Prevalence of Musculoskeletal and Metabolic Disorders in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis.

Introduction: Musculoskeletal disorders could be associated with metabolic disorders that are common after kidney transplantation, which could reduce the quality of life of patients. The aim of this study was to assess the prevalence of both musculoskeletal and metabolic disorders in kidney transplant patients. Methods: MEDLINE, CINAHL, Cochrane Library, EMBASE and Web of Science were searched from their inception up to June 2023. DerSimonian and Laird random-effects method was used to calculate pooled prevalence estimates and their 95% confidence intervals (CIs). Results: 21,879 kidney transplant recipients from 38 studies were analysed. The overall proportion of kidney transplant patients with musculoskeletal disorders was 27.2% (95% CI: 18.4-36.0), with low muscle strength (64.5%; 95% CI: 43.1-81.3) being the most common disorder. Otherwise, the overall proportion of kidney transplant patients with metabolic disorders was 37.6% (95% CI: 21.9-53.2), with hypovitaminosis D (81.8%; 95% CI: 67.2-90.8) being the most prevalent disorder. Conclusion: The most common musculoskeletal disorders were low muscle strength, femoral osteopenia, and low muscle mass. Hypovitaminosis D, hyperparathyroidism, and hyperuricemia were also the most common metabolic disorders. These disorders could be associated with poorer quality of life in kidney transplant recipients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023449171].

The immunodominance of antigenic site Sb on the H1 influenza virus hemagglutinin increases with high immunoglobulin titers of the cohorts and with young age, but not sex.

The head domain of the hemagglutinin of influenza viruses plays a dominant role in the antibody response due to the presence of immunodominant antigenic sites that are the main targets of host neutralizing antibodies. For the H1 hemagglutinin, five major antigenic sites defined as Sa, Sb, Ca1, Ca2, and Cb have been described. Although previous studies have focused on defining the hierarchy of the antigenic sites of the hemagglutinin in different human cohorts, it is still unclear if the immunodominance profile of the antigenic sites might change with the antibody levels of individuals or if other demographic factors (such as exposure history, sex, or age) could also influence the importance of the antigenic sites. The major antigenic sites of influenza viruses hemagglutinins are responsible for eliciting most of the hemagglutination inhibition antibodies in the host. To determine the antibody prevalence towards each major antigenic site, we evaluated the hemagglutination inhibition against a panel of mutant H1 viruses, each one lacking one of the "classic" antigenic sites. Our results showed that the individuals from the Stop Flu NYU cohort had an immunodominant response towards the sites Sb and Ca2 of H1 hemagglutinin. A simple logistic regression analysis of the immunodominance profiles and the hemagglutination inhibition titers displayed by each donor revealed that individuals with high hemagglutination inhibition titers against the wild-type influenza virus exhibited higher probabilities of displaying an immunodominance profile dominated by Sb, followed by Ca2 (Sb > Ca2 profile), while individuals with low hemagglutination inhibition titers presented a higher chance of displaying an immunodominance profile in which Sb and Ca2 presented the same level of immunodominance (Sb = Ca2 profile). Finally, while age exhibited an influence on the immunodominance of the antigenic sites, biological sex was not related to displaying a specific immunodominance profile.

The Impact of the Drying Process on the Antioxidant and Anti-Inflammatory Potential of Dried Ripe Coffee Cherry Pulp Soluble Powder.

Coffee fruit cascara, which is the skin and pulp of the coffee cherry, has been authorized as a novel food for commercialization in the European Union. The present research assessed the feasibility of using spray drying to produce a soluble powder called instant cascara (IC), employing sun-dried ripe coffee cherry pulp as a raw material. Although there were no significant differences (p > 0.05) in the overall antioxidant capacity between the freeze-dried and spray-dried samples, after an in vitro simulation of the digestion process, the spray-dried sample was significantly (p < 0.05) more antioxidant. Both samples reduced physiological intracellular ROS and significantly decreased (p < 0.05) the secretion of the pro-inflammatory factor NO. Alkaloids and phenolic compounds were detected in intestinal digests. In conclusion, spray drying is a good technique for producing IC as its use does not affect its properties and causes less environmental impact than freeze drying, as calculated by life cycle assessment. Sensory analysis did not show significant differences between the commercial beverage and the IC beverage in the adult population. IC at 10 mg/mL was significantly less accepted in adolescents than the commercial beverage. Future work will include the reformulation of the IC beverage at 10 mg/mL, which has antioxidant and anti-inflammatory potential, to increase its hedonic acceptance in all consumer segments.

Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination.

Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activity in vitro but several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.

Effectiveness of eHealth Interventions Promoting Physical Activity in Children and Adolescents: Systematic Review and Meta-Analysis.

BACKGROUND: eHealth interventions have been postulated as a feasible, acceptable, and possibly effective tool to promote physical activity (PA) among children and adolescents; however, a comprehensive quantitative analysis of the effects of eHealth interventions promoting PA is lacking. OBJECTIVE: This study aims to conduct a systematic review and meta-analysis on experimental studies reporting the effects of eHealth interventions aimed at promoting PA on PA parameters and sedentary behavior parameters in children and adolescents. METHODS: The CENTRAL, MEDLINE, Embase, and Web of Science databases were searched from inception to February 2022 for randomized controlled trials that analyzed the effects of eHealth interventions aimed at promoting PA on PA and sedentary parameters in children and adolescents. The Hartung-Knapp-Sidik-Jonkman random effects method was used to determine the mean differences (MDs) with their respective 95% CIs. The risk of bias was assessed using the Risk of Bias 2 (RoB2; Cochrane) tool and its extension for cluster randomized controlled trials. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. RESULTS: A total of 20 trials reporting the effects of different eHealth interventions aimed at promoting PA were included. Results for each parameter were as follows: counts per minute (MD -16.11 counts, 95% CI -122.76 to 90.53; k=3; n=402; I2=69%; favoring control), steps per day (MD 593.46 steps, 95% CI -2102.27 to 3289.19; k=2; n=152; I2=0%; favoring intervention [FI]), moderate to vigorous PA (MD -1.99 min/d, 95% CI -8.95 to 4.96; k=14; n=2336; I2=86%; favoring control), light PA (MD 3.28 min/d, 95% CI -15.48 to 22.04; k=5; n=355; I2=67%; FI), screen time (MD -31.48 min/d, 95% CI -68.62 to 5.65; k=5; n=904; I2=0%; FI), and sedentary time (MD -33.12 min/d, 95% CI -57.27 to -8.97; k=8; n=819; I2=75%; FI). Our results should be interpreted cautiously because of important limitations such as the scarcity of evidence, overall risk of bias, and low to very low certainty of evidence. CONCLUSIONS: We did not find conclusive evidence regarding the impact of PA-targeted eHealth interventions on PA parameters, but the very low certainty of evidence suggests that eHealth interventions may reduce sedentary time in children and adolescents. Our results may have important scientific implications as they highlight that the rapid development of eHealth interventions to promote PA lacks robust supporting evidence. TRIAL REGISTRATION: PROSPERO CRD42020211020; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=211020.

Proof-of-concept for multiple AON delivery by a single U7snRNA vector to restore splicing defects in ABCA4.

The high allelic heterogeneity in Stargardt disease (STGD1) complicates the design of intervention strategies. A significant proportion of pathogenic intronic ABCA4 variants alters the pre-mRNA splicing process. Antisense oligonucleotides (AONs) are an attractive yet mutation-specific therapeutic strategy to restore these splicing defects. In this study, we experimentally assessed the potential of a splicing modulation therapy to target multiple intronic ABCA4 variants. AONs were inserted into U7snRNA gene cassettes and tested in midigene-based splice assays. Five potent antisense sequences were selected to generate a multiple U7snRNA cassette construct, and this combination vector showed substantial rescue of all of the splicing defects. Therefore, the combination cassette was used for viral synthesis and assessment in patient-derived photoreceptor precursor cells (PPCs). Simultaneous delivery of several modified U7snRNAs through a single AAV, however, did not show substantial splicing correction, probably due to suboptimal transduction efficiency in PPCs and/or a heterogeneous viral population containing incomplete AAV genomes. Overall, these data demonstrate the potential of the U7snRNA system to rescue multiple splicing defects, but also suggest that AAV-associated challenges are still a limiting step, underscoring the need for further optimization before implementing this strategy as a potential treatment for STGD1.

