Inclusion as a multi-level concept.

Research on inclusion has proliferated in the last twenty years yielding over 188 articles [1] as both academics and practitioners have come to recognize that inclusion provides an opportunity for people of different backgrounds and identities to work together successfully. Inclusion research is wide-ranging and includes multiple actors from different levels of an organization. Studies of inclusion climate, leader inclusion, workgroup inclusion and interpersonal inclusion are reviewed as these inclusionary approaches help to create environments where employees feel like they belong and are valued for their uniqueness [2]. We highlight recent trends in the inclusion literature that intersect with diversity.

Real world impact of emicizumab & immunosuppression on Acquired Hemophilia A: A Multicenter US Cohort.

Acquired Hemophilia A (AHA) is an autoimmune bleeding disorder from anti-factor VIII (FVIII) antibodies with high morbidity and mortality due to bleeding and complications from immunosuppression (IST). To address the real-world implications of the FVIII mimetic antibody, emicizumab, and the role of IST, we retrospectively collected deidentified data on 62 AHA patients treated with off label emicizumab for a median of 10 weeks at 12 US hemophilia treatment centers. Most patients (95.2%) had acute bleeding at diagnosis with 62.9% having partial or no control of bleeds despite use of hemostatic agents at the time emicizumab was started. The main reason for initiating emicizumab was outpatient bleeding prophylaxis. After initiation of emicizumab, 87.1% had no additional bleeds. There were 6 breakthrough bleeds (2 spontaneous) in 5 patients and no fatal bleeding events on maintenance emicizumab. The mean breakthrough bleed rate per patient-week was 0.02 (95% CI 0.0 - 0.03) during the first 12 weeks of emicizumab for the 55 patients with at least 12 weeks of follow up. Of these patients, 92.7% received IST with 74.5% given rituximab-based regimens. Complete resolution of inhibitor and normalization of FVIII levels occurred in 56% overall and 63% of the patients treated with rituximab. Overall, the median time to discontinue emicizumab and IST was 18 weeks. Two patients had thrombotic events on emicizumab, but no adverse events were attributed to emicizumab and there were no infections due to IST. Emicizumab provides effective outpatient bleeding prophylaxis for AHA, and concurrent IST may further mitigate bleeding.

Prediction of pancreatic cancer in patients with new onset hyperglycemia: A modified ENDPAC model.

BACKGROUND/OBJECTIVES: The Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) model relies primarily on fasting glucose values. Health systems have increasingly shifted practice towards use of glycated hemoglobin (HbA1c) measurement. We modified the ENDPAC model using patients with new onset hyperglycemia. METHODS: Four cohorts of patients 50-84 years of age with HbA1c results ≥6.2-6.5 % in 2011-2018 were identified. A combine cohort was formed. A widened eligibility criterion was applied to form additional four individual cohorts and one combined cohort. The primary outcome was the diagnosis of pancreatic cancer within 3 years after the first elevated HbA1c testing. The performance of the modified ENDPAC model was evaluated by AUC, sensitivity, positive predictive value, cases detected, and total number of patients screened. RESULTS: The individual and combined cohorts consisted of 39,001-79,060 and 69,334-92,818 patients, respectively (mean age 63.5-65.0 years). The three-year PC incidence rates were 0.47%-0.54 %. The AUC measures were in the range of 0.75-0.77 for the individual cohorts and 0.75 for the combined cohorts. When the four individual cohorts were combined, more PC cases can be identified (149 by the combined vs. 113-116 by individual cohorts when risk score was 5+). Performance measures were compromised in nonwhites. Asian and Pacific islanders had lower sensitivity compared to other racial and ethnic groups (29 % vs. 50-60 %) when risk score was 5+. CONCLUSIONS: The modified ENDPAC model targets a broader population and thus identifies more high-risk patients for cancer screening. The differential performance needs to be considered when the model is applied to non-white population.

Third eyelid cartilage eversion in an adult mare.

