Rechallenge in idiosyncratic drug-induced liver injury: an analysis of cases in two large prospective registries according to existing definitions.

INTRODUCTION: Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries. METHODS: Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed. RESULTS: Of 1,418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. CONCLUSIONS: Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.

Gold(I) ion and the phosphine ligand are necessary for the anti-Toxoplasma gondii activity of auranofin.

Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondii's invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk population's exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.

Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet.

In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI.

In-Hospital influenza vaccination to prevent cardiorespiratory events in the first 45 days after acute coronary syndrome: A prespecified analysis of the VIP-ACS trial.

BACKGROUND: Influenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain. METHODS: The VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization). RESULTS: The trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70---1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71---1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48---1.39; P = 0.46). No serious adverse events were observed. CONCLUSION: In patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.

Impact of treating obesity hypoventilation syndrome on body mass index.

STUDY OBJECTIVES: To evaluate the impact of positive airway pressure (PAP) therapy on body mass index (BMI) in patients with obesity hypoventilation syndrome (OHS) associated with obstructive sleep apnea (OSA). METHODS: A systematic review using the following terms: "obesity hypoventilation syndrome" AND "treatment" AND "randomized" using Cochrane Central Register of Controlled Trials, Medline and Web of Science was performed from the first data available until February 10, 2023. The inclusion criteria were: (1) original article; (2) adult OHS with concomitant OSA (apnea-hypopnea index or AHI ≥5 events/h); (3) randomized trial with PAP arm and standard care (control); (4) BMI evaluation at baseline and after the first months. We performed an individual participant data meta-analysis of randomized controlled trials. RESULTS: Our initial search retrieved 32 articles and 3 randomized studies fulfilled study criteria and were included in the final analysis, leading to a total of 342 participants. Patients were predominantly females (62%) and had OHS associated with at least mild OSA. As compared to baseline, a decrease in BMI was observed at study endpoint but this difference was not different intergroups (-0.50 ± 1.49 and -0.50 ±1.83, in control and PAP groups respectively (p=0.939)). Weight change was not associate with PAP adherence, OSA severity or use of supplemental oxygen. CONCLUSIONS: In contrast to treatment of eucapnic OSA with PAP that is associated with weight gain, treatment of OSA+OHS patients with or without PAP is associated with weight loss. Future studies are necessary to elucidate the mechanism by which weight loss occurs.

Primary Prevention of Cardiovascular Disease at Community Clinics in the State of Sao Paulo, Brazil: Results from the Epidemiological Information Study of Communities.

Background: Primary prevention of cardiovascular disease (CVD) remains a major challenge, especially in communities of low- and middle-income countries with poor medical assistance influenced by distinct local, financial, infrastructural, and resource-related factors. Objective: This a community-based study aimed to determine the proportion and prevalence of uncontrolled cardiovascular risk factors (CRF) in Brazilian communities. Methods: The EPICO study was an observational, cross-sectional, and community clinic-based study. Subjects were living in Brazilian communities and were of both sexes and ≥18 years old, without a history of a stroke or myocardial infarction but presenting at least one of the following cardiovascular risk factors: hypertension, diabetes mellitus and hypercholesterolemia. The study was carried out in Brazil, including 322 basic health units (BHU) in 32 cities. Results: A total of 7,724 subjects with at least one CRF were evaluated, and one clinical visit was performed. Mean age was 59.2 years-old (53.7% were >60 years old). A total of 66.7% were women. Of the total, 96.2% had hypertension, 78.8% had diabetes mellitus type II, 71.1% had dyslipidemia, and 76.6% of patients were overweight/obese. Controlled hypertension (defined by <130/80 mmHg or <140/90 mmHg) was observed in 34.9% and 55.5% patients among respective criteria, the rates of controlled blood glucose in patients taking antidiabetic medications was 29.5%, and among those with documented dyslipidemia who received any lipid-lowering medication, only 13.9% had LDL-c on target. For patients presenting three CRF less than 1.9% had LDL-c < 100 mg/dL once their BP and blood glucose were on target. High education level as associated with blood pressure (BP) target of less than 130 / 80mm Hg. The glucose and LDL-c levels on target were associated with the presence of hypertension and diabetes mellitus. Conclusion: In Brazilian community clinics, regarding most patients in primary prevention, the CRF such as BP, blood glucose, and lipid levels are poorly controlled, with a majority of patients not achieving guidelines/recommendations.

