Sustainability of an Opt-Out Electronic-Health Record-based Tobacco Treatment Consult Service at a large safety-net hospital: A 6-year Analysis.

INTRODUCTION: Our safety-net hospital implemented a hospital-based tobacco treatment intervention in 2016. We previously showed the intervention, an "opt-out" Electronic Health Record (EHR)-based Best Practice Alert (BPA)+order-set that triggers consultation to an inpatient Tobacco Treatment Consult (TTC) service for all patients who smoke, improves smoking abstinence. We now report on sustainability, 6 years after inception. METHODS: We analyzed data collected between July 2016-June 2022 of patients documented as 'currently smoking' in the EHR. Across the 6 years, we used Pearson's correlation analysis to compare Adoption (clinician acceptance of the BPA+order-set, thus generating consultation to the TTC service); Reach (number of consultations completed by the TTC service); and Effectiveness (receipt of pharmacotherapy orders between patients receiving and not receiving consultations). RESULTS: Among 39,558 adult admissions (July 2016-June 2022) with "currently smoking" status in the EHR for whom the BPA triggered, clinicians accepted the TTC order-set on 50.4% (19,932/39,558), though acceptance varied across services [e.g., Cardiology (71%) and Obstetrics-Gynecology (12%)]. The TTC service consulted on 17% (6779/39,558) of patients due to staffing constraints. Consultations ordered (r=-0.28, p=0.59) and completed (r= 0.45, p=0.37) remained stable over six-years. Compared to patients not receiving consultations, patients receiving consultations were more likely to receive pharmacotherapy orders overall (inpatient: 50.8% vs 35.1%, p<.0001; at discharge: 27.1% vs 10%, p<.0001) and in each year. CONCLUSIONS: The "opt-out" EHR-based TTC service is sustainable, though many did not receive consultations due to resource constraints. Healthcare systems should elevate priority of hospital-based tobacco treatment programs to increase reach to underserved populations. IMPLICATIONS: Our study shows that opt-out approaches that utilize the EHR are a sustainable approach to provide evidence-based tobacco treatment to all hospitalized individuals who smoke, regardless of readiness to stop smoking and clinical condition.

Brucella abortus induces mast cell activation through TLR-2 and TLR-4.

The Gram-negative bacteria Brucella abortus is a major cause of brucellosis in animals and humans. The host innate immune response to B. abortus is mainly associated with phagocytic cells such as dendritic cells, neutrophils, and macrophages. However, as mast cells naturally reside in the main bacterial entry sites they may be involved in bacterial recognition. At present, little is known about the role of mast cells during B. abortus infection. The role of the innate immune receptors TLR2 and TLR4 in activation of mast cells by B. abortus (strain RB51) infection was analyzed in this study. The results showed that B. abortus did not induce mast cell degranulation, but did induce the synthesis of the cytokines IL-1ß, IL-6, TNF-α, CCL3, CCL4, and CCL5. Furthermore, B. abortus stimulated key cell signaling molecules involved in mast cell activation such as p38 and NF-κB. Blockade of the receptors TLR2 and TLR4 decreased TNF-α and IL-6 release by mast cells in response to B. abortus. Taken together, our results demonstrate that mast cells are activated by B. abortus and may play a role in inducing an inflammatory response during the initial phase of the infection.

Health-Related Quality of Life Scores and Values as Predictors of Mortality: A Scoping Review.

