(2):e295-e298.]., (Copyright 2017, SLACK Incorporated.)

In November 2015, the Association of American Medical Colleges (AAMC) held its annual meeting in Baltimore, Maryland. In response both to health and health care inequities faced by residents of Baltimore and to the imminent trial of the police officers charged with Freddie Gray's death, AAMC leaders thought it crucial to address issues of health inequity, social injustice, and the role an academic health center (AHC) can play in improving the health of the community it serves. In collaboration with community-engaged researchers from Johns Hopkins University and University of Maryland, Baltimore, AAMC staff interviewed Baltimore residents, soliciting their perspectives on how medical education, clinical care, and research can and should respond to social injustice and the social determinants of health. The authors used the resulting videoed interviews to frame a conversation during the annual meeting aimed at developing concrete actions that an individual, an institution, or the AAMC can take to address social injustice and health inequities in the Baltimore community and beyond. The robust conversation and the action steps identified by participants led to the development of a toolkit to build the capacity of AHCs and their communities to engage in similar, action-oriented programming. The success of the conversation inspired future meeting sessions that purposefully incorporate community voices and expertise. This Perspective presents results of this action planning and places the proposed set of activities within the current health care context to demonstrate how community expertise and wisdom can inform and advance efforts to improve the health of all.

Congenital or juvenile cataract is a disease condition in which opacification of the lenses is present at birth or manifests early in life. It has been attributed to different monogenic factors with a high degree of heterogeneity and is often studied using mouse models. A spontaneous mutation was identified in a mouse line selected for heat loss that influenced lens formation and resulted in juvenile cataracts in mice homozygous for the recessive allele. Genetic dissection of this selection line by combining high-density genotypes and homozygosity mapping uncovered a 906 kb fragment on MMU7 encompassing 21 SNPs split into two groups of consecutive, homozygous segments specific to the cataract phenotype. Haplotype analysis revealed a 197.5 kb segment unique to cataract-affected mice that included a single known transcript consisting of the first 14 exons of Sipa1l3. In this region, we discovered a deletion of 1114 bp at the mRNA level, spanning four coding exons, predicted to produce a truncated Sipa1l3 protein lacking a portion of a Rap-GAP domain and two other potentially vital domains. At the genome level, the deletion consisted of 16,733 bp. Genotyping across different samples confirmed that only affected mice were homozygous for the deletion and normal mice were either heterozygous or homozygous for the wild-type allele. Further studies will be required to determine the impact of the truncated Sipa1l3 domains on eye development.

Background: Men's lacrosse has been one of the fastest growing team sports in the United States, at both the collegiate and high school levels. Uniquely, it combines both continuous overhead and contact activity. Thus, an understanding of its injury epidemiology and mechanisms is vital. Shoulder injuries have been shown to be common in the sport, but thus far there has been no dedicated analysis of these injuries with which to better inform injury prevention strategies., Study Design: Descriptive epidemiology study., Methods: All athlete exposures (AEs) and shoulder injuries reported to the National Collegiate Athletic Association (NCAA) Injury Surveillance System for intercollegiate men's lacrosse athletes from 2004-2005 through 2008-2009 were collected. Type of injury was documented and the injury incidence per 1000 AEs was calculated. Event type, injury mechanism, specific injury, outcome, and time lost were recorded. Statistical analysis was performed using 95% CIs, calculated based on a normal approximation to Poisson distribution., Results: There were a total of 124 observed shoulder injuries during 229,591 monitored AEs. With weights, this estimates 1707 shoulder injuries over 2,873,973 AEs, for an incidence of 0.59 per 1000 AEs (95% CI, 0.56-0.62). The incidence of shoulder injury during competition was 1.89 per 1000 AEs (95% CI, 1.76-2.02), compared with 0.35 per 1000 AEs (95% CI, 0.33-0.38) during practice. Acromioclavicular joint injuries were most common (0.29 per 1000 AEs; 95% CI, 0.27-0.31). Labral injuries and instability events were also frequent (0.11 per 1000 AEs; 95% CI, 0.10-0.13). Player-to-player contact caused 57% of all shoulder injuries, with 25% due to contact with the playing surface. The average time lost was 11.0 days, with 41.9% of all shoulder injuries requiring ≥10 days. Clavicle fractures and posterior shoulder dislocation were particularly severe, with no athletes returning to play during the same season., Conclusion: Shoulder injuries are common in NCAA men's lacrosse and are an important source of lost playing time. Acromioclavicular injuries were the most frequent injury in this series, but labral and instability injuries were also common. In this increasingly popular contact sport, an understanding of the epidemiology and mechanism of shoulder injuries may be used to improve protective equipment and develop injury prevention., (© 2016 The Author(s).)