Association of daily steps on lipid and glycaemic profiles in children: The mediator role of cardiorespiratory fitness.

AIM: To analyse, in schoolchildren, the relationship between daily steps with metabolic parameters; and to examine whether this association is mediated by cardiorespiratory-fitness (CRF). METHODS: A cross-sectional analysis of baseline data from a feasibility trial was performed in children from two primary schools in Cuenca, Spain. Daily steps were measured using the Xiaomi MI Band 3. Lipid and glycaemic profiles were analysed from blood samples. CRF was assessed using the 20-m shuttle run test. ANCOVA models were used to test the mean differences by daily steps quartiles. Mediation analyses were conducted to examine whether CRF mediates the association between daily steps and lipid and glycaemic parameters. RESULTS: A total of 159 schoolchildren (aged 9-12 years, 53% female) were included in the analysis. Schoolchildren in the highest daily steps quartiles (>10 000 steps) showed significantly lower triglycerides and insulin levels (p = 0.004 and 0.002, respectively). This association did not remain after controlling for CRF. In mediation analyses, a significant indirect effect was observed through CRF in the relationship between daily steps with triglycerides and insulin. CONCLUSION: Children who daily accumulate more than 10 000 steps have better lipid and metabolic profile, and CRF mediated their relationship in schoolchildren.

Steps per day and health-related quality of life in schoolchildren: the mediator role of cardiorespiratory fitness.

To analyse the relationship between steps per day and health-related quality of life (HRQoL) and cardiorespiratory fitness (CRF) and to examine whether the relationship between steps per day and HRQoL is mediated by CRF in schoolchildren. This was a cross-sectional study including 501 schoolchildren (aged 9-12 years, 47% girls), from Cuenca, Spain. Steps per day were measured using the Xiaomi Mi Band 3 Smart Bracelet, HRQoL was estimated by the KIDSCREEN-27 questionnaire, and CRF was assessed using the 20-m shuttle run test. Analysis of covariance and multivariate analysis of covariance models showed that children with a higher mean number of steps per day (> 9000 steps/day) had better HRQoL (global score, and physical and psychological well-being) and higher CRF levels than their peers with a lower number of steps per day (p < 0.05); however, these differences were no longer significant when controlling for sex, age, mother's education level, and CRF (p > 0.05). Linear regression models estimated that each 1000-step increment was associated with better CRF (ß = 0.350; 95% CI, 0.192 to 0.508). In addition, the relationship between steps per day and HRQoL was mediated by CRF (p < 0.05).    Conclusion: Steps per day are a good metric to estimate daily physical activity because of its positive relationship with CRF. Moreover, those children taking more than 9000 steps per day are associated with higher levels of physical and psychological well-being. Finally, a substantial part of the improvement in HRQoL achieved through the increase in physical activity (steps per day) is mediated by CRF. What is Known: • Physical activity is known to have a positive impact on health-related quality of life in children. Steps per day are commonly used as a measure of physical activity. • Cardiorespiratory fitness is a recognized indicator of overall health in youth. What is New: • Increments of steps per day were associated with better CRF, with a nonlinear association after approximately 9000 steps/day. • Schoolchildren with > 9000 steps/ day showed better HRQoL.