Health-related quality of life (HRQoL) can be assessed through measures that can be generic or disease specific, encompass several independent scales, or employ holistic assessment (i.e., the derivation of composite scores). HRQoL measures may identify patients with differential risk profiles. However, the usefulness of generic and holistic HRQoL measures in identifying patients at higher risk of death is unclear. The aim of the present study was to undertake a scoping review of generic, holistic assessments of HRQoL as predictors of mortality in general non-patient populations and clinical sub-populations with specified conditions or risk factors in persons 18 years or older. Five databases were searched from 18 June to 29 June 2020 to identify peer-reviewed published articles. The searches were updated in August 2022. Reference lists of included and cited articles were also searched. Of 2552 articles screened, 110 met criteria for inclusion. Over one-third of studies were from North America. Most studies pertained to sub-populations with specified conditions and/or risk factors, almost a quarter for people with cardiovascular diseases. There were no studies pertaining to people with mental health conditions. Nearly three-quarters of the studies used a RAND Corporation QoL instrument, predominantly the SF-36, and nearly a quarter, a utility instrument, predominantly the EQ-5D. HRQoL was associated with mortality in 67 of 72 univariate analyses (92%) and 100 of 109 multivariate analyses (92%). HRQoL was found to be associated with mortality in the general population and clinical sub-populations with physical health conditions. Whether this relationship holds in people with mental health conditions is not known. HRQoL assessment may be useful for screening and/or monitoring purposes to understand how people perceive their health and well-being and as an indicator of mortality risk, encouraging better-quality and timely patient care to support and maximize what may be a patient's only modifiable outcome.

Warning labels on alcoholic beverage containers: a pilot randomized experiment among young adults in Mexico.

BACKGROUND: Little is known about the potential impacts of visible and up-to-date health warning labels on alcoholic beverage containers on a range of outcomes in low- and middle-income countries. We conducted an experimental study to test the potential impacts of visible health warning labels (on the principal panel of the package) on thinking about health risks, product attractiveness, visual avoidance, and intention to change alcohol use among students in Mexico aged 18-30 years. METHODS: A double-blind, parallel-group, online randomized trial was conducted from November 2021 to January 2022 in 11 states in Mexico. In the control group, participants were presented with the image of a conventional beer can with a fictional design and brand. In the intervention groups, the participants observed pictograms with a red font and white backgrounds (health warning label in red-HWL red) or with a black font and yellow backgrounds (health warning label in yellow-HWL yellow), located at the top, covering around one-third of the beer can. We used Poisson regression models -unadjusted and adjusted for covariates- to assess differences in the outcomes across study groups. RESULTS: Using intention-to-treat analysis (n = 610), we found more participants in groups HWL red and HWL yellow thought about the health risks from drinking beer compared to the control group [Prevalence Ratio (PR) = 1.43, CI95%:1.05,1.93 for HWL red; PR = 1.25, CI95%: 0.91, 1.71 for HWL yellow]. A lower percentage of young adults in the interventions vs control group considered the product attractive (PR 0.74, 95%CI 0.51, 1.06 for HWL red; PR 0.56, 95%CI 0.38, 0.83 for HWL yellow). Although not statistically significant, a lower percentage of participants in the intervention groups considered buying or consuming the product than the control group. Results were similar when models were adjusted for covariates. CONCLUSIONS: Visible health warning labels could lead individuals to think about the health risks of alcohol, reducing the attractiveness of the product and decreasing the intention to purchase and consume alcohol. Further studies will be required to determine which pictograms or images and legends are most contextually relevant for the country. TRIAL REGISTRATION: The protocol of this study was retrospectively registered on 03/01/2023: ISRCTN10494244.

Utilización de servicios de salud en México: cascada de atención primaria en 2022.

OBJETIVO: Presentar un panorama descriptivo de las elecciones de la población mexicana frente a una necesidad de salud en 2022. Material y métodos. Se utilizaron datos de la Encuesta Nacional de Salud y Nutrición Continua 2022. RESULTADOS: De 24.6% de la población que informó haber tenido una necesidad de salud en los últimos tres meses, 44% recibió atención en servicios públicos. El uso de servicios privados es extensivo a toda la población, pero fue más elevado en aquellos sin derechohabiencia. Se encontró que 71% de los motivos por los que las personas no se atendieran en el lugar que les correspondía de acuerdo con su derechohabiencia tuvo que ver con el acceso y 21% con la percepción de calidad. Entre los motivos de acceso para elegir el lugar donde se atendieron destacan la afiliación, la cercanía y el costo. En cuanto a la calidad, resaltan la atención rápida y la satisfacción con la atención. CONCLUSIONES: Con el fin de reducir la desigualdad de acceso y el gasto de bolsillo asociado con un mayor uso de servicios privados, sobre todo entre la población sin seguridad social, mejorar el acceso (como la distancia, los horarios de atención, las barreras burocráticas) puede ayudar a avanzar en este objetivo.

