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Brain damage triggers diverse cellular and molecular events, with astrocytes playing a crucial role in activating local neuroprotective and reparative signaling within damaged neuronal circuits. Here, we investigated reactive astrocytes using a multidimensional approach to categorize their responses into different subtypes based on morphology. This approach utilized the StarTrack lineage tracer, single-cell imaging reconstruction and multivariate data analysis. Our findings identified three profiles of reactive astrocyte responses, categorized by their effects on cell size- and shape- related morphological parameters: "moderate", "strong," and "very strong". We also examined the heterogeneity of astrocyte reactivity, focusing on spatial and clonal distribution. Our research revealed a notable enrichment of protoplasmic and fibrous astrocytes within the "strong" and "very strong" response subtypes. Overall, our study contributes to a better understanding of astrocyte heterogeneity in response to an injury. By characterizing the diverse reactive responses among astrocyte subpopulations, we provide insights that could guide future research aimed at identifying novel therapeutic targets to mitigate brain damage and promote neural repair.
Subject(s)
Astrocytes , Astrocytes/physiology , Animals , Mice , Cell Lineage/physiology , Cluster Analysis , Single-Cell AnalysisABSTRACT
INTRODUCTION: Gastric cancer (GC) is one of the most lethal malignancies worldwide. Helicobacter pylori is the primary cause of GC; therefore, its eradication reduces the risk of developing this neoplasia. There is extensive evidence regarding quadruple therapy with relevance to the European population. However, in Latin America, data are scarce. Furthermore, there is limited information about the eradication rates achieved by antibiotic schemes in European and Latin American populations. OBJECTIVE: To compare the effectiveness of standard triple therapy (STT), quadruple concomitant therapy (QCT), and bismuth quadruple therapy (QBT) in six centers in Europe and Latin America. METHODS: A retrospective study was carried out based on the LEGACy registry from 2017 to 2022. Data from adult patients recruited in Portugal, Spain, Chile, Mexico, and Paraguay with confirmed H. pylori infection who received eradication therapy and confirmatory tests at least 1 month apart were included. Treatment success by each scheme was compared using a mixed multilevel Poisson regression, adjusting for patient sex and age, together with country-specific variables, including prevalence of H. pylori antibiotic resistance (clarithromycin, metronidazole, and amoxicillin), and CYP2C19 polymorphisms. RESULTS: 772 patients were incorporated (64.64% females; mean age of 52.93 years). The total H. pylori eradication rates were 75.20% (255/339) with STT, 88.70% (159/178) with QCT, and 91.30% (191/209) with QBT. Both quadruple therapies (QCT-QBT) showed significantly higher eradication rates compared with STT, with an adjusted incidence risk ratio (IRR) of 1.25 (p: <0.05); and 1.24 (p: <0.05), respectively. The antibiotic-resistance prevalence by country, but not the prevalence of CYP2C19 polymorphism, showed a statistically significant impact on eradication success. CONCLUSIONS: Both QCT and QBT are superior to STT for H. pylori eradication when adjusted for country-specific antibiotic resistance and CYP2C19 polymorphism in a sample of individuals residing in five countries within two continents.
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BACKGROUND: Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown. METHODS: We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis. RESULTS: Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1-1.8 and OR: 1.5 95% CI:1.1-2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6-.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73-.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6-.8) along with female Asian population (HR: .40, 95% CI: .26-.62). CONCLUSIONS: After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.
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BACKGROUND: Humoral immune response against the pre-fusion (pre-F) conformation of respiratory syncytial virus (RSV) F protein has been proposed to play a protective role against infection. An RSV pre-F maternal vaccine has been recently approved in several countries to protect young infants against RSV. We aimed to assess serum IgG titers against the pre-F and post-F conformations of RSV F protein and their association with life-threatening RSV disease (LTD) in previously healthy infants. METHODS: A prospective cohort study including hospitalized infants <12 months with a first RSV infection was conducted during 2017-2019. Patients with LTD required intensive care and mechanical respiratory assistance. RSV pre-F exclusive and post-F antibody responses were determined by post-F competition and non-competition immunoassays, respectively, and neutralizing activity was measured by plaque reduction neutralization test. RESULTS: Fifty-eight patients were included; the median age was 3.5 months and 41 % were females. Fifteen patients developed LTD. RSV F-specific antibody titers positively correlated with neutralizing antibody titers in acute and convalescent phases but, importantly, they did not associate with LTD. Acute RSV pre-F exclusive and post-F IgG titers negatively correlated with patient age (P = 0.0007 and P < 0.0001), while a positive correlation was observed between the fold changes in RSV F-specific antibody titers between convalescent and acute phase and patient age (P = 0.0014 and P < 0.0001). Infants ≤2 months exhibited significantly lower fold-changes in RSV F-specific and neutralizing antibody titers between convalescence and acute phase than older infants. Additionally, acute RSV antibody titers showed no correlation with nasal RSV load and, furthermore, nasal viral load was not associated with the development of LTD. CONCLUSIONS: This study highlights that protection against life-threatening RSV disease is not necessarily antibody-dependent. Further characterization of the immune response against RSV and its role in protection against severe disease is important for the development of the safest possible preventive strategies.