Primary prevention of cardiovascular disease at community clinics in the state of Sao Paulo, Brazil: results from the epidemiological information study of communities

BACKGROUND: Primary prevention of cardiovascular disease (CVD) remains a major challenge, especially in communities of low- and middle-income countries with poor medical assistance influenced by distinct local, financial, infrastructural, and resource-related factors. OBJECTIVE: This a community-based study aimed to determine the proportion and prevalence of uncontrolled cardiovascular risk factors (CRF) in Brazilian communities. METHODS: The EPICO study was an observational, cross-sectional, and community clinic-based study. Subjects were living in Brazilian communities and were of both sexes and ≥18 years old, without a history of a stroke or myocardial infarction but presenting at least one of the following cardiovascular risk factors: hypertension, diabetes mellitus and hypercholesterolemia. The study was carried out in Brazil, including 322 basic health units (BHU) in 32 cities. RESULTS: A total of 7,724 subjects with at least one CRF were evaluated, and one clinical visit was performed. Mean age was 59.2 years-old (53.7% were >60 years old). A total of 66.7% were women. Of the total, 96.2% had hypertension, 78.8% had diabetes mellitus type II, 71.1% had dyslipidemia, and 76.6% of patients were overweight/obese. Controlled hypertension (defined by <130/80 mmHg or <140/90 mmHg) was observed in 34.9% and 55.5% patients among respective criteria, the rates of controlled blood glucose in patients taking antidiabetic medications was 29.5%, and among those with documented dyslipidemia who received any lipid-lowering medication, only 13.9% had LDL-c on target. For patients presenting three CRF less than 1.9% had LDL-c < 100 mg/dL once their BP and blood glucose were on target. High education level as associated with blood pressure (BP) target of less than 130 / 80mm Hg. The glucose and LDL-c levels on target were associated with the presence of hypertension and diabetes mellitus. CONCLUSION: In Brazilian community clinics, regarding most patients in primary prevention, the CRF such as BP, blood glucose, and lipid levels are poorly controlled, with a majority of patients not achieving guidelines/recommendations.

Factors associated with the survival of primary maxillary anterior teeth after intrusive luxation: a retrospective longitudinal study.

PURPOSE: To evaluate the survival rate of primary maxillary anterior teeth following intrusive luxation and identify associated factors. METHODS: A retrospective longitudinal study was conducted at a primary dental trauma centre using 88 dental records of children with intrusive luxation between 2007 and 2018. The variables of interest were time the tooth remained in the alveolus, degree of intrusion, accentuated overjet, lip protection, visible plaque, compromised germ of the permanent successor, clinical signs of infectious and inflammatory processes, endodontic treatment, pulp canal obliteration, sex, age at the time of trauma, family income, mother's schooling, and immediate care. Descriptive, bivariate, and Cox regression analyses were performed (p < 0.05; 95% CI). RESULTS: The 88 dental records of children with intrusive luxation included 128 teeth. Survival rate throughout the follow-up period was 65.6% (n = 84). Age older than three years and eight months (HR 2.28; 95% CI 1.04-4.99; p = 0.039), the development of an infectious process (HR 3.51; 95% CI 1.39-8.86; p = 0.008), development of an inflammatory process (HR 2.35; 95% CI 1.17-4.71; p = 0.016) and compromised germ of the permanent successor (HR 4.38; 95% CI 1.99-9.61; p < 0.001) were associated with a lower survival rate of intruded primary maxillary anterior teeth. CONCLUSION: The survival rate during the follow-up period of intruded primary maxillary anterior teeth was considered high. A significantly lower survival rate was associated with age, the occurrence of an infectious process and inflammatory process, and the compromised germ of the permanent successor.

Effects and mechanotransduction pathways of therapeutic ultrasound on healthy and osteoarthritic chondrocytes: a systematic review of in vitro studies.