A closer look at alcohol-induced changes in the ghrelin system: novel insights from preclinical and clinical data.

Ghrelin is a gastric-derived peptide hormone with demonstrated impact on alcohol intake and craving, but the reverse side of this bidirectional link, that is, the effects of alcohol on the ghrelin system, remains to be fully established. To further characterize this relationship, we examined (1) ghrelin levels via secondary analysis of human laboratory alcohol administration experiments with heavy-drinking participants; (2) expression of ghrelin, ghrelin receptor, and ghrelin-O-acyltransferase (GOAT) genes (GHRL, GHSR, and MBOAT4, respectively) in post-mortem brain tissue from individuals with alcohol use disorder (AUD) versus controls; (3) ghrelin levels in Ghsr knockout and wild-type rats following intraperitoneal (i.p.) alcohol administration; (4) effect of alcohol on ghrelin secretion from gastric mucosa cells ex vivo and GOAT enzymatic activity in vitro; and (5) ghrelin levels in rats following i.p. alcohol administration versus a calorically equivalent non-alcoholic sucrose solution. Acyl- and total-ghrelin levels decreased following acute alcohol administration in humans, but AUD was not associated with changes in central expression of ghrelin system genes in post-mortem tissue. In rats, alcohol decreased acyl-ghrelin, but not des-acyl-ghrelin, in both Ghsr knockout and wild-type rats. No dose-dependent effects of alcohol were observed on acyl-ghrelin secretion from gastric mucosa cells or on GOAT acylation activity. Lastly, alcohol and sucrose produced distinct effects on ghrelin in rats despite equivalent caloric value. Our findings suggest that alcohol acutely decreases peripheral ghrelin concentrations in vivo, but not in proportion to alcohol's caloric value or through direct interaction with ghrelin-secreting gastric mucosal cells, the ghrelin receptor, or the GOAT enzyme.

Health-related quality of life in people with psychotic disorders: The role of loneliness and its contributors.

BACKGROUND: Perception of loneliness has been identified as the strongest predictor of health-related quality of life assessed with the Assessment of Quality of Life-4D in people with psychotic disorders. We aimed to establish contributors to perceived loneliness, and ascertain the mediating role of loneliness in the relationship between identified contributors to loneliness and other known predictors of health-related quality of life with health-related quality of life. METHODS: Data for 1642 people collected as part of the 2010 Australian National Survey of Psychosis were analysed. Health-related quality of life was assessed using the Assessment of Quality of Life-4D, and loneliness through a single-item five-level categorical variable. To identify independent contributors to loneliness, a statistical model was constructed with reference to a theoretical model comprising 23 variables. A predictive model with health-related quality of life as the dependent variable was then developed and tested to assess the mediating role of loneliness. RESULTS: Nine contributors to loneliness were found (social dysfunction, experienced stigma, contact with friends, diagnosis, depressive symptoms, anxiety, mental health service utilisation, arthritis and traumatic events in childhood), with social dysfunction the strongest. In the prediction of health-related quality of life, all contributors to loneliness were partially mediated through loneliness (except service utilisation) as were negative symptoms and use of psychotropic/anticholinergic medications. CONCLUSION: Assuming a plausible causal model of mediation, loneliness was found to have direct and indirect effects on health-related quality of life in people with psychotic disorders. Findings add impetus to efforts to develop and trial strategies aimed at reducing loneliness in this population, and, in turn, improving their health-related quality of life.