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Sleep is indispensable for health and wellbeing, but its basic function remains elusive. The locus coeruleus (LC) powerfully promotes arousal by releasing noradrenaline. We found that noradrenaline transmission is reduced by prolonged wakefulness and restored during sleep. Fiber-photometry imaging of noradrenaline using its biosensor showed that its release evoked by optogenetic LC neuron activation was strongly attenuated by three hours of sleep deprivation and restored during subsequent sleep. This is accompanied by the reduction and recovery of the wake-promoting effect of the LC neurons. The reduction of both LC evoked noradrenaline release and wake-inducing potency is activity dependent, and the rate of noradrenaline transmission recovery depends on mammalian target of rapamycin (mTOR) signaling. The decline and recovery of noradrenaline transmission also occur in spontaneous sleep-wake cycles on a timescale of minutes. Together, these results reveal an essential role of sleep in restoring transmission of a key arousal-promoting neuromodulator.
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Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is one of the mechanisms contributing to increased severity during heterotypic, secondary infection. The complement protein C1q has been shown to reduce the magnitude of ADE in vitro. Therefore, we investigated the mechanisms of C1q modulation of ADE, focusing on processes of viral entry. Using a model of ADE of DENV-1 infection in human myeloid cell lines in the presence of monoclonal antibodies, 4G2 and 2H2, we found that C1q produced nearly a 40-fold reduction of ADE of DENV-1 in K562 cells, but had no effect in U937 cells. In K562 cells, C1q reduced adsorption of DENV-1/4G2 and exerted a dual inhibitory effect on adsorption and internalization of DENV-1/2H2. Distinct endocytic pathways in the presence of antibody corresponded to conditions where C1q produced a differential action. Also, C1q did not affect the intrinsic cell response mediated by FcγR in human myeloid cells. The modulation of ADE of DENV-1 by C1q is dependent on the FcγR expressed on immune cells and the specificity of the antibody comprising the immune complex. Understanding protective and pathogenic mechanisms in the humoral response to DENV infections is crucial for the successful design of antivirals and vaccines.
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Objective: This study examines factors predicting self-reported voice symptoms in call center workers. Methods: Multivariate analysis and predictive modeling assess personal, work-related, acoustic, and behavioral factors. Generalized Linear Models (GLMs) and Receiver Operating Characteristic (ROC) curves are employed. Results: Age and sleep patterns impacted voice quality and effort, while workplace factors influenced symptom perception. Unhealthy vocal behaviors related to tense voice and increased effort, while hydration was protective. Voice acoustics showed diagnostic potential, supported by ROC data. These findings emphasize voice symptom complexity in call center professionals, necessitating comprehensive assessment. Limitations: This study recognizes its limitations, including a moderate-sized convenience sample and reliance on PROM metrics. Future research should incorporate more objective measures in addition to self-reports and acoustic analysis. Value: This research provides novel insights into the interplay of personal, occupational, and voice-related factors in developing voice symptoms among call center workers. Predictive modeling enhances risk assessment and understanding of individual susceptibility to voice disorders. Conclusion: Results show associations between various factors and self-reported voice symptoms. Protective factors include sleeping more than six hours and consistent hydration, whereas risk factors include working conditions, such as location and behaviors like smoking. Diagnostic models indicate good accuracy for some voice symptom PROMs, emphasizing the need for comprehensive models considering work factors, vocal behaviors, and acoustic parameters to understand voice issues complexity.
