A New Quantitative Tool for the Ultrasonographic Assessment of Tendons: A Reliability and Validity Study on the Patellar Tendon.

Ultrasound is widely used for tendon assessment due to its safety, affordability, and portability, but its subjective nature poses challenges. This study aimed to develop a new quantitative analysis tool based on artificial intelligence to identify statistical patterns of healthy and pathological tendons. Furthermore, we aimed to validate this new tool by comparing it to experts' subjective assessments. A pilot database including healthy controls and patients with patellar tendinopathy was constructed, involving 14 participants with asymptomatic (n = 7) and symptomatic (n = 7) patellar tendons. Ultrasonographic images were assessed twice, utilizing both the new quantitative tool and the subjective scoring method applied by an expert across five regions of interest. The database contained 61 variables per image. The robustness of the clinical and quantitative assessments was tested via reliability analyses. Lastly, the prediction accuracy of the quantitative features was tested via cross-validated generalized linear mixed-effects logistic regressions. These analyses showed high reliability for quantitative variables related to "Bone" and "Quality", with ICCs above 0.75. The ICCs for "Edges" and "Thickness" varied but mostly exceeded 0.75. The results of this study show that certain quantitative variables are capable of predicting an expert's subjective assessment with generally high cross-validated AUC scores. A new quantitative tool for the ultrasonographic assessment of the tendon was designed. This system is shown to be a reliable and valid method for evaluating the patellar tendon structure.

Revisiting Hypertension Treatment in Patients With Chronic Kidney Disease.

Despite being the world's top risk factor for death and disability, hypertension awareness and control within the chronic kidney disease (CKD) population have decreased. This is particularly important considering the heightened severity and management challenges of hypertension in CKD patients, whose outcomes are often worse compared with persons with normal kidney function. Therefore, finding novel therapeutics to improve blood pressure control within this vulnerable group is paramount. Although medications that target the renin-angiotensin-aldosterone system remain a mainstay for blood pressure control in most stages of CKD, we discuss novel approaches that may expand their use in advanced CKD. We also review newer tools for blood pressure management that have emerged in recent years, including aldosterone synthase inhibitors, endothelin receptor antagonists, and renal denervation. Overall, the future of hypertension management in CKD appears brighter, with a growing arsenal of tools and a deeper understanding of this complex disease.

Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.

Observer-based differential evolution constrained control for safe reference tracking in robots.

Big torque inputs in controls could increase energy consumption, and big estimated perturbations in observers could produce device damages. Therefore, it would be interesting to propose a constrained control for safe reference tracking and a constrained observer for safe perturbation estimation in robots. Furthermore, the best gains in controls produce a balance between safe reference tracking and save energy consumption. Therefore, it would be interesting to propose a method to find the best gains. In this paper, an observer-based differential evolution constrained control is proposed for safe reference tracking in robots. The contributions are described as follows: (1) a constrained observer is proposed for safe perturbation estimation in robots, (2) a constrained control is proposed for safe reference tracking in robots, (3) a differential evolution optimizer is used to find the best gains in an observer-based constrained control, (4) the robust stability in an observer-based constrained control is assured, (5) the pseudo-code of an observer-based differential evolution constrained control is detailed. The proposed observer-based differential evolution constrained control is applied for safe reference tracking in two robots.

Comparative single-cell transcriptomic profile of hybrid immunity induced by adenovirus vector-based COVID-19 vaccines.

In this study, antibody response and a single-cell RNA-seq analysis were conducted on peripheral blood mononuclear cells from five different groups: naïve subjects vaccinated with AZD1222 (AZ) or Ad5-nCoV (Cso), individuals previously infected and later vaccinated (hybrid) with AZD1222 (AZ-hb) or Ad5-nCoV (Cso-hb), and those who were infected and had recovered from COVID-19 (Inf). The results showed that AZ induced more robust neutralizing antibody responses than Cso. The single-cell RNA data revealed a high frequency of memory B cells in the Cso and Cso-hb. In contrast, AZ and AZ-hb groups exhibited the highest proportion of activated naïve B cells expressing CXCR4. Transcriptomic analysis of CD4+ and CD8+ T cells demonstrated a heterogeneous response following vaccination, hybrid immunity, or natural infection. However, a single dose of Ad5-nCoV was sufficient to strongly activate CD4+ T cells (naïve and memory) expressing ANX1 and FOS, similar to the hybrid response observed with AZ. An interesting finding was the robust activation of a subset of CD8+ T cells expressing GZMB, GZMH, and IFNG genes in the Cso-hb group. Our findings suggest that both vaccines effectively stimulated the cellular immune response; however, the Ad5-nCoV induced a more robust CD8+ T-cell response in previously infected individuals.

