Structure-activity relationships of thiadiazole agonists of the human secretin receptor.

Agonists of the secretin receptor have potential applications for diseases of the cardiovascular, gastrointestinal, and metabolic systems, yet no clinically-active non-peptidyl agonists of this receptor have yet been developed. In the current work, we have identified a new small molecule lead compound with this pharmacological profile. We have prepared and characterized a systematic structure-activity series around this thiadiazole scaffold to better understand the molecular determinants of its activity. We were able to enhance the in vitro activity and to maintain the specificity of the parent compound. We found the most active candidate to be quite stable in plasma, although it was metabolized by hepatic microsomes. This chemical probe should be useful for in vitro studies and needs to be tested for in vivo pharmacological activity. This could be an important lead toward the development of a first-in-class orally active agonist of the secretin receptor, which could be useful for multiple disease states.

Establishment of a multisite umbrella cohort study protocol to describe the epidemiology and aetiologies of acute undifferentiated febrile illness in Latin America.

INTRODUCTION: Acute undifferentiated febrile illnesses (AUFIs) impose a large burden in the tropics. Understanding of AUFI's epidemiology is limited. Insufficient diagnostic capacity hinders the detection of outbreaks. The lack of interconnection in healthcare systems hinders timely response. We describe a protocol to study the epidemiology and aetiologies of AUFI and pathogen discovery in strategic areas of Latin America (LA). METHODS AND ANALYSIS: Global Infectious Diseases Network investigators comprising institutions in Colombia, Dominican Republic, México, Perú and the USA, developed a common cohort study protocol. The primary objective is to determine the aetiologies of AUFI at healthcare facilities in high-risk areas. Data collection and laboratory testing for viral, bacterial and parasitic agents are performed in rural and urban healthcare facilities and partner laboratories. Centralised laboratory and data management cores deploy diagnostic tests and data management tools. Subjects >6 years with fever for <8 days without localised infection are included in the cohort. They are evaluated during the acute and convalescent phases of illness. Study personnel collect clinical and epidemiological information. Blood, urine, nasal or pharyngeal swabs and saliva are collected in the acute phase and blood in convalescent phase. Specimens are banked at -80°C. Malaria, dengue and COVID-19 are tested onsite in the acute phase. The acute-phase serum is PCR tested for dengue, chikungunya, Venezuelan equine encephalitis, Mayaro, Oropouche, Zika, and yellow fever viruses. Paired convalescent and acute serum antibody titters are tested for arbovirus, Leptospira spp, and Rickettsia spp. Serum is used for viral cultures and next-generation sequencing for pathogen discovery. Analysis includes variable distributions, risk factors and regression models. Laboratory results are shared with health authorities and network members. ETHICS AND DISSEMINATION: The protocol was approved by local ethics committees and health authorities. The results will be published in peer-reviewed journals. All study results are shared with local and regional health authorities.

Anthropometry for predicting cardiometabolic disease risk factors in adolescents.

OBJECTIVE: Early screening prevents chronic diseases by identifying at-risk adolescents through anthropometric measurements, but predictive value in diverse groups is uncertain. METHODS: A cross-sectional analysis of 12- to 19-year-old individuals from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) assessed the predictive ability of BMI percentile, total body fat percentage, waist circumference (WC), and waist-hip ratio (WHR) for four cardiometabolic risk factors across race and ethnicity groups using receiver operating characteristic curves. RESULTS: The unweighted sample (N = 1194; 51.2% male individuals; 23.7% Hispanic, 13.2% non-Hispanic Black [NHB], 51.1% non-Hispanic White [NHW], 12.0% other/multirace) had a weighted prevalence of elevated blood pressure of 2.7%, hyperglycemia of 36.8%, hypertriglyceridemia of 4.8%, and low high-density lipoprotein (HDL) cholesterol of 15%. WHR (area under the curve [AUC] = 0.77), WC (AUC = 0.77), and BMI percentile (AUC = 0.73) outperformed total body fat percentage (AUC = 0.56) in predicting elevated blood pressure (p < 0.001 for all). BMI percentile was more accurate than total body fat percentage in predicting hypertriglyceridemia (AUC = 0.70 vs. 0.59; p = 0.02) and low HDL cholesterol (AUC = 0.69 vs. 0.59; p < 0.001). Race and ethnicity-based predictions varied: NHW adolescents had the highest AUC (0.89; p < 0.01) for elevated blood pressure prediction compared with Hispanic and NHB adolescents (AUC = 0.77 for both). Total body fat percentage was more accurate in predicting low HDL cholesterol among Hispanic versus NHW adolescents (AUC = 0.73 vs. 0.58; p = 0.04). CONCLUSIONS: WHR, WC, and BMI percentile are better predictors of cardiometabolic risk factors in adolescents than total body fat percentage. Predictive abilities differed by race and ethnicity, highlighting the importance of tailored risk assessment strategies.