Mechanisms of disease-modifying effect of saracatinib (AZD0530), a Src/Fyn tyrosine kinase inhibitor, in the rat kainate model of temporal lobe epilepsy.

We have recently demonstrated the role of the Fyn-PKCδ signaling pathway in status epilepticus (SE)-induced neuroinflammation and epileptogenesis in experimental models of temporal lobe epilepsy (TLE). In this study, we show a significant disease-modifying effect and the mechanisms of a Fyn/Src tyrosine kinase inhibitor, saracatinib (SAR, also known as AZD0530), in the rat kainate (KA) model of TLE. SAR treatment for a week, starting the first dose (25 mg/kg, oral) 4 h after the onset of SE, significantly reduced spontaneously recurring seizures and epileptiform spikes during the four months of continuous video-EEG monitoring. Immunohistochemistry of brain sections and Western blot analyses of hippocampal lysates at 8-day (8d) and 4-month post-SE revealed a significant reduction of SE-induced astrogliosis, microgliosis, neurodegeneration, phosphorylated Fyn/Src-419 and PKCδ-tyr311, in SAR-treated group when compared with the vehicle control. We also found the suppression of nitroxidative stress markers such as iNOS, 3-NT, 4-HNE, and gp91phox in the hippocampus, and nitrite and ROS levels in the serum of the SAR-treated group at 8d post-SE. The qRT-PCR (hippocampus) and ELISA (serum) revealed a significant reduction of key proinflammatory cytokines TNFα and IL-1ß mRNA in the hippocampus and their protein levels in serum, in addition to IL-6 and IL-12, in the SAR-treated group at 8d in contrast to the vehicle-treated group. These findings suggest that SAR targets some of the key biomarkers of epileptogenesis and modulates neuroinflammatory and nitroxidative pathways that mediate the development of epilepsy. Therefore, SAR can be developed as a potential disease-modifying agent to prevent the development and progression of TLE.

Inducible nitric oxide synthase inhibitor, 1400W, mitigates DFP-induced long-term neurotoxicity in the rat model.

Chemical nerve agents (CNA) are increasingly becoming a threat to both civilians and military personnel. CNA-induced acute effects on the nervous system have been known for some time and the long-term consequences are beginning to emerge. In this study, we used diisopropylfluorophosphate (DFP), a seizurogenic CNA to investigate the long-term impact of its acute exposure on the brain and its mitigation by an inducible nitric oxide synthase (iNOS) inhibitor, 1400W as a neuroprotectant in the rat model. Several experimental studies have demonstrated that DFP-induced seizures and/or status epilepticus (SE) causes permanent brain injury, even after the countermeasure medication (atropine, oxime, and diazepam). In the present study, DFP-induced SE caused a significant increase in iNOS and 3-nitrotyrosine (3-NT) at 24 h, 48 h, 7d, and persisted for a long-term (12 weeks post-exposure), which led to the hypothesis that iNOS is a potential therapeutic target in DFP-induced brain injury. To test the hypothesis, we administered 1400W (20 mg/kg, i.m.) or the vehicle twice daily for the first three days of post-exposure. 1400W significantly reduced DFP-induced iNOS and 3-NT upregulation in the hippocampus and piriform cortex, and the serum nitrite levels at 24 h post-exposure. 1400W also prevented DFP-induced mortality in <24 h. The brain immunohistochemistry (IHC) at 7d post-exposure revealed a significant reduction in gliosis and neurodegeneration (NeuN+ FJB positive cells) in the 1400W-treated group. 1400W, in contrast to the vehicle, caused a significant reduction in the epileptiform spiking and spontaneous recurrent seizures (SRS) during 12 weeks of continuous video-EEG study. IHC of brain sections from the same animals revealed a significant reduction in reactive gliosis (both microgliosis and astrogliosis) and neurodegeneration across various brain regions in the 1400W-treated group when compared to the vehicle-treated group. A multiplex assay from hippocampal lysates at 6 weeks post-exposure showed a significant increase in several key pro-inflammatory cytokines/chemokines such as IL-1α, TNFα, IL-1ß, IL-2, IL-6, IL-12, IL-17a, MCP-1, LIX, and Eotaxin, and a growth factor, VEGF in the vehicle-treated animals. 1400W significantly suppressed IL-1α, TNFα, IL-2, IL-12, and MCP-1 levels. It also suppressed DFP-induced serum nitrite levels at 6 weeks post-exposure. In the Morris water maze, the vehicle-treated animals spent significantly less time in the target quadrant in a probe trial at 9d post-exposure compared to their time spent in the same quadrant 11 days previously (i.e., 2 days prior to DFP exposure). Such a difference was not observed in the 1400W and control groups. However, learning and short-term memory were unaffected when tested at 10-16d and 28-34d post-exposure. Accelerated rotarod, horizontal bar test, and the forced swim test revealed no significant changes between groups. Overall, the findings from this study suggest that 1400W may be considered as a potential therapeutic agent as a follow-on therapy for CNA exposure, after controlling the acute symptoms, to prevent mortality and some of the long-term neurotoxicity parameters such as epileptiform spiking, SRS, neurodegeneration, reactive gliosis in some brain regions, and certain key proinflammatory cytokines and chemokine.