Central inhibition of HDAC6 re-sensitizes leptin signaling during obesity to induce profound weight loss.

Leptin resistance during excess weight gain significantly contributes to the recidivism of obesity to leptin-based pharmacological therapies. The mechanisms underlying the inhibition of leptin receptor (LepR) signaling during obesity are still elusive. Here, we report that histone deacetylase 6 (HDAC6) interacts with LepR, reducing the latter's activity, and that pharmacological inhibition of HDAC6 activity disrupts this interaction and augments leptin signaling. Treatment of diet-induced obese mice with blood-brain barrier (BBB)-permeable HDAC6 inhibitors profoundly reduces food intake and leads to potent weight loss without affecting the muscle mass. Genetic depletion of Hdac6 in Agouti-related protein (AgRP)-expressing neurons or administration with BBB-impermeable HDAC6 inhibitors results in a lack of such anti-obesity effect. Together, these findings represent the first report describing a mechanistically validated and pharmaceutically tractable therapeutic approach to directly increase LepR activity as well as identifying centrally but not peripherally acting HDAC6 inhibitors as potent leptin sensitizers and anti-obesity agents.

Sex differences in symptomatology and immune profiles of Long COVID.

Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection 1-7 . However, whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown. Here, we performed sex-based multi-dimensional immune-endocrine profiling of 165 individuals 8 with and without LC in an exploratory, cross-sectional study to identify key immunological traits underlying biological sex differences in LC. We found that female and male participants with LC experienced different sets of symptoms, and distinct patterns of organ system involvement, with female participants suffering from a higher symptom burden. Machine learning approaches identified differential sets of immune features that characterized LC in females and males. Males with LC had decreased frequencies of monocyte and DC populations, elevated NK cells, and plasma cytokines including IL-8 and TGF-ß-family members. Females with LC had increased frequencies of exhausted T cells, cytokine-secreting T cells, higher antibody reactivity to latent herpes viruses including EBV, HSV-2, and CMV, and lower testosterone levels than their control female counterparts. Testosterone levels were significantly associated with lower symptom burden in LC participants over sex designation. These findings suggest distinct immunological processes of LC in females and males and illuminate the crucial role of immune-endocrine dysregulation in sex-specific pathology.

Evidencia de la estimulación de puntos de acupuntura en el tratamiento de la hipogalactia: revisión sistemática con metaanálisis / Evidence of the acupuncture points stimulation for the treatment of hypogalactia: a systematic review and meta-analysis

Objetivo: Realizar una revisión de la literatura para analizar si la estimulación de puntos de acupuntura aumenta la cantidad de leche producida durante la lactancia. Método: Se recopilaron estudios de cinco bases de datos electrónicas siguiendo las recomendaciones internacionales para la elaboración de revisiones sistemáticas y metaanálisis. Los criterios de elegibilidad fueron artículos de texto completo en inglés o español con diseño de ensayos clínicos y estudios observacionales, sin restricción en el tiempo de publicación, en los cuales se hubiera evaluado el efecto de la estimulación de puntos de acupuntura en la mejora de la cantidad de lactancia mediante acupuntura convencional, electroacupuntura, láser, agujas de fuego, estimulación manual, Tui Na o catgut. Dos autores extrajeron de forma independiente los datos de las características y los resultados principales de los estudios seleccionados para su inclusión. Se realizaron las evaluaciones de riesgo de sesgo y de calidad (GRADE). Para la síntesis cuantitativa se calculó la diferencia de medias estandarizada para cada estudio individual seleccionado y luego se combinaron los datos mediante un metaanálisis de efectos aleatorios. Resultados: En la presente revisión se incluyeron un total de 14 estudios, la mayoría de ellos mostraron riesgo de sesgo y una calidad moderada. El metaanálisis mostró que la estimulación manual del punto de acupuntura aumenta la cantidad de leche materna (DME 95% IC=1,63 [1,13-2,13]; p<0,0001). Conclusión: La literatura sugiere que la estimulación manual de puntos de acupuntura mejora la cantidad de leche producida durante de lactancia.(AU)