Background: Despite the common nature of orthopaedic injuries in equestrian sports, there is no published review to specifically characterize orthopaedic injuries in equestrian athletes., Purpose: To characterize orthopaedic injury patterns in equine sports-related injuries and their treatment., Study Design: Systematic review; Level of evidence, 4., Methods: This review was performed through a PubMed, EMBASE, and Scopus query (from 1978 to June 2014) in the English literature using search terms "(equine-related OR equestrian-related OR horse-related OR equestrian OR equestrians) AND (injury OR injuries)." Only full-text studies reporting on orthopaedic injury patterns pertinent to equestrian sports in the United States (US) and the United Kingdom (UK) were included. Orthopaedic injuries were defined as those resulting in a fracture or dislocation. In all, 182 studies were excluded, leaving a total of 27 studies for evaluation. The studies included were analyzed for demographic and epidemiological data for orthopaedic injuries, including fractures and dislocations. Cranial and facial injuries were excluded from analysis., Results: The majority of those injured in the US were female (64.5%). The leading cause of injury in the US was falling from a horse. The use of protective equipment seemed to vary widely, with helmet use ranging from less than 6% up to 66.7%. In the UK, fractures were found to account for 17.4% of reported injures, compared with 33.6% of injuries in the US. The majority of fractures in US riders occurred in the upper extremities (50.7%)., Conclusion: This review helps characterize the epidemiology of equestrian injuries based on currently available data.

A new member of the chicken TNF superfamily has recently been identified, namely receptor activator of NF-κB ligand (RANKL), as have its signalling receptor, RANK, and its decoy receptor, osteoprotegerin (OPG). In mammals, RANKL and RANK are transmembrane proteins expressed on the surface of Th1 cells and dendritic cells (DC) respectively, whereas OPG is expressed as a soluble protein from osteoblasts and DC. Recombinant soluble chicken RANKL (chRANKL) forms homotrimers whereas chicken OPG (chOPG) forms homodimers, characteristic of these molecules in mammals. ChRANKL, chRANK and chOPG are expressed at the mRNA level in most tissues and organs. ChRANKL is transcriptionally regulated by Ca(2+) mobilisation and enhances the mRNA expression levels of pro-inflammatory cytokines in bone marrow-derived DC (BMDC); this is inhibited by both chOPG-Fc and soluble chRANK-Fc. However, chRANKL does not enhance the expression of cell surface markers in either BMDC or BM-derived macrophages (BMM). Furthermore, chRANKL enhances the survival of APC similar to its mammalian orthologue., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Piperine, an alkaloid from black pepper, is reported to have anticancer activities. In this study, we investigated the effect of piperine on the growth and motility of triple-negative breast cancer (TNBC) cells. Piperine inhibited the in vitro growth of TNBC cells, as well as hormone-dependent breast cancer cells, without affecting normal mammary epithelial cell growth. Exposure to piperine decreased the percentage of TNBC cells in the G2 phase of the cell cycle. In addition, G1- and G2-associated protein expression was decreased and p21(Waf1/Cip1) expression was increased in piperine-treated TNBC cells. Piperine also inhibited survival-promoting Akt activation in TNBC cells and caused caspase-dependent apoptosis via the mitochondrial pathway. Interestingly, combined treatment with piperine and γ radiation was more cytotoxic for TNBC cells than γ radiation alone. The in vitro migration of piperine-treated TNBC cells was impaired and expression of matrix metalloproteinase-2 and -9 mRNA was decreased, suggesting an antimetastatic effect by piperine. Finally, intratumoral administration of piperine inhibited the growth of TNBC xenografts in immune-deficient mice. Taken together, these findings suggest that piperine may be useful in the treatment of TNBC., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Most cancers arise and evolve as a consequence of somatic mutations. These mutations influence tumor behavior and clinical outcome. Consequently, there is considerable interest in identifying somatic variants within specific genes (such as BRAF, KRAS and EGFR) so that chemotherapy can be tailored to the patient's tumor genotype rather than using a generic treatment based on histological diagnosis alone. Owing to the heterogeneous nature of tumors, a somatic mutation may be present in only a subset of cells, necessitating the use of quantitative techniques to detect rare variants. The highly quantitative nature of next-generation sequencing (NGS), together with the ability to multiplex numerous samples, makes NGS an attractive choice with which to screen for somatic variants. However, the large volumes of sequence data present significant difficulties when applying NGS for the detection of somatic mutations. To alleviate this, we have developed methodologies including a set of data analysis programs, which allow the rapid screening of multiple formalin-fixed, paraffin-embedded samples for the presence of specified somatic variants using unaligned Illumina NGS data.