OBJECTIVE: To investigate the effects and mechanotransduction pathways of therapeutic ultrasound on chondrocytes. METHOD: PubMed, EMBASE and Web of Science databases were searched up to 19th September 2021 to identify in vitro studies exploring ultrasound to stimulate chondrocytes for osteoarthritis (OA) treatment. Study characteristics, ultrasound parameters, in vitro setup, and mechanotransduction pathways were collected. Risk of bias was judged using the Risk of Bias Assessment for Non-randomized Studies (RoBANS) tool. RESULTS: Thirty-one studies were included comprising healthy and OA chondrocytes and explants. Most studies had high risk of performance, detection and pseudoreplication bias due to lack of temperature control, setup calibration, inadequate semi-quantitatively analyzes and independent experiments. Ultrasound was applied to the culture plate via acoustic gel, water bath or culture media. Regardless of the setup used, ultrasound stimulated the cartilage production and suppressed its degradation, although the effect size was nonsignificant. Ultrasound inhibited p38, c-Jun N-terminal kinases (JNK) and factor nuclear kappa B (NFκB) pathways in OA chondrocytes to reduce apoptosis, inflammation and matrix degradation, while triggered phosphoinositide-3-kinase/akt (PI3K/Akt), extracellular signal-regulated kinase (ERK), p38 and JNK pathways in healthy chondrocytes to promote matrix synthesis. CONCLUSION: The included studies suggest that ultrasound application induces therapeutic effects on chondrocytes. However, these results should be interpreted with caution because high risk of performance, detection and pseudoreplication bias were identified. Future studies should explore the application of ultrasound on human OA chondrocytes cultures to potentiate the applicability of ultrasound towards cartilage regeneration of knee with OA.

Ejercicios multicomponente sobre la calidad de vida y el equilibrio en adultos mayores: Revisión sistemática y metaanálisis / Multicomponent exercises on quality of life and balance in older adults: Systematic review and meta-analysis

Antecedentes y objetivos: El envejecimiento implica cambios morfológicos, fisiológicos y neuromusculares como disminución progresiva de masa y fuerza muscular, lo que ocasiona pérdida de la independencia debido a alteraciones en el equilibrio, disminuyendo la calidad de vida. Se realizó una revisión sistemática con metaanálisis sobre la efectividad de los ejercicios multicomponente en la calidad de vida y el equilibrio en adultos mayores. Materiales y métodos Revisión sistemática con metaanálisis de ensayos controlados aleatorizados (ECA) de ejercicios multicomponente que evaluaron efectos en el equilibrio y calidad de vida en adultos mayores. Se buscaron ECA de manera sistemática y automatizada en las bases de datos Medline, Embase, Scopus, Cochrane Library, PubMed, PEDro. La calidad metodológica se evaluó con la herramienta de colaboración Cochrane. Los coeficientes del metaanálisis se representaron en diagramas de bosque. Resultados De los 110 registros encontrados se seleccionaron cinco para la síntesis cuantitativa. Se evaluaron 354 participantes en intervenciones entre un mes y 12 meses. El efecto general sobre la dimensión física de la calidad de vida fue de 0,322 (IC 95%: 0,053-0,590), en su dimensión mental fue de -0,076 (IC 95%: -0,344-0,191), mientras que para el equilibrio fue de 0,515 (IC 95%: 0,030-0,999). Conclusiones En adultos mayores, el entrenamiento multicomponente es una estrategia adecuada para incrementar el equilibrio, con la disminución del riesgo de caídas. Asimismo, permanece poco clara la combinación más efectiva de actividades de fuerza, equilibrio, aeróbicos y estiramientos. Los resultados no son conclusivos respecto al impacto positivo en el componente físico de la calidad de vida (AU)

Background and objectives: Aging involves morphological, physiological, and neuromuscular changes such as progressive decrease in muscle mass and strength. This modification causes loss of independence due to alterations in balance decreasing quality of life. The objective was to carry out a systematic review with meta-analysis on the effectiveness of multicomponent exercises on quality of life and balance in older adults. Materials and methods Systematic review with meta-analysis of randomized controlled trials (RCTs) of multicomponent exercises that evaluated effects on balance and quality of life in older adults. We searched for RCTs in a systematic and automated way in the databases Medline, Embase, Scopus, Cochrane Library, PubMed, PEDro. The methodological quality was assessed with the Cochrane collaboration tool. The coefficients of the meta-analysis were represented in forest plots. Result Of the 110 records found, five were selected for quantitative synthesis. 354 participants in interventions between one and twelve months were evaluated. The general effect on the physical dimension of quality of life was 0.322 (95% CI: 0.053−0.590), in its mental dimension it was −0.076 (95% CI: −0.344−0.191). While for equilibrium it was 0.515 (95% CI: 0.030−0.999). Conclusions In older adults, multicomponent training is an adequate strategy to increase balance, reducing the risk of falls. Also, the most effective combination of strength, balance, aerobic, and stretching activities remains unclear. Although the physical component of the quality of life has a positive impact, these results are not conclusive (AU)

Estimating the effective reproduction number for heterogeneous models using incidence data.

