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Abstract Background Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas). Results We identified four genes with SNPs that showed the strongest and most consistent associations with LDL-C and CAD: EBF1, PPP2R2B, SPOCK1, and PRELID2. The most significant results for association of SNPs with LDL-C were: EBF1, rs6865969, p = 0.01; PPP2R2B, rs2125443, p = 0.005; SPOCK1, rs17600115, p = 0.003; and PRELID2, rs10074645, p = 0.0002). The most significant results for CAD were EBF1, rs6865969, p = 0.007; PPP2R2B, rs7736604, p = 0.0003; SPOCK1, rs17170899, p = 0.004; and PRELID2, rs7713855, p = 0.003. Conclusion Using an intermediate disease-related quantitative trait of LDL-C we have identified four novel CAD genes, EBF1, PRELID2, SPOCK1, and PPP2R2B. These four genes should be further examined in future functional studies as candidate susceptibility loci for cardiovascular disease mediated through LDL-cholesterol pathways.

Abstract Background We previously identified a 40 Mb region of linkage on chromosome 1q in our early onset coronary artery disease (CAD) genome-wide linkage scan (GENECARD) with modest evidence for linkage (n = 420, LOD 0.95). When the data are stratified by acute coronary syndrome (ACS), this modest maximum in the overall group became a well-defined LOD peak (maximum LOD of 2.17, D1S1589/D1S518). This peak overlaps a recently identified inflammatory biomarker (MCP-1) linkage region from the Framingham Heart Study (maximum LOD of 4.27, D1S1589) and a region of linkage to metabolic syndrome from the IRAS study (maximum LOD of 2.59, D1S1589/D1S518). The overlap of genetic screens in independent data sets provides evidence for the existence of a gene or genes for CAD in this region. Methods A peak-wide association screen (457 SNPs) was conducted of a region 1 LOD score down from the peak marker (168–198 Mb) in a linkage peak for acute coronary syndrome (ACS) on chromosome 1, within a family-based early onset coronary artery disease (CAD) sample (GENECARD). Results Polymorphisms were identified within the 'family with sequence similarity 5, member C' gene (FAM5C) that show genetic linkage to and are associated with myocardial infarction (MI) in GENECARD. The association was confirmed in an independent CAD case-control sample (CATHGEN) and strong association with MI was identified with single nucleotide polymorphisms (SNPs) in the 3' end of FAM5C. FAM5C genotypes were also correlated with expression of the gene in human aorta. Expression levels of FAM5C decreased with increasing passage of proliferating aortic smooth muscle cells (SMC) suggesting a role for this molecule in smooth muscle cell proliferation and senescence. Conclusion These data implicate FAM5C alleles in the risk of myocardial infarction and suggest further functional studies of FAM5C are required to identify the gene's contribution to atherosclerosis.

The benefits of hip arthroscopic surgery for femoroacetabular impingement are well-established. Hip arthroscopic surgery rates have risen dramatically over the last decade. Some patients, however, may continue to experience hip symptoms after surgery and are dissatisfied with their inability to return to desired optimal activity levels. The purpose of the study is to understand the long-term outcomes of patients with painful hips after hip arthroscopy for femoroacetabular impingement. This is a retrospective study of the outcomes of painful hips after hip arthroscopy for femoroacetabular impingement, with four to 14-year follow-up from 2008 to 2022. A total of 84 hip arthroscopies were performed. Most of the patients had labral tear debridement and shaving of the aspherical femoral head also known as cam lesion, and five patients had repair for labral tear. There were eight patients who had bilateral hip involvement. There were 27 men and 57 females between the second to fifth decades. The electronic patient's records and radiological images were reviewed, and patient outcomes were graded as pain-free hip (asymptomatic) or painful hip (persistent pain and symptoms of instability). After hip arthroscopy surgery, 55% (46) of hips were graded pain-free in patients who were mostly in their 20s and 30s, while 45% (38) of hips had persistent pain. These patients were in their third or fifth decade. In the painful hip cohort, 33 patients had one hip arthroscopic surgery, while five patients had multiple repeat hip arthroscopies in the same hip over a three to six-year period. Bilateral hip arthroscopies were performed at different times in eight patients of which five individuals experienced painful hip outcomes. There were seven females and one male in their 30s and 40s. The labral tear was repaired in five patients, and two patients had painful hip outcomes. Both were females in their 20s and 30s. Patients with chronic painful hips after hip arthroscopic surgery were investigated to identify the cause of the pain. If no cause was established, then they were finally referred to pain specialist clinicians for pain management. This cohort had seven patients between 28 and 43 years. Six were female and one was male. Total hip replacement (THR) was performed in four patients (4.7%). Conversely, 95.3% of patients did not need THR during the study period of 14 years. Hip arthroscopy can be an effective treatment for femoroacetabular impingement. Careful patient selection and a holistic approach are vital for a good patient outcome. The success rate of the pain-free hip after hip arthroscopy decreases with increasing age of the patient, particularly in the female gender. Patients with grade II and more degenerative chondral changes do not perform well. Patients in their fourth and fifth decade can benefit from hip arthroscopy provided a comprehensive discussion of the expected outcomes is conducted prior to surgery. Overall, hip arthroscopy remains a valuable tool, but it is important to be conscious of its limitations and potential challenges., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Verma et al.)

Health care provider retention is important for mitigating workforce shortages in underserved areas. The National Health Service Corps (NHSC) provides loan repayment for a two or three-year service commitment from clinicians to work in underserved areas. Prior studies have mixed findings as to what influences clinician retention and have focused mainly on individual-level background characteristics. We used measures of NHSC clinicians' work environment during their service experience, in addition to background characteristics, to identify patterns of experiences, and assess whether these patterns were associated with post-service intentions. We observed that technical assistance and job resources were more influential on clinicians' intentions, compared to individual- or community-level characteristics. Organizations with efficient and supportive work environments may help retain clinicians in underserved areas., (© 2024. The Author(s).)