Internal world models in humans, animals, and AI.

How do brains-biological or artificial-respond and adapt to an ever-changing environment? In a recent meeting, experts from various fields of neuroscience and artificial intelligence met to discuss internal world models in brains and machines, arguing for an interdisciplinary approach to gain deeper insights into the underlying mechanisms.

Association of Social Support and Metabolic and Bariatric Surgery Completion Among Racially and Ethnically Diverse Patients.

PURPOSE: Metabolic and bariatric surgery (MBS) is presently the most evidence-based, effective treatment of obesity. Nevertheless, only half of the eligible individuals who are referred for this procedure complete it. This study aims to investigate the association between social support and MBS completion, considering race and ethnicity. METHODS: In this prospective cohort study, 413 participants were enrolled between 2019 and 2022. Using the 19-item Brief Family Relationship Scale, which comprises three subscales (eight-item Cohesion subscale, four-item Expressiveness subscale, and seven-item Conflict subscale), the quality of family relationship functioning was assessed. Multivariable logistic regression models were used to determine the association between MBS completion and social support status, adjusting for variables including race, ethnicity, age, gender, body mass index, and insurance. RESULTS: The mean age of the sample was 47.55 years (SD 11.57), with 87% of the participants being female and 39% non-Hispanic White. Nearly 35% of participants (n = 145) completed MBS. Multivariable logistic regression analysis showed overall cohesion (adjusted odds ratio [aOR], 1.52 [95% CI, 1.15-2.00]; p = .003) and overall expressiveness (aOR, 1.58 [95% CI, 1.22-2.05]; p < .001) were associated with higher odds of pursuing MBS. There was no significant interaction between overall cohesion, expressiveness, conflict, and race/ethnicity (p = .61, p = .63, p = .25, respectively). CONCLUSION: The findings indicated that there is a link between family-based social support and MBS completion, regardless of race and ethnicity. Future research should continue to explore the complex interplay between family dynamics and MBS outcomes, considering cultural variations to enhance the effectiveness of obesity interventions within diverse communities.

Disparities in Patient Family Social Determinants of Health in a Large Urban Pediatric Health System.

INTRODUCTION: This analysis sought to identify disparities in social determinants of health (SDOH) outcomes at a Texas pediatric hospital. METHODS: This retrospective study used electronic health records of pediatric patients families surveyed August -December 2022. Outcomes for health literacy, social support, food, transportation, energy, digital, and housing insecurity, and tobacco exposure were analyzed across demographic categories. RESULTS: Among 15,294 respondents to the survey (mean child age, 8.73 years; 43.68% Hispanic, 29.73% non-Hispanic White, 18.27% non-Hispanic Black, 6.79% other race/ethnicity; 53.95% male), 50.25% of respondents reported at least one SDOH, whereas 23.39% reported two or more SDOH. The most prevalent SDOH was lack of social support (3,456, 23.91%). Hispanic, non-Hispanic Black, and other race/ethnicity respondents, non-English speakers, and public insurance users had higher odds of reporting almost all SDOH in logistic regression models adjusted for age, race/ethnicity, language, gender, and insurance type. DISCUSSION: Race/ethnicity, language, and insurance type disparities were identified for all SDOH.