Thymoquinone (TQ) from black caraway seeds has several anticancer activities; however, its effect on triple-negative breast cancer (TNBC) cells that lack functional tumor suppressor p53 is not known. Here, we explored the growth inhibitory effect of TQ on 2 TNBC cell lines with mutant p53. Cell metabolism assays showed that TQ inhibited TNBC cell growth without affecting normal cell growth. Flow cytometric analyses of TQ-treated TNBC cells showed G1 phase cell cycle arrest and apoptosis characterized by the loss of mitochondrial membrane integrity. Western blots of lysates from TQ-treated TNBC cells showed cytochrome c and apoptosis-inducing factor in the cytoplasm, as well as caspase-9 activation consistent with the mitochondrial pathway of apoptosis. Caspase-8 was also activated in TQ-treated TNBC cells, although the mechanism of activation is not clear at this time. Importantly, TQ-induced apoptosis was only partially inhibited by zVAD-fmk, indicating a role for caspase-independent effector molecules. Poly(ADP-ribose) polymerase cleavage and increased γH2AX, as well as reduced Akt phosphorylation and decreased expression of X-linked inhibitor of apoptosis, were evident in TQ-treated cells. Finally, TQ enhanced cisplatin- and docetaxel-induced cytotoxicity. These findings suggest that TQ could be useful in the management of TNBC, even when functional p53 is absent.

Current methods for resolving genetically distinct subclones in tumor samples require somatic mutations to be clustered by allelic frequencies, which are determined by applying a variant calling program to next-generation sequencing data. Such programs were developed to accurately distinguish true polymorphisms and somatic mutations from the artifactual nonreference alleles introduced during library preparation and sequencing. However, numerous variant callers exist with no clear indication of the best performer for subclonal analysis, in which the accuracy of the assigned variant frequency is as important as correctly indicating whether the variant is present or not. Furthermore, sequencing depth (the number of times that a genomic position is sequenced) affects the ability to detect low-allelic fraction variants and accurately assign their allele frequencies. We created two synthetic sequencing datasets, and sequenced real KRAS amplicons, with variants spiked in at specific ratios, to assess which caller performs best in terms of both variant detection and assignment of allelic frequencies. We also assessed the sequencing depths required to detect low-allelic fraction variants. We found that VarScan2 performed best overall with sequencing depths of 100×, 250×, 500×, and 1,000× required to accurately identify variants present at 10%, 5%, 2.5%, and 1%, respectively., (© 2013 WILEY PERIODICALS, INC.)

