Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths.

BACKGROUND: Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. METHODS: In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. RESULTS: During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. CONCLUSIONS: In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

Resistance Exercise Sessions Comprising Multijoint vs. Single-Joint Exercises Result in Similar Metabolic and Hormonal Responses, But Distinct Levels of Muscle Damage in Trained Men.

ABSTRACT: Barbosa, PH, Bueno de Camargo, JB, Jonas de Oliveira, J, Reis Barbosa, CG, Santos da Silva, A, Dos-Santos, JW, Verlengia, R, Barreira, J, Braz, TV, and Lopes, CR. Resistance exercise sessions comprising multijoint vs. single-joint exercises result in similar metabolic and hormonal responses, but distinct levels of muscle damage in trained men. J Strength Cond Res 38(5): 842-847, 2024-Resistance-type exercise (RE) elicits distinct acute metabolic and hormonal responses, which can be modulated by the manipulation of training variables. The purpose of this study was to compare the metabolic (blood lactate and estimated lactic anaerobic system energy expenditure) and hormonal (growth hormone [GH]) responses to RE sessions composed exclusively of multijoint (MULTI) or single-joint (SINGLE) exercises. Assessments of creatine kinase (CK) levels were also performed. In a crossover design, 10 recreationally resistance-trained men (age: 26.9 ± 3.0 years, total body mass: 83.2 ± 13.8 kg; height: 176 ± 7.0 cm; training experience: 5.5 ± 2.4 years) were randomly submitted to both protocols. Blood collections were made pre, 3 minutes after, and 36 hours after each experimental session. No significant difference between MULTI vs. SINGLE was observed for the rises in blood lactate (p = 0.057) and GH (p = 0.285) levels. For CK, a significant difference between the protocols was noted, in which MULTI resulted in significant rises after 3 minutes (p = 0.017) and 36 hours (p = 0.043) compared with SINGLE. In conclusion, the findings of this study suggest that resistance-trained individuals display similar metabolic and hormonal responses when performing MULTI and SINGLE exercise protocols. Also, RE sessions comprising MULTI exercises induce a higher magnitude of muscle damage, which may require a longer recovery period compared with SINGLE.

Effect of increased alcohol consumption during COVID-19 pandemic on alcohol-associated liver disease: A modeling study.

BACKGROUND AND AIMS: Alcohol consumption increased during the COVID-19 pandemic in 2020 in the United States. We projected the effect of increased alcohol consumption on alcohol-associated liver disease (ALD) and mortality. APPROACH AND RESULTS: We extended a previously validated microsimulation model that estimated the short- and long-term effect of increased drinking during the COVID-19 pandemic in individuals in the United States born between 1920 and 2012. We modeled short- and long-term outcomes of current drinking patterns during COVID-19 (status quo) using survey data of changes in alcohol consumption in a nationally representative sample between February and November 2020. We compared these outcomes with a counterfactual scenario wherein no COVID-19 occurs and drinking patterns do not change. One-year increase in alcohol consumption during the COVID-19 pandemic is estimated to result in 8000 (95% uncertainty interval [UI], 7500-8600) additional ALD-related deaths, 18,700 (95% UI, 17,600-19,900) cases of decompensated cirrhosis, and 1000 (95% UI, 1000-1100) cases of HCC, and 8.9 million disability-adjusted life years between 2020 and 2040. Between 2020 and 2023, alcohol consumption changes due to COVID-19 will lead to 100 (100-200) additional deaths and 2800 (2700-2900) additional decompensated cirrhosis cases. A sustained increase in alcohol consumption for more than 1 year could result in additional morbidity and mortality. CONCLUSIONS: A short-term increase in alcohol consumption during the COVID-19 pandemic can substantially increase long-term ALD-related morbidity and mortality. Our findings highlight the need for individuals and policymakers to make informed decisions to mitigate the impact of high-risk alcohol drinking in the United States.

Estimating Joint Health State Utility Algorithms Under Partial Information.

