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Background and objective Sexual minorities experience large-scale mental health disparities, yet recent national data on them remains scarce. This study aimed to examine the prevalence of depressive and anxiety symptoms by sexual orientation in a nationally representative sample of adults in the United States (US). Methods This cross-sectional analysis utilized data from 26,311 adults in the 2022 National Health Interview Survey. Sexual orientation was classified as sexual minority (gay/lesbian, bisexual, or other non-heterosexual identity) or heterosexual. Self-reported depression was assessed using the eight-item Patient Health Questionnaire (PHQ-8), and anxiety was evaluated using the seven-item Generalized Anxiety Disorder Scale (GAD-7). Logistic regression models were employed to compare mental health outcomes between sexual minority and heterosexual respondents. Results Sexual minorities comprised 6.6% of the weighted sample. Compared to heterosexuals, sexual minorities were younger, more often female, unmarried, and had higher poverty despite greater employment (all p<0.001). Approximately half of sexual minorities screened positive for depression (49.0%) and anxiety (44.3%), compared to 19.5% and 16.4% of heterosexuals, respectively. After covariate adjustment, sexual minorities had over three-fold higher odds of depression [odds ratio (OR): 3.27; 95% confidence interval (CI): 2.86-3.73] and anxiety (OR: 2.97; 95% CI: 2.57-3.42). The prevalence was highest among sexual minority youth, with depression in 54.9-61.1% and anxiety in 49.0-59.2%, depending on income levels. Conclusions In this nationally representative study, sexual minorities demonstrated a high burden of depression and anxiety symptoms compared to heterosexuals. Sexual orientation independently predicted mental health disparities beyond other sociodemographic characteristics. Targeted interventions are recommended to address psychiatric disease disparities that disproportionately impact vulnerable sexual minority subgroups.
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CASE: A 48-year-old man presented to a Level 1 trauma center after a motor vehicle crash with a right irreducible posterior hip dislocation and ipsilateral fractures of the femoral head and segmental femur shaft. This injury was managed with open reduction and internal fixation and antegrade intramedullary nailing. CONCLUSION: This is the first report of a combined irreducible femoral head fracture-dislocation and a segmental femur fracture, a rare injury that requires a stepwise approach to operative management of each injury. Surgeons must recognize the clinical and radiographic findings associated with irreducible hip dislocations in the setting of ipsilateral fractures to the femoral head and shaft.
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Femoral Fractures , Humans , Male , Middle Aged , Femoral Fractures/surgery , Femoral Fractures/diagnostic imaging , Hip Dislocation/surgery , Hip Dislocation/diagnostic imaging , Accidents, Traffic , Femur Head/injuries , Femur Head/surgery , Femur Head/diagnostic imaging , Hip Fractures/surgery , Hip Fractures/diagnostic imaging , Fracture Fixation, Internal/methods , Fracture Fixation, IntramedullaryABSTRACT
Objectives: Chondrocyte metabolic dysfunction plays an important role in osteoarthritis (OA) development during aging and obesity. Protein post-translational modifications (PTMs) have recently emerged as an important regulator of cellular metabolism. We aim to study one type of PTM, lysine malonylation (MaK) and its regulator Sirt5 in OA development. Methods: Human and mouse cartilage tissues were used to measure SIRT5 and MaK levels. Both systemic and cartilage-specific conditional knockout mouse models were subject to high-fat diet (HFD) treatment to induce obesity and OA. Proteomics analysis was performed in Sirt5 -/- and WT chondrocytes. SIRT5 mutation was identified in the Utah Population Database (UPDB). Results: We found that SIRT5 decreases while MAK increases in the cartilage during aging. A combination of Sirt5 deficiency and obesity exacerbates joint degeneration in a sex dependent manner in mice. We further delineate the malonylome in chondrocytes, pinpointing MaK's predominant impact on various metabolic pathways such as carbon metabolism and glycolysis. Lastly, we identified a rare coding mutation in SIRT5 that dominantly segregates in a family with OA. The mutation results in substitution of an evolutionally invariant phenylalanine (Phe-F) to leucine (Leu-L) (F101L) in the catalytic domain. The mutant protein results in higher MaK level and decreased expression of cartilage ECM genes and upregulation of inflammation associated genes. Conclusions: We found that Sirt5 mediated MaK is an important regulator of chondrocyte cellular metabolism and dysregulation of Sirt5-MaK could be an important mechanism underlying aging and obesity associated OA development.