PURPOSE: To describe the first report of third eyelid cartilage eversion in an adult American Quarter Horse mare. CASE PRESENTATION: A 22-year-old American Quarter Horse mare presented to the University of Missouri Veterinary Health Center Equine Hospital for a 2-week history of a third eyelid cartilage abnormality of the left eye with no known recent trauma. Complete ophthalmic examination revealed third eyelid cartilage eversion of the left nictitans. The abnormal scrolled cartilage was surgically excised using a handheld cautery unit and submitted for histopathologic evaluation. RESULTS: Histopathologic findings displayed normal third eyelid cartilage, without evidence of neoplasia or inflammation. Mucosal hyperplasia and increased vascularity of the submucosa were observed. The horse healed well after electrocautery excision and normal third eyelid conformation was restored. CONCLUSION: To the authors' knowledge, this is the first report of an acquired, presumed spontaneous, third eyelid cartilage eversion in a horse.

Evaluation and Surgical Management of Pediatric Cutaneous Melanoma and Atypical Spitz and Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children's Oncology Group.

PURPOSE: The purpose of this study was to develop recommendations for the diagnostic evaluation and surgical management of cutaneous melanoma (CM) and atypical Spitz tumors (AST) and non-Spitz melanocytic tumors (melanocytomas) in pediatric (age 0-10 years) and adolescent (age 11-18 years) patients. METHODS: A Children's Oncology Group-led panel with external, multidisciplinary CM specialists convened to develop recommendations on the basis of available data and expertise. RESULTS: Thirty-three experts from multiple specialties (cutaneous/medical/surgical oncology, dermatology, and dermatopathology) established recommendations with supporting data from 87 peer-reviewed publications. RECOMMENDATIONS: (1) Excisional biopsies with 1-3 mm margins should be performed when feasible for clinically suspicious melanocytic neoplasms. (2) Definitive surgical treatment for CM, including wide local excision and sentinel lymph node biopsy (SLNB), should follow National Comprehensive Cancer Network Guidelines in the absence of data from pediatric-specific surgery trials and/or cohort studies. (3) Accurate classification of ASTs as benign or malignant is more likely with immunohistochemistry and next-generation sequencing. (4) It may not be possible to classify some ASTs as likely/definitively benign or malignant after clinicopathologic and/or molecular correlation, and these Spitz tumors of uncertain malignant potential should be excised with 5 mm margins. (5) ASTs favored to be benign should be excised with 1- to 3-mm margins if transected on biopsy. (6) Re-excision is not necessary if the AST does not extend to the biopsy margin(s) when complete/excisional biopsy was performed. (7) SLNB should not be performed for Spitz tumors unless a diagnosis of CM is favored on clinicopathologic evaluation. (8) Non-Spitz melanocytomas have a presumed increased risk for progression to CM and should be excised with 1- to 3-mm margins if transected on biopsy. (9) Re-excision of non-Spitz melanocytomas is not necessary if the lesion is completely excised on biopsy.

MISIP: a data standard for the reuse and reproducibility of any stable isotope probing-derived nucleic acid sequence and experiment.

DNA/RNA-stable isotope probing (SIP) is a powerful tool to link in situ microbial activity to sequencing data. Every SIP dataset captures distinct information about microbial community metabolism, process rates, and population dynamics, offering valuable insights for a wide range of research questions. Data reuse maximizes the information derived from the labor and resource-intensive SIP approaches. Yet, a review of publicly available SIP sequencing metadata showed that critical information necessary for reproducibility and reuse was often missing. Here, we outline the Minimum Information for any Stable Isotope Probing Sequence (MISIP) according to the Minimum Information for any (x) Sequence (MIxS) framework and include examples of MISIP reporting for common SIP experiments. Our objectives are to expand the capacity of MIxS to accommodate SIP-specific metadata and guide SIP users in metadata collection when planning and reporting an experiment. The MISIP standard requires 5 metadata fields-isotope, isotopolog, isotopolog label, labeling approach, and gradient position-and recommends several fields that represent best practices in acquiring and reporting SIP sequencing data (e.g., gradient density and nucleic acid amount). The standard is intended to be used in concert with other MIxS checklists to comprehensively describe the origin of sequence data, such as for marker genes (MISIP-MIMARKS) or metagenomes (MISIP-MIMS), in combination with metadata required by an environmental extension (e.g., soil). The adoption of the proposed data standard will improve the reuse of any sequence derived from a SIP experiment and, by extension, deepen understanding of in situ biogeochemical processes and microbial ecology.