Objective: To perform a literature review aimed to analyze if acupoint stimulation increases lactation quantity. Method: Studies were collected from five electronic databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews. Eligibility criteria were full-text articles in English or Spanish with clinical trial design and observational studies, with no restriction on time of publication, in which the effect of acupoint stimulation on improving the quantity of lactation by conventional acupuncture, electroacupuncture, laser, fire needling, manual stimulation, tuina or catgut had been evaluated. Two authors independently extracted data for the characteristics and main outcomes of the studies selected for inclusion. The risk of bias (RoB 2 and Robins-I) and the quality assessments (GRADE) were performed. For the quantitative synthesis, the standardized mean difference was calculated for each individual study selected and then the data were combined using a random-effects meta-analysis. Results: A total of 14 studies were included in the present review. Most of the included studies exhibited some concerns in the risk of bias assessment. The quality of the studies was moderate. The meta-analysis showed that manual acupoint stimulation improves the lactation quantity (SMD 95% CI=1.63 [1.13-2.13]; p<0.0001). Conclusion: The literature suggests that manual stimulation of acupuncture points improves the amount of milk produced during lactation.(AU)

Chitosan for the treatment of inflammationof the oral mucosa: A systematic review / Chitosán para el tratamiento de la inflamación de la mucosa oral: una revisión sistemática

Background: Chitosan is a cheap, accessible, nontoxic, biocompatible, and biodegradable compound. Also, thispolysaccharide possesses antibacterial and anti-inflammatory properties. Consequently, a wide range of chitosanapplications in the dentistry field has been explored. This work aimed to conduct a systematic review to addressthe clinical efficacy of chitosan for the treatment of oral mucositis.Material and Methods: The design of the included studies were observational studies, randomized clinical trials(RCT), and non-randomized clinical trials (non-RCT), whereas, a series of cases, in vivo, and in vitro studies wereexcluded. The search was performed in PubMed, Web of Science, Scopus, Dentistry and Oral Sciences Source,and ClinicalTrials. Gray literature was searched at Google Scholar. Relevant data from all included studies wererecorded. The risk of bias (using RoB 2) and the quality (using Grading of Recommendations Assessment, Devel-opment, and Evaluation, GRADE) assessments were carried out.Results: From the 8413 records screened, 5 clinical trials fully met the eligibility criteria, which comprised a totalof 192 participants suffering oral lesions and pain related to oral mucositis. 100% of the included studies exhibiteda high risk of bias. The quality of the studies was between low and very low.Conclusions: The results of the included studies suggest that chitosan can diminish pain and improve the healingof ulcers in oral mucositis. However, there is no conclusive evidence of chitosan as a superior treatment for oralmucositis compared with other current therapies.(AU)

Digital Health Interventions for Heart Failure Management in Underserved Rural Areas of the United States: A Systematic Review of Randomized Trials.