Adaptation of a standardized lifestyle intervention to maximize health outcomes in adolescent metabolic and bariatric surgery patients.

BACKGROUND: Metabolic and bariatric surgery (MBS) is safe and efficacious in treating adolescents with severe obesity. Behavioral/lifestyle programs can support successful preparation for surgery and post-MBS weight loss, but no standardized lifestyle intervention exists for adolescents. Here we describe the process of developing and adapting the Diabetes Prevention Program Group Lifestyle Balance (DPP/GLB) curriculum to support adolescents pre- and post-MBS. METHODS: We collected both qualitative and quantitative data from a diverse group of adolescents (N = 19, mean age 15.2 years, range 13-17, 76% female, 42% non-Hispanic Black, 41% Hispanic, 17% other). Additionally, we included data from 13 parents, all of whom were mothers. These participants were recruited from an adolescent MBS program at Children's Health System of Texas. In an online survey, we asked participants to rank their preferences and interests in DPP/GLB content topics. We complemented these results with in-depth interviews from a subset of 10 participants. This qualitative data triangulation informed the development of the TeenLYFT lifestyle intervention program, designed to support adolescents who were completing MBS and described here. This program was adapted from adolescent and parent DPP/GLB content preferences, incorporating the social cognitive model (SCM) and the socioecological model (SEM) constructs to better cater to the needs of adolescent MBS patients. RESULTS: Adolescents' top 3 ranked areas of content were: (1) steps to adopt better eating habits and healthier foods; (2) healthy ways to cope with stress; and (3) steps to stay motivated and manage self-defeating thoughts. Nearly all adolescent participants preferred online delivery of content (versus in-person). Mothers chose similar topics with the addition of information on eating healthy outside the home. Key themes from the adolescent qualitative interviews included familial support, body image and self-confidence, and comorbidities as key motivating factors in moving forward with MBS. CONCLUSIONS: The feedback provided by both adolescents and parents informed the development of TeenLYFT, an online support intervention for adolescent MBS candidates. The adapted program may reinforce healthy behaviors and by involving parents, help create a supportive environment, increasing the likelihood of sustained behavior change. Understanding adolescent/parent needs to support weight management may also help healthcare providers improve long-term health outcomes for this patient population.

Suitability of containerized toxicant to control Solenopsis invicta (Hymenoptera: Formicidae) threatening cave species in Bexar County, Texas.

Several protected troglobitic invertebrate species are known to occur in caves on Joint Base San Antonio-Camp Bullis, Bexar County, Texas, United States. The United States Fish and Wildlife Service (USFWS) identified red-imported fire ant Solenopsis invicta (hereafter RIFA) (Buren 1972) as the primary threat to cave species' nutrient sources, cave crickets, Ceuthophilus secretus (Scudder 1894). Per the service's recommendations, Joint Base San Antonio-Camp Bullis currently implements boiling water mound injections with digging for RIFA control. However, treatment effectiveness is highly variable and largely dependent on the time of day, weather, and personnel diligence. Toxicants have been used for RIFA treatment throughout the world, but concerns exist that traditional applications of toxicant bait around caves might be accessible and inadvertently affect nontarget arthropods, including cricket populations. To mitigate this accessibility, physically limiting access to the toxicant from crickets may be an option. Our objectives were to (i) compare and evaluate the effectiveness of Amdro (Hydramethylnon) and Advion (Indoxacarb) granular baits housed in Ants-No-More Bait Stations (Kness MFG. Inc., Albia, IA) and (ii) evaluate the distance of effectiveness of each bait within a bait station. Ultimately, we observed a 98% reduction in RIFA mound abundance from both baits. Additionally, RIFA mounds within 10 m of the containerized toxicant were reduced by 70%. Our pilot study suggested that Ants-No-More Bait Stations are an effective way to reduce RIFA mounds by 70% if placed 10 m from each other. In practice, this could include bait stations completely covering a particular distance to a cave entrance or fewer bait stations in a ring barrier at a single radial distance to a cave entrance. Containerized toxicants may be a cost-effective and safe RIFA control option around protected cave environments, but further studies are needed to determine potential effects on nontarget arthropods, optimal bait station configuration, and potential effects of biomagnification.