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Reading proficiency is important because it has life-long consequences and influences success in other academic areas. Many students with behavior problems are poor readers and many students with learning disabilities have more behavior problems than their typical peers. We conducted a correlational meta-analysis to examine the association between reading and externalizing behavior in students ages 5-12. We identified 33 studies that reported 88 effect sizes. Using a random-effects linear regression model with robust variance estimation, we found a significant, negative correlation (r= -0.1698, SE = 0.01, p < 0.0001) between reading and externalizing behavior. We tested several moderators related to measurement and sample characteristics. We found that rater type, behavior dimension (e.g., aggression), time between longitudinal measurement points, age of the sample, and percentage male of the sample moderated the relation between reading and behavior. Whether the reading assessment measured comprehension or word reading and socioeconomic status of the sample did not moderate the relation. Understanding the association between reading and externalizing behavior has implications for disability identification and intervention practices for children in elementary school. Future research should examine shared cognitive factors and environmental influences that explain the relation between the constructs.
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Reading , Humans , Child , Male , Female , Child, Preschool , Dyslexia/physiopathology , Problem Behavior/psychologyABSTRACT
Most Escherichia coli isolates from humans do not utilize D-sucrose as a substrate for fermentation or growth. Previous work has shown that the Csc pathway allows some E. coli to utilize sucrose for slow growth, and this pathway has been engineered in E. coli W strains to enhance use of sucrose as a feedstock for industrial applications. An alternative sucrose utilization pathway, Scr, was first identified in Klebsiella pneumoniae and has been reported in some E. coli and Salmonella enterica isolates. We show here that the Scr pathway is native to an important subset of E. coli phylogroup B2 lineages that lack the Csc pathway but grow rapidly on sucrose. Laboratory E. coli strains derived from MG1655 (phylogroup A, ST10) are unable to utilize sucrose and lack the scr and csc genes, but a recombinant plasmid-borne scr locus enables rapid growth on and fermentation of sucrose. Genome analyses of Enterobacteriaceae indicate that the scr locus is widespread in other Enterobacteriaceae; including Enterobacter and Klebsiella species, and some Citrobacter and Proteus species. In contrast, the Csc pathway is limited mostly to E. coli, some Shigella species (in which csc loci are rendered non-functional by various mutations), and Citrobacter freundii. The more efficient Scr pathway likely has greater potential than the Csc pathway for bioindustrial applications of E. coli and other Enterobacteriaceae using sucrose as a feedstock.
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BACKGROUND: Traumatologists are unable to predict hip instability based on CT scans and standard radiographs in posterior wall (PW) fractures comprising <50-60 % of the wall, necessitating an examination under anesthesia (EUA). Risk factors for instability have not been clarified, but acetabular dysplasia has been theorized as a potential etiology. Unfortunately, dysplasia is difficult to evaluate in the traumatic setting. The purpose of this study was to compare acetabular morphology between unstable and stable fractures with a novel method to detect dysplasia. METHODS: Patients ≥ 18 years old with a PW fracture that underwent an EUA from 2013 to 2023 were retrospectively identified. For our experimental measurements, the axial distances on CT between the acetabular dome, lateral acetabular opening, and femoral head vertex were recorded. Acetabular geometry was quantified at these levels. Conventional dysplasia metrics (e.g., Tonnis angle) were obtained. Variables were compared between stable and unstable fractures. RESULTS: 58 patients met inclusion criteria with 42 stable versus 16 unstable fractures. Unstable fractures had higher distances between the acetabular dome and femoral head vertex (p > 0.05). They had more cranial fracture exit points (p = 0.0015), lower femoral head coverage (p = 0.0102), and lower posterior acetabular sector angles (p = 0.0281). No other differences in acetabular geometry, demographics, injury characteristics, or other markers of dysplasia were identified. CONCLUSIONS: Unstable hips demonstrated a more recessed acetabular dome when compared to stable hips. Posterior acetabular femoral head coverage and cranial fracture exit point may be related to hip instability. A larger sample size is needed to validate these findings.