OBJECTIVES: We explored the performance of existing joint health state utility estimators when data are not available on utilities that isolate single-condition health states excluding any co-occurring condition. METHODS: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions-III, we defined 2 information sets: (1) a full-information set that includes the narrowly defined health state utilities used in most studies that test the performance of joint health state utility estimators, and (2) a limited information set that includes only the more broadly defined health state utilities more commonly available to researchers. We used an example of alcohol use disorder co-occurring with cirrhosis of the liver, depressive disorder, or nicotine use disorder to illustrate our analysis. RESULTS: We found that the performance of joint health state utility estimators is appreciably different under limited information than under full information. Full-information estimators typically overestimate the joint state utility, whereas limited-information estimators underestimate the joint state utility, except for the minimum estimator, which is overestimated in all cases. CONCLUSIONS: Researchers using joint health state utility estimators should understand the information set available to them and use methodological guidance appropriate for that information set. We recommend the minimum estimator under limited information based on its ease of use, consistency (and therefore a predictable direction of bias), and lower root mean squared error.

Synergistic Effects of Warming and Internal Nutrient Loading Interfere with the Long-Term Stability of Lake Restoration and Induce Sudden Re-eutrophication.

Phosphorus (P) precipitation is among the most effective treatments to mitigate lake eutrophication. However, after a period of high effectiveness, studies have shown possible re-eutrophication and the return of harmful algal blooms. While such abrupt ecological changes were attributed to the internal P loading, the role of lake warming and its potential synergistic effects with internal loading, thus far, has been understudied. Here, in a eutrophic lake in central Germany, we quantified the driving mechanisms of the abrupt re-eutrophication and cyanobacterial blooms in 2016 (30 years after the first P precipitation). A process-based lake ecosystem model (GOTM-WET) was established using a high-frequency monitoring data set covering contrasting trophic states. Model analyses suggested that the internal P release accounted for 68% of the cyanobacterial biomass proliferation, while lake warming contributed to 32%, including direct effects via promoting growth (18%) and synergistic effects via intensifying internal P loading (14%). The model further showed that the synergy was attributed to prolonged lake hypolimnion warming and oxygen depletion. Our study unravels the substantial role of lake warming in promoting cyanobacterial blooms in re-eutrophicated lakes. The warming effects on cyanobacteria via promoting internal loading need more attention in lake management, particularly for urban lakes.

Association between physical activity measured by accelerometry and cognitive function in older adults: a systematic review.

OBJECTIVE: To analyze studies that investigated the association between physical activity assessed by accelerometry and cognitive function in older people. METHODS: A systematic review was carried out in four electronic databases (PubMed, Web of Science, Scopus, and SportsDiscus). RESULTS: In total, 195 records were identified. Fifty-two studies were selected for a full evaluation; 23 were selected according to the inclusion criteria adopted and divided into four chapters (characteristics of the studies, the association between physical activity level and cognitive function decline, effects of physical activity in reducing the chances of cognitive function decline and effects of physical activity on brain plasticity. The cross-sectional studies had an average score of 7 points, and the cohort studies obtained 10 points, indicating the high quality of the selected studies. Seven studies indicated an association between Moderate to vigorous physical activities (MVPA) and cognitive function, two specifically indicated a reduction in the chances of cognitive function decline according to the interquartile of MVPA, and three studies indicated improvements in MVPA in brain plasticity. CONCLUSION: Measured by accelerometry, seems to be favorably associated with important outcomes in cognitive function assessed through questionnaires, imaging analyses, and biochemical markers with older adults.

Analysis of Susceptibility to Degradation of Water Ecosystem Services as a Tool for Land Use Planning: a Case Study in a Small Brazilian Watershed.

Mapping priority areas for environmental conservation and restoration is essential to informing policy formulation and decision-making. This study proposes a methodology based on multicriteria analysis and on-site assessment to develop environmental zoning that enhances the provision of water ecosystem services (WES) from Brazil's Água Quente River Basin. Integrated analysis of multiple criteria enabled identification of degrees of susceptibility to degradation, assessment of effects of land-use changes between 1990 and 2020, and validation of the study's methodology via field protocol. The results indicated that the spatial and temporal patterns of WES susceptibility to degradation varied little within the study area with the most critical levels occurring primarily in the Agua Quente's floodplain, where there are sandy textured soils and coverage with a low degree of soil protection. Zoning analysis designates 40% of the basin`s area as consolidated use, 28% for environmental conservation, 19% as anthropic use, and 13% for environmental restoration. Field analysis indicates that the occurrence of degraded areas and pollution by solid waste and urban effluents are relevant factors that affect the basin's water resources. Linear regression analysis indicated a good fit between the data modeled by the multicriteria analysis and those observed on-site (R² = 0.6 p < 0.05). The study's method is effective and its structure can be used in other river basins, as its approach is simple and flexible and can be readily adjusted to fit the characteristics of the study site.