Objective: This study was conducted to determine whether fetal position at the time of preterm premature rupture of membranes (PPROM) diagnosis affects outcomes., Study Design: A retrospective study was designed to assess differences in outcomes between cephalic and noncephalic presentation at PPROM diagnosis between 24 and 34 weeks' gestation., Results: Five hundred sixty-six cases of PPROM were identified; 108 cases (19.1%) were noncephalic at time of PPROM diagnosis. The 2 groups were similar with regard to demographics. Although membrane rupture and delivery occurred earlier in the noncephalic group, there was no difference in latency between groups (cephalic group, 6.22 days vs noncephalic group, 7.85 days; P = .07). Noncephalic pregnancies were substantially more likely to be complicated by oligohydramnios, abruption, intrauterine fetal death, and infectious morbidity., Conclusion: Noncephalic presentation at the time of diagnosis of PPROM independently and significantly increases the risk of maternal complications in such affected pregnancies., (Copyright © 2013 Mosby, Inc. All rights reserved.)

We describe a sensitive technique for mutation detection using clonal sequencing. We analyzed DNA extracted from 13 cancer cell lines and 35 tumor samples and applied a novel approach to identify disease-associated somatic mutations. By matching reads against an index of known variants, noise can be dramatically reduced, enabling the detection and quantification of those variants, even when they are present at less than 1% of the total sequenced population; this is comparable to, or better than, current diagnostic methods. Following the identification or exclusion of known variants, unmatched reads are grouped for BLAST searching to identify novel variants or contaminants. Known variants, novel variants, and contaminants were readily identified in tumor tissue using this approach. Our approach also enables an estimation of the per-base sequencing error rate, providing a confidence threshold for interpretation of the results in the clinic. This novel approach has immediate applicability to clinical testing for disease-associated genetic variants., (© 2012 Wiley Periodicals, Inc.)

The rate of anterior cruciate ligament (ACL) rupture is three times higher in female athletes than in male athletes. Intrinsic factors such as increased quadriceps angle and increased posterior tibial slope may predispose girls and women to ACL injury. Compared with males, females have smaller notch widths and smaller ACL cross-sectional area; however, no conclusive correlation between ACL size and notch dimension exists, especially in relation to risk of ACL injury. Female athletes who land with the knees in inadequate flexion and in greater-than-normal valgus and external rotation are at increased risk of ACL injury. No conclusive link has been made between ACL injury and the menstrual cycle. Neuromuscular intervention protocols have been shown to reduce the rate of injury in girls and women. Females are more likely than males to have a narrow A-shaped intercondylar notch, and special surgical considerations are required in such cases. Following ACL reconstruction, female athletes are more likely than male athletes to rupture the contralateral ACL; however, males and females are equally likely to rupture the reconstructed knee. Although self-reported outcomes in the first 2 years following reconstruction are worse for females than for males, longer-term studies demonstrate no difference between males and females.