Purpose: Bariatric surgery is considered the main treatment option for patients with severe obesity. The objective of our study is to compare intra- and postoperative outcomes between the robotic and laparoscopic approaches within the sleeve gastrectomy (SG), duodenal switch (DS), and Roux-en-Y gastric bypass (RYGB)., Materials and Methods: The data from the MBSAQIP were collected for patients who underwent SG, DS, and RYGB between 2015 and 2021. The postoperative and procedural outcomes including 30-day morbidity and mortality as well as operation length were analyzed using regression models., Results: Our analysis included 1,178,886 surgeries with SG comprising the majority (70%) followed by RYGB (28%) and DS (1%). Other than a higher adjusted risk of unplanned reoperation for robotic RYGB (relative risk (RR) 1.07) and a statistically significant higher rate of postoperative wound disruption in robotic SG for robotic surgery (RR 1.56), there were no statistically significant between-approach differences including infection, wound disruption, death, or reoperation for DS, RYGB, or SG. Our data showed no significant difference in anastomotic leak rate between laparoscopic and robotic approaches in either the DS (p = 0.521) or RYGB (p = 0.800) procedures. Across our study period, the median operation lengths decreased significantly per year for both the robotic SG and DS., Conclusions: Robotic and laparoscopic bariatric surgical procedures have statistically similar 30-day patient outcomes. Robotic bariatric procedures do have significantly longer median operative times than laparoscopic procedures. The decision to use a robotic approach or laparoscopic approach should be made based upon surgeon experience and possibly cost., (© 2024. The Author(s).)

[ 11 C]Carfentanil ([ 11 C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [ 11 C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [ 11 C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO 2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [ 11 C]CFN PET scans over a wide range of molar activities. Baseline [ 11 C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BP ND ) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained < 40 ng/kg (~ 10% MOR occupancy in rats), baseline MOR availability was significantly decreased. For test-retest variability (TRTV), better reproducibility was achieved by controlling CFN injected mass to limit the difference between scans. Taken together, we report significant cardiorespiratory depression and a paradoxical influence on baseline MOR availability at conventional tracer doses in rats. Our findings might reflect changes in cerebral blood flow, changes in receptor affinity, or receptor internalization, and merits further mechanistic investigation. In conclusion, rat [ 11 C]CFN PET requires stringent quality assurance of radiotracer synthesis and mass injected to avoid pharmacological effects and limit potential influences on MOR quantification and reproducibility., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Our aim was to determine the need for otolaryngology care within the homeless population, identify barriers to access that the homeless population may face, and develop a model system which would address these needs with respect to the barriers., Methods: A retrospective chart review of 812 patients seen between 1/25/16-3/21/2020 was performed. Charts were obtained from homeless patients seen at free general clinics held shelters in Chicago, IL (781 charts) and in Champaign, IL (31 charts). Records reporting at least one otolaryngology disease in a patient experiencing homelessness were included in this study. Patients were considered homeless if they resided at the shelter at the time of their appointment. To determine common barriers to care, a simple yes/no questionnaire was administered to residents at west-side Chicago homeless shelters. Questions addressed barriers to health care access that had been mentioned by patients seen at free clinics., Results: Chart review findings demonstrated that 14.3% (n = 142) of all homeless patients seen at free in-shelter clinics were seen for ENT-related disorders. Survey results revealed that 76.3% (n = 71) of respondents believed that telemedicine services would be useful in shelters. 74.2% (n = 69) stated they were unable to afford prescribed medications. 93.5% (n = 87) stated that better access to transportation would increase their likelihood of seeking care., Conclusions: In our attempt to bridge this inequity, we have launched a hybrid in-person/virtual care program to improve access to otolaryngology care for the homeless community., Level of Evidence: N/A Laryngoscope, 134:2705-2709, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

The global energy crisis has spurred a shift from conventional to clean and sustainable energy sources. Biomass derived from microalgae is emerging as an alternative energy source with diverse applications. Despite the numerous advantages of microalgae, large-scale biomass harvesting is not economical and convenient. Self-flocculation is considered an effective phenomenon facilitated by extracting the flocculating substances from microalgae that assist aggregation of algal cells into flocs. A novel cellulose-based bioflocculant has been synthesized from sewage water grown Chlorella sorokiniana and Scenedesmus abundans for harvesting application. The produced bioflocculant amounted to 38.5% and 19.38% of the dry weight of S. abundans and C. sorokiniana, respectively. Analysis via FTIR, XRD, and FESEM-EDX revealed the presence of cellulose hydroxyapatite (HA) in algae-derived cellulose. Harvesting efficiencies of 95.3% and 89.16% were attained for S. abundans and C. sorokiniana, respectively, at a dosage of 0.5 g/L. Furthermore, the bioflocculant was recovered, enabling its reuse with recovery efficiencies of 52% and 10% for S. abundans and C. sorokiniana, respectively. This simple and efficient approach has the potential to replace other harvesting methods, thereby contributing to the economic algal biofuel production., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: The National Health Service Corps (NHSC) Loan Repayment Program (LRP) expansion in fiscal year (FY) 2019 intended to improve access to medication for opioid use disorder (MOUD) by adding more clinicians who could prescribe buprenorphine. However, some clinicians still face barriers to prescribing, which may vary between rural and nonrural areas., Objective: To examine the growth in buprenorphine prescribing by NHSC clinicians for Medicaid beneficiaries during the NHSC LRP expansion and describe the challenges to prescribing that persist in rural and nonrural areas., Design, Setting, and Participants: This cross-sectional study analyzed preexpansion and postexpansion Medicaid claims data to evaluate the percentage of prescriptions of buprenorphine filled during FY 2017 through 2021. This study also analyzed challenges and barriers to prescribing MOUD between rural and urban areas, using results from annual surveys conducted with NHSC clinicians and sites from FY 2019 through FY 2021., Exposure: Prescribing of buprenorphine by NHSC clinicians., Main Outcomes and Measures: The main outcomes were the percentage and number of Medicaid beneficiaries with opioid use disorder (OUD) who filled a prescription for buprenorphine before and after the LRP expansion and the challenges NHSC clinicians and sites faced in providing substance use disorder and OUD services. Survey results were analyzed using descriptive statistics., Results: During FYs 2017 through 2021, 7828 NHSC clinicians prescribed buprenorphine (standard LRP: mean [SD] age, 38.1 [8.4] years and 4807 females [78.9%]; expansion LRPs: mean [SD] age, 39.4 [8.1] years and 1307 females [75.0%]). A total of 3297 NHSC clinicians and 4732 NHSC sites responded to at least 1 survey question to the 3 surveys. The overall percentage of Medicaid beneficiaries with OUD who filled a prescription for buprenorphine during the first 2.5 years post expansion increased significantly from 18.9% before to 43.7% after expansion (an increase of 123 422 beneficiaries; P < .001). The percentage more than doubled among beneficiaries living in areas with a high Social Vulnerability Index score (from 17.0% to 36.7%; an increase of 31 964) and among beneficiaries living in rural areas (from 20.8% to 55.7%; an increase of 45 523). However, 773 of 2140 clinicians (36.1%; 95% CI, 33.6%-38.6%) reported a lack of mental health services to complement medication for OUD treatment, and 290 of 1032 clinicians (28.1%; 95% CI, 24.7%-31.7%) reported that they did not prescribe buprenorphine due to a lack of supervision, mentorship, or peer consultation., Conclusions and Relevance: These findings suggest that although the X-waiver requirement has been removed and Substance Abuse and Mental Health Services Administration guidelines encourage all eligible clinicians to screen and offer patients with OUD buprenorphine, as permissible by state law, more trained health care workers and improved care coordination for counseling and referral services are needed to support comprehensive OUD treatment.