Objetivo: Este estudio examina los factores que predicen los síntomas de voz en los trabajadores de call centers. Métodos: Se utilizan análisis multivariados y modelos predictivos para evaluar factores personales, laborales, acústicos y de comportamiento. Se emplean Modelos Lineales Generalizados (GLM) y curvas ROC. Resultados: La edad y los patrones de sueño afectaron la calidad vocal y el esfuerzo, mientras que los factores laborales influyeron en la percepción de síntomas. Los comportamientos vocales no saludables se relacionaron con voz tensa y mayor esfuerzo, mientras que la hidratación fue protectora. Los parámetros acústicos de voz mostraron potencial diagnóstico respaldado por datos de ROC. Los hallazgos subrayan complejidad de síntomas vocales en profesionales de centros de llamadas, requiriendo una evaluación integral. Limitaciones: Este estudio reconoce sus limitaciones, que incluyen una muestra de conveniencia de tamaño moderado y la dependencia de medidas PROMs. Futuras investigaciones deberían incorporar medidas objetivas, además de los autorreportes y análisis acústico. Importancia: Esta investigación aporta nuevos conocimientos sobre factores personales, laborales y síntomas de voz en trabajadores de call centers. El modelado predictivo mejora la evaluación de riesgos y la comprensión de la susceptibilidad individual a trastornos de la voz. Conclusión: Los resultados muestran asociaciones entre diversos factores y los síntomas vocales reportados. Los factores de protección incluyen dormir más de seis horas y una hidratación constante; los factores de riesgo incluyen las condiciones de trabajo, como la ubicación y comportamientos como fumar. Los modelos de diagnóstico indican una buena precisión para algunas PROMs de síntomas de la voz, lo que subraya la necesidad de modelos integrales que tengan en cuenta los factores laborales, los comportamientos vocales y los parámetros acústicos para comprender la complejidad de los problemas de la voz.
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Background: Access to audiology services for older adults residing in sparsely populated regions is often limited compared to those in central urban areas. The geographic accessibility to follow-up care, particularly the influence of distance, may contribute to an increased risk of hearing aid abandonment. Objective: To assess the association between the home-to-healthcare-calibration-center distance and hearing aid abandonment among older adults fitted in the Chilean public health system. Methods: 455 patients who received hearing aids from two public hospitals in two regions were considered. Univariate and multivariate Poisson regression models with robust variance estimation were used to analyze the association between the geographical distance and hearing aid abandonment, accounting for confounding effects. Results: Approximately 18% of the sample abandoned the hearing aid, and around 50% reported using the hearing aid every day. A twofold increase in distance between home and the hearing center yielded a 35% (RR = 1.35; 95% CI: 1.04-1.74; p = 0.022) increased risk of hearing aid abandonment. Also, those in the second quintile had a 2.17 times the risk of abandoning the hearing aid compared to the first quintile (up to 2.3 km). Under the assumption that patients reside within the first quintile of distance, a potential reduction of 45% in the incidence of hearing aid abandonment would be observed. The observed risk remained consistent across different statistical models to assess sensitivity. Conclusion: A higher distance between the residence and the healthcare center increases hearing aid abandonment risk. The association may be explained by barriers in purchasing supplies required to maintain the device (batteries, cleaning elements, potential repairs, or maintenance).
Subject(s)
Health Services Accessibility , Hearing Aids , Humans , Hearing Aids/statistics & numerical data , Female , Aged , Male , Health Services Accessibility/statistics & numerical data , Aged, 80 and over , Chile , Hearing Loss/rehabilitationABSTRACT
Viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), use respiratory epithelial cells as an entry point for infection. Within the nasal cavity, the olfactory epithelium (OE) is particularly sensitive to infections which may lead to olfactory dysfunction. In patients suffering from coronavirus disease 2019, deficits in olfaction have been characterized as a distinctive symptom. Here, we used the K18hACE2 mice to study the spread of SARS-CoV-2 infection and inflammation in the olfactory system (OS) after 7â d of infection. In the OE, we found that SARS-CoV-2 selectively targeted the supporting/sustentacular cells (SCs) and macrophages from the lamina propria. In the brain, SARS-CoV-2 infected some microglial cells in the olfactory bulb (OB), and there was a widespread infection of projection neurons in the OB, piriform cortex (PC), and tubular striatum (TuS). Inflammation, indicated by both elevated numbers and morphologically activated IBA1+ cells (monocyte/macrophage lineages), was preferentially increased in the OE septum, while it was homogeneously distributed throughout the layers of the OB, PC, and TuS. Myelinated OS axonal tracts, the lateral olfactory tract, and the anterior commissure, exhibited decreased levels of 2',3'-cyclic-nucleotide 3'-phosphodiesterase, indicative of myelin defects. Collectively, our work supports the hypothesis that SARS-CoV-2 infected SC and macrophages in the OE and, centrally, microglia and subpopulations of OS neurons. The observed inflammation throughout the OS areas and central myelin defects may account for the long-lasting olfactory deficit.