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Acetabulum , Tomography, X-Ray Computed , Humans , Acetabulum/diagnostic imaging , Acetabulum/injuries , Male , Female , Retrospective Studies , Middle Aged , Adult , Joint Instability/diagnostic imaging , Joint Instability/physiopathology , Hip Dislocation/diagnostic imaging , Hip Dislocation/pathology , Hip Fractures/diagnostic imaging , Hip Fractures/pathology , Aged , Risk Factors , Femur Head/diagnostic imaging , Femur Head/pathologyABSTRACT
OBJECTIVE: We have previously shown that the anti-cancer peptide PNC-27 kills cancer cells by co-localizing with membrane-expressed HDM-2, resulting in transmembrane pore formation causing extrusion of intracellular contents. We have also observed cancer cell mitochondrial disruption in PNC-27-treated cancer cells. Our objectives are to determine: 1. if PNC-27 binds to the p53 binding site of HDM-2 (residues 1-109) in the cancer cell membrane and 2. if this peptide causes selective disruption of cancer cell mitochondria. METHODS: For aim 1, we incubated MIA-PaCa-2 human pancreatic carcinoma cells with PNC-27 in the presence of a monoclonal antibody against the amino terminal p53 binding site of HDM-2 to determine if it, but not negative control immune serum, blocks PNC-27-induced tumor cell necrosis. For the second aim, we incubated these cells with PNC-27 in the presence of two specific dyes that highlight normal organelle function: mitotracker for mitochondria and lysotracker for lysosomes. We also performed immuno-electron microscopy (IEM) with gold-labeled anti-PNC-27 antibody on the mitochondria of these cells treated with PNC-27. RESULTS: Monoclonal antibody to the p53 binding site of HDM-2 blocks PNC-27-induced cancer cell necrosis, whereas negative control immune serum does not. The mitochondria of PNC-27-treated cancer cells fail to retain mitotracker dye while their lysosomes retain lysotracker dye. IEM of the mitochondria cancer cells reveals gold particles present on the mitochondrial membranes. CONCLUSIONS: PNC-27 binds to the p53 binding site of HDM-2 (residues 1-109) inducing transmembrane pore formation and cancer cell necrosis. Furthermore, this peptide enters cancer cells and binds to the membranes of mitochondria, resulting in their disruption.
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Cell Membrane , Mitochondrial Membranes , Proto-Oncogene Proteins c-mdm2 , Humans , Cell Membrane/metabolism , Cell Membrane/drug effects , Mitochondrial Membranes/metabolism , Mitochondrial Membranes/drug effects , Proto-Oncogene Proteins c-mdm2/metabolism , Cell Line, Tumor , Tumor Suppressor Protein p53/metabolism , Antineoplastic Agents/pharmacology , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondria/pathology , Peptide Fragments/metabolism , Peptide Fragments/pharmacology , Protein Binding/drug effects , Peptides/pharmacology , Peptides/metabolism , NecrosisABSTRACT
INTRODUCTION: Early operative intervention in orthopaedic injuries is associated with decreased morbidity and mortality. Relevant process measures (e.g. femoral shaft fixation <24 hours) are used in trauma quality improvement programs to evaluate performance. Currently, there is no mechanism to account for patients who are unable to undergo surgical intervention (i.e. physiologically unstable). We characterized the factors associated with patients who did not meet these orthopaedic process measures. METHODS: A retrospective cohort study of patients from 35 ACS-COT verified Level 1 and Level 2 trauma centers was performed utilizing quality collaborative data (2017-2022). Inclusion criteria were adult patients (≥18 years), ISS ≥5, and a closed femoral shaft or open tibial shaft fracture classified via the Abbreviated Injury Scale version 2005 (AIS2005). Relevant factors (e.g. physiologic) associated with a procedural delay >24 hours were identified through a multivariable logistic regression and the effect of delay on inpatient outcomes was assessed. A sub-analysis characterized the rate of delay in "healthy patients". RESULTS: We identified 5,199 patients with a femoral shaft fracture and 87.5% had a fixation procedure, of which 31.8% had a delay, and 47.1% of those delayed were "healthy." There were 1,291 patients with an open tibial shaft fracture, 92.2% had fixation, 50.5% had an irrigation and debridement and 11.2% and 18.7% were delayed, respectively. High ISS, older age and multiple medical comorbidities were associated with a delay in femur fixation, and those delayed had a higher incidence of complications. CONCLUSIONS: There is a substantial incidence of surgical delays in some orthopaedic trauma process measures that are predicted by certain patient characteristics, and this is associated with an increased rate of complications. Understanding these factors associated with a surgical delay, and effectively accounting for them, is key if these process measures are to be used appropriately in quality improvement programs. LEVEL OF EVIDENCE: Level III; Therapeutic/Care Management.