Background: Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact to the cardiorespiratory systems. The mechanisms underlying tobacco smoke toxicity in skeletal muscle are not fully resolved. In this study, the role of the aryl hydrocarbon receptor (AHR), a transcription factor known to be activated with tobacco smoke, was investigated., Methods: AHR related gene (mRNA) expression was quantified in skeletal muscle from adult controls and patients with chronic obstructive pulmonary disease (COPD), as well as mice with and without cigarette smoke exposure. Utilizing both skeletal muscle-specific AHR knockout mice exposed to chronic repeated (5 days per week for 16 weeks) cigarette smoke and skeletal muscle-specific expression of a constitutively active mutant AHR in healthy mice, a battery of assessments interrogating muscle size, contractile function, mitochondrial energetics, and RNA sequencing were employed., Results: Skeletal muscle from COPD patients (N = 79, age = 67.0 ± 8.4 years) had higher levels of AHR (P = 0.0451) and CYP1B1 (P < 0.0001) compared to healthy adult controls (N = 16, age = 66.5 ± 6.5 years). Mice exposed to cigarette smoke displayed higher expression of Ahr (P = 0.008), Cyp1b1 (P < 0.0001), and Cyp1a1 (P < 0.0001) in skeletal muscle compared to air controls. Cigarette smoke exposure was found to impair skeletal muscle mitochondrial oxidative phosphorylation by ~50% in littermate controls (Treatment effect, P < 0.001), which was attenuated by deletion of the AHR in muscle in male (P = 0.001), but not female, mice (P = 0.37), indicating there are sex-dependent pathological effects of smoking-induced AHR activation in skeletal muscle. Viral mediated expression of a constitutively active mutant AHR in the muscle of healthy mice recapitulated the effects of cigarette smoking by decreasing muscle mitochondrial oxidative phosphorylation by ~40% (P = 0.003)., Conclusions: These findings provide evidence linking chronic AHR activation secondary to cigarette smoke exposure to skeletal muscle bioenergetic deficits in male, but not female, mice. AHR activation is a likely contributor to the decline in muscle oxidative capacity observed in smokers and AHR antagonism may provide a therapeutic avenue aimed to improve muscle function in COPD., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Purpose: To compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months., Methods: This was a retrospective chart review of treatment-naïve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F)., Results: A total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p > 0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p < 0.001 and PCV, r = - 0.06; p = 0.74) and the need for fewer anti-VEGF injections (n-AMD, r = - 0.53; p < 0.001 and PCV, r = - 0.09; p = 0.58)., Conclusion: PEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months., (© 2024. The Author(s).)