Economic Evaluation of Interventions to Address Opioid Misuse: A Systematic Review of Methods Used in Simulation Modeling Studies.

OBJECTIVES: Several evidence-based interventions exist for people who misuse opioids, but there is limited guidance on optimal intervention selection. Economic evaluations using simulation modeling can guide the allocation of resources and help tackle the opioid crisis. This study reviews methods employed by economic evaluations using computer simulations to investigate the health and economic effects of interventions meant to address opioid misuse. METHODS: We conducted a systematic mapping review of studies that used simulation modeling to support the economic evaluation of interventions targeting prevention, treatment, or management of opioid misuse or its direct consequences (ie, overdose). We searched 6 databases and extracted information on study population, interventions, costs, outcomes, and economic analysis and modeling approaches. RESULTS: Eighteen studies met the inclusion criteria. All of the studies considered only one segment of the continuum of care. Of the studies, 13 evaluated medications for opioid use disorder, and 5 evaluated naloxone distribution programs to reduce overdose deaths. Most studies estimated incremental cost per quality-adjusted life-years and used health system and/or societal perspectives. Models were decision trees (n = 4), Markov (n = 10) or semi-Markov models (n = 3), and microsimulations (n = 1). All of the studies assessed parameter uncertainty though deterministic and/or probabilistic sensitivity analysis, 4 conducted formal calibration, only 2 assessed structural uncertainty, and only 1 conducted expected value of information analyses. Only 10 studies conducted validation. CONCLUSIONS: Future economic evaluations should consider synergies between interventions and examine combinations of interventions to inform optimal policy response. They should also more consistently conduct model validation and assess the value of further research.

Scaling Up Hepatitis C Prevention and Treatment Interventions for Achieving Elimination in the United States: A Rural and Urban Comparison.

In the United States, hepatitis C virus (HCV) transmission is rising among people who inject drugs (PWID). Many regions have insufficient prevention intervention coverage. Using modeling, we investigated the impact of scaling up prevention and treatment interventions on HCV transmission among PWID in Perry County, Kentucky, and San Francisco, California, where HCV seroprevalence among PWID is >50%. A greater proportion of PWID access medication-assisted treatment (MAT) or syringe service programs (SSP) in urban San Francisco (established community) than in rural Perry County (young, expanding community). We modeled the proportion of HCV-infected PWID needing HCV treatment annually to reduce HCV incidence by 90% by 2030, with and without MAT scale-up (50% coverage, both settings) and SSP scale-up (Perry County only) from 2017. With current MAT and SSP coverage during 2017-2030, HCV incidence would increase in Perry County (from 21.3 to 22.6 per 100 person-years) and decrease in San Francisco (from 12.9 to 11.9 per 100 person-years). With concurrent MAT and SSP scale-up, 5% per year of HCV-infected PWID would need HCV treatment in Perry County to achieve incidence targets-13% per year without MAT and SSP scale-up. In San Francisco, a similar proportion would need HCV treatment (10% per year) irrespective of MAT scale-up. Reaching the same impact by 2025 would require increases in treatment rates of 45%-82%. Achievable provision of HCV treatment, alongside MAT and SSP scale-up (Perry County) and MAT scale-up (San Francisco), could reduce HCV incidence.

Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis.

Creatine supplements are intended to improve performance, but there are indications that it can overwhelm liver and kidney functions, reduce the quality of life, and increase mortality. Therefore, this is the first systematic review and meta-analysis study that aimed to investigate creatine supplements and their possible renal function side effects. After evaluating 290 non-duplicated studies, 15 were included in the qualitative analysis and 6 in the quantitative analysis. The results of the meta-analysis suggest that creatine supplementation did not significantly alter serum creatinine levels (standardized mean difference = 0.48, 95% confidence interval 0.24-0.73, P = .001, I2 = 22%), and did not alter plasma urea values (standardized mean difference = 1.10, 95% confidence interval 0.34-1.85, P = .004, I2 = 28%). The findings indicate that creatine supplementation does not induce renal damage in the studied amounts and durations.