BACKGROUND: Heart failure disproportionately affects individuals residing in rural areas, leading to worse health outcomes. Digital health interventions have been proposed as a promising approach for improving heart failure management. This systematic review aims to identify randomized trials of digital health interventions for individuals living in underserved rural areas with heart failure. METHODS AND RESULTS: We conducted a systematic review by searching 6 databases (CINAHL, EMBASE, MEDLINE, Web of Science, Scopus, and PubMed; 2000-2023). A total of 30 426 articles were identified and screened. Inclusion criteria consisted of digital health randomized trials that were conducted in underserved rural areas of the United States based on the US Census Bureau's classification. Two independent reviewers screened the studies using the National Heart, Lung, and Blood Institute tool to evaluate the risk of bias. The review included 5 trials from 6 US states, involving 870 participants (42.9% female). Each of the 5 studies employed telemedicine, 2 studies used remote monitoring, and 1 study used mobile health technology. The studies reported improvement in self-care behaviors in 4 trials, increased knowledge in 2, and decreased cardiovascular mortality in 1 study. However, 3 trials revealed no change or an increase in health care resource use, 2 showed no change in cardiac biomarkers, and 2 demonstrated an increase in anxiety. CONCLUSIONS: The results suggest that digital health interventions have the potential to enhance self-care and knowledge of patients with heart failure living in underserved rural areas. However, further research is necessary to evaluate their impact on clinical outcomes, biomarkers, and health care resource use. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022366923.

Design and Implementation of an Electronic Health Record-Integrated Hypertension Management Application.

BACKGROUND: High blood pressure affects approximately 116 million adults in the United States. It is the leading risk factor for death and disability across the world. Unfortunately, over the past decade, hypertension control rates have decreased across the United States. Prediction models and clinical studies have shown that reducing clinician inertia alone is sufficient to reach the target of ≥80% blood pressure control. Digital health tools containing evidence-based algorithms that are able to reduce clinician inertia are a good fit for turning the tide in blood pressure control, but careful consideration should be taken in the design process to integrate digital health interventions into the clinical workflow. METHODS: We describe the development of a provider-facing hypertension management platform. We enumerate key steps of the development process, including needs finding, clinical workflow analysis, treatment algorithm creation, platform design and electronic health record integration. We interviewed and surveyed 5 Stanford clinicians from primary care, cardiology, and their clinical care team members (including nurses, advanced practice providers, medical assistants) to identify needs and break down the steps of clinician workflow analysis. The application design and development stage were aided by a team of approximately 15 specialists in the fields of primary care, hypertension, bioinformatics, and software development. CONCLUSIONS: Digital monitoring holds immense potential for revolutionizing chronic disease management. Our team developed a hypertension management platform at an academic medical center to address some of the top barriers to adoption and achieving clinical outcomes. The frameworks and processes described in this article may be used for the development of a diverse range of digital health tools in the cardiovascular space.

Evidence of the acupuncture points stimulation for the treatment of hypogalactia: A systematic review and meta-analysis.

OBJECTIVE: To perform a literature review aimed to analyze if acupoint stimulation increases lactation quantity. METHOD: Studies were collected from five electronic databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews. Eligibility criteria were full-text articles in English or Spanish with clinical trial design and observational studies, with no restriction on time of publication, in which the effect of acupoint stimulation on improving the quantity of lactation by conventional acupuncture, electroacupuncture, laser, fire needling, manual stimulation, tuina or catgut had been evaluated. Two authors independently extracted data for the characteristics and main outcomes of the studies selected for inclusion. The risk of bias (RoB 2 and Robins-I) and the quality assessments (GRADE) were performed. For the quantitative synthesis, the standardized mean difference was calculated for each individual study selected and then the data were combined using a random-effects meta-analysis. RESULTS: A total of 14 studies were included in the present review. Most of the included studies exhibited some concerns in the risk of bias assessment. The quality of the studies was moderate. The meta-analysis showed that manual acupoint stimulation improves the lactation quantity (SMD 95% CI = 1.63 [1.13-2.13]; p < 0.0001). CONCLUSION: The literature suggests that manual stimulation of acupuncture points improves the amount of milk produced during lactation.

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.

Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology. Methods: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-ß and CNTF, among soluble analytes. Conclusions: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.

Resident training in interventional pathology: Ultrasound-guided fine-needle aspiration and rapid on site evaluation-5 years of teaching experience in a single university hospital.