Subject(s)
COVID-19 , Myelin Sheath , Olfactory Bulb , Olfactory Mucosa , SARS-CoV-2 , Animals , COVID-19/pathology , COVID-19/complications , Mice , Olfactory Mucosa/pathology , Olfactory Mucosa/virology , Olfactory Bulb/pathology , Olfactory Bulb/virology , Myelin Sheath/pathology , Myelin Sheath/metabolism , Microglia/pathology , Microglia/metabolism , Microglia/virology , Mice, Transgenic , Angiotensin-Converting Enzyme 2/metabolism , Olfaction Disorders/pathology , Olfaction Disorders/virology , Disease Models, Animal , Male , Inflammation/pathology , Inflammation/virology , Macrophages/pathology , FemaleABSTRACT
OBJECTIVE: COVID-19 upsurge in orotracheal intubation (OTI) has opened a new opportunity for studying associated complications. Vocal fold motion impairment (VFMI) is a known complication of OTI. The present study sought to determine the impact of OTI and prolonged OTI on the risk of developing VFMI; to identify both risk and protective factors associated with it. STUDY DESIGN: Retrospective cohort study. SETTING: Multicenter. METHODS: Medical charts were reviewed for all patients that received invasive mechanical ventilation with a subsequent flexible laryngoscopic assessment between March 2020 and March 2022. The main outcomes were the presence of VFMI, including immobility (VFI) and hypomobility (VFH). RESULTS: A total of 155 patients were included, 119 (76.8%) COVID-19 and 36 (23.2%) non-COVID-19 patients; overall 82 (52.9%) were diagnosed with VFMI. Eighty (52.3%) patients underwent a tracheostomy. The median (IQR) intubation duration was 18 (11-24.25) days, while the median (IQR) time to tracheostomy was 22 (16-29). In the adjusted model, we observed there was a 68% increased risk for VFMI from day 21 of intubation (RR: 1.68; 95% CI 1.07-2.65; P = 0.025). CONCLUSIONS: VFMI is a frequent complication in severely ill patients that undergo intubation. A prolonged OTI was associated with an increased risk of VFMI, highlighting the importance of timely tracheostomy. Further research is needed to confirm these findings in other subsets of critically ill patients.
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Numerous factors can increase the risk of severe influenza; however, a majority of severe cases occur in previously healthy children. Identification of high-risk children is important for targeted preventive interventions and prompt treatment. The aim of this study was to evaluate MUC5AC as a biomarker for influenza disease severity in children. For this, a prospective cohort study was conducted in 2019. Children hospitalized with acute respiratory infection (ARI) with confirmed positive influenza infection were enrolled. Influenza cases were identified by reverse transcriptase-polymerase chain reaction. Life-threatening disease (LTD) was defined by the need for intensive care and ventilatory support. MUC5AC, epidemiologic, and clinical risk factors were assessed. Three hundred and forty-two patients were hospitalized with ARI, of which 49 (14%) had confirmed influenza infection and 6 (12%) of them developed LTD. MUC5AC levels were higher in those patients with mild disease compared to cases with poorer outcomes. Our results show that the severity of influenza infection in children is significantly associated with low levels of MUC5AC. These findings suggest its potential as a suitable biomarker for predicting disease severity.