Corneal transplantation and concomitant SARS-CoV-2 infection: a case report / Transplante de córnea e infecção concomitante por SARS-CoV-2: relato de caso

ABSTRACT This report was aimed at presenting a case of neurotrophic keratitis and concomitant SARS-CoV-2 infection in a patient who has recently undergone a corneal DALK transplant. One month after corneal transplantation with adequate corneal epithelialization, the patient presented neurotrophic keratitis with a torpid course of the corneal transplant coinciding with a SARS-CoV-2 infection, with an excessive host immune response. In addition, the patient presented a re-positivization of nasopharyngeal polymerase chain reaction of SARS-CoV-2 with past disease after starting treatment with autologous serum eye drops. The implications at the ophthalmological level of SARS-CoV-2 infection may be clarified as the time the illness progresses and we learn more about how it acts. In this case, the disparity of signs and symptoms, the antecedent of corneal surgery, and the possibility of a herpetic infection as a cause of the primary leukoma suggested neurotrophic keratitis. Nonetheless, the involvement of systemic SARS-CoV-2 infection in the process, triggering an excessive host immune response at the corneal level with an increase in inflammatory cytokines must be taken into account. No relationship was found between treatment with autologous serum and re-positivization of nasopharyngeal polymerase chain reaction, presenting the patient a favorable response to treatment.

RESUMO O objetivo deste relato foi apresentar um caso de ceratite neurotrófica e infecção concomitante por SARS-CoV-2 em paciente submetido recentemente a transplante de córnea DALK. Um mês após o transplante de córnea com adequada epitelização da córnea, o paciente apresentou ceratite neurotrófica com curso tórpido do transplante de córnea, coincidindo com infecção por SARS-CoV-2, com resposta imune excessiva do hospedeiro. Além disso, o paciente apresentou repositivização da reação em cadeia da polimerase nasofaríngeo de SARS-CoV-2, com doença pregressa após iniciar tratamento com colírio de soro autólogo. As implicações a nível oftalmológico da infecção por SARS-CoV-2, podem ser esclarecidas à medida que a doença progride e aprendemos mais sobre sua forma de atuação. Neste caso, a disparidade de sinais e sintomas, o antecedente de cirurgia de córnea e a possibilidade de infecção herpética como causa do leucoma primário sugeriram ceratite neurotrófica. No entanto, deve-se levar em consideração o envolvimento da infecção sistêmica por SARS-CoV-2 no processo, desencadeando uma resposta imune excessiva do hospedeiro no nível da córnea, com aumento de citocinas inflamatórias. Não foi encontrada relação entre o tratamento com soro autólogo e a repositivização da reação em cadeia da polimerase nasofaríngea, apresentando ao paciente uma resposta favorável ao tratamento.

Chimeric hemagglutinin split vaccines elicit broadly cross-reactive antibodies and protection against group 2 influenza viruses in mice.

Seasonal influenza virus vaccines are effective when they are well matched to circulating strains. Because of antigenic drift/change in the immunodominant hemagglutinin (HA) head domain, annual vaccine reformulations are necessary to maintain a match with circulating strains. In addition, seasonal vaccines provide little to no protection against newly emerging pandemic strains. Sequential vaccination with chimeric HA (cHA) constructs has been proven to direct the immune response toward the immunosubdominant but more conserved HA stalk domain. In this study, we show that immunization with group 2 cHA split vaccines in combination with the CpG 1018 adjuvant elicits broadly cross-reactive antibodies against all group 2 HAs, as well as systemic and local antigen-specific T cell responses. Antibodies elicited after sequential vaccination are directed to conserved regions of the HA such as the stalk and the trimer interface and also to the N2 neuraminidase (NA). Immunized mice were fully protected from challenge with a broad panel of influenza A viruses.

Understanding the Raman enhancement of carbon nanohorns labelled with organic dyes.

Carbon nanohorns have been non-covalently functionalized with two different benzothiadiazoloquinoxalines prepared via Stille cross-coupling reactions under solvent-free conditions and microwave irradiation. The close interactions between these organic molecules and the nanostructures resulted in a prominent Raman enhancement, which makes them attractive candidates for multiple applications. A complete experimental physico-chemical characterization has been combined with in silico studies to understand these phenomena. The processability of the hybrids was exploited to prepare homogeneous films on substrates with different natures.

Parents' Perceptions of Children's and Adolescents' Use of Electronic Devices to Promote Physical Activity: Systematic Review of Qualitative Evidence.