An evaluation of multidrug-resistant Escherichia coli isolates in urinary tract infections from Aguascalientes, Mexico: cross-sectional study.

BACKGROUND: Uropathogenic Escherichia coli (UPEC) are one of the main bacteria causing urinary tract infections (UTIs). The rates of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increased dramatically in recent years and could difficult the treatment. METHODS: The aim of the study was to determine multidrug-resistant bacteria, antibiotic resistance profile, virulence traits, and genetic background of 110 E. coli isolated from community (79 isolates) and hospital-acquired (31 isolates) urinary tract infections. The plasmid-mediated quinolone resistance genes presence was also investigated. A subset of 18 isolates with a quinolone-resistance phenotype was examined for common virulence genes encoded in diarrheagenic and extra-intestinal pathogenic E. coli by a specific E. coli microarray. RESULTS: Female children were the group most affected by UTIs, which were mainly community-acquired. Resistance to trimethoprim-sulfamethoxazole, ampicillin, and ampicillin-sulbactam was most prevalent. A frequent occurrence of resistance toward ciprofloxacin (47.3%), levofloxacin (43.6%) and cephalosporins (27.6%) was observed. In addition, 63% of the strains were multidrug-resistant (MDR). Almost all the fluoroquinolone (FQ)-resistant strains showed MDR-phenotype. Isolates from male patients were associated to FQ-resistant and MDR-phenotype. Moreover, hospital-acquired infections were correlated to third generation cephalosporin and nitrofurantoin resistance and the presence of kpsMTII gene. Overall, fimH (71.8%) and fyuA (68.2%), had the highest prevalence as virulence genes among isolates. However, the profile of virulence genes displayed a great diversity, which included the presence of genes related to diarrheagenic E. coli. Out of 110 isolates, 25 isolates (22.7%) were positive to qnrA, 23 (20.9%) to qnrB, 7 (6.4%) to qnrS1, 7 (6.4%) to aac(6')lb-cr, 5 (4.5%) to qnrD, and 1 (0.9%) to qnrC genes. A total of 12.7% of the isolates harbored blaCTX-M genes, with blaCTX-M-15 being the most prevalent. CONCLUSIONS: Urinary tract infection due to E. coli may be difficult to treat empirically due to high resistance to commonly used antibiotics. Continuous surveillance of multidrug resistant organisms and patterns of drug resistance are needed in order to prevent treatment failure and reduce selective pressure. These findings may help choosing more suitable treatments of UTI patients in this region of Mexico.

Inulin Potential for Enzymatic Obtaining of Prebiotic Oligosaccharides.

