Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Xanthine Dehydrogenase Is a Modulator of Dopaminergic Neurodegeneration in Response to Bacterial Metabolite Exposure in C. elegans.

Oxidative stress is a contributing factor to Parkinson's disease (PD). Considering the prevalence of sporadic PD, environmental exposures are postulated to increase reactive oxygen species and either incite or exacerbate neurodegeneration. We previously determined that exposure to the common soil bacterium, Streptomyces venezuelae (S. ven), enhanced oxidative stress and mitochondrial dysfunction in Caenorhabditis elegans, leading to dopaminergic (DA) neurodegeneration. Here, S. ven metabolite exposure in C. elegans was followed by RNA-Seq analysis. Half of the differentially identified genes (DEGs) were associated with the transcription factor DAF-16 (FOXO), which is a key node in regulating stress response. Our DEGs were enriched for Phase I (CYP) and Phase II (UGT) detoxification genes and non-CYP Phase I enzymes associated with oxidative metabolism, including the downregulated xanthine dehydrogenase gene, xdh-1. The XDH-1 enzyme exhibits reversible interconversion to xanthine oxidase (XO) in response to calcium. S. ven metabolite exposure enhanced XO activity in C. elegans. The chelation of calcium diminishes the conversion of XDH-1 to XO and results in neuroprotection from S. ven exposure, whereas CaCl2 supplementation enhanced neurodegeneration. These results suggest a defense mechanism that delimits the pool of XDH-1 available for interconversion to XO, and associated ROS production, in response to metabolite exposure.

The effects of inspiratory muscle training with pulmonary rehabilitation on NSCLC patients during radiation therapy: A pilot clinical study.

BACKGROUND: The effects of inspiratory muscle training (IMT) with pulmonary rehabilitation (PR) on patients with non-small cell lung cancer (NSCLC) receiving radiotherapy (RT) have not previously been reported. This pilot study aimed to determine the effectiveness of IMT with PR on respiratory muscles and exercise capacity of NSCLC patients receiving RT. METHODS: We retrospectively analyzed 20 patients who underwent RT for NSCLC. The rehabilitation included IMT, stretching, strengthening, and aerobic exercises three times a week for 4 weeks with concurrent RT. IMT training lasted 10 min, consisting of one cycle of 30 breaths using the Powerbreathe KH1 device in the hospital by a physical therapist. Patients underwent two IMT sessions at home daily at an intensity of approximately 30%-50% of the participant's maximum inspiratory muscle pressure (MIP) using the threshold IMT tool. We analyzed the results from the respiratory muscle strength test, pulmonary function test, 6-min walk test (6MWT), cardiopulmonary function test, cycle endurance test (CET), Inbody test, grip measurement, knee extensor/flexor strength measurement, Cancer Core Quality of Life Questionnaire (EORTCQ-C30), and NSCLC 13 (EORTC-LC13). RESULTS: There were no adverse events during evaluation and IMT with PR. MIP (60.1 ± 25.1 vs. 72.5 ± 31.9, p = 0.005), 6MWT (439.2 ± 97.1 vs. 60.7 ± 97.8, p = 0.002), CET (181.39 ± 193.12 vs. 123.6 ± 87.6, p = 0.001), knee extensor (14.4 ± 5.3 vs. 17.4 ± 5, p = 0.012), and knee flexor (14.0 ± 5.2 vs. 16.9 ± 5.5, p = 0.004) significantly improved after IMT with PR. CONCLUSION: IMT with PR appears effective on respiratory muscles and exercise capacity without adverse events in NSCLC patients who underwent RT.

Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts.