The effective reproduction number, R ( t ) , plays a key role in the study of infectious diseases, indicating the current average number of new infections caused by an infected individual in an epidemic process. Estimation methods for the time evolution of R ( t ) , using incidence data, rely on the generation interval distribution, g(τ), which is usually obtained from empirical data or theoretical studies using simple epidemic models. However, for systems that present heterogeneity, either on the host population or in the expression of the disease, there is a lack of data and of a suitable general methodology to obtain g(τ). In this work, we use mathematical models to bridge this gap. We present a general methodology for obtaining explicit expressions of the reproduction numbers and the generation interval distributions, within and between model sub-compartments provided by an arbitrary compartmental model. Additionally, we present the appropriate expressions to evaluate those reproduction numbers using incidence data. To highlight the relevance of such methodology, we apply it to the spread of COVID-19 in municipalities of the state of Rio de Janeiro, Brazil. Using two meta-population models, we estimate the reproduction numbers and the contributions of each municipality in the generation of cases in all others.

Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.

AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.

[Psychometric evaluation of breastfeeding self efficiency scale in chilean sample]. / Evaluación psicométrica de la escala de autoeficacia de la lactancia materna, en una muestra chilena.

Breastfeeding self-efficacy is one of the indicators associated with the mental health of puerperal women and the maintenance of exclusive breastfeeding. OBJECTIVE: To evaluate the psychometric properties of an instrument to measure self-efficacy to breastfeed on the second postpartum day in the Chilean population. SUBJECTS AND METHOD: A convenience sample of 320 puerperal women who volunteered to participate in an interview on their second postpartum day was evaluated. Reliability was evaluated using the coefficient Cronbach's alpha. To assess its factorial structure, an exploratory factor analysis was performed. RESULTS: The results indicate that the final instrument, which has the factors "Intrapersonal Thoughts", composed of six items and "Breastfeeding Techniques", composed of eight items, presented an internal consistency by factor and total scale of F1 = 0.90, F2 = 0.91, and Total = 0.94, respectively. CONCLUSION: The breastfeeding self-efficacy scale showed good psychome tric characteristics during the second postpartum day among Chilean puerperal women.

Impact of untreated dental caries and dental pain on sadness related to oral health of Brazilian children.

PURPOSE: Children should feel sad when they believe that a negative outcome is permanent. The sadness that an oral problem might bring tends to contribute to children's loneliness and increase the social stress levels. The aim of this study was to evaluate the impact of untreated dental caries, dental pain, malocclusion, and traumatic dental injury on prevalence of sadness related to oral health among Brazilian children. METHODS: This cross-sectional study was carried out with 397 children aged 8-10 years randomly selected from public and private schools in Diamantina, Brazil. The Brazilian version of the CPQ8-10 was applied. Sadness was collected through the question, "In the last month how often did you feel sad because of your teeth or mouth?" and dental pain through the question, "In the last month, how many times have you had pain in your teeth?" One calibrated examiner (Kappa value intra examiner: 0.77-0.91; Kappa value inter examiner: 0.80-1.00) performed the exam for dental caries (DMFT), malocclusion (DAI), and dental trauma (O'Brien). Parents answered questions addressing socioeconomic issues. Descriptive analyses, Chi-square test, and hierarchical Poisson regression models were performed (IC 95%; p < 0.05)." RESULTS: The prevalence of sadness related to oral health was 30.5% (n = 121). Sadness related to oral health was associated with untreated dental caries (PR: 1.46; 95% CI 1.32-2.46; p = 0.001 ) and dental pain (PR: 2.91; 95% CI 2.00-4.22; p < 0.001). Other clinical variables analyzed (traumatic dental injury and malocclusion) were not significantly associated with sadness related to oral health. CONCLUSIONS: Children with untreated dental caries and dental pain presented a higher report of sadness related to oral health.