Oligosaccharides have been marketed since the 80s as low-calorie agents and recently have gained interest in the pharmaceutical and food industry as functional sweeteners and prebiotic enriching population of Bifidobacteria. Currently, they have an approximated value of $200 per kg and recently, inulin has been proposed as a feedstock for production of oligosaccharides through selective hydrolysis by action of endoinulinase. High optimum temperature (60°C) and thermostability are two important criteria that determine suitability of this enzyme for industrial applications as well as enzyme cost, a major limiting factor. Significant reduction in cost can be achieved by employing low-value and abundant inulin-rich plants as Jerusalem artichoke, dahlia, yacon, garlic, and onion, among others. In general, the early harvested tubers of these plants contain a greater amount of highly polymerized sugar fractions, which offer more industrial value than late-harvested tubers or those after storage. Also, development of recombinant microorganisms could be useful to reduce the cost of enzyme technology for large-scale production of oligosaccharides. In the case of fungal inulinases, several studies of cloning and modification have been made to achieve greater efficiency. The present paper reviews inulin from vegetable sources as feedstock for oligosaccharides production through the action of inulinases, the impact of polymerization degree of inulin and its availability, and some strategies to increase oligosaccharide production.

Effect of Photoperiod On Permethrin Resistance In Aedes aegypti.

Living organisms have been exposed to light-dark cycles that allowed them to adapt to different ecological niches. Circadian cycles affect hormone release, metabolism, and response to xenobiotic compounds. Current studies have shown that insect susceptibility to toxic agents depends on circadian cycles, mainly because the biochemical processes involved in detoxification and responses to oxidative stress are modulated by this process. The goal of this study was to determine the effect of photoperiod on resistance to permethrin in Aedes aegypti . Collections of Ae. aegypti from 4 locations in Yucatan, southern Mexico, were subjected to 2 different photoperiod schemes: dark (0 h light:24 h dark) and natural photoperiod (12 h light:12 h dark). The comparison of both photoperiods was evaluated with respect to permethrin resistance using bottle bioassays and by monitoring the possible mechanism related such as enzymatic activity and by the frequency of 2 knockdown resistance mutations in the voltage-dependent sodium channel gene (V1016I and F1534C). The susceptible strain was used as a reference. The mosquitoes in dark photoperiod showed a reduction in resistance to the pyrethroid. The α-esterases and glutathione S-transferase enzymatic activities showed lower levels in the dark photoperiod, and the frequencies of V1016I knockdown resistance mutation showed significant difference between photoperiod schemes.

Susceptibility to chlorpyrifos in pyrethroid-resistant populations of Aedes aegypti (Diptera: Culicidae) from Mexico.

Resistance to the organophosphate insecticide chlorpyrifos was evaluated in females from six strains of Aedes aegypti (L.) that expressed high levels of cross-resistance to eight pyrethroid insecticides. Relative to LC50 and LC90 at 24 h of a susceptible New Orleans (NO) strain, three strains were highly resistant to chlorpyrifos (Coatzacoalcos, resistance ratio [RRLC90 = 11.97; Pozarica, RRLC90 = 12.98; and Cosoleacaque, RRLC50 = 13.94 and RRLC90 = 17.57), one strain was moderately resistant (Veracruz, RRLC90 = 5.92), and two strains were susceptible (Tantoyuca and Martinez de la Torre, RRLC50 and RRLC90 < 5) in bottle bioassays according to Centers for Disease Control and Prevention. Furthermore, high levels of alpha- or beta-esterase activity in the sample populations were correlated with resistance, suggesting that esterase activity may be a mechanism causing the development of organophosphate resistance in these populations. Overall, the populations in this study were less resistant to chlorpyrifos than to pyrethroids. Rotation of insecticides used in control activities is recommended to delay or minimize the occurrence of high levels of resistance to chlorpyrifos among local populations of Ae. aegypti. The diagnostic dose and diagnostic time for chlorpyrifos resistance monitoring was determined to be 85 microg per bottle and 30 min, respectively, using the susceptible NO strain.