Utilizing the atto-zeptomole sensitivity of UPLC-accelerator mass spectrometry (UPLC-AMS), we previously demonstrated significant first-pass metabolism following escalating (25-250 ng) oral micro-dosing in humans of [14C]-benzo[a]pyrene ([14C]-BaP). The present study examines the potential for supplementation with Brussels sprouts (BS) or 3,3'-diindolylmethane (DIM) to alter plasma levels of [14C]-BaP and metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [14C]-BaP. Volunteers were dosed with [14C]-BaP following fourteen days on a cruciferous vegetable restricted diet, or the same diet supplemented for seven days with 50 g of BS or 300 mg of BR-DIM® prior to dosing. BS or DIM reduced total [14C] recovered from plasma by 56-67% relative to non-intervention. Dietary supplementation with DIM markedly increased Tmax and reduced Cmax for [14C]-BaP indicative of slower absorption. Both dietary treatments significantly reduced Cmax values of four downstream BaP metabolites, consistent with delaying BaP absorption. Dietary treatments also appeared to reduce the T1/2 and the plasma AUC(0,∞) for Unknown Metabolite C, indicating some effect in accelerating clearance of this metabolite. Toxicokinetic constants for other metabolites followed the pattern for [14C]-BaP (metabolite profiles remained relatively consistent) and non-compartmental analysis did not indicate other significant alterations. Significant amounts of metabolites in plasma were at the bay region of [14C]-BaP irrespective of treatment. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen.

Perceived Stress, Resilience, and Wellbeing in Seasoned Isha Yoga Practitioners Compared to Matched Controls During the COVID-19 Pandemic.

Background: Yoga practices, including breathing, meditation, and posture protocols (asanas), have been shown to facilitate physical and mental wellbeing. Methods: Seasoned yoga practitioners were recruited from the Isha Foundation. Recruitment of the comparison group was achieved using snowball sampling and were not yoga practitioners. Participants in the non-yoga group were randomized to a 3-min Isha practice or a comparator group asked to perform 15-min of daily reading. Participants completed a series of web-based surveys (REDCap) at baseline, 6, and 12 weeks. These surveys include validated scales and objective questions on COVID-19 infection and medical history. The validated questionnaires assess for: perceived stress (PSS), mood states [anxiety and depression (PHQ-4), joy (DPES-Joy subscale)], mindfulness attention and awareness (MAAS), resilience (BRS), mental wellbeing (WEMWBS) and recovery from traumatic event (PTGI). Weekly activity diaries were employed as a tool for collecting compliance information from study participants. Perceived stress scale scores were identified as primary outcome for this study. Findings: The median Perceived Stress Scale (PSS) score for the yoga practitioners compared to the active and placebo comparators was significantly lower at all time-points: baseline: 11 [IQR 7-15] vs. 16 [IQR 12-21] in both the active and placebo comparators (p < 0.0001); 6 weeks: 9 [IQR 6-13] vs. 12 [IQR 8-17] in the active comparator and 14 [IQR 9-18] in the placebo comparator (p < 0.0001); and 12 weeks: 9 [IQR 5-13] vs. 11.5 [IQR 8-16] in the active comparators and 13 [IQR 8-17] in the placebo comparator (p < 0.0001). Among the randomized participants that were compliant for the full 12 weeks, the active comparators had significantly lower median PSS scores than the placebo comparators 12 weeks [10 (IQR 5-14) vs. 13 (IQR 8-17), p = 0.017]. Further, yoga practitioners had significantly lower anxiety at all three-time points (p < 0.0001), lower depression at baseline and 6 weeks (p < 0.0003), and significantly higher wellbeing (p < 0.0001) and joy (p < 0.0001) at all three-time points, compared to the active and placebo comparator groups. Interpretation: The lower levels of stress, anxiety, depression, and higher level of wellbeing and joy seen in the yoga practitioners compared to the active and placebo comparators illustrate the impact of regular yoga practices on mental health even during the pandemic. Trial Registration: ClinicalTrials.gov, identifier: NCT04498442.

Treatment retention, return to use, and recovery support following COVID-19 relaxation of methadone take-home dosing in two rural opioid treatment programs: A mixed methods analysis.