Subject(s)
Biomarkers , Influenza, Human , Mucin 5AC , Severity of Illness Index , Humans , Influenza, Human/diagnosis , Influenza, Human/virology , Male , Female , Biomarkers/blood , Mucin 5AC/metabolism , Prospective Studies , Child, Preschool , Infant , Child , Risk Factors , Hospitalization , Adolescent , Respiratory Tract Infections/virology , Respiratory Tract Infections/diagnosisABSTRACT
In recent years, the quest to advance fuel cell technologies has intensified, driven by the imperative to reduce reliance on hydrocarbon-derived fuels and mitigate pollutant emissions. Proton exchange membranes are a critical material of fuel cell technologies. The potential of ionic liquid-based polymer inclusion membranes or ionogels for proton exchange membrane fuel cells (PEMFCs) has recently appeared. Thermal stability, SEM-EDX characterization, NMR and IR characterization, thermogravimetric analysis, ion exchange capacity, and water uptake are key properties of these membranes which need to be investigated. In this work, ionogel based on quaternary ammonium salts, such as [N8,8,8,1+][Cl-], [N8,8,8,1+][Br-], and [N8-10,8-10,8-10,1+][Cl-] in various compositions with poly(vinyl chloride) are extensively studied and characterized based on those key properties. The best properties were obtained when a quaternary ammonium cation was combined with a bromide anion. Finally, ionogels are tested in microbial fuel cells. Microbial fuel cells based on the ionogel reach a maximum of 147 mW/m2, which represents 55% of the reference membrane (Nafion 212). These results indicate that we still have the possibility of improvement through the appropriate selection of the cation and anion of the ionic liquid. Overall, the promise of ionogel membranes as a viable alternative in fuel cell applications has been demonstrated.
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Introduction: Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE); however, it has been suggested that it may play a crucial role in reducing infections in these populations. Aim: To evaluate the role of rifaximin in preventing frequent cirrhosis-related infections [spontaneous bacterial peritonitis, pneumonia, urinary tract infection (UTI), and bacteremia], Clostridioides difficile infection, and all-cause mortality, as well as determining adverse effects and adherence to the drug. Methods: A retrospective cohort study was conducted on decompensated cirrhotic patients with history of HE between January 2017 and November 2022 at a university center. Patients with cirrhosis, regardless of their etiology and severity, were included in the study, encompassing both hospitalized and outpatient cases. The statistical analysis included adjusted general linear models, Poisson regressions, and propensity score matching. Results: We included 153 patients. The mean age in the cohort was 60.2 ± 12.3 years and 67 (43.8%) were women. The main cause of cirrhosis was metabolic dysfunction-associated steatotic liver disease 52 (38%), and the median Model of End-Stage Liver Disease sodium was 16.5 (7-32). In the cohort, 65 (45%) patients used rifaximin. The mean follow-up was 32 months. Eighty-five patients with infectious events were recorded, and a total of 164 infectious events were registered. The main infectious events were UTIs (62, 37.8%) and pneumonia (38, 23.2%). The use of rifaximin was associated with lower infection rates, displaying an incidence rate ratio (IRR) of 0.64 [95% confidence interval (CI) (0.47-0.89); p = 0.008]. However, no discernible impact on mortality outcome was observed [IRR 1.9, 95% CI (0.9-4.0); p = 0.09]. There were no reported adverse effects, and no patient discontinued the therapy due to adverse effects. Conclusion: The use of rifaximin significantly reduces infections in patients with cirrhosis and HE. Despite rifaximin was associated with a decreased all-cause mortality, this impact was not statistically significant in the adjusted analysis.
Assessing the impact of rifaximin on infections in cirrhosis This study aimed to investigate the role of rifaximin, an antibiotic commonly used to treat hepatic encephalopathy, in preventing infections and mortality in patients with cirrhosis. The retrospective cohort study included 153 decompensated cirrhotic patients with a history of hepatic encephalopathy, covering the period from January 2017 to November 2022 at a university center. Results showed that 45% of the patients in the cohort used rifaximin, and the mean follow-up duration was 32 months. A total of 164 infectious events were recorded during the study, with urinary tract infections (37.8%) and pneumonia (23.2%) being the most common. The use of rifaximin was associated with a significant reduction in infection rates, with an incidence rate ratio of 0.64 (95% CI [0.47-0.89]; p=0.008). However, there was no statistically significant impact on all-cause mortality (IRR 1.9, 95% CI [0.9-4.0]; p=0.09). Notably, no adverse effects were reported, and no patient discontinued rifaximin therapy due to adverse effects. In conclusion, rifaximin demonstrated a noteworthy reduction in infections among cirrhotic patients with hepatic encephalopathy. Although a decrease in all-cause mortality was observed with rifaximin use, this effect did not reach statistical significance in the adjusted analysis. The study supports the potential benefits of rifaximin in preventing infections in this vulnerable patient population without apparent adverse effects. Further research may provide additional insights into the long-term impact of rifaximin on mortality outcomes in cirrhotic patients.