Postpartum Management of Hypertensive Disorders of Pregnancy in Six Large U.S. Hospital Systems: Descriptive Review and Identification of Clinical and Research Gaps.

Hypertensive disorders of pregnancy (HDPs) are a key contributor to maternal morbidity and mortality. Several gaps in knowledge remain regarding best practices in the postpartum management of HDPs. In this review, we describe postpartum HDPs management among six large academic U.S. hospital systems: Medical College of Wisconsin, University of Pittsburgh, University of Wisconsin-Madison, Northwestern University, University of Minnesota, and Boston Medical Center. We identified that all six health systems discharge patients with HDPs diagnosed with a blood pressure (BP) cuff and use the same two antihypertensive medications, nifedipine and labetalol, as first- and second-line treatment of HDPs. Northwestern University routinely adds oral furosemide for 5 days for patients with BP that exceeds 150/100 mm Hg. Most hospital systems administer magnesium sulfate routinely when readmission for HDPs occurs. In contrast, there was variation in BP threshold for antihypertensive treatment initiation, use of remote BP monitoring program, use of a transition clinic, delivery or lack of education on long-term cardiovascular disease risk, and BP management through the first 6 weeks postpartum and beyond. Based on the clinical review, we identified clinical gaps and formulated considerations for research priorities in the field of postpartum HDPs management. KEY POINTS: · Several gaps in knowledge remain regarding best practices in postpartum management of HDPs.. · There is a variation in the BP threshold for antihypertensive treatment initiation.. · Data are lacking on the reduction in severe maternal morbidity (SMM) and racial disparities in SMM with remote monitoring..

Birth outcomes following bictegravir exposure during pregnancy.

OBJECTIVE: Bictegravir is increasingly prescribed as a co-formulated tablet with tenofovir alafenamide and emtricitabine to pregnant persons with HIV (PWH) despite limited pregnancy and birth outcome data. We sought to provide birth outcome data following exposure to bictegravir during pregnancy. DESIGN: We conducted a descriptive analysis of infants born to pregnant PWH 18-45 years of age enrolled in at least one Pediatric HIV/AIDS Cohort Study (PHACS)-affiliated study who received bictegravir for ≥7 days during pregnancy and completed follow-up through delivery. METHODS: The outcomes of interest were gestational age at birth, preterm birth (<37 weeks' gestation), gestational-age adjusted birth weight (BWZ) and length (BLZ) z-scores, small for gestational age (SGA, birthweight <10th percentile), congenital anomalies, neonatal deaths in the first 28 days of life, and infant HIV status. RESULTS: A total of 177 infants born to 170 unique PWH were exposed to bictegravir for ≥7 days during gestation; 55% were exposed to bictegravir from the time of conception. Median gestational age at birth was 38.1 weeks. The prevalence of preterm birth was 15.8% and SGA was 9.3%. Mean BWZ and BLZ were -0.48 and 0.03. No neonatal deaths or perinatal HIV transmissions were reported. Among 126 infants exposed to first-trimester bictegravir, 7 (5.6%) had major congenital anomalies with no specific pattern suggestive of a syndrome. CONCLUSIONS: These findings provide preliminary data without significant safety concerns for fetal bictegravir exposure in this United States cohort. Comparative data and continued surveillance of outcomes among infants exposed to bictegravir during gestation are warranted.

Oxysterol binding protein regulates the resolution of TLR-induced cytokine production in macrophages.