INTRODUCTION: Despite the established role of the interventional pathologist, their diagnostic performance is difficult to establish. At least in Spain training of pathology residents in ultrasound-guided interventional procedures for specimen collection is limited or absent in most institutions. We present our teaching experience in the instruction of ultrasound-guided fine-needle aspiration (FNA) to pathology residents in a tertiary-level hospital. MATERIALS AND METHODS: The training of pathology residents who rotated through the interventional unit of the pathology department and the application of ultrasound-guided FNA and rapid on-site evaluation (U-ROSE) was documented over 5 years. The training period was broken down into learning phases and included the number of ultrasound-guided FNA performed, anatomical location, and their diagnostic performance, among other aspects. RESULTS: Nineteen (19) pathology residents were trained in U-ROSE, and performed a total of 4003 procedures, with a mean of 211 per resident. In 53% of cases only one pass was required for an adequated sample. The specimen was diagnostic in more than 97% of cases. The most frequently sampled anatomical sites were the thyroid gland (n = 2347), followed by lymph node (n = 667), soft tissues (n = 663) and salivary glands (n = 322). CONCLUSION: The results support the training programme followed by pathology residents in learning U-ROSE, which is essential to lay the foundations for the future interventional pathologist.

Genetic high-gain controller to improve the position perturbation attenuation and compact high-gain controller to improve the velocity perturbation attenuation in inverted pendulums.

From the control theory, bigger observer and controller gains are utilized to improve the position perturbation attenuation, while smaller observer and controller gains are utilized to improve the velocity perturbation attenuation. Therefore, it would be interesting to suggest optimizers to find the best observer and controller gains to improve the position or velocity perturbation attenuation. In this investigation, a high-gain controller is suggested to obtain the perturbation attenuation, a genetic high-gain controller is suggested to improve the position perturbation attenuation, and a compact high-gain controller is suggested to improve velocity perturbation attenuation in inverted pendulums. The high-gain controller utilizes a high-gain observer and a high-gain estimator to obtain the state and perturbation estimation. The genetic high-gain controller utilizes a genetic optimizer to find the best observer and controller gains. The compact high-gain controller utilizes a compact optimizer to find the best observer and controller gains. The suggested high-gain controllers are compared with the simplex and bat controllers to improve the position or velocity perturbation attenuation in two inverted pendulums.

Acute pesticide poisoning: Comparison of epidemiological characteristics between the rural and urban population

Objective: To analyze the behavior of pesticide poisoning associated with lethality in rural and urban populations in Colombia from 2007 to 2017. Methodology: Retrospective observational study that included a descriptive cross-sectional study and an ecological design that analyzed aggregate measures of morbidity, mortality, and risk attributable to the population in rural and urban areas. In the cross-sectional study, the relative risk was estimated to measure the factors associated with lethality among intoxications using Poisson regression with logarithmic function. For the time series, the trends were established with simple linear regression, and the seasonal decomposition was performed using the multiplicative model. Autocorrelations were tested using the Box-Ljung statistic. Results: Between 2007-2017; 89 490 cases were reported. The Morbidity due to poisoning showed a higher proportion in the rural population 36.03 cases per 100 000; this indicator was three times higher than in urban areas (12.33 cases per 100 000). The mortality rates in rural and urban areas were 1.00 and 0.13 cases per 100 000, respectively. The relative risk of fatality in case of intoxication was associated with the intention of suicide in the rural population Relative Risk (RR): 5.9 (95% CI: 5.0-6.9). Conclusion: A higher proportion of lethality associated with these events occurred in populations living in rural areas and reporting cases of suicidal intent. In addition, morbidity and mortality due to pesticide poisoning had the highest proportion in rural areas and a growing trend over time.