Intake, digestibility, ingestive behavior and performance of goats fed spineless cactus genotypes resistant to carmine cochineal / Consumo, digestibilidade, comportamento ingestivo e desempenho de caprinos alimentados com genótipos de palma forrageira resistentes à cochonilha-do-carmim

The objective was to evaluate the intake and digestibility of nutrients, ingestive behavior, and performance of goats fed with spineless cactus genotypes resistant to carmine cochineal (Miúda or Orelha de Elefante Mexicana (OEM). Thirty castrated male goats, without defined breed, aged 12 to 14 months, with an average body weight of 19.0±2.8kg, were distributed in a completely randomized design among three treatments (Control - Tifton hay, Miúda, and OEM) and ten replicates; the initial weight was considered as the covariate. The intake of organic matter (OM), neutral detergent fiber (NDF) was highest in the control treatment, while the intake of NFC was higher in the OEM diet. Treatments containing forage cactus showed the highest digestibility of DM, OM, and NFC. The animals fed the control diet spent more time on rumination and total chewing, but the time spent feeding or feeding efficiency, and performance did not differ. The use of spineless cactus genotypes resistant to carmine cochineal (Miúda and Orelha de Elefante Mexicana) in a diet for goats, in the amount of 450g/kg of DM does not interfere with the performance of the animals and improves the digestibility of OM and NFC.(AU)

Objetivou-se com o presente estudo avaliar o consumo e a digestibilidade de nutrientes, o comportamento ingestivo e o desempenho de caprinos alimentados com genótipos de palma forrageira resistentes à cochonilha-carmim (miúda ou orelha-de-elefante-mexicana (OEM). Trinta cabritos machos, castrados, sem raça definida, com idades entre 12 e 14 meses e peso corporal médio de 19,0±2,8kg, foram distribuídos em delineamento inteiramente ao acaso, em três tratamentos (controle - feno de tifton; miúda e OEM) e 10 repetições; o peso inicial foi considerado a covariável. O consumo de matéria orgânica (MO) e de fibra em detergente neutro (FDN) foi maior no tratamento controle; enquanto a ingestão de CNF foi maior na dieta OEM. Tratamentos contendo palma forrageira apresentaram as maiores digestibilidades de MS, MO e CNF. Os animais alimentados com a dieta controle gastaram mais tempo em ruminação e em mastigação total, mas o tempo gasto com alimentação ou a eficiência alimentar e o desempenho não diferiram. A utilização de genótipos de palma forrageira resistentes à cochonilha-carmim (miúda e orelha-de-elefante-mexicana) na dieta de caprinos, na quantidade de 450g/kg de MS, não interfere no desempenho dos animais e melhora a digestibilidade de MO e CNF.(AU)

HIV-Infected Naïve Patients Exhibit Endothelial Dysfunction Concomitant with Decreased Natural Antibodies Against Defined Apolipoprotein B Autoantigens. / Pacientes Naïve Infectados por HIV Apresentam Disfunção Concomitante com Diminuição de Anticorpos Naturais contra Autoantígenos Derivados da Apolipoproteína B Definidos.

BACKGORUND: Traditional and HIV-defined risk factors may be associated with an increase in cardiovascular events. Recent studies have suggested that the humoral immune response to modified LDL may be associated with the process of atherosclerosis. OBJECTIVES: To evaluate the presence of anti-oxLDL and apolipoprotein B-derived peptides in the blood, and their association with the endothelial function in HIV-infection. METHODS: This study consecutively included subjects matched for age, gender, and demographic data in two groups: (1) HIV-infected and naïve for antiviral therapy and (2) uninfected individuals. Subclinical atherosclerosis was assessed by intimal-media thickness, using ultrasonography of the carotid arteries. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery by ultrasonography. Autoantibodies (IgM, IgG) anti-oxidized low-density lipoprotein (oxLDL), anti-apolipoprotein B-peptide fragments (ApoB-D and 0033G-Cys peptides), and cytokine levels were evaluated by ELISA. RESULTS: This study's results showed no difference in subclinical atherosclerosis between groups; however, HIV-infected subjects showed a lower FMD, when compared to non-infected subjects. Therefore, HIV-infected subjects showed higher levels of inflammatory cytokines, titers of IgG anti-oxLDL, and IgG anti-ApoB-D. In contrast, titers of IgM anti-ApoB-D were lower in HIV-infected individuals and associated with reduced endothelial functions. CONCLUSIONS: This study's results show that HIV infection, in naïve subjects, is associated with endothelial dysfunction and a decline of natural antibodies to apo-B antigens.