Thymoquinone (TQ), a bioactive component of black caraway seed (Nigella sativa) oil, is reported to have antineoplastic properties. In this study we investigated the effect of TQ on a panel of human breast cancer cell lines. Cell viability assays showed that TQ killed T-47D, MDA-MB-231, and MDA-MB-468 cells via p53-independent induction of apoptosis; however, MCF-7 cells were refractory to the cytotoxic action of TQ. Western Blot analysis showed that MCF-7 cells expressed high levels of cytoprotective NADPH quinone oxidoreductase 1 (NQO1), which was responsible for TQ-resistance since inhibition of NQO1 with dicoumarol rendered MCF-7 cells TQ-sensitive. These findings may be clinically important when considering TQ as a possible adjunct treatment for breast cancer since a high percentage of breast tumors express NQO1., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aromatase inhibitors (AIs) are recommended as adjuvant endocrine therapy for postmenopausal women with hormone-responsive breast cancer. With the widespread use of AI adjuvant endocrine therapy, a significant profile of musculoskeletal symptoms has emerged. Moderate to severe musculoskeletal symptoms have led some women to discontinue therapy, compromising the survival benefit. The etiology of AI-related musculoskeletal symptoms is poorly understood, which challenges development of effective management strategies. The purpose of this article is to describe AI-related musculoskeletal symptoms, review possible causes, provide assessment guidelines, and recommend management strategies based on the best available evidence. Little evidence exists for effective management strategies of AI-related musculoskeletal symptoms, and randomized clinical trials are needed to establish effective interventions. A thorough musculoskeletal assessment can help guide clinical decision making for the best individual management approach. Providers need to manage symptoms with the best available evidence to minimize symptom distress and maximize adherence to AI therapy.

Purpose: Recent evidence has demonstrated the importance of dissection in the correct tissue plane for the resection of colon cancer. We have previously shown that meticulous mesocolic plane surgery yields better outcomes and that the addition of central vascular ligation produces an oncologically superior specimen compared with standard techniques. We aimed to assess the effect of surgical education on the oncological quality of the resection specimen produced., Methods: We received clinicopathological data and specimen photographs from 263 resections for primary colon cancer from 6 hospitals in the Capital and Zealand regions of Denmark before a national training program. Ninety-three cases were from Hillerød Hospital, where surgeons had previously implemented a surgical educational training program in complete mesocolic excision with central vascular ligation and adopted the procedure as standard practice. The specimen photographs were assessed for the plane of surgery and tissue morphometry was performed., Results: Hillerød specimens had a higher rate of mesocolic plane surgery (75% vs 48%; P < .0001) compared with the other hospitals. The surgeons at Hillerød Hospital also removed a greater length of colon in both fresh (median, 315 vs 247 mm; P < .0001) and fixed (269 vs 207 mm; P < .0001) specimens with a greater distance between the tumor and the closest vascular tie in both fresh (105 vs 84 mm; P = .006) and fixed (82 vs 67 mm; P = .002) specimens. This resulted in the removal of more mesentery in both fresh (14,466 vs 8706 mm; P < .0001) and fixed (9418 vs 6789 mm; P < .0001) specimens and a greater median lymph node yield (28 vs 18; P < .0001)., Conclusions: We have shown that adoption of complete mesocolic excision with central vascular ligation results in a change to the production of an oncologically superior specimen compared with standard techniques. This should improve outcomes toward those reported by centers that have long practiced meticulous colon cancer surgery.

Background: The in situ forces of the anteromedial (AM) and posterolateral bundles (PL) of the anterior cruciate ligament (ACL) under simulated functional loads such as simulated muscle loads have not been reported. These data are instrumental for improvement of the anatomical double-bundle ACL reconstruction., Hypothesis: The load-sharing patterns of the 2 bundles are complementary under simulated muscle loads., Study Design: Descriptive laboratory study., Methods: Eight cadaveric knees in this study were sequentially studied using a robotic testing system. Each knee was tested under 3 external loading conditions including (1) a 134-N anterior tibial load; (2) combined rotational loads of 10 N x m of valgus and 5 N x m internal tibial torques; and (3) a 400-N quadriceps muscle load with the knee at 0 degrees , 15 degrees , 30 degrees , 60 degrees , and 90 degrees of flexion. The in situ forces of the 2 bundles of ACL were determined using the principle of superposition., Results: Under the anterior tibial load, the PL bundle carried peak loads at full extension and concurrently had significantly lower force than the AM bundle throughout the range of flexion (P <.05). Under the combined rotational loads, the PL bundle contributed to carrying the load between 0 degrees and 30 degrees , although less than the AM bundle. Under simulated muscle loads, both bundles carried loads between 0 degrees and 30 degrees . There was no significant difference between the 2 bundle forces at all flexion angles (P > .05)., Conclusion: Under externally applied loads, in general, the AM bundle carried a greater portion of the load at all flexion angles, whereas the PL bundle only shared the load at low flexion angles. The bundles functioned in a complementary rather than a reciprocal manner to each other., Clinical Relevance: The data appear to support the concept that both bundles function in a complementary manner. Thus, how to re-create the 2 bundle functions in an ACL reconstruction should be further investigated.

