Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults.

BACKGROUND: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. METHODS: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. FINDINGS: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. INTERPRETATION: Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. FUNDING: The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.

Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review.

Given the typical age onset of schizophrenia, there are tremendous economic and social impacts that extend beyond the person and their families. One critical determinant of the diseases' impact is the patient's adherence to antipsychotic drug treatment. Approved in 2015 for the treatment of schizophrenia, paliperidone palmitate (Invega Trinza, a 3-month injection, noted as PP3M) is a second-generation long-acting injectable antipsychotic medication. Among the different formulations offered for palmitate paliperidone, including the 1 and 3-month formulations, the longer duration 3-month formulation was better at preventing relapse in schizophrenic patients. To date, different formulations of palmitate paliperidone that have been studied on relapse episodes of schizophrenia include once-daily extended-release oral paliperidone (ORAL paliperidone), once-monthly paliperidone palmitate (PP1M), and once-every-3-months paliperidone palmitate (PP3M). Post-hoc analyses show that patients who were withdrawn from PP1M paliperidone had the least risk of relapse, followed by patients withdrawn from PP3M and patients withdrawn from ORAL paliperidone. PP3M was better at preventing relapse compared to ORAL paliperidone. The results demonstrated that 50% of patients who were withdrawn from ORAL paliperidone, PP1M, or PP3M remained relapse-free for ~2, 6, and 13 months, respectively. Compared to PP1M, PP3M is just as safe and effective and has the added advantage of increased adherence related to a longer dose interval, decreasing the risk of relapse.

Naltrexone Implant for Opioid Use Disorder.

The continued rise in the availability of illicit opioids and opioid-related deaths in the United States has left physicians, researchers, and lawmakers desperate for solutions to this ongoing epidemic. The research into therapeutic options for the treatment of opioid use disorder (OUD) began with the introduction of methadone in the 1960s. The approval of oral naltrexone initially showed much promise, as the drug was observed to be highly potent in antagonizing the effects of opioids while producing no opioid agonist effects of its own and having a favorable side effect profile. Patients that routinely take their naltrexone reported fewer days of heroin use and had more negative drug tests than those without treatment. Poor outcomes in OUD patients treated with naltrexone have been directly tied to short treatment time. Studies have shown that naltrexone given orally vs. as an implant at the 6-month interval showed a higher non-compliance rate among those who used oral medications at the 6-month mark and a slower return to use rate. There were concerns that naltrexone could possibly worsen negative symptoms seen in opiate use disorder related to blockade of endogenous opioids that are important for pleasurable stimuli. Studies have shown that naltrexone demonstrated no increase in levels of anxiety, depression and anhedonia in participants and another study found that those treated with naltrexone had a significant reduction in mental health-related hospitalizations. The latter study also concluded that there was no increased risk for mental health-related incidents in patients taking naltrexone via a long-acting implant. Although not yet FDA approved in the United States, naltrexone implant has shown promising results in Europe and Australia and may provide a novel treatment option for opioid addiction.

Calidad de vida de la población de 50-80 años, participantes del conflicto político-militar, Guarjila, Chalatenango, marzo-agosto 2019 / Quality of life of the population aged 50-80 years, participants in the political-military conflict, Guarjila, Chalatenango, March-August 2019

Propósito: establecer mecanismos y estrategias de promoción y prevención para que contribuyan a mejorar la calidad de vida de la población del Cantón Guarjila, donde las instituciones responsables aborden esta problemática identificada. Material y método: investigación de tipo descriptivo, corte transversal con enfoque cuantitativo, se realizó trabajo de campo y revisión documental. Resultados: en cuanto a los resultados más relevantes se encuentran: lo relacionado con las características sociodemográficas, identificándose que en la distribución de edades destacan que la población de 50 a 60 años predomina con 54%, el género femenino prevalece en un 59%,y un 38% no poseen ningún grado de escolaridad. En cuanto a las condiciones de salud, el 56% de la población padece una enfermedad o secuela del cual el 43% manifestó sentir un grado de afectación por las lesiones físicas sufridas durante el conflicto político militar, el 99% de la población expresó haber sido víctima de violación a sus derechos humanos durante los 12 años del conflicto, el 94% expresó que no tienen buena salud mental, el 55% manifestó no recibir invitación para participar en los grupos de autoayuda. Lo relacionado con la atención en salud, el 60% de la población siempre recibir atención especializada en la unidad de salud familiar u hospital, al 65% le proporcionan sus medicamentos en los establecimientos antes mencionados, el 60% de los encuestados refirió no pertenecer a ningún grupo de autoayuda. Conclusiones: un porcentaje significativo de la población no pertenecen a ningún grupo de autoayuda, por la carencia de apoyo de las instituciones de la comunidad, esto disminuye la motivación de las personas mayores para buscar ayuda profesional y perjudica su estado de salud en general. Recomendaciones: promover el fortalecimiento y creación de grupos de autoayuda para mejorar la autoestima, motivación, desarrollo personal y sobre todo tener en cuenta la opinión de la persona sobre su estado de salud