Outcomes for 160 Consecutive Lateral Arm Free Flaps for Head and Neck Reconstruction.

OBJECTIVE: Examine outcomes for lateral arm autologous tissue transfer in head and neck reconstruction. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary cancer center. METHODS: All patients who underwent traditional lateral arm, extended lateral arm, and lateral forearm flaps for head and neck reconstruction from 2012 to 2022 were assessed. Disabilities of the arm, shoulder, and hand (DASH) was measured. Factors associated with complications and enteral or mixed diet were evaluated by multivariable regression. RESULTS: Among 160 patients followed for a median of 2.3 ± 2.1 years, defects were 54% oral tongue, 18% external, 9% maxilla, 8% buccal mucosa, 9% floor of mouth, and 3% pharynx. Flap types (and median pedicle lengths) were 41% traditional lateral arm (8 cm), 25% extended lateral arm (11.5 cm), and 34% lateral forearm (14 cm). All donor sites were closed primarily; 19.6% and 0% of patients had increased DASH scores 2 and 12 weeks after reconstruction. Major complications occurred in 18.1% of patients, including 6.3% reoperation, 6.9% readmission, 3.7% fistula, and 1.8% flap loss. Complications were independently associated with peripheral vascular disease (odds ratio [OR]: 5.71, 95% confidence interval [CI]: 1.5-21.6, P = .01), pharyngeal defects (OR: 11.3, 95% CI: 1.4-94.5, P = .025), and interposition vein grafts (OR: 3.78, 95% CI: 1.1-13.3, P = .037). CONCLUSION: The lateral arm free flap was safe, versatile, and reliable for head and neck reconstruction with low donor-site morbidity. Complications occurred in a fifth of patients and were associated with peripheral vascular disease, pharyngeal defects, and vein grafts.

Factors Associated with the Decision to Complete Bariatric Metabolic Surgery among a Racially and Ethnically Diverse Sample of Adults: A Classification and Regression Tree Analysis.

BACKGROUND: Less than 50% of eligible candidates who are referred complete Bariatric Metabolic Surgery (BMS). The factors influencing the decision to complete BMS, particularly how these factors vary across different racial and ethnic groups, remain largely unexplored. METHODS: This prospective cohort study included adult patients referred to a bariatric surgeon or obesity medicine program between July 2019-September 2022. Sociodemographic characteristics, body mass index (BMI), anxiety, depression, body appreciation, and patient-physician relationship information were collected via survey and electronic health records. The association between BMS completion and potential decision-driving factors was examined using Classification and Regression Tree (CART) analysis. RESULTS: A total of 406 BMS -eligible patients participated in the study (mean [SD] age: 47.5 [11.6] years; 87.2% women; 18.0% Hispanic, 39% non-Hispanic Black [NHB], and 39% non-Hispanic White [NHW]; mean [SD] BMI: 45.9 [10.1] kg/m2). A total of 147 participants (36.2%) completed BMS. Overall, the most influential factor driving the decision to complete BMS was younger age (< 68.4 years), higher patient satisfaction, and BMI (≥ 38.0 kg/m2). Hispanic participants prioritized age (< 55.4 years), female sex, and body appreciation. For NHB participants, the highest ranked factors were age < 56.3 years, BMI ≥ 35.8 kg/m2, and higher patient satisfaction. For NHW patients, the most influential factors were age (39.1 to 68.6 years) and higher body appreciation. CONCLUSION: These findings highlight racial and ethnic group differences in the factors motivating individuals to complete BMS. By acknowledging these differences, healthcare providers can support patients from different backgrounds more effectively in their decision-making process regarding BMS.

Impact of employment status and work setting on body weight and health behaviors among people with obesity.