Susceptibility to insecticides and resistance mechanisms in Aedes aegypti from the Colombian Caribbean Region.

We determined the susceptibility to insecticides and the biochemical and molecular mechanisms involved in resistance in nine populations of Aedes aegypti (L.) of the Colombian Caribbean region. Bioassays were performed on larvae for susceptibility to temephos and on adults to the insecticides malathion, fenitrothion, pirimiphos-methyl, permethrin, deltamethrin, λ-cyhalothrin and cyfluthrin. The resistance ratio (RR) for each insecticide in the populations was determined, using the susceptible Rockefeller strain as a susceptible control. Additionally, we evaluated the response of the populations to the diagnostic dose (DD) of the organochlorine pesticide DDT. The following biochemical mechanisms associated with resistance were studied: α-esterases, ß-esterases, mixed-function oxidases (MFO), glutathione s-transferases (GST) and insensitive acetylcholinesterase (iAChE) as well as the presence of kdr I1,016 mutation and its frequency. All populations studied showed susceptibility to the organophosphates evaluated (RR < 5-fold), except for the Puerto Colombia and Soledad populations which showed high resistance (RR 15-fold) and moderate resistance (RR 5-fold) to temephos, respectively, and Sincelejo (Sucre) with moderate resistance to pirimiphos-methyl (RR 5-fold). All populations evaluated with DD of DDT were found to be resistant with 2-28% of mortality. Variability was observed in the resistance to pyrethroids: permethrin (RR 1.2- to 30.8-fold), deltamethrin RR 0.9- to 37.8-fold), λ-cyalothrin (RR 3.4- to 83-fold) and cyfluthrin (RR 0.3- to 33.8-fold). Incipiently α-esterases and MFO levels were found in the Valledupar population; MFO showed the same profile in Cienaga and GST in the Sincelejo population, all other populations showed unaltered profiles of the enzymes evaluated. The kdr I1,016 mutation was found in all populations evaluated with variability in its allelic and genotypic frequencies.

Widespread Resistance to Temephos in Aedes aegypti (Diptera: Culicidae) from Mexico.

Organic synthetic insecticides continue to be part of the arsenal for combating vector-borne diseases in Mexico. Larvicides are a fundamental part of the process in programs for mosquito control, temephos being one of the most widely used in Mexico. In the present study, we analyzed the frequency of temephos resistance in twenty-three Aedes aegypti populations using the discriminating concentration (DC) of 0.012 mg/L. We also tested 5× DC (0.6 mg/L) and 10× DC (0.12 mg/L) of temephos. The resistance distribution to temephos was interpolated to unsampled sites using the inverse distance weighting (IDW) method. The populations of Ae. aegypti showed a high frequency of resistance (1× DC) with mortality rates below 93% in 22 of the 23 populations analyzed. Moderate resistance intensity (5× DC) was found in 78% of the populations, and high intensity (10× DC) in 30%. Predicted mortality was below 60% in the populations of the Pacific Coast, along the Gulf of Mexico, and in the state of Coahuila in Northeastern Mexico in relation to 1× DC; the Pacific Coast and Northeast patterns hold for 5× and 10× DC. The results suggest the need for rotation of the larvicide to effectively control the larval populations of the vector in the country.

Diabetic Ketoacidosis in Type 1 Diabetes Onset in Latin American Children.