Background: Excess aldosterone accelerates chronic kidney disease progression. This phase 2 clinical trial assessed BI 690517, an aldosterone synthase inhibitor, for efficacy, safety, and dose selection., Methods: This was a multinational, randomised, controlled, phase 2 trial. People aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 30 to less than 90 mL/min/1·73 m 2 , a urine albumin to creatinine ratio (UACR) of 200 to less than 5000 mg/g, and serum potassium of 4·8 mmol/L or less, taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, were enrolled. Participants were randomly assigned (1:1) to 8 weeks of empagliflozin or placebo run-in, followed by a second randomisation (1:1:1:1) to 14 weeks of treatment with once per day BI 690517 at doses of 3 mg, 10 mg, or 20 mg, or placebo. Study participants, research coordinators, investigators, and the data coordinating centre were masked to treatment assignment. The primary endpoint was the change in UACR measured in first morning void urine from baseline (second randomisation) to the end of treatment. This study is registered with ClinicalTrials.gov (NCT05182840) and is completed., Findings: Between Feb 18 and Dec 30, 2022, of the 714 run-in participants, 586 were randomly assigned to receive BI 690517 or placebo. At baseline, 33% (n=196) were women, 67% (n=390) were men, 42% (n=244) had a racial identity other than White, and mean participant age was 63·8 years (SD 11·3). Mean baseline eGFR was 51·9 mL/min/1·73 m 2 (17·7) and median UACR was 426 mg/g (IQR 205 to 889). Percentage change in first morning void UACR from baseline to the end of treatment at week 14 was -3% (95% CI -19 to 17) with placebo, -22% (-36 to -7) with BI 690517 3 mg, -39% (-50 to -26) with BI 690517 10 mg, and -37% (-49 to -22) with BI 690517 20 mg monotherapy. BI 690517 produced similar UACR reductions when added to empagliflozin. Investigator-reported hyperkalaemia occurred in 10% (14/146) of those in the BI 690517 3 mg group, 15% (22/144) in the BI 690517 10 mg group, and 18% (26/146) in the BI 690517 20 mg group, and in 6% (nine of 147) of those receiving placebo, with or without empagliflozin. Most participants with hyperkalaemia did not require intervention (86% [72/84]). Adrenal insufficiency was an adverse event of special interest reported in seven of 436 study participants (2%) receiving BI 690517 and one of 147 participants (1%) receiving matched placebo. No treatment-related deaths occurred during the study., Interpretation: BI 690517 dose-dependently reduced albuminuria with concurrent renin-angiotensin system inhibition and empagliflozin, suggesting an additive efficacy for chronic kidney disease treatment without unexpected safety signals., Funding: Boehringer Ingelheim., Competing Interests: Declaration of interests KRT reports grants for investigator-initiated research from NIDDK, NHLBI, NCATS, NIMHD, NIH Data Science office, Travere, Bayer, and Goldfinch Bio; contracts from CDC; consulting fees from Boehringer Ingelheim, Janssen, Novo Nordisk, AstraZeneca, Bayer, Eli Lilly, Gilead, and Merck Sharp & Dohme; payment for manuscript writing for Boehringer Ingelheim, Novo Nordisk, Bayer, Eli Lilly, and Gilead; payment of honoraria for Novo Nordisk, AstraZeneca, Bayer, Eli Lilly, and Gilead; payment for travel for Novo Nordisk; travel to meetings from Novo Nordisk; chair and member of a data safety monitoring committee for NIDDK and George Clinical; and leadership role for the American Society of Nephrology. MEC reports grants for investigator-initiated research and research funding from Baxter and Fresenius; and payment of honoraria for lectures, presentations, and education events from AstraZeneca, Fresenius, Bayer, Pfizer, and Bracepharma. MLC reports research grant support from NIH and NIDDK (all to the University of Minnesota and Cleveland Clinic) and research grant support sponsored by Bayer Pharmaceuticals (all to the University of Minnesota); consulting fees from Bayer Pharmaceuticals, Novo Nordisk, and AstraZeneca; payment for speaker bureaus and educational events from Bayer Pharmaceuticals; payment of honoraria for lectures and educational events from Cardiorenal Connections, Heart in Diabetes, Translational Medicine Academy, and the American College of Cardiology; support to attend investigator meetings for Kidney Precision Medicine Project from the NIH and NIDDK, American Diabetes Association meetings from NIH and NIDDK, and University of Minnesota and American Society of Nephrology meetings from NIH and NIDDK and Cleveland Clinic Foundation (all to the University of Minnesota); participation on and site principle investigator for the Data Safety Monitoring Board for Preventing Early Renal Loss in Diabetes Study for NIH and NIDDK (all to the University of Minnesota); and attendee of Kidney Disease Improving Global Outcomes writing group meetings. DC reports research grants from Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL Behring, and Novo Nordisk; consulting fees from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi Tanabe, AbbVie, Janssen, Bayer, Prometic, Bristol Myers Squibb, Maze, Gilead, CSL Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK, and Novo Nordisk; payment of honoraria for lectures and advisory boards from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi Tanabe, Janssen, Bayer, and Novo Nordisk; support for traveling to and attending meetings from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Janssen, Bayer, and Novo Nordisk; and receipt of a drug for research from AstraZeneca. HJLH reports funding to conduct clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and Novo Nordisk (all to the University of Groningen); consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Behring, DImerix, Eli Lilly, Fresenius, Gilead, Janssen, Novo Nordisk, Novartis, and Travere Therapeutics; payment of honoraria for lectures from AstraZeneca, Novo Nordisk, and Bayer; support for traveling to and attending the American Diabetes Association meeting and American Society of Nephrology meeting from AstraZeneca and Eli Lilly (to HJLH and the University of Groningen); and receipt of the study drug from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and Novo Nordisk. MN reports donations for research through Shogaku Kifu practice from KyowaKiirin, Mitsubishi Tanabe, Chugai, Boehringer Ingelheim, Torii, Takeda, Daiichi Sankyo, and JT; consulting fees from KyowaKiirin and Mitsubishi Tanabe; and payment of honoraria for lectures from KyowaKiirin, Mitsubishi Tanabe, Bayer, Astellas, JT, and AstraZeneca. RCR reports participation as a trial investigator for Novo Nordisk and AstraZeneca; consulting fees from Boehringer Ingelheim, Bayer, AstraZeneca, Chinook, and Novo Nordisk; payment of honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Amgen, and Bayer; and voluntary membership of the steering committee for World Kidney Day and of the Diabetes Committee. AS reports research contracts from Boehringer Ingelheim, Mineralysis, ProKidney, Reata, and Novartis; consulting fees from Boehringer Ingelheim, Ardelyx, and Pro Kidney; payment of honoraria for presentations from ProKidney, Boehringer Ingelheim, AstraZeneca, and Bayer; and participation on an Advisory Board for Travere, Boehringer Ingelheim, and Reata. DdZ reports consulting fees from Bayer, Fresenius, and Travere. PR reports grants and payment of honoraria for lectures, educational events, and steering group participation from AstraZeneca, Bayer, and Novo Nordisk (all to the Steno Diabetes Center Copenhagen); payment of honoraria for lectures and participation in advisory boards from Boehringer Ingelheim, Sanofi, Abbott, and Astellas (all to the Steno Diabetes Center Copenhagen). SJH, LC, SVS, and ZS are employees of Boehringer Ingelheim. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Evidence-based noninvasive caries therapies for initial caries lesions are available in the United States. Fundamental differences between noninvasive therapies and the traditional surgical dental approach warrant a study of the financial scalability., Methods: The financial costs and benefits of fee-for-service clinics and payors were compared across 11 scenarios simulating the treatment of 1,000 initial caries lesions during a 3-year period. The scenarios included varying combinations of noninvasive therapies (that is, silver diamine fluoride, self-assembling peptide P 11 -4, and glass ionomer therapeutic sealants), no treatment, and various rates of 1- through 3-surface restorations to an estimated 2022 practice model. We used a decision tree microsimulation model for deterministic and probabilistic sensitivity analyses. We derived assumptions from an initial lesion and noninvasive therapy-focused cohort study with operations data from 16 sites accepting Medicaid in Alabama as a case study and clinical data from all 92 sites., Results: In comparison with the 2022 practice model assumed for this study, scenarios that produce mutually beneficial results for payors' savings and clinics' net profits and profit margins include self-assembling peptide P 11 -4, silver diamine fluoride on nonesthetic surfaces, and a mix of 3 noninvasive therapies. When considering the limited resources of chair and clinician time, the same scenarios, as well as silver diamine fluoride with restorations, emerged with substantially higher clinic net profit., Conclusions: Hypothetical scenarios that include noninvasive therapies and minimize restorations achieve improved outcomes for all parties., Practical Implications: Payors and clinicians should explore and implement noninvasive caries therapies to improve oral health for all. This study was registered at ClinicalTrials.gov. The registration number is NCT04933331., (Copyright © 2023 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) commonly perioperatively in the United States., Setting: Tertiary care academic medical center., Design: Prospective laboratory investigation., Methods: 8 commercially available NSAIDs (3 branded, 5 generic) were tested: branded bromfenac 0.07%, generic bromfenac 0.09%, diclofenac 0.1%, flurbiprofen 0.03%, generic ketorolac 0.5%, branded ketorolac 0.5%, ketorolac 0.47%, and branded nepafenac 0.3%. 10 bottles of each medication were tested, with an additional bottle tested for expulsion force requirements. A double-blinded method was used to measure the actual bottle fill volume and number of drops per bottle. The total cost per drop was calculated using published cash prices. Force requirements were measured using a customized force gauge apparatus. Formulations were compared using the Kruskal-Wallis test, followed by pairwise comparisons with the Dwass, Steel, Critchlow-Fligner Method., Results: 2 branded NSAIDs (bromfenac and nepafenac) had slightly lower-than-sticker volumes while generics other than ketorolac had higher-than-sticker volumes. Diclofenac and branded bromfenac had the highest and lowest adjusted number of drops respectively. Generic bromfenac and generic ketorolac had the highest and lowest adjusted volume compared with sticker volume respectively. Branded bromfenac was the most expensive medication, while generic diclofenac was the least expensive. Force expulsion requirements varied significantly among generic and branded NSAIDs., Conclusions: Volume fill levels, patient-incurred costs, and expulsion force requirements per bottle of topical NSAID medications vary significantly. Surgeons may wish to consider these factors when deciding how best to use these medications perioperatively., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Natural killer (NK) cells are critical modulators of HIV transmission and disease. Recent evidence suggests a loss of NK cell cytotoxicity during aging, yet analysis of NK cell biology and aging in people with HIV (PWH) is lacking. Herein, we perform comprehensive analyses of people aging with and without HIV to determine age-related NK phenotypic changes. Utilizing high-dimensional flow cytometry, we analyze 30 immune-related proteins on peripheral NK cells from healthy donors, PWH with viral suppression, and viremic PWH. NK cell phenotypes are dynamic across aging but change significantly in HIV and on antiretroviral drug therapy (ART). NK cells in healthy aging show increasing ⍺4β7 and decreasing CCR7 expression and a reverse phenomenon in PWH. These HIV-associated trafficking patterns could be due to NK cell recruitment to HIV reservoir formation in lymphoid tissue or failed mucosal signaling in the HIV-infected gut but appear to be tight delineators of age-related NK cell changes., Competing Interests: Declaration of interests All authors report no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Black Men who have Sex with Men (MSM) Initiative was implemented at eight sites to engage and retain Black MSM in HIV medical care and supportive services (SS) by addressing their behavioral health (BH) care needs. Using a pre-post design and generalized logistic mixed-effects models adjusting for patient-level random effects, site, baseline age, and baseline mental health status, we evaluated whether participants experienced increased postintervention attainment of (1) Awareness of HIV medical care, BH care, and SS; (2) Screening, referral, linkage, receipt, and engagement in HIV care, BH care, and SS; and (3) Retention, antiretroviral therapy prescription, and suppressed viral load. Among 758 evaluated participants, the proportion of participants who were aware of, screened for, screened positive for, and referred to BH and SS, retention in care (72% to 79%), and viral load suppression (68% to 75%) increased between baseline and postintervention. Among participants who screened positive and received BH services were statistically more likely to be linked to [OR, 1.34 (95% CI: 1.08-1.66)] and retained in [OR, 1.36 (95% CI: 1.00-1.83)] care. Among those who screened positive and received SS were statistically more likely to be retained in care [OR, 1.54 (95% CI: 1.07-2.22)]. Measures of linkage to care declined significantly during the study period, perhaps because of COVID-19 that delayed in-person care. This study suggests that interventions designed to increase utilization of BH services and SS can be effective at improving retention in care and viral load suppression among Black MSM, at least among those currently using HIV services.