OBJECTIVES: In March 2020, the Substance Abuse and Mental Health Services Administration permitted Opioid Treatment Programs (OTPs) to relax restrictions on take-home methadone and promoted telehealth to minimize potential exposures to COVID-19. We assessed the effects of COVID-19-related changes on take-home methadone dosing in two OTPs serving five rural Oregon counties. METHODS: We used a mixed-methods convergent design. The OTPs extracted urine drug test (UDT) results, take-home methadone regimens, and treatment retention from the electronic health record (EHR) for patients (n = 377). A mixed-effects negative binomial regression model assessed patient-level differences in take-home doses before and after the COVID-19 policy changes and the associations with treatment discontinuation, and UDT positivity. Semi-structured qualitative interviews (n = 32) explored patient reactions to increased take-home dosing and reduced clinic visits to provide context for quantitative findings. RESULTS: The number of take-home doses increased in the post-COVID-19 period for patients engaged in treatment for more than 180 days (median: 8 vs 13 take-home doses per month, p = 0.011). Take-homes did not increase for patients with fewer days of treatment. Each percentage point increase in take-home dosing above what would be expected without COVID-19 policy changes was negatively associated with the percent of UDT positive for opioids (B = -0.12, CI [-0.21, -0.04], p = 0.005) and the probability of treatment discontinuation (aOR = 0.97, CI [0.95, 0.99], p = 0.003). Qualitative analysis revealed three themes explaining how increased take-home dosing supported recovery: 1) value of feeling trusted with increased responsibility; 2) reduced travel time permitted increased employment and recreation; and 3) reduced exposure to individuals less stable in recovery and potential triggers. CONCLUSIONS: Take-home methadone dose relaxations were associated with increased methadone take-home doses, improved retention, and decreased UDT opioid positive results among clinically stable patients. Qualitative findings suggest that fewer take-home restrictions are feasible and desirable and do not pose safety or public health harms.

Long-term Efficacy and Safety of Up to 108 Weeks of Ixekizumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis: The IXORA-PEDS Randomized Clinical Trial.

Importance: About 1% of children and adolescents worldwide are affected by plaque psoriasis. Objective: To evaluate the long-term efficacy and safety of ixekizumab for pediatric patients with moderate to severe psoriasis. Design, Setting, and Participants: This multicenter randomized clinical trial (IXORA-PEDS) evaluated pediatric patients with plaque psoriasis. Participants were aged 6 years to younger than 18 years; had moderate to severe psoriasis, which was defined as Psoriasis Area and Severity Index (PASI) of 12 or higher, static Physician's Global Assessment (sPGA) score of 3 or higher, and psoriasis-affected body surface area of 10% or greater at screening and baseline; were candidates for phototherapy or systemic therapy; or had psoriasis that was not adequately controlled by topical therapies. Data analysis, which followed the intention-to-treat principle, was conducted from May to October 2021. Interventions: Pediatric patients were randomized 2:1 to receive either a weight-based dose of ixekizumab every 4 weeks or placebo. After a 12-week placebo-controlled period, patients entered a 48-week, open-label ixekizumab maintenance period (weeks 12-60), followed by an extension period that lasted through 108 weeks. A substudy evaluated the randomized withdrawal of ixekizumab after week 60. Main Outcomes and Measures: Efficacy outcomes at week 108 included the percentage of patients achieving 75% (PASI 75), 90% (PASI 90), or 100% (PASI 100) improvement from baseline; an sPGA score of 0 or 1 or score of 0; and improvement of 4 points or higher from baseline in the Itch Numeric Rating Scale. Safety outcomes included assessments of adverse events (AEs), including treatment-emergent AEs, serious AEs, and AEs of special interest, as well as improvement from baseline in a range of challenging body areas. Missing data for categorical outcomes were imputed using modified nonresponder imputation. Results: A total of 171 patients (mean [SD] age, 13.5 [3.04] years; 99 female children [57.9%]) were randomized to either ixekizumab (n = 115) or placebo (n = 56). Of 166 patients who entered the maintenance period, 139 (83.7%) completed week 108 of the trial. Primary and gated secondary end points were sustained through week 108, with patients achieving PASI 75 (91.7% [n = 86]), PASI 90 (79.0% [n = 74]), PASI 100 (55.1% [n = 52]), sPGA 0 or 1 (78.3% [n = 74]), and sPGA 0 (52.4% [n = 49]). Fifty-five patients (78.5%) reported an Itch Numeric Rating Scale improvement of 4 points or higher. In patients who received ixekizumab, at week 108, clearance of nail psoriasis was reported in 68.1% (n = 28), clearance of palmoplantar psoriasis was reported in 90.0% (n = 10), clearance of scalp psoriasis was reported in 76.2% (n = 83), and clearance of genital psoriasis was reported in 87.5% (n = 24). There were no new safety findings during weeks 48 to 108 of the trial, including no new cases of inflammatory bowel disease or candida infection. Conclusions and Relevance: Results of this study showed improvements across patient-reported outcomes and objective measures of complete skin clearance of psoriasis among pediatric patients who received ixekizumab, and these response rates were sustained through week 108 of the trial. Safety of ixekizumab was consistent with previously reported findings in this population and the known safety profile of this treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT03073200.