BACKGROUND: The impact of employment and the work-from-home (WFH) setting on body weight among people with obesity is unknown. OBJECTIVE: This study examined the relationship between employment status, WFH setting, and change in body weight among adults with obesity during the COVID-19 pandemic. METHODS: Patients from an obesity medicine clinic completed an online survey in 2022 to assess health, work, and lifestyle behaviors. Multiple regression models examined the association between WFH status and change in body weight. RESULTS: The analytical sample included 380 patients (81.9% female, mean age 52.5 years, mean body mass index 43.25, 50.0% non-Hispanic White, 25.7% non-Hispanic Black, 18.7% Hispanic, 5.7% other ethnicity). During the pandemic, 28.7% were employed in a WFH setting (73.4% of this subgroup were in a WFH setting only), 36.1% were employed but not in a WFH setting, 11.8% were unemployed, and 23.4% were retired. Mean body weight change for participants who partially WFH during the pandemic was +5.4 (±7.2) % compared to those completely WFH -0.3 (±9.8) % (P = 0.006). After adjusting for key demographics, participants who were partially WFH gained 7.8% more weight compared to those completely WFH (ß= 7.28, SE = 1.91, p < 0.001). The most significant predictors for weight gain after adjusting for WFH frequency (partially vs. completely) included overeating (aOR 11.07, 95% CI 3.33-36.77), more consumption of fast food (aOR 7.59, 95% 2.41-23.91), and depression (aOR 6.07, 95% CI 1.97-18.68). CONCLUSION: These results show that during the COVID-19 pandemic, the WFH hybrid (combination of office and WFH) setting is associated with greater weight gain compared to those who completely WFH in people with obesity. Risk factors include overeating, higher fast food consumption, and depression.

Gestational Serum Retinol Deficiency Is Associated with Enamel Hypoplasia.

Enamel hypoplasia (EH) is a prevalent developmental defect of teeth that can result from various insults, including prenatal nutrient deficiencies. This study aimed to evaluate the association between prenatal serum retinol deficiency and EH in the deciduous teeth of offspring at 2-y of age. A cohort of 1,450 pregnant women was enrolled, and their prenatal nutritional status was assessed between 12 and 14 wk of gestation. Maternal serum retinol, serum 25-hydroxyvitamin D (25OHD), hemoglobin, body mass index, and birth outcomes, infant feeding practices, family socioeconomic status, and demographic information were recorded. Oral health examinations were conducted for the children semiannually, and EH was diagnosed using the Modified DDE index on all the surfaces of erupted teeth. A modified Poisson regression analysis was used to assess the cumulative risk of EH over a period of 2-y. A total of 920 (63.4%) mother-child pairs completed the study, and the cumulative EH prevalence among offspring after 2-y of follow-up was 16.5% (N = 152; 87/1,114 children in the first year and 132/920 in the second year, with 20/920 having EH only in the first year). After adjusting for potential confounders, maternal serum retinol deficiency significantly increased the risk of deciduous EH (risk ratio [RR], 2.0; 95% confidence interval [CI], 1.1-3.7). In addition, deficient serum 25OHD (RR, 6.5; 95% CI, 4.0-10.7), caesarean delivery (RR, 1.6; 95% CI, 1.0-2.4), Muslim (RR, 2.9; 95% CI, 2.0-4.1) and Christian (RR, 2.4; 95% CI, 1.6-3.5) versus Hindu religions, and very preterm birth (RR, 1.7; 95% CI, 1.1-2.9) increased the risk of EH. Children presenting with EH had 2 or more teeth affected, and the maxillary incisors were the most frequently affected, followed by the first primary molars and canines. In conclusion, maternal serum retinol deficiency during the 12 to 14 wk of gestation may increase the risk of deciduous EH, besides the well-established 25OHD deficiency.

Using the Photoluminescence Color Change in Cesium Lead Iodide Nanoparticles to Monitor the Kinetics of an External Organohalide Chemical Reaction by Halide Exchange.

In this work, we demonstrate a photoluminescence-based method to monitor the kinetics of an organohalide reaction by way of detecting released bromide ions at cesium lead halide nanoparticles. Small aliquots of the reaction are added to an assay with known concentrations of CsPbI3, and the resulting Br-to-I halide exchange (HE) results in rapid and sensitive wavelength blueshifts (Δλ) due to CsPbBrxI3-x intermediate concentrations, the wavelengths of which are proportional to concentrations. An assay response factor, C, relates Δλ to Br- concentration as a function of CsPbI3 concentration. The observed kinetics, as well as calculated rate constants, equilibrium, and activation energy of the solvolysis reaction tested correspond closely to synthetic literature values, validating the assay. Factors that influence the sensitivity and performance of the assay, such as CsPbI3 size, morphology, and concentration, are discussed.