Toll-like receptors (TLRs) on macrophages sense microbial components and trigger the production of numerous cytokines and chemokines that mediate the inflammatory response to infection. Although many of the components required for the activation of the TLR pathway have been identified, the mechanisms that appropriately regulate the magnitude and duration of the response and ultimately restore homeostasis are less well understood. Furthermore, a growing body of work indicates that TLR signaling reciprocally interacts with other fundamental cellular processes, including lipid metabolism but only a few specific molecular links between immune signaling and the macrophage lipidome have been studied in detail. Oxysterol-binding protein (Osbp) is the founding member of a family of lipid-binding proteins with diverse functions in lipid sensing, lipid transport, and cell signaling but its role in TLR responses is not well defined. Here, we demonstrate that altering the state of Osbp with its natural ligand, 25-hydroxycholesterol (25HC), or pharmacologically, sustains and thereby amplifies Tlr4-induced cytokine production in vitro and in vivo. CRISPR-induced knockdown of Osbp abrogates the ability of these ligands to sustain TLR responses. Lipidomic analysis suggested that the effect of Osbp on TLR signaling may be mediated by alterations in triglyceride production and treating cells with a Dgat1 inhibitor, which blocks triglyceride production and completely abrogates the effect of Osbp on TLR signaling. Thus, Osbp is a sterol sensor that transduces perturbations of the lipidome to modulate the resolution of macrophage inflammatory responses.

Post-Dobbs Abortion Restrictions and the Families They Leave Behind.

The June 24, 2022 US Supreme Court decision in Dobbs v Jackson Women's Health Organization resulted in an expansive restriction on abortion access that had been constitutionally guaranteed for nearly half a century. Currently, 14 states have implemented complete bans on abortion with very limited exceptions, and an additional 7 states have implemented abortion bans at 6 to 18 weeks' gestation. It has been well demonstrated that restrictive policies disproportionately limit abortion access for minoritized people and people of low socioeconomic status; the financial and geographic barriers of these post-Dobbs restrictions will only exacerbate this disparity. Proponents of abortion restrictions, who identify as pro-life, assert that these policies are essential to protect children, women, and families. We examine whether the protection of these groups extends past conception by evaluating the association between state abortion legislation and state-based policies and programs designed to provide medical and social support for children, women, and families. We found that states with the most restrictive post-Dobbs abortion policies in fact have the least comprehensive and inclusive public infrastructure to support these groups. We suggest further opportunities for advocacy. (Am J Public Health. 2024;114(10):1043-1050. https://doi.org/10.2105/AJPH.2024.307792).

Tumor-infiltrating lymphocytes in necrotic tumors after melanoma neoadjuvant anti-PD1 therapy correlate with pathological response and recurrence-free survival.

PURPOSE: Neoadjuvant anti-PD1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TILs), and more TILs are associated with better treatment response. A major pathological response (MPR) in melanoma after neoadjuvant anti-PD1 therapy usually comprises tumor necrosis and fibrosis. The role of TILs in necrotic tumor necrosis (nTILs) has not been explored. EXPERIMENTAL DESIGN: We performed CD3 and CD8 immunohistochemical stains on 41 melanomas with geographic necrosis. 14 were immunotherapy-naïve, and 27 had been treated with one dose of neoadjuvant anti-PD-1 in two clinical trials. CD3+ and CD8+ nTILs were graded as absent/minimal or moderate/brisk. The percentage of necrotic areas in the tumor bed before and after treatment was quantified. Endpoints were MPR and 5-year recurrence-free survival (RFS). RESULTS: In the immunotherapy-naïve cohort, 3/14 (21%) specimens had moderate/brisk CD3+, and 2/14 (14%) had moderate/brisk CD8+ nTILs. In the treated cohort, 16/27 (59%) specimens had moderate/brisk CD3+, and 15/27 (56%) had moderate/brisk CD8+ nTILs, higher than the naïve cohort (CD3, p=0.046; CD8, p=0.018). Tumor necrosis was significantly increased after anti-PD1 therapy (p=0.007). In the treated cohort, moderate/brisk CD3+ and CD8+ nTILs correlated with MPR (p=0.042, p=0.019, respectively). Treated patients with moderate/brisk CD3+ nTILs had higher 5-year RFS than those with absent/minimal nTILs (69% versus 0%; p=0.006). This persisted on multivariate analysis (HR 0.16, 95% CI 0.03-0.84, p=0.03), adjusted for pathologic response, which was borderline significant (HR 0.26, 95% CI 0.07-1.01, p=0.051). CONCLUSIONS: CD3+ and CD8+ nTILs are associated with pathological response and 5-year RFS in melanoma patients after neoadjuvant anti-PD1 therapy.