BACKGROUND: The use of physical activity (PA) electronic devices offers a unique opportunity to engage children and adolescents in PA. For this age group (2-17 years), parents play a key role in promoting healthy lifestyles and regulating the use of electronic devices. Therefore, parents' perceptions of the use of electronic devices for PA in children and adolescents are critical for efficient intervention. OBJECTIVE: The aim of this qualitative systematic review was to improve the understanding of parents' perceptions of the use of electronic devices for PA in children and adolescents. METHODS: A systematic search of electronic databases (Medline/PubMed, SPORTDiscus, Web of Science, Scopus, OpenGrey, and Deep Blue) was conducted. Studies from inception (2010) to May 2022 were identified. Qualitative studies on the perceptions of healthy children's and adolescents' (aged 2-17 years) parents regarding PA interventions performed on electronic devices were included according to the Cochrane Qualitative and Implementation Methods Group Guidance Series and the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) statement. The Joanna Briggs Institute Qualitative Assessment and Review Instrument was used for methodological validity. RESULTS: In total, 18 studies with 410 parents, mostly mothers, were included. Parents' perceptions were grouped into 4 categories: usefulness, advantages, general perceptions (electronic devices for health promotion, preferences for real-life PA, and concerns), and acceptability (barriers and facilitators) of electronic devices for PA. Parents perceived electronic devices as useful for increasing PA, learning new skills, and increasing motivation for PA and valued those devices that promoted socialization and family and peer bonding. In terms of general perceptions, parents had positive attitudes toward PA electronic devices; however, they preferred outdoor and real-life PA, especially for preschoolers and children. Concerns, such as physical and psychological harm, addiction, conflicts, and compliance difficulties, were found. Facilitators were identified as ease of use, appropriate feedback, promotion of socialization, and motivational strategies, such as rewards, challenges, and attractiveness. Barriers, such as discomfort, price, and difficulties in using or understanding electronic devices, were also identified. For older children and adolescents, parents were more concerned about high levels of screen time and setting limits on electronic devices and therefore preferred PA electronic devices rather than traditional ones. CONCLUSIONS: Overall, the participants had positive attitudes toward electronic devices for PA and perceived them as an effective way to promote PA in children and adolescents. They also perceived several benefits of using electronic devices, such as health promotion, increased awareness and motivation, and socialization, as well as barriers, facilitators, and age differences. The results of this study could provide researchers with insights into designing more effective, age-appropriate PA electronic devices for children and adolescents and improving adherence to their use. TRIAL REGISTRATION: PROSPERO CRD42021292340; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=292340.

Effect of coenzyme Q10 on cardiac function and survival in heart failure: an overview of systematic reviews and meta-analyses.

Heart failure (HF) is associated with a deficiency in blood levels of coenzyme Q10 (CoQ10), and its supplementation has been proposed. The aim of this systematic review was to synthesise the available evidence on the effects of CoQ10 on cardiac function and quality of life in HF. A systematic search of Medline, Scopus, Web of Science and the Cochrane Library was conducted from inception until March 2023. Meta-analyses measuring the effect of CoQ10 on cardiac function [i.e., ejection fraction (EF), cardiac output (CO), cardiac index (CI), stroke volume (SV)], quality of life [i.e., mortality, exercise capacity, and New York Heart Association (NYHA) classification], and CoQ10 levels in HF were included. Ten meta-analyses met the inclusion criteria. CoQ10 had an effect on EF in 6 of the 9 studies, with an increase of 1.77% (0.10, 3.44) to 3.81% (1.22, 6.40), while it had an effect on CO, CI and SV in one of the two studies. Moreover, CoQ10 did not improve exercise capacity and only one study showed an effect on NYHA classification, while there was a risk ratio (RR) of 0.69 (0.50, 0.95) to 0.58 (0.35, 0.95) in favour of CoQ10 for mortality and a RR of 0.62 (0.49, 0.78) for hospitalisations. Finally, CoQ10 levels were found to increase by 1.40 µg mL-1 in all studies. CoQ10 showed a possible beneficial effect on heart function, which was associated with a reduction in mortality and hospitalisations. However, more research is needed into the conditions that may optimise CoQ10 therapy.