FUNDAMENTO: Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose. OBJETIVOS: Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV. MÉTODOS: Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA. RESULTADOS: Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas. CONCLUSÕES: Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.

Pacientes Naïve Infectados por HIV Apresentam Disfunção Concomitante com Diminuição de Anticorpos Naturais contra Autoantígenos Derivados da Apolipoproteína B Definidos / HIV-Infected Naïve Patients Exhibit Endothelial Dysfunction Concomitant with Decreased Natural Antibodies Against Defined Apolipoprotein B Autoantigens

Fundamento: Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose. Objetivos: Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV. Métodos: Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA. Resultados: Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas. Conclusões: Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.

Abstract Backgorund: Traditional and HIV-defined risk factors may be associated with an increase in cardiovascular events. Recent studies have suggested that the humoral immune response to modified LDL may be associated with the process of atherosclerosis. Objectives: To evaluate the presence of anti-oxLDL and apolipoprotein B-derived peptides in the blood, and their association with the endothelial function in HIV-infection. Methods: This study consecutively included subjects matched for age, gender, and demographic data in two groups: (1) HIV-infected and naïve for antiviral therapy and (2) uninfected individuals. Subclinical atherosclerosis was assessed by intimal-media thickness, using ultrasonography of the carotid arteries. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery by ultrasonography. Autoantibodies (IgM, IgG) anti-oxidized low-density lipoprotein (oxLDL), anti-apolipoprotein B-peptide fragments (ApoB-D and 0033G-Cys peptides), and cytokine levels were evaluated by ELISA. Results: This study's results showed no difference in subclinical atherosclerosis between groups; however, HIV-infected subjects showed a lower FMD, when compared to non-infected subjects. Therefore, HIV-infected subjects showed higher levels of inflammatory cytokines, titers of IgG anti-oxLDL, and IgG anti-ApoB-D. In contrast, titers of IgM anti-ApoB-D were lower in HIV-infected individuals and associated with reduced endothelial functions. Conclusions: This study's results show that HIV infection, in naïve subjects, is associated with endothelial dysfunction and a decline of natural antibodies to apo-B antigens.

Evaluation of 68Ga-DOTATATE uptake at the pituitary region and the biochemical response to somatostatin analogs in acromegaly.

PURPOSE: Acromegaly is associated with many comorbidities and increased mortality. The first-line treatment is transsphenoidal surgery. However, many patients also need adjuvant drug treatment after surgery. Somatostatin analog (SSA), which suppresses GH secretion by somatotrophs by binding to the SSTR2 receptor, is the first choice. Nevertheless, 50% of patients are partially or totally resistant to SSA, so predictive factors of response are helpful to individualize drug treatment. 68GaDOTATATE PET/CT has emerged as the gold-standard method in the diagnosis and follow-up of gastroenteropancreatic neuroendocrine tumors, which also express SSTR. Our objective was to evaluate whether 68Ga-DOTATATE uptake (SUV max) at the pituitary region of patients on SSA therapy would be useful as a drug response predictor without the need of tumoral tissue. METHODS: Fifteen acromegalics patients on SSA treatment for at least 6 months were underwent to 68Ga-DOTATATE PET/CT at the nuclear medicine service. There was an SSA complete response group (n = 5), defined as GH < 1 µg/L and IFG-1 in the normal range for gender and age, and a group that did not meet these criteria (n = 10). RESULTS: As a result, we did not find out a significantly higher SUV max in the complete response group (p = 0.0576) to SSA. However, we found a significant inverse relationship between postoperative GH values and the SUVmax at the sella turcica (p = 0.0188), probably reflecting tumor SSTR2 expression. CONCLUSION: Thus, after this initial evaluation, 68GaDOTATATE PET/CT should be better studied to assess its usefulness in the follow-up of acromegalic patients.