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BACKGROUND: Risk factors of acute compartment syndrome (ACS) of the leg include tibial fractures followed by soft tissue injuries. METHODS: Data collected from the National Trauma Data Bank (NTDB) between 2017 and 2019 were analyzed for adult patients with lower extremity fractures, including proximal tibia, tibial shaft, and distal tibia. The primary outcome was a diagnosis of ACS. RESULTS: There were 1052/220,868 patients with lower extremity fractures with a concomitant diagnosis of compartment syndrome. Our study has shown that patients with a BMI of ≥30 had a lower incidence of compartment syndrome when compared with patients with a BMI of 25-29 and controlled for fracture type. Increased age ≥55 in males, and females between 65 and 84, also demonstrated a decreased risk. Proximal tibial fractures (n â= â54,696) were significantly associated with ACS compared to midshaft (n â= â42,153) and distal (n â= â100,432), p â< â0.0001. CONCLUSION: We found that being overweight decreases risk for development of compartment syndrome in patients with lower extremity fractures. This big data study aids in establishing risk factors for development of ACS in adult trauma patients.
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Compartment Syndromes , Databases, Factual , Obesity , Tibial Fractures , Humans , Male , Female , Compartment Syndromes/epidemiology , Compartment Syndromes/etiology , Compartment Syndromes/diagnosis , Middle Aged , Aged , Adult , Obesity/complications , Obesity/epidemiology , Risk Factors , Age Factors , Aged, 80 and over , Tibial Fractures/epidemiology , Tibial Fractures/complications , United States/epidemiology , Incidence , Lower Extremity/injuries , Retrospective StudiesABSTRACT
PURPOSE: To review outcomes of spinopelvic dissociation treated with open lumbopelvic fixation. METHODS: We reviewed all cases of spinopelvic dissociation treated at three Level-I trauma centers with open lumbopelvic fixation, including those with adjunctive percutaneous fixation. We collected demographic data, associated injuries, pre- and postoperative neurologic status, pre- and postoperative kyphosis, and Roy-Camille classification. Outcomes included presence of union, reoperation rates, and complications involving hardware or wound. RESULTS: From an initial cohort of 260 patients with spinopelvic dissociation, forty patients fulfilled inclusion criteria with a median follow-up of 351 days. Ten patients (25%) had a combination of percutaneous iliosacral and open lumbopelvic repair. Average pre- and postoperative kyphosis was 30 degrees and 26 degrees, respectively. Twenty patients (50%) had neurologic deficit preoperatively, and eight (20%) were unknown or unable to be assessed. All patients presenting with bowel or bladder dysfunction (n = 12) underwent laminectomy at time of surgery, with 3 patients (25%) having continued dysfunction at final follow-up. Surgical site infection occurred in four cases (10%) and wound complications in two (5%). All cases (100%) went on to union and five patients (13%) required hardware removal. CONCLUSION: Open lumbopelvic fixation resulted in a high union rate in the treatment of spinopelvic dissociation. Approximately 1 in 6 patients had a wound complication, the majority of which were surgical site infections. Bowel and bladder dysfunction at presentation were common with the majority of cases resolving by final follow-up when spinopelvic dissociation had been treated with decompression and stable fixation.
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Fracture Fixation, Internal , Lumbar Vertebrae , Humans , Male , Female , Adult , Middle Aged , Lumbar Vertebrae/surgery , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/methods , Spinal Fractures/surgery , Pelvic Bones/injuries , Pelvic Bones/surgery , Reoperation/statistics & numerical data , Retrospective Studies , Treatment Outcome , Kyphosis/surgery , Kyphosis/etiology , Postoperative Complications/etiology , Young Adult , Laminectomy/adverse effects , Laminectomy/methods , Surgical Wound Infection/etiology , AgedABSTRACT
Multiple myeloma (MM) is an osteolytic malignancy that is incurable due to the emergence of treatment resistant disease. Defining how, when and where myeloma cell intrinsic and extrinsic bone microenvironmental mechanisms cause relapse is challenging with current biological approaches. Here, we report a biology-driven spatiotemporal hybrid agent-based model of the MM-bone microenvironment. Results indicate MM intrinsic mechanisms drive the evolution of treatment resistant disease but that the protective effects of bone microenvironment mediated drug resistance (EMDR) significantly enhances the probability and heterogeneity of resistant clones arising under treatment. Further, the model predicts that targeting of EMDR deepens therapy response by eliminating sensitive clones proximal to stroma and bone, a finding supported by in vivo studies. Altogether, our model allows for the study of MM clonal evolution over time in the bone microenvironment and will be beneficial for optimizing treatment efficacy so as to significantly delay disease relapse.