Ionic liquid-based dispersive liquid-liquid microextraction of anthelmintic drug residues in small-stock meat followed by LC-ESI-MS/MS detection.

An ionic liquid-based dispersive liquid-liquid microextraction (IL-DLLME) of 20 anthelmintic drugs followed and detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed, optimized, and validated. The parameters affecting the anthelmintic extraction efficiencies such as selection of extraction solvent (ionic liquids), selection of disperser solvent, volume of extraction solvent, volume of disperser solvent, pH of the aqueous phase, extraction time, salt addition, and centrifugation time were optimized. Validation was conducted according to ISO/IEC 17025:2017 and Commission Implementing Regulation (EU) 2021/808 of 22 March 2021. Validation parameters such as calibration function, matrix effect, limit of detection (LOD), limit of quantification (LOQ), decision limit (CCα), accuracy, and precision were established. Coefficient of determination (R 2) values ranging from .99938 to .99995 were obtained using the matrix calibration curve spiked at 0, 0.25, 1.0, 1.5, and 2.0 times MRL. The LODs and LOQs were calculated using the standard deviation of the response and the slopes of the calibration curves ranged from 0.35 to 26.1 µg/kg and from 1.2 to 87.0 µg/kg, respectively, and were dependent on calibration range. The CCα values ranged from 23 to 1022.0 µg/kg and are also dependent on the MRL concentration levels. The coefficient of variation (CV) values calculated are within the reproducibility range of 16%-30% adapted from the Horwitz Equation CV = 2(1-0.5 log C) and ranged from 1.7% to 16.9%. The developed and validated and the standard QuEChERS method were compared. The IL-DLLME LC-MS/MS method was applied to 32 small stock (18 caprine [goat] and 14 ovine [sheep]) liver samples received from municipal abattoirs at Botswana National Veterinary Laboratory for the analysis of anthelmintic drug residues. The results obtained indicated that the anthelmintic drug residues were all below the detection capability, and therefore, the samples were passed as fit for human consumption.

Persistent symptoms and conditions among children and adolescents hospitalised with COVID-19 illness: a qualitative study.

OBJECTIVES: There is limited in-depth research exploring persistent symptoms and conditions among children and adolescents who contracted COVID-19 illness that required hospitalisation. The main objective of this study was to conduct qualitative interviews among families who had a child hospitalised with COVID-19 illness to elucidate their child's physical, mental and social health outcomes months after initial acute infection. DESIGN, SETTING AND PARTICIPANTS: A qualitative study that composed of in-depth interviews among families with a child hospitalised with COVID-19 illness in one large urban US paediatric healthcare system. Parents (N=25) were recruited from an ongoing quantitative study to estimate the prevalence of long COVID in children hospitalised with COVID-19 illness. During in-depth interviews, parents were invited to describe their child's post-COVID-19 symptoms and experiences. Interviews were audiotaped, transcribed and coded in NVivo. RESULTS: Seven themes were identified concerning the child's prolonged COVID-19 experiences: (1) post-traumatic stress disorder, (2) social anxiety, (3) severe symptoms on reinfection, (4) worsened pre-existing conditions, (5) lack of insurance coverage for costly treatments, (6) access and utilisation of support systems and (7) overall resilience and recovery. Four parent-specific themes were identified: (1) fear of COVID-19 unknowns, (2) mixed messaging from health information sources, (3) schools being both a support system and a hindrance and (4) desire for and access to support systems. CONCLUSIONS: A subset of children who were hospitalised with COVID-19 illness are experiencing a range of serious mental health impacts related to persistent COVID-19 symptoms. Clinical and public health support strategies should be developed to support these children and their families as they reintegrate in school, social and community activities.