Rupture of the distal biceps tendon accounts for 10% of all biceps brachii ruptures. Injuries typically occur in the dominant elbow of men aged 40 to 49 years during eccentric contraction of the biceps. Degenerative changes, decreased vascularity, and tendon impingement may precede rupture. Although nonsurgical management is an option, healthy, active persons with distal biceps tendon ruptures benefit from early surgical repair, gaining improved strength in forearm supination and, to a lesser degree, elbow flexion. Biomechanical studies have tested the strength and displacement of various repairs; the suspensory cortical button technique exhibits maximum peak load to failure in vitro, and suture anchor and interosseous screw techniques yield the least displacement. Surgical complications include sensory and motor neurapraxia, infection, and heterotopic ossification. Current trends in postoperative rehabilitation include an early return to motion and to activities of daily living.

The transcription factor hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in tumour growth and progression, and HIF-1 is regulated through a number of signalling pathways. Here, we investigated the involvement of the mitogen-activated protein kinase (MAPK) signalling pathway in HIF-1 regulation. We found that overexpression of wild-type (WT) extracellular signal regulated protein kinase 1 (ERK1) greatly potentiated HIF-1 activation in hypoxia and HIF-1alpha induced in response to insulin growth-like factor 1 (IGF-1). Conversely, treatment of tumour cells with the MEK1/2 inhibitors PD98059 or U0216, or expression of a dominant-negative form of ERK1 blocked HIF-1 activation in hypoxia without affecting HIF-1alpha induction, localization or binding of HIF-1beta. Interestingly however, the highly selective MEK1/2 inhibitor PD184352 did not inhibit HIF-1 activity or vascular endothelial growth factor (VEGF) induced in response to hypoxia but blocked HIF-1alpha protein and HIF-1 activity induced by IGF-1 stimulation without affecting HIF-1alpha mRNA levels. Finally, we found that ERK5 phosphorylation status was not significantly affected by hypoxia in the presence or absence of PD184352. Taken together, our data suggest that although ERK1/2 signalling is important for HIF-1alpha induction and HIF-1 activity in response to IGF-1, it is dispensable for the induction of HIF-1alpha and activation of HIF-1 in response to hypoxia.

Background: We hypothesized that there no need to position the foot in plantarflexion after operative repair of an Achilles tendon rupture., Methods: In five fresh cadaver lower extremity specimens, the static tension in the Achilles tendon was measured as the ankle was sequentially dorsiflexed from 30, to 20, to 10, to 0 degrees of plantarflexion. The tendon was then transected and repaired using a modified Krakow locking loop suture technique. The tension in the tendon was again measured as the foot was sequentially dorsiflexed through the same range of motion: 30, to 20, to 10, to 0 degrees. The repair was then tensile tested to failure., Results: The intact Achilles tendons generated on average 10 N, 10 N, 15.8 N and 31.9.0 N of tension at 30, 20, 10, and 0 degrees of plantarflexion, respectively. After a modified Krakow locking loop repair, the tension across the repair site was 10 N, 11.46 N, 18.4 N, and 30.3 N at 30, 20, 10, and 0 degrees of plantarflexion. Thus, moving the ankle from 30 degrees to neutral placed an additional force of 21.9 N on the intact tendon and 20.3 N on the repaired tendon. The mean tensile strength of the modified Krakow repair was 598.6 N (range 167 1129 N)., Conclusions: The tension in the repaired tendon at neutral position is only a small percentage (6.4%) of the strength of the tendon when operatively repaired by a modified Krakow locking loop suture technique., Clinical Relevance: Our results suggest that the ankle joint does not have to be positioned in plantarflexion after operative repair using the described technique.