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Multiple Myeloma , Humans , Bone and Bones/pathology , Chronic Disease , Drug Resistance , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/genetics , Tumor MicroenvironmentABSTRACT
ABSTRACT: Gun violence is an epidemic throughout the United States and is increasing around the world-it is a public health crisis. The impact of gun violence is not limited to the victims (our patients); it also extends to the physicians and caregivers who are taking care of these patients every day. Even more broadly, gun violence affects those living and going to work in potentially dangerous environments. The "vicarious trauma" that is experienced in these situations can have long-term effects on physicians, nurses, and communities. Importantly, socioeconomic disparities and community deprivation strongly correlate with gun violence. Systemic factors that are deeply ingrained in our society can increase concerns for these underrepresented patient populations and cause increased stressors with substantial health consequences, including delayed fracture-healing and poorer overall health outcomes. It is incumbent on us as physicians to take an active role in speaking up for our patients. The importance of advocacy efforts to change policy (not politics) and continue to push for improvement in the increasingly challenging environments in which patients and physicians find themselves cannot be overstated. Multiple national organizations, including many orthopaedic and general surgery associations, have made statements advocating for change. The American College of Surgeons, in collaboration with many other medical organizations, has supported background checks, registration, licensure, firearm education and training, safe storage practices, red flag laws, addressing mental health issues, and more research to better inform an approach going forward and to address the root causes of violence. We encourage the orthopaedic surgery community to stand together to protect each other and our patients, both physically and mentally, with agreement on these principles.
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BACKGROUND: Despite the increased risk of attrition for women and minority residents during orthopaedic residency, there is currently a paucity of research examining the training environment of these residents. To address this, we examined how well-being constructs may differ for women or minority residents compared with their peers, and whether these residents report experiencing more mistreatment during residency. QUESTIONS/PURPOSES: (1) How does the psychologic wellbeing of women and minority residents compare with that of their peers regarding the constructs of burnout, lifestyle satisfaction, social belonging, and stereotype threat? (2) Do reported mistreatment experiences during residency differ among women and minority residents compared with their peers? (3) Is there a difference in the proportion of women and minority orthopaedic residents with thoughts of leaving residency compared with their peers? METHODS: Seventeen orthopaedic residency programs in the 91 programs comprising the Collaborative Orthopaedic Educational Research Group agreed to participate in the study. Program directors sent an anonymous one-time survey with two reminders to all orthopaedic residents at their respective institutions. The survey instrument comprised validated and previously used instruments with face validity designed to measure burnout, satisfaction, duty-hour violations, belonging, stereotype threat, mistreatment, and thoughts of leaving residency, in addition to demographic information. Forty-three percent (211 of 491) of residents responded to the survey. Race or ethnicity data were combined into "White" and "underrepresented in orthopaedics" (URiO), which included residents who self-identified as Asian, African American, Hispanic or Latino, Native American, or other, given that these groups are all underrepresented racial and ethnic groups in orthopaedics. The demographic makeup of our study, 81% men and 75% White, is roughly comparable to the current demographic makeup of orthopaedic residency programs, which is 82% men and 74% White. Data were analyzed using chi-square tests, Fisher exact tests, and t-tests as appropriate. For comparisons of Likert scale measures, we used an anchor-based approach to determining the minimum detectable change (MDC) and set the MDC as a 1-point difference on a 5-point scale and a 1.5-point difference on a 7-point scale. Stereotype threat is reported as the mean âµ from the neutral response, and âµ of 1.5 or greater was considered significant. RESULTS: Women residents were more likely than men to report experiencing emotional exhaustion (odds ratio 2.18 [95% confidence interval 1.1 to 4.5]; p = 0.03). Women reported experiencing stereotype threat regarding their identity as women surgeons (mean âµ 1.5 ± 1.0). We did not identify a difference in men's and women's overall burnout (OR 1.4 [95% CI 0.7 to 3.0]; p = 0.3), lifestyle satisfaction across multiple domains, or sense of social belonging (men: 4.3, women 3.6; mean difference 0.7 [95% CI 0.4 to 0.9]; p < 0.001). We did not identify differences in overall burnout (OR 1.5 [95% CI 0.8 to 3.0]; p = 0.2), lifestyle satisfaction across multiple domains, sense of social belonging (White: 4.2, URiO: 3.9; mean difference 0.3 [95% CI 0.17 to 0.61]; p < 0.001), or stereotype threat (mean âµ 0.8 ± 0.9) between White and URiO surgeons. Women were more likely than men to report experiencing mistreatment, with 84% (32 of 38) of women and 43% (70 of 164) of men reporting mistreatment at least a few times per year (OR 7.2 [95% CI 2.8 to 18.1]; p < 0.001). URiO residents were more likely than White residents to report experiencing mistreatment overall, with 65% (32 of 49) of URiO residents and 45% (66 of 148) of White residents reporting occurrences at least a few times per year (OR 2.3 [95% CI 1.2 to 4.6]; p = 0.01). Women were more likely than men to report experiencing gender discrimination (OR 52.6 [95% CI 18.9 to 146.1]; p < 0.001), discrimination based on pregnancy or childcare status (OR 4.3 [95% CI 1.4 to 12.8]; p = 0.005), and sexual harassment (OR 11.8 [95% CI 4.1 to 34.3]; p < 0.001). URiO residents were more likely than White residents to report experiencing racial discrimination (OR 7.8 [95% CI 3.4 to 18.2]; p < 0.001). More women than men had thoughts of leaving residency (OR 4.5 [95% CI 1.5 to 13.5]; p = 0.003), whereas URiO residents were not more likely to have thoughts of leaving than White residents (OR 2.2 [95% CI 0.7 to 6.6]; p = 0.1). CONCLUSION: Although we did not detect meaningful differences in some measures of well-being, we identified that women report experiencing more emotional exhaustion and report stereotype threat regarding their identity as women surgeons. Women and URiO residents report more mistreatment than their peers, and women have more thoughts of leaving residency than men. These findings raise concern about some aspects of the training environment for women and URiO residents that could contribute to attrition during training. CLINICAL RELEVANCE: Understanding how well-being and mistreatment affect underrepresented residents helps in developing strategies to better support women and URiO residents during training. We recommend that orthopaedic governing bodies consider gathering national data on resident well-being and mistreatment to identify specific issues and track data over time. Additionally, departments should examine their internal practices and organizational culture to address specific gaps in inclusivity, well-being, and mechanisms for resident support.
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Burnout, Professional , Internship and Residency , Minority Groups , Orthopedics , Physicians, Women , Humans , Female , Burnout, Professional/psychology , Burnout, Professional/epidemiology , Minority Groups/psychology , Male , Physicians, Women/psychology , Adult , Orthopedics/education , Job Satisfaction , Stereotyping , Surveys and Questionnaires , Attitude of Health Personnel , Peer Group , Sex Factors , Orthopedic Surgeons/psychology , Education, Medical, Graduate , Sexism/psychologyABSTRACT
ABSTRACT: Damage-control resuscitation in the care of critically injured trauma patients aims to limit blood loss and prevent and treat coagulopathy by combining early definitive hemorrhage control, hypotensive resuscitation, and early and balanced use of blood products (hemostatic resuscitation) and the use of other hemostatic agents. This clinical protocol has been developed to provide evidence-based recommendations for optimal damage-control resuscitation in the care of trauma patients with hemorrhage.
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Blood Coagulation Disorders , Hemostatics , Surgeons , Wounds and Injuries , Adult , Humans , Hemorrhage/etiology , Hemorrhage/prevention & control , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/therapy , Resuscitation/methods , Clinical Protocols , Wounds and Injuries/complications , Wounds and Injuries/surgeryABSTRACT
Herein we report the first enantioselective total synthesis of (+)-incargranine A, in nine steps. The total synthesis was enabled by an enantioselective intramolecular organocatalysed desymmetrising Michael addition of a malonamate ester to a linked dienone substrate that established pivotal stereocentres with excellent enantio- and complete diastereoselectivity. Furthermore, a key hemiaminal intermediate was accessed by developing an iridium-catalysed reductive cyclisation, and the scope of this transformation was explored to produce a range of bicyclic hemiaminal motifs. Once installed, the hemiaminal motif was used to initiate a biomimetic cascade to access the natural product directly in a single step.