Importance: The Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use aimed to improve antibiotic prescribing in ambulatory care practices by engaging clinicians and staff to incorporate antibiotic stewardship into practice culture, communication, and decision-making. Little is known about implementation of antibiotic stewardship in ambulatory care practices., Objective: To examine changes in visits and antibiotic prescribing during the AHRQ Safety Program., Design, Setting, and Participants: This cohort study evaluated a quality improvement intervention in ambulatory care throughout the US in 389 ambulatory care practices from December 1, 2019, to November 30, 2020., Exposures: The AHRQ Safety Program used webinars, audio presentations, educational tools, and office hours to engage stewardship leaders and clinical staff to address attitudes and cultures that challenge judicious antibiotic prescribing and incorporate best practices for the management of common infections., Main Outcomes and Measures: The primary outcome of the Safety Program was antibiotic prescriptions per 100 acute respiratory infection (ARI) visits. Data on total visits and ARI visits were also collected. The number of visits and prescribing rates from baseline (September 1, 2019) to completion of the program (November 30, 2020) were compared., Results: Of 467 practices enrolled, 389 (83%) completed the Safety Program; of these, 292 (75%) submitted complete data with 6 590 485 visits to 5483 clinicians. Participants included 82 (28%) primary care practices, 103 (35%) urgent care practices, 34 (12%) federally supported practices, 39 (13%) pediatric urgent care practices, 21 (7%) pediatric-only practices, and 14 (5%) other practice types. Visits per practice per month decreased from a mean of 1624 (95% CI, 1317-1931) at baseline to a nadir of 906 (95% CI, 702-1111) early in the COVID-19 pandemic (April 2020), and were 1797 (95% CI, 1510-2084) at the end of the program. Total antibiotic prescribing decreased from 18.2% of visits at baseline to 9.5% at completion of the program (-8.7%; 95% CI, -9.9% to -7.6%). Acute respiratory infection visits per practice per month decreased from baseline (n = 321) to a nadir of 76 early in the pandemic (May 2020) and gradually increased through completion of the program (n = 239). Antibiotic prescribing for ARIs decreased from 39.2% at baseline to 24.7% at completion of the program (-14.5%; 95% CI, -16.8% to -12.2%)., Conclusions and Relevance: In this study of US ambulatory practices that participated in the AHRQ Safety Program, significant reductions in the rates of overall and ARI-related antibiotic prescribing were noted, despite normalization of clinic visits by completion of the program. The forthcoming AHRQ Safety Program content may have utility in ambulatory practices across the US.