Routine Use of Low-Molecular-Weight Heparin For Deep Venous Thrombosis Prophylaxis After Foot and Ankle Surgery: A Cost-Effectiveness Analysis.

The purpose of the present study was to determine whether certain foot/ankle surgeries would benefit from the routine use of low-molecular-weight heparin (LMWH) as postoperative deep venous thrombosis prophylaxis. We conducted a formal cost-effectiveness analysis using a decision analytic tree to explore the healthcare costs and health outcomes associated with a scenario of no prophylaxis and a scenario of routine LMWH prophylaxis for 4 weeks. The 2 scenarios were compared for 5 procedures: (1) Achilles tendon repair (ATR), (2) total ankle arthroplasty (TAA), (3) hallux valgus surgery (HVS), (4) hindfoot arthrodesis (HA), and (5) ankle fracture surgery (AFS). The outcomes assessed included short- and long-term costs, quality-adjusted life-years (QALYs), and incremental cost per QALY gained. The costs were evaluated from the healthcare system perspective and are expressed in U.S. dollars at a 2015 price base. In the short term, routine prophylaxis was always associated with greater costs compared with no prophylaxis. For ATR, TAA, HA, and AFS, prophylaxis was associated with slightly better health outcomes; however, the gain in QALYs was minimal compared with the cost of prophylaxis (incremental cost-effectiveness ratio well above $50,000/QALY threshold). For HVS, prophylaxis was associated with both worse health outcomes and greater costs. In the long term, routine prophylaxis was always associated with worse health outcomes and either cost more (HA, AFS, HVS) or saved very little (ATR, TAA). We concluded that policies encouraging the routine use of LMWH after foot/ankle surgery are unlikely to be cost-effective. Decisions to perform prophylaxis should be on a case-by-case basis and should emphasize individual patient risk factors.

Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats.

Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be associated with abnormal HPG function. A strong negative correlation between the hyperleptinemia and lower Kiss responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads to toxic effects direct on the HPG axis and/or indirectly by abnormal metabolic regulation of the HPG axis.

Regulation of CFTR Expression and Arginine Vasopressin Activity Are Dependent on Polycystin-1 in Kidney-Derived Cells.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple, progressive, fluid-filled renal cysts that distort the renal parenchyma, leading to end-stage renal failure, mainly after the fifth decade of life. ADPKD is caused by a mutation in the PKD1 or PKD2 genes that encode polycystin-1 (PC-1) and polycystin-2 (PC-2), respectively. PC-1 is an important regulator of several signaling pathways and PC-2 is a nonselective calcium channel. The CFTR chloride channel is responsible for driving net fluid secretion into the cysts, promoting cyst growth. Arginine vasopressin hormone (AVP), in turn, is capable of increasing cystic intracellular cAMP, contributing to cell proliferation, transepithelial fluid secretion, and therefore to disease progression. The aim of this study was to assess if AVP can modulate CFTR and whether PC-1 plays a role in this potential modulation. METHODS: M1 cells, derived from mouse cortical collecting duct, were used in the current work. The cells were treated with 10-7 M AVP hormone and divided into two main groups: transfected cells superexpressing PC-1 (Transf) and cells not transfected (Ctrl). CFTR expression was assessed by immunodetection, CFTR mRNA levels were quantified by quantitative reverse transcription-polymerase chain reaction, and CFTR net ion transport was measured using the Ussing chamber technique. RESULTS: AVP treatment increased the levels of CFTR protein and mRNA. CFTR short-circuit currents were also increased. However, when PC-1 was overexpressed in M1 cells, no increase in any of these parameters was detected. CONCLUSIONS: CFTR chloride channel expression is increased by AVP in M1 cells and PC-1 is capable of regulating this modulation.

In vitro activity of 3ß-O-tigloylmelianol from Guarea kunthiana A. Juss (Meliaceae) on oogenesis and ecdysis of the cattle tick Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae).