OBJECTIVE: To describe the patterns of diabetic ketoacidosis (DKA) occurrence in children newly diagnosed with type 1 diabetes (T1DM) across several Latin American pediatric diabetes centers from 2018 to 2022. METHODS: A retrospective chart review included children under 18 with new-onset T1DM from 30 Latin American pediatric diabetes centers (Argentina, Chile, and Peru) between 30 December 2018 and 30 December 2022. Multiple logistic regression models examined the relationships between age, gender, medical insurance, BMI, and DKA at new-onset T1DM. As far as we know, there are no large studies in Latin American countries exploring the patterns of DKA in new-onset T1DM. RESULTS: A total of 2,026 (983 females) children, median age 9.12 (5.8 -11.7) years with new-onset-T1DM were included. Approximately 50% had no medical insurance. Mean glucose values were 467 mg/dL, pH 7.21, bicarbonate 13 mEq/L, HbA1c 11.3%, and BMI 18. The frequency of DKA was 1,229 (60.7%), out of which only 447 (36%) were severe. There was a significant decrease in the frequency of DKA as age increased: 373 (70.2%) in children under 6, 639 (61.6%) in those between 6 and 12, 217 and (47.5%) in those over 12. Children with medical insurance (58.8%) had a significantly lower frequency of DKA than those without (62.7%). The multiple logistic regression models showed that DKA was significantly and inversely associated with age [OR, 0.72 (95% CI 0.60-0.86)], BMI [OR, 0.95 (95% CI 0.92-0.99)], and medical insurance [OR, 0.75 (95% CI 0.60-0.94)] adjusted for sex. CONCLUSION: Latin American children with new-onset T1DM exhibited a substantial occurrence of DKA. Younger ages and the lack of medical insurance were significantly associated with DKA in new-onset T1DM.

Genetic or pharmacological GHSR blockade has sexually dimorphic effects in rodents on a high-fat diet.

The stomach-derived hormone ghrelin regulates essential physiological functions. The ghrelin receptor (GHSR) has ligand-independent actions; therefore, GHSR gene deletion may be a reasonable approach to investigate the role of this system in feeding behaviors and diet-induced obesity (DIO). Here, we investigate the effects of a long-term (12-month) high-fat (HFD) versus regular diet on obesity-related measures in global GHSR-KO and wild-type (WT) Wistar male and female rats. Our main findings are that the GHSR gene deletion protects against DIO and decreases food intake during HFD in male but not in female rats. GHSR gene deletion increases thermogenesis and brain glucose uptake in male rats and modifies the effects of HFD on brain glucose metabolism in a sex-specific manner, as assessed with small animal positron emission tomography. We use RNA-sequencing to show that GHSR-KO rats have upregulated expression of genes responsible for fat oxidation in brown adipose tissue. Central administration of a novel GHSR inverse agonist, PF-5190457, attenuates ghrelin-induced food intake, but only in male, not in female mice. HFD-induced binge-like eating is reduced by inverse agonism in both sexes. Our results support GHSR as a promising target for new pharmacotherapies for obesity.

Resistance to malathion and deltamethrin in Aedes aegypti (Diptera: Culicidae) from western Venezuela.

Resistance to the insecticides deltamethrin and malathion and the enzymes associated with metabolic resistance mechanisms were determined in four field populations of Aedes aegypti (L.) from western Venezuela during 2008 and 2010 using the bottle assay and the microplate biochemical techniques. For deltamethrin, mortality rates after 1 h exposure and after a 24-h recovery period were determined to calculate the 50% knock-downconcentration (KC50) and the lethal concentration (LC50), respectively. For malathion, mortality was recorded at 24 h to determine the LC50. For deltamethrin, resistance ratios of knock-down resistance and postrecovery were determined by calculating the RRKC50 and RRLC50, comparing the KC50 and LC50 values of the field populations and those of the susceptible New Orleans strain. Knock-down resistance to deltamethrin was moderate in the majority of the populations in 2008 (RRKC50 values were between 5- and 10-fold), and only one population showed high resistance in 2010 (RRKC50 > 10-fold). Moderate and high postrecovery resistance to deltamethrin was observed in the majority of the populations for 2008 and 2010, respectively. There was significantly increased expression of glutathione-S-tranferases and mixed-function oxidases. All populations showed low resistance to malathion in 2008 and 2010 with significantly higher levels of alpha-esterases for 2008 and 2010 and beta-esterases for 2008.