Design and implementation of a Type-2 hybrid, prospective randomized trial of opioid agonist therapies integration into primary care clinics in Ukraine.

INTRODUCTION: Ukraine has high HIV prevalence, concentrated among people who inject drugs (PWID), mostly of opioids. Maintenance on opioid agonist therapies (OAT) is the most effective evidence-based treatment for opioid use disorder. As PWID experience high morbidity and mortality from preventable and treatable non-communicable diseases, international agencies recommend integrating OAT into primary care centers (PCC). METHODS: A randomized, type-2 hybrid implementation trial was carried out to compare outcomes of OAT integration in PCC to OAT delivery at specialty treatment centers (STC) - standard-of-care. Tele-education supporting PCC providers in managing OAT, HIV, tuberculosis and non-communicable diseases along with pay-for-performance incentives were used to facilitate implementation. Consenting patients underwent 1:2 randomization to either STC or PCC. Quality health indicators (QHIs), a composite percentage of recommended primary and specialty services accessed by patients (blood/urine tests, cancer screenings, etc.), were defined as efficacy outcomes and were assessed by participant self-report at baseline and every 6 months over 24 months and electronic chart reviews after the completion of the follow-up. The primary outcome is defined as the difference in composite QHI scores at 24 months, in which a repeated measures likelihood-based mixed model with missing at random assumptions will be used. Providers at PCC completed surveys at baseline, 12 and 24 months to assess implementation outcomes including changes in stigma and attitudes towards OAT and PWID. PRELIMINARY RESULTS: Among the 1459 participants allocated to STC (N = 509) or PCC (N = 950), there were no differences in clinical and demographic characteristics. Self-reported prevalences were available for HIV (42 %), HCV (57 %), and prior tuberculosis (17 %). Study retention at 6, 12, 18, and 24 months was as 91 %, 85 %, 80 %, and 74 %, respectively. CONCLUSION: PWID have a high prevalence of medical comorbidities and integrating OAT into primary care settings has the potential to improve the health of PWID. Findings from this study can help guide implementation of integrated care in Ukraine and throughout similar low-resource, high-burden countries in the Eastern European and Central Asian region.

Review of skin grafting in equine wounds: indications and techniques.

Skin grafting is a simple technique that can be performed by equine practitioners to improve cosmetic outcomes in wounds with large skin defects that would not heal functionally or cosmetically with standard wound therapy interventions. Successful skin grafting is not difficult but relies upon appropriate preparation of the wound bed and effective immobilisation of the grafted area after skin graft placement. Prior to grafting, the wound bed should be treated with a moist wound healing dressing to prepare the granulation tissue bed to receive the graft. For best results, skin grafts should be placed in wounds free of infection with healthy granulation tissue, and motion should be reduced in the graft region in the early postoperative period. When successful, skin grafts cover granulation tissue and encourage wound contraction and epithelialisation while decreasing exuberant granulation tissue resulting in a more cosmetic result. This review will advance practitioners' understanding of skin grafting in horses, including graft classification and techniques, donor site selection, recipient site preparation, postoperative management strategies to optimise graft retention and ongoing research in this field.

A Computational Approach in the Systematic Search of the Interaction Partners of Alternatively Spliced TREM2 Isoforms.

Alzheimer's disease is the most common form of dementia, characterized by the pathological accumulation of amyloid-beta (Aß) plaques and tau neurofibrillary tangles. Triggering receptor expressed on myeloid cells 2 (TREM2) is increasingly recognized as playing a central role in Aß clearance and microglia activation in AD. The TREM2 gene transcriptional product is alternatively spliced to produce three different protein isoforms. The canonical TREM2 isoform binds to DAP12 to activate downstream pathways. However, little is known about the function or interaction partners of the alternative TREM2 isoforms. The present study utilized a computational approach in a systematic search for new interaction partners of the TREM2 isoforms by integrating several state-of-the-art structural bioinformatics tools from initial large-scale screening to one-on-one corroborative modeling and eventual all-atom visualization. CD9, a cell surface glycoprotein involved in cell-cell adhesion and migration, was identified as a new interaction partner for two TREM2 isoforms, and CALM, a calcium-binding protein involved in calcium signaling, was identified as an interaction partner for a third TREM2 isoform, highlighting the potential role of cell adhesion and calcium regulation in AD.