Status of Glucocorticoid-Induced Osteoporosis Preventive Care in Korea: A Retrospective Cohort Study on the Korean National Health Insurance Service Database.

Background and Objectives: It is crucial to prevent osteoporosis in patients receiving long-term glucocorticoid (GC) treatment. This study aimed to investigate the frequency and associated factors of preventive care for glucocorticoid-induced osteoporosis (GIOP) in Korea. Materials and Methods: Using the Korean National Health Insurance Service database, we identified 37,133 individuals aged ≥ 20 years who commenced long-term (≥90 days) oral GC between 2011 and 2012. High-quality GIOP preventive care was defined as either a bone mineral density (BMD) test, calcium and/or vitamin D supplementation, or prescription osteoporosis medications within 6 months of GC initiation. Multivariable logistic regression models were used to calculate odds ratios (ORs) for associated factors for high-quality GIOP preventive care. Results: The mean age was 49.8 years, and 18,476 (49.8%) patients were female. The frequency of high-quality GIOP preventive care was only 3.68% (BMD test, 1.46%; osteoporosis medications, 1.65%; calcium/vitamin D, 1.63%). Increasing age (OR = 2.53, p < 0.001; 40-49 years, OR = 3.99, p < 0.001; 50-59 years, OR = 5.17, p < 0.001; 60-69 years, OR = 8.07, p < 0.001; ≥70 years, respectively), systemic autoimmune disease (OR = 3.08, p < 0.001), rural residence (OR = 1.19, p = 0.046), concomitant hyperthyroidism (OR = 1.58, p = 0.007), and malignancy (OR = 1.59, p < 0.001) were significantly associated with a higher likelihood of receiving high-quality GIOP preventive care. Male sex (OR = 0.26, p < 0.001) and GC prescription in primary care clinics and nursing hospitals (OR = 0.66, p < 0.001) were associated with a lower rate of high-quality GIOP preventive care. Conclusions: Most Korean patients treated with GC did not receive appropriate preventive care for GIOP in real-world practice. More efforts are needed by clinicians to prevent, screen, and treat GIOP.

Local Anesthesia Alone for Postaxial Polydactyly Surgery in Infants.

BACKGROUND: Surgical excision for postaxial polydactyly type B is advocated to avoid long-term complications. Excision with local anesthesia (LA) in infancy represents a safe and effective treatment for this condition, although general anesthesia (GA) is employed by many surgeons. We present a comparison of surgical outcomes, cost, and time between LA and GA to support widespread change in management. METHODS: A retrospective review of patients under 12 months of age undergoing surgical polydactyly excision by a single surgeon was performed. Anesthesia type, patient demographics, and complications were recorded. Comparisons were made between LA and GA groups on procedure cost, operating time, length of stay (LOS), and time from procedure end to discharge. Stepwise forward regression was used to identify the best model for predicting total costs. RESULTS: Ninety-one infants with a mean age of 3 months (±1.9) were examined; 51 (56%) underwent LA alone, 40 (44%) underwent GA. Mean operating time was 11.53 ± 4.36 minutes, with no difference observed between anesthesia groups (P = .39). LA infants had a significantly shorter LOS (2.5 vs 3.5 hours; P < .05), quicker postoperative discharge (32 vs 65 minutes, P < .05), and fewer overall expenses, 2803 vs 6067 U.S. dollars (USD), P < .05. Two minor surgical complications (1 in each group) were reported. CONCLUSIONS: This study demonstrates significantly decreased cost, LOS, and time to discharge using LA alone for surgical excision of postaxial polydactyly type B. Results suggest the approach is quick, economical, and avoids the risks of GA in early infancy.