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OBJECTIVES: To describe outcomes following humerus aseptic nonunion surgery in patients whose initial fracture was treated operatively and to identify risk factors for nonunion surgery failure in the same population. DESIGN: Retrospective case series. SETTING: Eight, academic, level 1 trauma centers. PATIENTS SELECTION CRITERIA: Patients with aseptic humerus nonunion (OTA/AO 11 and 12) after the initial operative management between 1998 and 2019. OUTCOME MEASURES AND COMPARISONS: Success rate of nonunion surgery. RESULTS: Ninety patients were included (56% female; median age 50 years; mean follow-up 21.2 months). Of 90 aseptic humerus nonunions, 71 (78.9%) united following nonunion surgery. Thirty patients (33.3%) experienced 1 or more postoperative complications, including infection, failure of fixation, and readmission. Multivariate analysis found that not performing revision internal fixation during nonunion surgery (n = 8; P = 0.002) and postoperative de novo infection (n = 9; P = 0.005) were associated with an increased risk of recalcitrant nonunion. Patient smoking status and the use of bone graft were not associated with differences in the nonunion repair success rate. CONCLUSIONS: This series of previously operated aseptic humerus nonunions found that more than 1 in 5 patients failed nonunion repair. De novo postoperative infection and failure to perform revision internal fixation during nonunion surgery were associated with recalcitrant nonunion. Smoking and use of bone graft did not influence the success rate of nonunion surgery. These findings can be used to give patients a realistic expectation of results and complications following humerus nonunion surgery. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Fractures, Bone , Fractures, Ununited , Humeral Fractures , Humans , Female , Middle Aged , Male , Fractures, Ununited/surgery , Fractures, Ununited/etiology , Retrospective Studies , Fractures, Bone/surgery , Humerus/surgery , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Treatment Outcome , Fracture Healing , Humeral Fractures/etiology , Bone Plates/adverse effectsABSTRACT
Reliable maps of species distributions are fundamental for biodiversity research and conservation. The International Union for Conservation of Nature (IUCN) range maps are widely recognized as authoritative representations of species' geographic limits, yet they might not always align with actual occurrence data. In recent area of habitat (AOH) maps, areas that are not habitat have been removed from IUCN ranges to reduce commission errors, but their concordance with actual species occurrence also remains untested. We tested concordance between occurrences recorded in camera trap surveys and predicted occurrences from the IUCN and AOH maps for 510 medium- to large-bodied mammalian species in 80 camera trap sampling areas. Across all areas, cameras detected only 39% of species expected to occur based on IUCN ranges and AOH maps; 85% of the IUCN only mismatches occurred within 200 km of range edges. Only 4% of species occurrences were detected by cameras outside IUCN ranges. The probability of mismatches between cameras and the IUCN range was significantly higher for smaller-bodied mammals and habitat specialists in the Neotropics and Indomalaya and in areas with shorter canopy forests. Our findings suggest that range and AOH maps rarely underrepresent areas where species occur, but they may more often overrepresent ranges by including areas where a species may be absent, particularly at range edges. We suggest that combining range maps with data from ground-based biodiversity sensors, such as camera traps, provides a richer knowledge base for conservation mapping and planning.
Combinación de censos con fototrampas y mapas de extensión de la UICN para incrementar el conocimiento sobre la distribución de las especies Resumen Los mapas confiables de la distribución de las especies son fundamentales para la investigación y conservación de la biodiversidad. Los mapas de distribución de la Unión Internacional para la Conservación de la Naturaleza (UICN) están reconocidos como representaciones de autoridad de los límites geográficos de las especies, aunque no siempre se alinean con los datos actuales de su presencia. En los mapas recientes de área de hábitat (ADH), las áreas que no son hábitat han sido eliminadas de la distribución de la UICN para reducir los errores de comisión, pero su concordancia con la presencia actual de las especies tampoco ha sido analizada. Analizamos la concordancia entre la presencia registrada por los censos de fototrampas y pronosticamos la presencia a partir de los mapas de la UICN y de ADH de 510 especies de mamíferos de talla mediana a grande en 80 áreas de muestreo de fototrampas. Las cámaras detectaron sólo el 39% de las especies esperadas con base en la distribución de la UICN y los mapas de ADH en todas las áreas; el 85% de las disparidades con la UICN ocurrieron dentro de los 200 km a partir del borde de la distribución. Sólo el 4% de la presencia de las especies fue detectada por las cámaras ubicadas fuera de la distribución de la UICN. La probabilidad de disparidad entre las cámaras y la UICN fue significativamente mayor para los mamíferos de talla pequeña y para los especialistas de hábitat en las regiones Neotropical e Indomalaya y en áreas con doseles forestales más bajos. Nuestros hallazgos sugieren que los mapas de distribución y ADH pocas veces subrepresentan las áreas con presencia de las especies, pero con frecuencia pueden sobrerrepresentar la distribución al incluir áreas en donde las especies pueden estar ausentes, en particular los bordes de la distribución. Sugerimos que la combinación de los mapas de distribución con los sensores de biodiversidad en tierra, como las fototrampas, proporciona una base más rica de conocimiento para el mapeo y la planeación de la conservación.