Objectives: To prospectively study the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy., Methods: We conducted a prospective, observational study at 28 neurology outpatient clinics in India from June 2017 to October 2019. Consecutive patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy were initiated on clobazam. Patients were followed up at 1, 3, 6, 9, and 12 months. Seizure control and adverse events were assessed through personal interviews and seizure diaries., Results: Out of 475 eligible patients, data of 429 patients (men: 65.5%) were evaluated (46 excluded due to protocol deviations). The median age was 25 (range, 3-80 years) years and the median duration of epilepsy was 3 (0.1-30) years. The majority of patients had focal epilepsy (55.0%) and genetic generalized epilepsy (40.1%). The one-year follow-up was completed by 380 (88.5%) patients. At one-year follow-up, 317 (83.4%; N = 380) patients in the study remained seizure free. These 317 patients who were seizure free at 12 months comprised 73.9% of the evaluable population (N = 429). In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment. During one-year follow-up, a total of 113 (22.6%) patients experienced at least one adverse event which included 103 (20.6%) patients who experienced 386 episodes of seizures., Conclusion: The study provides preliminary evidence that clobazam is effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy., Trial Registration Number: CTRI/2017/12/010906., Competing Interests: Declaration of interest Parthasarathy Satishchandra is on the Advisory Board of Sanofi India, Abbott India, and Eisai Pharma. Chaturbhuj Rathore has received speaker's honoraria from Sanofi India and Abbott India. Lokesh Lingappa is on advisory board for Sanofi, Abbott, and Dr. Reddy’s Laboratories. Sujatha Shetty and Deepa Chodankar are Sanofi employees and may hold shares and/or stock options in the company. All other authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Neuromyelitis optica (NMO) is a central demyelinating disorder, predominantly affecting the optic nerves and spinal cord and autoimmune basis. We aimed to analyze the clinical, laboratory, and imaging features associated with NMO spectrum disorders (NMOSD) according to the aquaporin 4 antibody (AQP4-Ab) serology status., Methods: The inclusion of the patients was based on the Wingerchuk criteria (2006) for NMO, known antibody status and has minimum 1-year follow-up. We analyzed and compared 46 patients with known antibody status., Results: AQP4-Ab positivity was 56.5%. The male to female ratio in the seropositive group was 1:7.7 and 1:1.2 in the seronegative group. The mean age of onset in seropositive patients was 36.8 years (vs 28.8 years in seronegative NMOSD patients). Clinical feature, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) features were also different, but data from two subsets did not reach statistical significance. The relapse rate was higher in AQP4 positive NMOSD (84.6% vs 55% in the seronegative group). The recovery rate for AQP4 positive patients was poor (15%)., Summary: We found differences in age, gender, and prognosis between the two groups. Antibody status may be a guiding factor in deciding the treatment approach during the first attack of NMOSD., Competing Interests: None

Intra-alveolar microvesicles (MVs) are important mediators of inter-cellular communication within the alveolar space, and are key components in the pathophysiology of lung inflammation such as acute respiratory distress syndrome (ARDS). Despite the abundance of data detailing the pro-inflammatory effects of MVs, it remains unclear how MVs interact or signal with target cells in the alveolus. Using both in vivo and in vitro alveolar models, we analyzed the dynamics of MV uptake by resident alveolar cells: alveolar macrophages and epithelial cells. Under resting conditions, the overwhelming majority of MVs were taken up by alveolar macrophages. However, following lipopolysaccharide (LPS)-mediated inflammation, epithelial cells internalized significantly more MVs (p<0.01) whilst alveolar macrophage internalization was significantly reduced (p<0.01). We found that alveolar macrophages adopted a pro-inflammatory phenotype after internalizing MVs under resting conditions, but reduction of MV uptake following LPS pre-treatment was associated with loss of inflammatory phenotype. Instead, MVs induced significant epithelial cell inflammation following LPS pre-treatment, when MV internalization was most significant. Using pharmacological inhibitors, we interrogated the mechanisms of MV internalization to identify which endocytic pathways and cell surface receptors are involved. We demonstrated that epithelial cells are exclusively dependent on the clathrin and caveolin dependent endocytotic pathway, whereas alveolar macrophage uptake may involve a significant phagocytic component. Furthermore, alveolar macrophages predominantly engulf MVs via scavenger receptors whilst, epithelial cells internalize MVs via a phosphatidylserine/integrin receptor mediated pathway (specifically alpha V beta III), which can be inhibited with phosphatidylserine-binding protein (i.e. annexin V). In summary, we have undertaken a comprehensive evaluation of MV internalization within the alveolar space. Our results demonstrate that different environmental conditions can modulate MV internalization, with inflammatory stimuli strongly enhancing epithelial cell uptake of MVs and inducing epithelial cell activation. Our data reveal the unique mechanisms by which alveolar macrophages and epithelial cells internalize MVs thereby elucidating how MVs exert their pathophysiological effect during lung inflammation and injury. As MVs are potential novel therapeutic targets in conditions such as ARDS, these data provide crucial insights into the dynamics of MV-target cell interactions and highlight potential avenues for researchers to modulate and inhibit their pro-inflammatory actions within the alveolar space., 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 Soni, O’Dea, Abe, Khamdan, Shah, Sarathchandra, Wilson and Takata.)