Sweetened beverages, snacks and overweight: findings from the Young Lives cohort study in Peru.

OBJECTIVE: To determine the association between consumption of snacks and sweetened beverages and risk of overweight among children. DESIGN: Secondary analysis of the Young Lives cohort study in Peru. SETTING: Twenty sentinel sites from a total of 1818 districts available in Peru. SUBJECTS: Children in the younger cohort of the Young Lives study in Peru, specifically those included in the third (2009) and the fourth (2013) rounds. RESULTS: A total of 1813 children were evaluated at baseline; 49·2 % girls and mean age 8·0 (sd 0·3) years. At baseline, 3·3 (95 % CI 2·5, 4·2) % reported daily sweetened beverage consumption, while this proportion was 3·9 (95 % CI 3·1, 4·9) % for snacks. Baseline prevalence of overweight was 22·0 (95 % CI 20·1, 23·9) %. Only 1414 children were followed for 4·0 (sd 0·1) years, with an overweight incidence of 3·6 (95 % CI 3·1, 4·1) per 100 person-years. In multivariable analysis, children who consumed sweetened beverages and snacks daily had an average weight increase of 2·29 (95 % CI 0·62, 3·96) and 2·04 (95 % CI 0·48, 3·60) kg more, respectively, than those who never consumed these products, in approximately 4 years of follow-up. Moreover, there was evidence of an association between daily consumption of sweetened beverages and risk of overweight (relative risk=2·12; 95 % CI 1·05, 4·28). CONCLUSIONS: Daily consumption of sweetened beverages and snacks was associated with increased weight gain v. never consuming these products; and in the case of sweetened beverages, with higher risk of developing overweight.

Improvement of the lytic properties of a beta-1,3-glucanase by directed evolution.

BGLII is a bacterial endoglucanase that hydrolyzes the beta-1,3-glucan present in yeast cell walls, resulting in lysis of Saccharomyces cerevisiae. As a result of this property, BGLII is considered a potential tool for downstream processing and recovery of biotechnological products produced in yeast. Here we describe the improvement of the yeast lytic activity of BGLII, achieved by a directed evolution approach involving random mutagenesis and screening for variants with improved catalytic activity, combined with site-directed mutagenesis. A BGLII variant having three times the wild-type hydrolytic activity on laminarin was identified. The purified enzyme also exhibited higher lytic activity on yeast cells. Mutations causing the improvements are located very close to each other in the amino acid sequence, suggesting that the region should be considered as a target for further improvements of the glucanase activity. These results demonstrate the feasibility of molecular evolution methods for the improvement of the BGLII hydrolytic activity, and open a window for further improvement of this or other properties in glycosyl hydrolases in general.

Estimation of the dietary intake of cadmium, lead, mercury, and arsenic by the population of Santiago (Chile) using a Total Diet Study.

Dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the population of Santiago (Chile) was determined using a Total Diet Study in the market basket modality. After conducting a survey of the foods consumed in the last 24 h, the most consumed food products were included in the basket. Subsequently, they were cooked or prepared according to typical Chilean procedures and grouped into 17 food categories according to their chemical characteristics. The fish and shellfish group had the highest contents of As (1351 ng/g wet weight, ww), Cd (277 ng/g ww), and Hg (48 ng/g ww), while the sugar group had the highest content of Pb (251 ng/g ww). For a person with a body weight of 68 kg, the dietary intakes of As (77 microg/day), Cd (20 microg/day), Hg (5 microg/day), and Pb (206 microg/day) are lower than the provisional tolerable weekly intake values established by the FAO/WHO. Consequently, the total intakes of As, Cd, Hg, and Pb in Santiago (Chile) are within the limits estimated as safe.