ABSTRACT
Background Chronic liver diseases account for approximately 1.9 million deaths globally every year and negatively affect health-related quality of life. Early detection of liver disease may enable timely treatment, potentially improving patient outcomes. This study aimed to determine the prevalence and determinants of liver steatosis and fibrosis in US adults with no previously diagnosed liver condition. Methods We conducted an observational, nationally representative, cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) conducted from January 2017 to March 2020. Study participants were 7,391 adults aged 21 and older with no history of diagnosed liver disorders who underwent vibration-controlled transient elastography (VCTE) to determine liver steatosis and fibrosis. Controlled attenuation parameter (CAP) values between 248 and 267 dB/m were classified as mild steatosis, and those over 267 dB/m as advanced steatosis. Liver stiffness measurement (LSM) values between 7.65 and 13 kPa were classified as moderate/severe fibrosis, and those over 13 kPa as cirrhosis. Covariates included age, sex, race, body mass index (BMI), diabetes mellitus, kidney disease, smoking history, alcohol intake, alanine aminotransferase (ALT), aspartate aminotransferase (AST), physical activity, sedentary time, and sleep time. The associations of subject characteristics with liver CAP and LSM were evaluated using survey multivariable linear regression. Shapley Additive Explanations values determined the relative importance of each attribute in the model. The discriminative performance of classification models was assessed using the area under the receiver operating characteristic (AUROC) curve. Results The population prevalence of liver steatosis was 57.2% (10.2% mild; 47.0% advanced). The relative importance of covariates in predicting liver CAP was 63.1% for BMI, 10.7% for ALT, and less than 10% for the other covariates. The prevalence of significant fibrosis was 11.4% (8.3% moderate/severe fibrosis; 3.1% cirrhosis). The relative importance of covariates in predicting LSM was 67.3% for BMI and less than 10% for the other covariates. BMI alone demonstrated acceptable discriminative performance in classifying varying severities of steatosis and fibrosis (AUROC range 72%-78%) at cutoffs between 28 and 33 kg/m2. Conclusions Undiagnosed chronic liver disease based on VCTE findings is highly prevalent among US adults, particularly in obese individuals. Efforts to increase awareness about liver disease and to reconsider existing BMI thresholds for liver disease screening may be warranted.
ABSTRACT
BACKGROUND: The increasing incidence of Plasmodium knowlesi malaria poses a significant challenge to efforts to eliminate malaria from Malaysia. Macaque reservoirs, outdoors-biting mosquitoes, human activities, and agricultural work are key factors associated with the transmission of this zoonotic pathogen. However, gaps in knowledge regarding reasons that drive malaria persistence in rural Kudat, Sabah, Northern Borneo remain. This study was conducted to address this knowledge gap, to better understand the complexities of these entangled problems, and to initiate discussion regarding new countermeasures to address them. This study aims to highlight rural community members' perspectives regarding inequities to health relating to P. knowlesi malaria exposure. METHODS: From January to October 2022, a study using qualitative methods was conducted in four rural villages in Kudat district of Sabah, Malaysia. A total of nine in-depth interviews were conducted with community and faith leaders, after the completion of twelve focus group discussions with 26 photovoice participants. The interviews were conducted using the Sabah Malay dialect, audio-recorded, transcribed, and translated into English. The research team led the discussion and analysis, which was approved by participants through member checking at the community level. RESULTS: Participants identified disparity in health as a key issue affecting their health and livelihoods. Injustice in the social environment was also identified as a significant challenge, including the importance of listening to the voices of affected communities in disentangling the social and economic phenomena that can impact malaria control. Specific concerns included inadequate access to health-related resources and degradation of the environment. Participants recommended improving access to water and other necessities, increasing the availability of malaria control commodities in healthcare facilities, and developing sustainable programs to reduce socioeconomic disparities. CONCLUSION: Inequities to health emerged as a key concern for malaria control in rural Kudat, Sabah. A locally targeted malaria programme cantered on improving the social and economic disparities associated with health outcomes, could be a potential strategy for malaria prevention in such areas. Community-level perspectives gathered from this study can be used as a foundation for future discussions and dialogues among policymakers and community members for achieving greater transparency, improving social equity, and interoperability in addressing P. knowlesi malaria control.