The additive memory and healthspan enhancement effects by the combined treatment of mature silkworm powders and Korean angelica extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Silkworm (Bombyx mori) and Korean angelica (KoAg; Angelica gigas Nakai) have been widely used as traditional oriental medicines in Korea, China, and Japan to treat various diseases such as anemia, cold, diabetes, palsy, stroke, etc. Steamed and freeze-dried mature silkworm powder, also known as HongJam (HJ), and extracts of KoAg root (KoAgE) are currently sold in Korea as functional foods to improve memory, cognition, and liver functions. However, the molecular and pharmacological basis for the improvement of brain functions of HJ and KoAgE has not yet been elucidated. AIM OF STUDY: This study aimed to elucidate the molecular basis underlying the memory-enhancing effects of HJ and KoAgE and determine whether administration of HJ and KoAgE complexes (HJ+KoAgC) has additive memory and healthspan-enhancing effects. MATERIALS AND METHODS: The MCI mouse models generated by intraperitoneal injection of Scopolamine (Sco-IP) were orally administered with HJ and KoAgE alone or as complexes. Their memory-enhancing effects were examined on spatial, fear-aggravated, and social memories and compared with control or Donepezil (Dp) treatment. The activities of mitochondria complex (MitoCom) I-IV and acetylcholinesterase (AChE) and the amounts of ATP in the mouse brains were examined. The Drosophila model was used to investigate lifespan- and healthspan-promoting effects of HJ+KoAgC. RESULTS: Administration of HJ+KoAgC produced more memory-enhancing effects than administration of HJ or KoAgE alone or Dp. The increase in MitoCom I-IV activities and ATP amounts and the decrease in AChE activities in the mouse brains were the molecular basis for the memory enhancement. The greatest improvement in memory and mitochondrial function was observed when the mice were administered the 1:0.8 ratio of HJ+KoAgC. Administration of HJ+KoAgC to Drosophila prolonged the lifespan and the healthspan and increased the amounts of ATP. CONCLUSION: HJ+KoAgC had superior effects on memory improvement and healthspan extension by increasing mitochondrial activities and ATP amounts in treated animal models.

Utilizing feline oral squamous cell carcinoma patients to develop NQO1-targeted therapy.

Developing effective therapies for the treatment of advanced head-and-neck squamous cell carcinoma (HNSCC) remains a major challenge, and there is a limited landscape of effective targeted therapies on the horizon. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a 2-electron reductase that is overexpressed in HNSCC and presents as a promising target for the treatment of HNSCC. Current NQO1-targeted drugs are hindered by their poor oxidative tolerability in human patients, underscoring a need for better preclinical screening for oxidative toxicities for NQO1-bioactivated small molecules. Herein, we describe our work to include felines and feline oral squamous cell carcinoma (FOSCC) patients in the preclinical assessment process to prioritize lead compounds with increased tolerability and efficacy prior to full human translation. Specifically, our data demonstrate that IB-DNQ, an NQO1-targeted small molecule, is well-tolerated in FOSCC patients and shows promising initial efficacy against FOSCC tumors in proof-of-concept single agent and radiotherapy combination cohorts. Furthermore, FOSCC tumors are amenable to evaluating a variety of target-inducible couplet hypotheses, evidenced herein with modulation of NQO1 levels with palliative radiotherapy. The use of felines and their naturally-occurring tumors provide an intriguing, often underutilized tool for preclinical drug development for NQO1-targeted approaches and has broader applications for the evaluation of other anticancer strategies.