Pharmacogenetic dosing improves the accuracy of warfarin dosing, but current pharmacogenetic dosing algorithms are less accurate in populations of African ancestry. The cytochrome P450 2C9*5 (CYP2C9*5) allele is found almost exclusively in populations of African ancestry, and in vitro studies suggest CYP2C9*5 is associated with reduced clearance of warfarin. The clinical relevance of this single-nucleotide variation (SNV) (formerly SNP) is uncertain. In this multicentered study of 2,298 patients (49% female, 35% Black) taking warfarin, we quantified the association between the CYP2C9*5 allele and warfarin requirements. The CYP2C9*5 SNV was present in 2.3% of Black and 0.07% of White patients. Without taking CYP2C9*5 into account, pharmacogenetic algorithms that include other SNVs overestimated the warfarin dose by 30% (95% confidence interval (19-40%), P < 0.001), an average of 1.87 mg/day (SD 1.64) in heterozygotes (P < 0.001). Noncarriers required a slightly (0.23 mg/day, SD 2.09) higher than predicted dose. Genotyping for CYP2C9*5 corrected the potential overdose and halved overall dosing error in heterozygotes. Patients carrying CYP2C9*5 require a clinically relevant reduction in warfarin dose. Given the potential to improve the accuracy and safety of warfarin dosing in populations of African ancestry, we have incorporated this SNV into a nonprofit website to assist warfarin initiation (www.WarfarinDosing.org)., (© 2022 The Authors. Clinical Pharmacology & Therapeutics © 2022 American Society for Clinical Pharmacology and Therapeutics.)

Purpose: To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic steroids commonly used in the United States., Setting: Tertiary care academic referral center., Design: Prospective laboratory investigation., Methods: 8 commercially available medications were tested: loteprednol 0.5%, loteprednol gel 0.5%, loteprednol gel 0.38%, difluprednate 0.05%, generic fluorometholone 0.1%, branded fluorometholone 0.1%, generic prednisolone 1.0%, and branded prednisolone 1.0%. 10 bottles of each medication were tested. A double-blinded method was used to measure actual bottle fill volume and number of drops dispensed per bottle. The total perioperative cost per drop was calculated for each medication using a mean cash price. Force requirements were measured using a customized force gauge apparatus. Formulations were compared using Kruskal-Wallis 1way analysis of variances., Results: All formulations were able to cover postoperative periods commensurate with commonly used dosing regimens for cataract surgery. All medications had greater than sticker volume. Loteprednol 0.5% suspension and branded fluorometholone had the highest and lowest number of drops among the medications tested, respectively. Loteprednol 0.38% gel was the most expensive medication, whereas generic prednisolone 1.0% was the least expensive. Gel and branded formulations of ophthalmic steroids required less expulsion force compared with other tested formulations., Conclusions: Volume fill levels, patient-incurred costs, and expulsion force requirements per bottle of topical steroid medications vary widely. Clinicians may wish to consider these findings when determining their perioperative prescribing regimen., (Copyright © 2021 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

While glucocorticoids act via the glucocorticoid receptor (GR; NR3C1) to reduce the expression of many inflammatory genes, repression is not an invariable outcome. Here, we explore synergy occurring between synthetic glucocorticoids (dexamethasone and budesonide) and proinflammatory cytokines (IL1B and TNF) on the expression of the toll-like receptor 2 (TLR2). This effect is observed in epithelial cell lines and both undifferentiated and differentiated primary human bronchial epithelial cells (pHBECs). In A549 cells, IL1B-plus-glucocorticoid-induced TLR2 expression required nuclear factor (NF)-κB and GR. Likewise, in A549 cells, BEAS-2B cells, and pHBECs, chromatin immunoprecipitation identified GR- and NF-κB/p65-binding regions ∼32 kb (R1) and ∼7.3 kb (R2) upstream of the TLR2 gene. Treatment of BEAS-2B cells with TNF or/and dexamethasone followed by global run-on sequencing confirmed transcriptional activity at these regions. Furthermore, cloning R1 or R2 into luciferase reporters revealed transcriptional activation by budesonide or IL1B, respectively, while R1+R2 juxtaposition enabled synergistic activation by IL1B and budesonide. In addition, small-molecule inhibitors and siRNA knockdown showed p38α MAPK to negatively regulate both IL1B-induced TLR2 expression and R1+R2 reporter activity. Finally, agonism of IL1B-plus-dexamethasone-induced TLR2 in A549 cells and pHBECs stimulated NF-κB- and interferon regulatory factor-dependent reporter activity and chemokine release. We conclude that glucocorticoid-plus-cytokine-driven synergy at TLR2 involves GR and NF-κB acting via specific enhancer regions, which combined with the inhibition of p38α MAPK promotes TLR2 expression. Subsequent inflammatory effects that occur following TLR2 agonism may be pertinent in severe neutrophilic asthma or chronic obstructive pulmonary disease, where glucocorticoid-based therapies are less efficacious., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim and Objective: Streptococcus mutans ( S. mutans ) shows increased resistance to currently available antibiotics and chemotherapeutics. The present study compares the effectiveness of chlorhexidine and Herbal mouth rinse against salivary S. mutans in children with mixed dentition., Materials and Methods: Subjects ( n = 60) with mixed dentition were selected for the study. Caries status was recorded using Nyvard's criteria. Baseline saliva samples were collected and assessed for quantifying S. mutans . Subjects were instructed to rinse their mouths with 0.2 % w/v chlorhexidine and herbal mouth rinse for 7 days. Saliva samples were collected after 7 days and assessed for S. mutans . After a run-in period of 21 days, both the mouth rinses were crossed over according to the Latin square design, and a similar procedure was carried out. Later, determination of mean colony-forming units (CFU/mL) from the saliva samples was done. For statistical analysis, Kolmogorov and Mann-Whitney U tests were applied., Results: Both the groups showed a significant reduction in S. mutans count, at baseline and 7 days ( p = 0.0001), and the reduction of S. mutans count in herbal mouth rinse as compared to chlorhexidine mouth rinse ( p = 0.0209) was statistically significant., Conclusion: Herbal mouth rinse proved to have better antimicrobial efficacy than Chlorhexidine mouth rinse., How to Cite This Article: Shah SV, Badakar CM, Hugar SM, et al. Antimicrobial Efficacy of Chlorhexidine and Herbal Mouth Rinse on Salivary Streptococcus mutans in Children with Mixed Dentition: A Randomized Crossover Study. Int J Clin Pediatr Dent 2022;15(1):99-103., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; The Author(s).)