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Latin America presents a high prevalence of Helicobacter pylori(Hp) infection. Between1996-2003, the prevalence in Santiago, Chile, was 70%; recent studies indicate a decreasein this infection. Updating the frequency of Hp is crucial due to its associated health impact. OBJECTIVE: Our objective was to describe the trend in Hp infection in patients undergoingambulatory esophagogastroduodenoscopy (EGD) in a Chilean population. MATERIALS AND METHODS: A retrospective observational study was conducted on patients over 18 years old who attended a first EGD with a rapid urease test between 2010-2020. Time trendswere described through time series analysis. A Poisson model was constructed to estimatethe risk of infection, adjusted for age and gender. RESULTS: 11,355 patients were included[66.9% females; mean age 52 years; Hp 41.6%]. Male gender presented a higher frequencyof Hp infection [RR 1.13; (95% CI: 1.08-1.18)].Hp frequency infection decreased significantlyfrom 45.1% in 2010 to 29% in 2020, with a 36% lower probability of Hp infection in 2020 compared to 2010 [RR 0.64;(95% CI: 0.55-0.74)]. A progressive decline in Hp infectiontrend was projected, reaching values close to 25% by year 2025. CONCLUSION: A significantreduction in Hpinfection was observed between 2010-2020. This decrease could be explained by the implementation of public health policies in the last decade associated with socio-sanitary changes.
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Helicobacter Infections , Helicobacter pylori , Humans , Chile/epidemiology , Helicobacter Infections/epidemiology , Helicobacter Infections/diagnosis , Male , Female , Middle Aged , Retrospective Studies , Adult , Aged , Prevalence , Endoscopy, Digestive System , Young Adult , Endoscopy, Gastrointestinal , Time FactorsSubject(s)
Cardiovascular Diseases , Health Policy , Liver Diseases , Neoplasms , Social Work , Humans , Cardiovascular Diseases/mortality , Cardiovascular Diseases/prevention & control , Liver Diseases/mortality , Neoplasms/mortality , Social Work/organization & administration , Public Health/methodsABSTRACT
One-dimensional metal halide perovskites are among the most promising candidate materials for optoelectronic devices. However, the heterogeneity and fast degradation of perovskite nanowires (NWs) and nanorods (NRs) synthesized using conventional approaches impose a bottleneck for their optoelectronic applications. Recently, all-inorganic perovskite CsPbBr3 NRs with tailored dimensions, crafted using an amphiphilic bottlebrush-like block copolymer (BBCP) as nanoreactors, have demonstrated enhanced stabilities. Herein, we report the electronic investigation into these template-grown CsPbBr3 NRs using dielectric force microscopy (DFM), a contactless, nondestructive imaging technique. All freshly prepared CsPbBr3 NRs exhibited ambipolar behaviors for up to two months after sample synthesis. A transition from ambipolar to p-type behaviors occurred after two months, and nearly all NRs completed the transition within two weeks. Moreover, template-grown CsPbBr3 NRs displayed better nanoscale electronic homogeneity compared to their conventional counterparts. The improved electronic uniformity and nanoscale homogeneity place the template-grown CsPbBr3 NRs in a unique advantageous position for optoelectronic applications.
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BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .
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Diarrheagenic E. coli (DEC) strains are one of the most important etiology factors causing diarrhea in children worldwide, especially in developing countries. DEC strains have characteristic virulence factors; however, other supplemental virulence genes (SVG) may contribute to the development of diarrhea in children. Therefore, this study aimed to determine the prevalence of DEC in children with diarrhea in southwestern Mexico and to associate childhood symptoms, SVG, and pathotypes with diarrhea-causing DEC strains. DEC strains were isolated from 230 children with diarrhea aged 0-60 months from the state of Oaxaca, southwestern Mexico; clinical data were collected, and PCR was used to identify SVG and pathotypes. Antibiotic resistance profiling was performed on DEC strains. 63% of samples were DEC positive, single or combined infections (two (21%) or three strains (1.3%)) of aEPEC (51%), EAEC (10.2%), tEPEC (5.4%), DAEC (4.8%), ETEC (4.1%), EIEC (1.4%), or EHEC (0.7%) were found. Children aged ≤ 12 and 49-60 months and symptoms (e.g., fever and blood) were associated with DEC strains. SVG related to colonization (nleB-EHEC), cytotoxicity (sat-DAEC and espC-tEPEC), and proteolysis (pic-aEPEC) were associated with DECs strains. E. coli phylogroup A was the most frequent, and some pathotypes (aEPEC-A, DAEC-B), and SVG (espC-B2, and sat-D) were associated with the phylogroups. Over 79% of the DEC strains were resistant to antibiotics, and 40% were MDR and XDR, respectively. In conclusion aEPEC was the most prevalent pathotype in children with diarrhea in this region. SVG related to colonization, cytotoxicity, and proteolysis were associated with diarrhea-producing DEC strains, which may play an essential role in the development of diarrhea in children in southwestern Mexico.