Preservation of protective capacity of hyperimmune anti-Stx2 bovine colostrum against enterohemorrhagic Escherichia coli O157:H7 pathogenicity after pasteurization and spray-drying processes.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a major etiologic agent that causes bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is the main virulence factor of EHEC responsible for the progression to HUS. Although many laboratories have made efforts to develop an effective treatment for Stx-mediated HUS, a specific therapy has not been found yet. Human consumption of bovine colostrum is known to have therapeutic effects against several gastrointestinal infections because of the peptide and proteins (including antibodies) with direct antimicrobial and endotoxin-neutralizing effects contained in this fluid. We have previously demonstrated that colostrum from Stx type 2 (Stx2)-immunized pregnant cows effectively prevents Stx2 cytotoxicity and EHEC O157:H7 pathogenicity. In this study we evaluated the preservation of the protective properties of hyperimmune colostrum against Stx2 (HIC-Stx2) after pasteurization and spray-drying processes by performing in vitro and in vivo assays. Our results showed that reconstituted HIC-Stx2 colostrum after pasteurization at 60°C for 60 min and spray-dried under optimized conditions preserved specific IgG that successfully neutralized Stx2 cytotoxicity on Vero cells. Furthermore, this pasteurized/dehydrated and reconstituted HIC-Stx2 preserved the protective capacity against EHEC infection in a weaned mice model. The consumption of hyperimmune HIC-Stx2 bovine colostrum could be effective for HUS prevention in humans as well as in EHEC control in calves. However, further studies need to be done to consider its use for controlling EHEC infections.

Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids: JACC Focus Seminar.

Omega-3 polyunsaturated fatty acids (PUFAs) are a key component of a heart-healthy diet. For patients without clinical atherosclerotic cardiovascular disease, 2 or more servings of fatty fish per week is recommended to obtain adequate intake of omega-3 PUFAs. If this not possible, dietary supplementation with an appropriate fish oil may be reasonable. Supplementation with omega-3 PUFA capsules serves 2 distinct but overlapping roles: treatment of hypertriglyceridemia and prevention of cardiovascular events. Marine-derived omega-3 PUFAs reduce triglycerides and have pleiotropic effects including decreasing inflammation, improving plaque composition and stability, and altering cellular membranes. Clinical trial data have shown inconsistent results with omega-3 PUFAs improving cardiovascular outcomes. In this paper, the authors provide an overview of PUFAs and a summary of key clinical trial data. Recent trial data suggest the use of prescription eicosapentaenoic acid ethyl ester for atherosclerotic cardiovascular disease event reduction in selected populations.

Gastric antral vascular ectasia in a patient with lupus undergoing hemodialysis: a case report.

BACKGROUND: Gastric antral vascular ectasia (GAVE), associated with autoimmune diseases, such as systemic lupus erythematosus, and hepatic or renal disorders, is a rare cause of gastrointestinal bleeding. We report the case of a patient with lupus erythematosus undergoing hemodialysis with an uncorrectable anemia caused by GAVE. CASE PRESENTATION: A 76-year-old Korean woman with lupus undergoing hemodialysis frequently complained of symptoms or signs associated with anemia, such as dizziness, dyspnea, hypotension, melena, and hematemesis. Gastrointerstinal endoscopy revealed multiple erythematous and hyperemic mucosal lesions at the distal antrum without active bleeding, a finding compatible with GAVE. Although she frequently complained of symptoms or signs associated with anemia and had frequent gastrointestinal endoscopies with or without pre-emptive argon plasma coagulation, her clinical status is relatively stable, and she is undergoing maintenance hemodialysis without anticoagulants. CONCLUSION: This clinical case suggests that GAVE should be considered as a cause of the anemia resistant to erythropoiesis-stimulating agents and iron supplementation in patients with chronic kidney disease and lupus.

Green Tea Encourages Growth of Akkermansia muciniphila.