Background: Although HIV antiretroviral treatment (ART) access and uptake have increased among racial/ethnic minority individuals, lower rates of ART adherence and viral suppression persist, especially among Black men who have sex with men (BMSM) compared with their White counterparts., Setting: Black men who have sex with men living with HIV (BMSM+) residing in Los Angeles County (N = 124) were recruited in-person (eg, clinic) and online (eg, social networking apps)., Methods: Participants completed a cross-sectional survey measuring demographic characteristics, structural syndemics (poverty, criminal justice involvement, and housing instability), and psychosocial syndemics (mental health and substance use). A text message survey assessed missed doses of ART over the past week. Zero-inflated Poisson regression models were used to evaluate variables associated with the number of missed doses of ART., Results: On average, participants missed 1.30 doses of ART (SD = 2.09) and reported structural syndemics: poverty (56.1%), criminal justice involvement (36.6%), housing instability (26.3%), and psychosocial syndemics: childhood sexual abuse (51.8%), intimate partner violence (16.9%), depression (39%), and problem alcohol use (15.5%). After controlling for employment, age, education, and psychosocial syndemics, participants with a one-point increase in structural syndemic indicators were found to be 1.63 times more likely to have missed a dose of ART., Conclusions: Structural syndemic were associated with ART nonadherence among BMSM+ after adjusting for demographic and psychosocial factors. HIV treatment interventions that incorporate financial incentives, legal support, and housing may help improve ART adherence among BMSM+. Findings suggest that key priorities to ending the HIV epidemic must include structural interventions that alleviate poverty, eliminate disproportionate policing and criminalization, and end homelessness., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Granulocytes mediate broad immunoprotection through phagocytosis, extracellular traps, release of cytotoxic granules, antibody effector functions and recruitment of other immune cells against pathogens. However, descriptions of granulocytes in HIV infection and mucosal tissues are limited. Our goal was to characterize granulocyte subsets in systemic, mucosal and lymphoid tissues during lentiviral infection using the rhesus macaque (RM) model. Mononuclear cells from jejunum, colon, cervix, vagina, lymph nodes, spleen, liver and whole blood from experimentally naïve and chronically SHIVsf162p3-infected RM were analysed by microscopy and polychromatic flow cytometry. Granulocytes were identified using phenotypes designed specifically for RM: eosinophils-CD45 +  CD66 +  CD49d + ; neutrophils-CD45 +  CD66 +  CD14 + ; and basophils-CD45 +  CD123 +  FcRε + . Nuclear visualization with DAPI staining and surface marker images by ImageStream (cytometry/microscopy) further confirmed granulocytic phenotypes. Flow cytometric data showed that all RM granulocytes expressed CD32 (FcRγII) but did not express CD16 (FcRγIII). Additionally, constitutive expression of CD64 (FcRγI) on neutrophils and FcRε on basophils indicates the differential expression of Fc receptors on granulocyte subsets. Granulocytic subsets in naïve whole blood ranged from 25·4% to 81·5% neutrophils, 0·59% to 13·3% eosinophils and 0·059% to 1·8% basophils. Interestingly, elevated frequencies of circulating neutrophils, colorectal neutrophils and colorectal eosinophils were all observed in chronic lentiviral disease. Conversely, circulating basophils, jejunal eosinophils, vaginal neutrophils and vaginal eosinophils of SHIVsf162p3-infected RM declined in frequency. Overall, our data suggest modulation of granulocytes in chronic lentiviral infection, most notably in the gastrointestinal mucosae where a significant inflammation and disruption occurs in lentivirus-induced disease. Furthermore, granulocytes may migrate to inflamed tissues during infection and could serve as targets of immunotherapeutic intervention., (© 2021 John Wiley & Sons Ltd.)

Background: The concept of reflective practice is at the center of professional practice, allowing a bridge between theory and practice and learning from our own experiences in an ongoing process. Understanding what learners need such as regular observation of work, more responsibility, and technical and problem-solving with answers allows the teacher to help learners to progress to independence in pursing their own learning needs. Therefore, it is important that medical educators continually reflect and evaluate teaching ability to meet learners' needs and provide evidence to support it., Materials and Methods: A prospective, qualitative study was carried out using a combination of questionnaires and observed assessments. The study participants consisted of twenty final-year medical students from King's College London and took place at a hospital education center in the UK, April 2019. Two educational sessions were delivered by a doctor to the study group and a video recording was conducted. The educator completed a reflective portfolio using feedback questionnaires, peer observation forms, and observation of the video recording, and the results were analyzed using a video critique tool., Results: Twenty learner feedback forms were completed, and a peer observation form was completed. This allowed a critical analysis of educator performance, reflection, and improvement. This was further solidified by in-depth analysis and critique of teaching session playback video., Discussion: This study evaluates a medical student teaching program using a reflective portfolio. This study confirms the effectiveness of using a reflective portfolio to enhance the teaching experience. Video analysis can be self-critical, however this study shows how it is useful to review human experience first-hand, and identifying any specific techniques that create a positive or negative change can enable educators to improve as time progresses., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Education and Health Promotion.)

HIV/SIV infections lead to massive loss of mucosal CD4 + T cells and breakdown of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one of the most understudied mucosal environments, the oral cavity, during HIV-induced immunosuppression results in significant microbial and neoplastic co-morbidities and contributes to and predicts distal disease complications. In this study we evaluated the effects of oral probiotic supplementation (PBX), which can stimulate and augment inflammatory or anti-inflammatory pathways, on early SIV infection of rhesus macaques. Our study revealed that similar to the GI mucosae, oral CD4 + T cells were rapidly depleted, and as one of the first comprehensive analyses of the oral microflora in SIV infection, we also observed significant modulation among two genera, Porphyromonas and Actinobacillus, early after infection. Interestingly, although PBX therapy did not substantially protect against oral dysbiosis or ameliorate cell loss, it did somewhat dampen inflammation and T cell activation. Collectively, these data provide one of the most comprehensive evaluations of SIV-induced changes in oral microbiome and CD4 + T cell populations, and also suggest that oral PBX may have some anti-inflammatory properties in lentivirus infections., (© 2021. The Author(s).)