Intelligence quotient-genotype association in dystrophinopathies: A systematic review and meta-analysis.

AIMS: Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD) are associated with intelligence quotients (IQs) lower than the normative values, and it is suggested that IQ is negatively correlated with the number of affected isoforms (i.e., Dp427, Dp140 and Dp71). Therefore, the objective of this meta-analysis was to estimate the IQ, and the IQ-genotype association according to the altered dystrophin isoforms, in the population with BMD or DMD. METHODS: A systematic search in Medline, Web of Science, Scopus and the Cochrane Library was conducted from inception to March 2023. Observational studies that determined the IQ and/or the IQ by genotype in the population with BMD or DMD were included. Meta-analyses of IQ, IQ by genotype and IQ-genotype association by comparing IQ according to the genotype were conducted. The results are shown as the mean/mean differences and 95% confidence intervals. RESULTS: Fifty-one studies were included. The IQ in BMD was 89.92 (85.84, 94.01) and in DMD was 84.61 (82.97, 86.26). Moreover, the IQ for Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71+ was 90.62 (86.72, 94.53) and 80.73 (67.49, 93.98) in BMD, while the IQ for Dp427-/Dp140+/Dp71+, Dp427-/Dp140-/Dp71+ and Dp427-/Dp140-/Dp71- was 93.05 (89.42, 96.67), 81.78 (77.23, 86.32) and 49.19 (40.47, 57.90) in DMD. Finally, in DMD, Dp427-/Dp140-/Dp71+ vs Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71- vs Dp427-/Dp140-/Dp71+ were associated with -10.73 (-14.66, -6.81) and -36.14 (-48.87, -23.41) points, respectively. CONCLUSIONS: The IQ in BMD and DMD was lower than the normative values. Moreover, in DMD, there is a synergistic association between the number of affected isoforms and IQ.

Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico.

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain.

Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1- microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.

Comparative effectiveness of different types of exercise in reducing arterial stiffness in children and adolescents: a systematic review and network meta-analysis.

OBJECTIVE: Arterial stiffness is an early and detectable marker of vascular changes leading to atherosclerotic cardiovascular disease (ACVD). Our objective was to compare the effectiveness of different types of exercise in reducing arterial stiffness in children and adolescents. DESIGN: A systematic review and network meta-analysis (NMA) was conducted including experimental studies reporting the effects of exercise interventions on pulse wave velocity (PWV) in children and adolescents. DATA SOURCES: Cochrane Central Register of Controlled Trials, EMBASE (via Scopus), PubMed (via Medline) and Web of Science from database inception to 25 March 2022. ELIGIBILITY CRITERIA: Experimental studies reporting the effects of exercise interventions on PWV in children and adolescents. RESULTS: Fourteen studies were included in the NMA, all of them were randomised controlled trials except one quasi-experimental study, with an overall risk of bias of some concern. Regarding PWV reduction, all exercise modalities were more effective than control, with standardised mean difference ranging from -1.93 (95% CI: -2.84 to -1.02) and -1.11 (95% CI: -2.01 to -0.21) for aerobic exercise and high intensity interval training (HIIT), respectively, to -0.59 (95% CI: -1.39 to 0.22) for combined exercise. Only sensorimotor training was not superior to the control group 0.11 (95% CI: -1.10 to 1.32). CONCLUSION: Our results support that exercise interventions, especially aerobic exercise or HIIT, can improve arterial stiffness at early ages. The potential to address ACVD early and mitigate long-term consequences via exercise interventions in children and adolescents with higher arterial stiffness requires further investigation. PROSPERO REGISTRATION NUMBER: CRD42022322536.

Unified Method for Target and Non-Target Monitoring of Pesticide Residues in Fruits and Fruit Juices by Gas Chromatography-High Resolution Mass Spectrometry.