Trillions of microorganisms reside in the hosts' gut. Since diverse activities of gut microbiota affect the hosts' health status, maintenance of gut microbiota is important for maintaining human health. Green tea (GT) has multiple beneficial effects on energy metabolism with antiobesity, antidiabetic, and hypolipidemic properties. As GT contains a large amount of bioactive ingredients (e.g., catechins), which can be metabolized by microorganisms, it would be feasible that consumption of GT may cause compositional changes in gut microbiota, and that the changes in gut microbiota would be associated with the beneficial effects of GT. In this study, we demonstrated that consumption of GT extract relieves high-fat diet-induced metabolic abnormalities. Interestingly, GT administration significantly encouraged the growth of Akkermansia muciniphila (Akkermansia), a beneficial microorganism to relieve obesity and related metabolic disorders. Finally, we found that epigallocatechin gallate is the component of GT that stimulates the growth of Akkermansia. According to these data, we propose that GT could be a prebiotic agent for Akkermansia to treat metabolic syndromes.

Optimizing screening and management of cardiovascular health in prostate cancer: A review.

In clinical practice, cancer management does not consistently encompass screening and identification of cardiovascular (CV) risk. The use of androgen deprivation therapy (ADT) in prostate cancer has been associated with increased CV risk and development of metabolic syndrome, necessitating identification of patients at risk in this population (e.g., those with pre-existing CV disease). A multidisciplinary team of Canadian physicians was assembled to develop a series of recommendations intended to identify patients who may benefit from optimal management of their CV disease and/or modification of cardiac risk factors. A key goal was the development of a simple screening tool for identification of patients with pre-existing CV disease. This simple and inclusive set of recommendations are intended for use within urology clinics to facilitate holistic approaches and simplify the management of patients.

Management of Plaque Psoriasis With Biologic Therapies in Women of Child-Bearing Potential Consensus Paper.

BACKGROUND: Plaque psoriasis (PsO) is a chronic inflammatory disease that often presents at peak reproductive age in women of child-bearing potential (WOCBP). With the emergence of biologic therapies to treat PsO, guidance on disease management in WOCBP is needed to inform treatment decisions before, during, and after pregnancy. OBJECTIVES: To develop a practical, up-to-date consensus document, based on available evidence and expert opinion where evidence was lacking, in order to guide both Canadian and international clinicians treating PsO in WOCBP. METHODS: A panel of 9 Canadian dermatologists with extensive clinical experience managing PsO reviewed the relevant literature from the past 25 years in 3 key domains: overview of PsO in WOCBP and clinical considerations, treatment considerations, and postpartum considerations. The structured literature search focused on WOCBP treated with TNF-alpha inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab), IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab), IL-12/23 inhibitors (ustekinumab), and IL-17 inhibitors (brodalumab, ixekizumab, secukinumab). This literature review, along with clinical expertise and opinion, was used to develop concise and clinically relevant consensus statements to guide practical management of PsO in WOCBP. Experts voted on the statements using a modified Delphi process and prespecified agreement cut-off of 75%. RESULTS AND IMPLICATIONS: After review, discussion, and voting on 19 draft consensus statements at an in-person meeting and remotely, 12 consensus statements were approved by the expert panel. The statements presented here will guide healthcare providers in practical disease management using biologic therapies for the treatment of PsO in WOCBP.

Feeding high-oleic peanuts to meat-type broiler chickens enhances the fatty acid profile of the meat produced.

Early feeding trials using peanut meal prepared from normal-oleic peanuts helped to identify peanuts as a suitable alternative feed ingredient for poultry. Yet no studies to date have examined the use of high-oleic peanuts (HO-PN) as a feed ingredient for meat type chickens. Therefore, this study aimed to determine the effect of feeding whole unblanched HO-PN on the fatty acid profile of the meat produced from broilers. At hatch male chicks were randomly placed in raised wire cages, in 10 replicate pens per treatment with 10 chicks per pen, and fed with one of the 3 isocaloric, isonitrogenous diets ad libitum for 42 days: (1) conventional control of soybean meal + corn, (2) 10 to 12% HO-PN and corn diet, or (3) control diet spiked with ≈6.0% oleic acid oil. All body weights (BW) were collected, and broiler selection for processing was determined by individual BW within one-half a standard deviation of the experiment 42-D mean BW, with one bird selected per pen (10 replicate pens per treatment, 3 treatments, 10 birds selected per treatment, yielding a total sample size of 30 birds). Performance was determined weekly and breast samples were analyzed for fatty acid and amino acid profile. All data was analyzed using analysis of variance, with t-test mean comparisons at P < 0.05. BW were similar between broilers fed the HO-PN and control diet, while feed conversion ratio of broilers fed the HO-PN diet was significantly higher at weeks 2, 4, and 6 in comparison to the other treatments (P ≤ 0.03). Broilers fed with HO-PN diet had reduced carcass and pectoralis major weights in comparison to the other treatments. Chicken breast from broilers fed the HO-PN diet had significantly reduced saturated and trans fatty acid content in comparison to the controls (P ≤ 0.0002). Although additional studies must be conducted, this study suggests that feeding whole unblanched HO-PN to broiler chickens may serve as a means to enrich the meat produced with unsaturated fatty acids.