We evaluated the effects of 3ß-O-tigloylmelianol from Guarea kunthiana A. Juss (Meliaceae) on oogenesis, as a larvicide and on ecdysis of the larvae and the nymphs of the cattle tick Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae). On the oogenesis' test, 48 engorged females were divided into three groups, evaluated at 24, 48 and 72 h post-treatment. Half of the females were treated with 0.01% 3ß-O-tigloylmelianol diluted in distilled water and 5% dimethyl sulfoxide (DMSO), while the other half (controls) were exposed to distilled water and 5% DMSO. After treatment, the ovaries were weighed in order to measure the gonadosomatic index (GSI) and were also subjected to standard histological technical tests. On the larvicide and ecdysis' tests, 3ß-O-tigloylmelianol was tested at concentrations of 0.01, 0.005, 0.0025 and 0.00125%. Compared with the controls, there was a reduction of GSI of approximately 50% on the treated group, which started at 48 h post treatment. Overall, the protolimonoid 3ß-O-tigloylmelianol has caused a significant reduction in the number of oocytes. It has also caused alteration of the cytoplasmic and germinal vesicle diameters. Morphological changes, such as vacuolization, chorion irregularity which has modified the oocytes' morphology as well as alterations on the yolk's granules were also observed. The compound was not larvicide, however, interfered in the ecdysis of the larvae and the nymphs. This study shows that the protolimonoid 3ß-O-tigloylmelianol from G. kunthiana acts on oogenesis and ecdysis of R. (B.) microplus, but not as larvicide, indicating that it acts on the endocrine system of the tick.

Utility of inline milk fat and protein ratio to diagnose subclinical ketosis and to assign propylene glycol treatment in lactating dairy cows.

The objective was to identify a fat-to-protein ratio (FPR) cut-off to diagnose subclinical ketosis (SCK) and to evaluate the effect of propylene glycol (PPG) treatment of cows with high FPR. The optimized cut-off was > 1.42; sensitivity (Se) = 92%; specificity (Sp) = 65%. A cut-off > 1.5 was selected for the PPG trial for balanced Se-Sp. Fat-to-protein ratio cut-offs > 1.25, 1.35, 1.50, 1.60, and 1.70 resulted in Se-Sp of 100% to 49%, 96% to 59%, 75% to 78%, 33% to 90%, and 8% to 96%, respectively. The proportions of cows with FPR > 1.25, 1.35, 1.42, 1.50, 1.60, and 1.70 were 60%, 50%, 44%, 30%, 14%, and 6%, respectively. Incidences of clinical ketosis and milk yield were similar between cows that received 400 mL of PPG (n = 34) and control cows (n = 38). Prevalence of SCK at enrollment was 29.2%; therefore, FPR > 1.5 is not indicated for treatment. Lower cut-offs should be used for screening.

Utilité du ratio de matière grasse et de protéine sur la ligne de traite pour diagnostiquer une cétose subclinique et assigner le traitement au propylèneglycol chez les vaches laitières en lactation. L'objectif consistait à identifier un seuil du ratio de matière grasse et de protéine (RMGP) pour diagnostiquer une cétose subclinique et évaluer l'effet du traitement au propylèneglycol (PPG) chez les vaches présentant un RMGP élevé. Le seuil optimisé était de > 1,42; la sensibilité (Se) = 92 %; la spécificité (Sp) = 65 %. Un seuil de > 1,5 a été choisi pour l'essai au PPG pour des Se-Sp équilibrées. Des seuils de ratios de matière grasse et protéine de > 1,25, 1,35, 1,50, 1,60 et 1,70 ont produit des Se-Sp de 100 % et 49 %, de 96 % et 59 %, 75 % et 78 %, de 33 % et 90 % et de 8 % et 96 %, respectivement. Les proportions des vaches avec un RMGP de > 1,25, 1,35, 1,42, 1,50, 1,60 et 1,70 étaient de 60 %, 50 %, 44 %, 30 %, 14 % et 6 %, respectivement. L'incidence de cétose clinique et la production de lait étaient semblables entre les vaches qui avaient reçu 400 mL de PPG (n = 34) et les vaches témoins (n = 38). La prévalence de cétose subclinique au recrutement était de 29,2 %; par conséquent, un RMGP de > 1,5 n'est pas indiqué pour le traitement. Des seuils inférieurs devraient être utilisés pour le dépistage.(Traduit par Isabelle Vallières).