A new polyvalent wide-scope analytical method, valid for both raw and processed (juices) fruits, combining target and non-target strategies, has been developed and validated to determine low concentrations of 260 pesticides, as well as many potential non-target substances and metabolites. The target approach has been validated according to SANTE Guide requirements. Trueness, precision, linearity, and robustness values were validated in raw fruit (apple) and juice (apple juice) as representative solid and liquid food commodities. Recoveries were between 70-120% and two ranges of linearity were observed: 0.5-20 µg kg-1 (0.5-20 µg L-1 apple juice) and 20-100 µg kg-1 (20-100 µg L-1 apple juice). The limits of quantification (LOQs) reached were lower than 0.2 µg kg-1 in apple (0.2 µg L-1 apple juice) in most cases. The developed method, based on QuEChERS extraction followed by gas chromatography-high resolution mass spectrometry (GC-HRMS), achieves part-per-trillions lower limits, which allowed the detection of 18 pesticides in commercial samples. The non-target approach is based on a retrospective analysis of suspect compounds, which has been optimized to detect up to 25 additional compounds, increasing the scope of the method. This made it possible to confirm the presence of two pesticide metabolites which were not considered in the target screening, phtamlimide and tetrahydrophthalimide.

An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination.

NDV-HXP-S is a recombinant Newcastle disease virus-based vaccine against SARS-CoV-2, which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that used for the production of the vast majority of influenza virus vaccines. Here, we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a phase 1 clinical study in Thailand. The SARS-CoV-2 neutralizing and spike protein binding activity of NDV-HXP-S postvaccination serum samples was compared to that of samples from mRNA BNT162b2 (Pfizer) vaccinees. Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of BNT162b2 vaccinees, whereas spike protein binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from mRNA vaccinees. This led us to calculate ratios between binding and neutralizing antibody titers. Samples from NDV-HXP-S vaccinees had binding to neutralizing activity ratios that were lower than those of BNT162b2 sera, suggesting that NDV-HXP-S vaccination elicits a high proportion of neutralizing antibodies and low non-neutralizing antibody titers. Further analysis showed that, in contrast to mRNA vaccination, which induces strong antibody titers to the receptor binding domain (RBD), the N-terminal domain, and the S2 domain, NDV-HXP-S vaccination induced an RBD-focused antibody response with little reactivity to S2. This finding may explain the high proportion of neutralizing antibodies. In conclusion, vaccination with inactivated NDV-HXP-S induces a high proportion of neutralizing antibodies and absolute neutralizing antibody titers that are comparable to those elicited by mRNA vaccination.

Association between severe hypoglycaemia and risk of dementia in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

The aim of this systematic review was to analyse whether there is an association between severe hypoglycaemia and the incidence of dementia in patients with type 2 diabetes mellitus. We systematically searched the MEDLINE, Scopus, and Cochrane databases from their inception until September 2022 for observational studies on the association between hypoglycaemia and the risk of dementia. The DerSimonian and Laird method was used to compute a pooled estimate of the risk for such association. Risk ratio (RR) and its respective 95% confidence interval (95% CI). Two analyses were performed to estimate the risk of dementia: (i) any hypoglycaemia versus no hypoglycaemia and (ii) a dose-response analysis for one, two, or more than three hypoglycemic events versus no hypoglycaemia. PROSPERO registration number CRD42020219200. Seven studies were included. The pooled RR for the association of severe hypoglycaemia and risk of dementia was 1.47 (95% CI: 1.24-1.74). When the dose-response trend was analysed, the pooled RR for the risk of dementia was increased according to the hypoglycaemia events as follows: 1.29 (95% CI: 1.15-1.44) for one hypoglycemic event; 1.68 (95% CI: 1.38-2.04) for two hypoglycemic events; and 1.99 (95% CI: 1.48-2.68) for three or more hypoglycemic events. Our study demonstrates a 54% higher risk of dementia among people who suffer a hypoglycaemia event compared to nonhypoglycaemia. Considering our results and the prevalence of people suffering from diabetes mellitus, health education for both newly diagnosed and already diagnosed people could be a useful tool for glycaemic control, thus avoiding hypoglycaemic events.