Incomplete recovery from rocuronium-induced muscle relaxation in patients with amyotrophic lateral sclerosis using sugammadex: A case report.

INTRODUCTION: Patients with motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), have higher sensitivity to nondepolarizing neuromuscular blocking agents (NMBAs) and are at higher risk for a residual block. For this reason, the use of NMBAs such as rocuronium has been limited owing to the delayed reversal of muscle relaxation. It was recently reported that rapid and effective reversal of muscle relaxation occurs when sugammadex, a muscle relaxant reversal drug, is administered to patients in ALS with rocuronium-induced muscle relaxation. However, in this paper, we report the incomplete recovery and recurarization of muscle relaxation after sugammadex administration in ALS patients, and delayed recovery of muscle relaxation after additional administration of sugammadex. PATIENT CONCERNS: A 71-year-old male patient with ALS received general anesthesia for laparoscopic nephroureterectomy. DIAGNOSIS: The patient was diagnosed with ALS 2 years earlier, and scheduled to undergo laparoscopic nephroureterectomy for ureteral cancer. INTERVENTION: We used sugammadex for the reversal of deep neuromuscular block. We measured a train-of-four (TOF) count of 4 and a TOF ratio of 54% at about 8 min after administration of 4 mg/kg sugammadex. However, then the TOF count decreased to 1 to 3 and tidal volume (TV) decreased to < 100 mL. Therefore, an additional 50 mg sugammadex was administered intravenously 12 min after the first dose of sugammadex was injected. OUTCOMES: The patient's vital signs were stable and his recovery from anesthesia was uneventful. Therefore, he was discharged to the intensive care unit. The patient had aspiration pneumonia symptoms owing to dysphagia on the third postoperative day, but after the symptoms improved he was transferred to the hospital for rehabilitation of dysphagia and dyspnea. CONCLUSION: It is critical to monitor whether muscle relaxation is sufficiently reversed when using sugammadex in ALS patients. Further research is needed to determine the appropriate dose of sugammadex for muscle relaxation reversal.

Comparison of volumetric and shape changes of subcortical structures based on 3-dimensional image between obesity and normal-weighted subjects using 3.0 T MRI.

The morphological changes of the brain, particularly in the integrity of white and gray matter and the cortical thickness of brain, have been investigated extensively in obese patients. While there has been a growing amount of evidence indicating that subcortical structures are associated with obesity, studies on the volume of subregional level including shape alterations using high-field MRI are very sparse. The aim of this study was to evaluate and compare the volumes of 14 subcortical structures (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens) in obese and normal-weighted subjects using 3T MRI for high resolution imaging. Fifty-four volunteers, 27 obesity (age = 23.15 ± 3.22, body mass index (BMI) = 30.12 ± 3.77) and 27 normal weighted controls (age = 26.1 ± 5.78, BMI = 21.76 ± 1.74) participated in the study. Through volumetric analysis, we found that the obese subjects had enlarged bilateral thalamus, putamen, pallidus and hippocampus, reduced bilateral caudate in obese groups in comparison to normal-weighted groups. Furthermore, we found that the medial-dorsal part of bilateral caudate significantly shrank while the lateral-dorsal part of bilateral thalamus significantly increased through vertex-based analysis (p < 0.05). Thus, based on our evidence, we suggest that subcortical structures are associated with feeding behavior and sensory function in obese patients.