3ß-O-tigloylmelianol from Guarea kunthiana: a new potential agent to control Rhipicephalus (Boophilus) microplus, a cattle tick of veterinary significance.

Chemical investigation of Guarea kunthiana fruits, guided by their effect on the reproductive cycle of engorged females of the cattle tick Rhipicephalus (Boophilus) microplus-a major economic problem to the livestock industry worldwide-led to isolation of 3ß-O-tigloylmelianol, a new protolimonoid, from the bioactive hexane phase obtained by partitioning the crude ethanol extract. An adult immersion test was performed. The compound strongly inhibited egg-laying and hatchability (99.2% effectiveness at a 0.01% concentration). Melianone, isolated from the same phase, yielded unremarkable results in the adult immersion test. From the dichloromethane phase, melianol, melianodiol, meliantriol, and a new protolimonoid, 3ß-O-tigloylmeliantriol, were isolated, all of which, in the same manner as melianone, exhibited unremarkable results in the test. The structures of new and known compounds were mostly established by 1D- and 2D-NMR analyses and mass spectrometry data. This is the first report on the bioactivity of protolimonoids on the reproductive cycle of engorged females of R. (B.) microplus. 3ß-O-Tigloylmelianol proved a promising candidate for the development of a biocontrol agent against the cattle tick investigated, as an alternative to environmentally hazardous synthetic acaricides.

Simulated impact of medicaid expansion on the economic burden of opioid use disorder in North Carolina.

BACKGROUND: Opioid use disorder (OUD) imposes significant costs on state and local governments. Medicaid expansion may lead to a reduction in the cost burden of OUD to the state. METHODS: We estimated the health care, criminal justice and child welfare costs, and tax revenue losses, attributable to OUD and borne by the state of North Carolina in 2022, and then estimated changes in the same domains following Medicaid expansion in North Carolina (adopted in December 2023). Analyses used existing literature on the national and state-level costs attributable to OUD to estimate individual-level health care, criminal justice, and child welfare system costs, and lost tax revenues. We combined Individual-level costs and prevalence estimates to estimate costs borne by the state before Medicaid expansion. Changes in costs after expansion were computed based on a) medication for opioid use disorder (MOUD) access for new enrollees and b) shifting of responsibility for some health care costs from the state to the federal government. Monte Carlo simulation accounted for the impact of parameter uncertainty. Dollar estimates are from the 2022 price year, and costs following the first year were discounted at 3 %. RESULTS: In 2022, North Carolina incurred costs of $749 million (95 % credible interval [CI]: $305 M-$1,526 M) associated with OUD (53 % in health care, 36 % in criminal justice, 7 % in lost tax revenue, and 4 % in child welfare costs). Expanding Medicaid lowered the cost burden of OUD incurred by the state. The state was predicted to save an estimated $72 million per year (95 % CI: $6 M-$241 M) for the first two years and $30 million per year (95 % CI: -$28 M-$176 M) in subsequent years. Over five years, savings totaled $224 million (95 % CI: -$47 M-$949 M). CONCLUSION: Medicaid expansion has the potential to decrease the burden of OUD in North Carolina, and policymakers should expedite its implementation.

Population genetics and genomics of Triatoma brasiliensis (Hemiptera, Reduviidae) in an area of high pressure of domiciliary infestation in Northeastern Brazil.