Subject(s)
Escherichia coli Infections , Escherichia coli , Child , Humans , Escherichia coli/genetics , Escherichia coli Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Virulence , Mexico , Drug Resistance, Bacterial , Diarrhea/epidemiologyABSTRACT
Previous studies have compared levobupivacaine versus ropivacaine in various peripheral nerve blocks in terms of block duration, quality of analgesia, and onset time, but this has not occurred in the PENG block. Here, a single-center, randomized, and controlled clinical trial is presented. One hundred and twenty patients older than 65 years suffering from hip fractures and surgically treated at our institution under spinal anesthesia were eligible for participation; of them, one hundred and eight were analyzed. Patients were randomized to receive ultrasound-guided PENG blocks using 20 mL of either 0.25% levobupivacaine or 0.375% ropivacaine (both of which are equipotent concentrations). The primary endpoint was to compare the analgesic duration (time to first rescue) and analgesic quality (pain scores using the VAS, PAINAD, and AlgoPlus scales) between the groups. Secondary endpoints included comparing the onset time, describing the need for and type of rescue analgesics, and possible associated adverse effects. There were no statistically significant differences in analgesic duration between levobupivacaine (median 861.0, IQR 960) and ropivacaine (median 1205.0, IQR 1379; p = 0.069). Likewise, the quality of analgesia and onset time were comparable among the groups. A small number of patients required opioids as rescue analgesics (4.6%). The possible associated adverse effects included postoperative infection (11.1%) and delirium (2.8%).
ABSTRACT
INTRODUCTION: Gastric cancer (GC) is the first cause of cancer-related death in Chile and 6th in Latin America and the Caribbean (LAC). Helicobacter pylori (H. pylori) is the main gastric carcinogen, and its treatment reduces GC incidence and mortality. Esophageal-gastro-duodenoscopy (EGD) allows for the detection of premalignant conditions and early-stage GC. Mass screening programs for H. pylori infection and screening for premalignant conditions and early-stage GC are not currently implemented in LAC. The aim of this study is to establish recommendations for primary and secondary prevention of GC in asymptomatic standard-risk populations in Chile. METHODS: Two on-line synchronous workshops and a seminar were conducted with Chilean experts. A Delphi panel consensus was conducted over 2 rounds to achieve>80% agreement on proposed primary and secondary prevention strategies for the population stratified by age groups. RESULTS: 10, 12, and 12 experts participated in two workshops and a seminar, respectively. In the Delphi panel, 25 out of 37 experts (77.14%) and 28 out of 52 experts (53.85%) responded. For the population aged 16-34, there was no consensus on non-invasive testing and treatment for H. pylori, and the use of EGD was excluded. For the 35-44 age group, non-invasive testing and treatment for H. pylori is recommended, followed by subsequent test-of-cure using non-invasive tests (stool antigen test or urea breath test). In the ≥45 age group, a combined strategy is recommended, involving H. pylori testing and treatment plus non-invasive biomarkers (H. pylori IgG serology and serum pepsinogens I and II); subsequently, a selected group of subjects will undergo EGD with gastric biopsies (Sydney Protocol), which will be used to stratify surveillance according to the classification Operative Link for Gastritis Assessment (OLGA); every 3 years for OLGA III-IV and every 5 years for OLGA I-II. CONCLUSION: A "test-and-treat" strategy for H. pylori infection based on non-invasive studies (primary prevention) is proposed in the 35-44 age group, and a combined strategy (serology and EGD) is recommended for the ≥45 age group (primary and secondary prevention). These strategies are potentially applicable to other countries in LAC.