Objetivo: Analizar el comportamiento de las intoxicaciones por plaguicidas en poblaciones rurales y urbanas asociadas a la letalidad en Colombia durante 2007-2017. Metodología: Estudio observacional retrospectivo que incluyó: un estudio descriptivo transversal y un diseño ecológico que analizó medidas agregadas de morbilidad, mortalidad y riesgo atribuibles a la población en áreas rurales y urbanas. En el estudio transversal se estimó el riesgo relativo para medir los factores asociados a la letalidad entre las intoxicaciones mediante regresión de Poisson con función logarítmica. Para la serie de tiempo, las tendencias se establecieron con regresión lineal simple y la descomposición estacional se realizó mediante el modelo multiplicativo. Las autocorrelaciones se probaron mediante el estadístico Box-Ljung. Resultados: Entre 2007-2017; Se notificaron 89 490 casos. La Morbilidad por intoxicación presentó mayor proporción en la población rural 36,03 casos por 100 000; este indicador fue tres veces mayor que en las áreas urbanas (12,33 casos por 100 000). Las tasas de mortalidad en el área rural y urbana fueron de 1,00 y 0,13 casos por 100 000, respectivamente. El riesgo relativo de fatalidad en caso de intoxicación se asoció con la intención de suicidio en la población rural RR: 5,9 (IC 95%: 5,0-6,9). Conclusión: Una mayor proporción de letalidad asociada a estos eventos ocurrió en poblaciones que viven en áreas rurales y reportan casos de intención suicida. Además, la morbilidad y mortalidad por intoxicación por plaguicidas tuvo la mayor proporción en las zonas rurales y una tendencia creciente en el tiempo.

Objetivo: Analisar o comportamento das intoxicações por agrotóxicos em populações rurais e urbanas associadas à letalidade na Colômbia durante 2007-2017. Metodologia: Estudo observacional retrospectivo que incluiu: estudo transversal descritivo e delineamento ecológico que analisou medidas agregadas de morbidade, mortalidade e risco atribuíveis à população em áreas rurais e urbanas. No estudo transversal, o risco relativo foi estimado para medir os fatores associados à letalidade entre as intoxicações por meio da regressão de Poisson com função logarítmica. Para as séries temporais, as tendências foram estabelecidas com regressão linear simples e a decomposição sazonal foi realizada usando o modelo multiplicativo. As autocorrelações foram testadas usando a estatística Box-Ljung. Resultados: Entre 2007-2017; 89.490 casos foram notificados. A Morbidade por intoxicação apresentou maior proporção na população rural 36,03 casos por 100.000; este indicador foi três vezes superior ao das zonas urbanas (12,33 casos por 100 000). As taxas de mortalidade nas áreas rural e urbana foram de 1,00 e 0,13 casos por 100.000 habitantes, respectivamente. O risco relativo de fatalidade em caso de intoxicação associou-se à intenção de suicídio na população rural RR: 5,9 (IC 95%: 5,0-6,9). Conclusão: Maior proporção de letalidade associada a esses eventos ocorreu em populações residentes em áreas rurais e com relato de casos de intenção suicida. Além disso, a morbimortalidade por intoxicação por agrotóxicos teve maior proporção na zona rural e tendência crescente ao longo do tempo.

Development of a Multispecies Double-Antigen Sandwich ELISA Using N and RBD Proteins to Detect Antibodies against SARS-CoV-2.

SARS-CoV-2 infects humans and a broad spectrum of animal species, such as pets, zoo animals, and nondomestic animals. Monitoring infection in animals is important in terms of the risk of interspecies transmission and the emergence of new viral variants. Economical, fast, efficient, and sensitive diagnostic tests are needed to analyze animal infection. Double-antigen sandwich ELISA has the advantage of being multispecies and can be used for detecting infections caused by pathogens that infect several animal hosts. This study aimed to develop a double-antigen sandwich ELISA using two SARS-CoV-2 proteins, N and RBD. We compared its performance, when using these proteins separately, with an indirect ELISA and with a surrogate virus neutralization test. Positive and negative controls from a cat population (n = 31) were evaluated to compare all of the tests. After confirming that double-antigen sandwich ELISA with both RBD and N proteins had the best performance (AUC= 88%), the cutoff was adjusted using positive and negative samples from cats, humans (n = 32) and guinea pigs (n = 3). The use of samples from tigers (n = 2) and rats (n = 51) showed good agreement with the results previously obtained using the microneutralization test. Additionally, a cohort of samples from dogs with unknown infection status was evaluated. These results show that using two SARS-CoV-2 proteins in the double-antigen sandwich ELISA increases its performance and turns it into a valuable assay with which to monitor previous infection caused by SARS-CoV-2 in different animal species.

Distinguishing features of long COVID identified through immune profiling.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.