Partial-thickness rotator cuff tears are not a single entity; rather, they represent a spectrum of disease states. Although often asymptomatic, they can be significantly disabling. Overhead throwing athletes with partial-thickness rotator cuff tears differ with respect to etiology, goals, and treatment from older, nonathlete patients with degenerative tears. Pathogenesis of degenerative partial-thickness tears is multifactorial, with evidence of intrinsic and extrinsic factors playing key roles. Diagnosis of partial-thickness rotator cuff tears should be based on the patient's symptoms together with magnetic resonance imaging studies. Conservative treatment is successful in most patients. Surgery generally is considered for patients with symptoms of sufficient duration and intensity. The role of acromioplasty has not been clearly delineated, but it should be considered when there is evidence of extrinsic causation for the partial-thickness rotator cuff tear.

Study Design: Complete cervical disc complex extrusion, defined as the extrusion of both cartilaginous end-plates, the entire nucleus pulposus, and portions of the anulus fibrosus, is rare. A case of complete cervical disc complex extrusion with spinal cord injury in the absence of facet dislocation or subluxation in an obtunded patient is reported., Objective: To report an unusual presentation of spinal cord injury and the occurrence of complete traumatic cervical disc complex extrusion in the absence of facet dislocation and normal plain radiographic findings., Summary of Background Data: Traumatic cervical disc herniation occurs in 54% to 80% of patients with facet dislocation. A report of complete extrusion of a cervical intervertebral disc complex (cartilaginous endplate, anulus, and nucleus pulposus) with spinal cord injury in the absence of dislocation has not been described, to the best of the authors' knowledge., Methods: A clinical and radiographic review of such a case of complete traumatic cervical disc complex herniation in the absence of dislocation was performed., Results: Plain radiographic imaging did not show any injury. A nondisplaced fracture of the left inferior facet joint was evident on computed tomography. The diagnosis of C4-C5 intervertebral disc extrusion was made only after magnetic resonance imaging. The vacuum effect of complete disc extrusion created a "white-out" appearance to the disc space on the sagittal T2 magnetic resonance image. The patient underwent anterior cervical discectomy and fusion with additional posterior cervical fusion. He subsequently regained functional strength against gravity in two of four limbs. He remains completely paraparetic in the left upper extremity and partially paraparetic in the left lower extremity., Conclusion: The case report highlights the occurrence of complete traumatic cervical disc extrusion in the absence of facet dislocation with normal plain radiographic findings and consequent spinal cord injury, which can accompany such an injury.

Objective: In recent years it has become evident that tissue cyclooxygenase-2 (COX-2) may play a role in carcinogenesis and tumor malignancy. There is now a mounting body of information that strongly implies that COX-2 inhibitors may be of some value in the management of patients with carcinomas, and most recently several similar reports have appeared relating to sarcomas., Methods: The authors studied 32 samples of cartilage tumors from our tumor tissue bank for the presence of COX-2 by a Western blot technique. There were 29 patients from whom the samples were obtained, including 8 with enchondromas and 21 with chondrosarcomas., Results: Thirteen of the 24 chondrosarcoma samples and none of the 8 enchondromas were positive for COX-2. An attempt was made to correlate these results with clinical data including age, gender, staging according to the Musculoskeletal Tumor Society, anatomical site, ploidic pattern, presence of metastases and death rate but no statistically valid correlation could be found., Conclusion: It is evident that COX-2 may play some role in chondrosarcoma but not in the benign enchondroma and that further studies with COX-2 inhibitors are warranted., (Copyright 2004 S. Karger AG, Basel)