Clinical characteristics associated with problematic pornography use among individuals seeking treatment for opioid use disorder.

Background and Aims: Many jurisdictions are experiencing opioid epidemics. Opioid use disorder (OUD) often co-occurs with other psychiatric disorders including behavioral addictions like gambling disorder. However, little is known regarding the frequency and correlates of problematic pornography use (PPU) among people seeking treatment for OUD. Here we aimed to investigate PPU and its correlates in people seeking OUD treatment. Method: From October 2018 to March 2020, 1,272 individuals seeking OUD treatment were screened for PPU by completing the Brief Pornography Screen (BPS), a 5-item instrument validated for assessing PPU. Self-reported data were used. Results: Among the sample there were 707 (60%) males and 565 (40%) females. The mean age of participants was 37.9 ± 10.5 years (range 18-73), there were 707 (60%) males and 565 (40%) females, 14.4% (n = 183) exhibited low positive BPS scores (1 ≤ score ≤4), and 4.5% of the sample (n = 57) screened positive for PPU (BPS score ≥4). Individuals screening positive for PPU versus negative were mostly male (77%), scored higher on measures of impulsivity in the domains of positive urgency, negative urgency, and sensation-seeking and demonstrated more psychopathology on measures of substance use, psychotic symptoms, emotional lability, depression/functioning and self-harm. Discussion and Conclusion: A minority of individuals seeking treatment for OUD screened positive for PPU. Among individuals with OUD, those screening positive (versus negative) for PPU were more impulsive and experienced more psychiatric symptoms, suggesting the need for additional investigation and screening for and addressing PPU in people with OUD.

Second-Trimester Ultrasound Receipt Mediates the Relationship Between Public Insurance and Prenatal Diagnosis of a Congenital Heart Defect.

OBJECTIVE: To delineate the mechanism behind insurance-related disparities in the prenatal diagnosis of a congenital heart defect (CHD). METHODS: This was a retrospective analysis of electronic health records of pregnant individuals whose infants received CHD surgery between 2019 and 2020 in the third-largest United States metropolitan area. The outcome was whether a prenatal diagnosis was received. The exposure was the pregnant individual's insurance status. The mediator was second-trimester ultrasound receipt. Control variables included sociodemographic and clinical characteristics of the pregnant individual and infant. The relationships between exposure, mediator, and outcome were quantified using mediation analysis with multivariable fixed-effects regression. RESULTS: In total, 496 pregnant individuals met inclusion criteria; 215 (43.3%) were publicly insured and 305 (61.5%) had prenatal diagnosis. In bivariate regressions, public insurance was associated with a 12.6% lower probability (CI 3%-21%) of prenatal diagnosis. In multivariable models, public insurance was associated with 13.2% lower probability (CI 2%-25%) of second-trimester ultrasound receipt but was no longer associated with prenatal diagnosis after adjusting for second-trimester ultrasound receipt, suggesting a possible mediation effect. Mediation analysis confirmed that second-trimester ultrasound receipt mediated 39% of the relationship between public insurance and prenatal diagnosis. CONCLUSION: An appreciable portion of insurance-related differences in prenatal CHD diagnosis is due to the lower frequency of second-trimester ultrasound receipt among those with public insurance.

Design and Pilot Implementation of an ECHO Module on Hepatitis C Virus Infection During Pregnancy.

We developed a Project ECHO® module to offer prenatal providers training on engaging in shared decision-making about hepatitis C virus (HCV) treatment during pregnancy. In this pilot program, the ECHO module addressing HCV during pregnancy and the potential benefits of treatment was associated with increases in self-efficacy scores among participants.