Understanding the population dynamics of vectors is crucial for effective control of vector-borne diseases. In the Northeastern Brazilian semi-arid region, Triatoma brasiliensis persists as the most significant Chagas disease vector, frequently displaying recurrent domiciliary infestations. This situation raises relevant public health concerns in the municipality of Currais Novos in the state of Rio Grande do Norte. This area has experienced a high prevalence of peridomiciliary re-infestations by T. brasiliensis, coupled with elevated rates of Trypanosoma cruzi infection. Therefore, we assessed the distribution of genetic variation via mitochondrial Cytochrome b gene (MT-CYB) sequencing (n = 109) and single nucleotide polymorphisms (SNPs, n = 86) to assess the gene flow among distinct populations distributed in varied geographic spots and environments, mainly sylvatic and peridomiciliary. Insects were collected from rural communities at Currais Novos, enclosed within a 16 km radius. Sampling included 13 populations: one intradomiciliary, eight peridomiciliary, and four sylvatic. Furthermore, an external population located 220 km from Currais Novos was also included in the study. The method employed to obtain SNP information relied on ddRAD-seq genotyping-by-sequencing (GBS), enabling a genome-wide analysis to infer genetic variation. Through AMOVA analysis of MT-CYB gene variation, we identified four distinct population groups with statistical significance (FCT= 0.42; p<0.05). We identified a total of 3,013 SNPs through GBS, with 11 loci showing putative signs of being under selection. The variation based on 3,002 neutral loci evidenced low genetic structuration based on low FST values (p>0.05), indicating local panmixia. However, resampling algorithms pointed out that three samples from the external population were assigned (>98 %) in a cluster contrasting from the ones putatively under local panmixia - validating the newly applied genome-wide marker for studies on the population genetics at finer-scale resolution for T. brasiliensis. The presence of population structuring in some of the sampled points, as suggested by the mitochondrial marker, leads us to assume that infestations were probably initiated by small populations of females - demographic event poses a risk for rapid re-infestations. The local panmictic pattern revealed by the GBS marker poses a challenge for vector control measures, as re-infestation foci may be distributed over a wide geographical and ecological range. In such instances, vectors exhibit reduced susceptibility to conventional insecticide spraying operations since sylvatic populations are beyond the reach of these interventions. The pattern of infestation exhibited by T. brasiliensis necessitates integrating innovative strategies into the existing control framework, holding the potential to create a more resilient and adaptive vector control program. In our dataset, the results demonstrated that the genetic signals from both markers were complementary. Therefore, it is essential to consider the nature and inheritance pattern of each marker when inferring the pattern of re-infestations.

From molecules to ecosystems: Insights into a network of interactions for a Chagas disease outbreak using Triatoma brasiliensis as natural samplers.

Exploring the dynamics of disease transmission involves an understanding of complex interactions within the eco-epidemiologic framework. In the context of Chagas disease (CD), elements are mainly represented by the interactions among the pathogen, insect vector, host, humans and the environment. We performed quantitative and qualitative analyses on a dataset derived from 98 Triatoma brasiliensis infected by trypanosomatids, which were linked to a CD outbreak in the semi-arid region of northeastern Brazil. We extracted invertebrate-derived DNA (iDNA) from these insects, comprising 18 populations around the outbreak area, each indicative of various strata of anthropogenic influence. Food source (FS) diversity, representing potential parasite reservoirs, was determined through mitochondrial gene (cyt b) sequencing of vertebrates, and parasite genotyping was accessed using fluorescent amplified fragment barcodes (FFLB) of trypanosomatids. We also assessed the residents' awareness of breeding sites for CD vectors in the inspected houses. The quantification of Trypanosoma cruzi was estimated via real-time PCR and is denominated here as the average parasite load (PL) per insect (T. cruzi/intestinal unit). We aimed to address vector-parasite-host-environment interactions that were discussed based on their significance among the components. Notably, among the significant interactions, we observed that the PL in the insects was significantly influenced by FS. Infected insects that fed on the classic reservoir, Didelphis albiventris, and Galea spixii exhibited higher PLs, compared to those that fed on Kerodon rupestris (p < 0.04)-a primary host. While D. albiventris is already recognized as a synanthropic species, we propose that G. spixii may also be undergoing a synanthropic process. Conversely, domestic cats are frequently identified as FS in infected insects from the sylvatic environment, suggesting a possible change in their behavior towards a wild state. Therefore, we propose that neglected anthropogenic actions have facilitated the reciprocal (sylvatic-peridomestic) circulation of T. cruzi-especially noted for TcI because it was predominant in insects found in peridomestic environments. Residents are often unaware of the existence of insect breeding grounds near their homes, particularly when it involves the storage of materials without planning for use, such as piles of tiles, bricks and wood. Although indirect inferences about the interaction among vector-parasite-host-environment are still incipient, we highlight the potential use of vectors as natural samplers of biological and ecological components in transmitting the disease.