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BackgroundRecently published studies have reported association of COVID-19 vaccine ChAdOx1-S (Vaxzevria) with Guillain Barré Syndrome (GBS). Less is known about the safety of other COVID-19 vaccines with respect to GBS outcome. This study investigated the association of COVID-19 vaccines with GBS in more than 15 million persons aged ≥12 years in Italy.MethodsStudy population was all individuals aged ≥12 years who received at least one dose of COVID-19 vaccines, admitted to emergency care/hospital for GBS from 27 December 2020-30 September 2021 in Italy. Identification of GBS cases and receipt of at least one dose of mRNA-1273 (Elasomeran), BNT162b2 (Tozinameran), ChAdOx1-S (Vaxzevria) and Ad26.COV2.S (Janssen) through record linkage between regional health care and vaccination registries. Relative Incidence (RI) was estimated Self-controlled case series method adapted to event-dependent exposure using in the 42-day exposure risk period after each dose compared with other observation periods.ResultsIncreased risk of GBS was found after first (RI = 6.83; 95% CI 2.14-21.85) and second dose (RI = 7.41; 2.35-23.38) of mRNA-1273 and first dose of ChAdOx1-S (RI = 6.52; 2.88-14.77). Analysis by age found an increased risk among those aged≥60 years after first (RI = 8.03; 2.08-31.03) and second dose (RI = 7.71; 2.38-24.97) of mRNA-1273. The first dose of ChAdOx1-S was associated with GBS in those aged 40-59 (RI = 4.50; 1.37-14.79) and in those aged ≥ 60 years (RI = 6.84; 2.56-18.28).ConclusionsmRNA-1273 and ChAdOx1-S vaccines were associated with an increased risk of GBS however this risk resulted in a small number of excess cases. Limitations were loss of GBS outpatient cases and imprecision of the estimates in the subgroup analysis due to a low number of events.

BackgroundFollowing the low incidence rates of non-SARS-CoV-2 respiratory viruses registered during the strict lockdown enforced in the pandemic, a resurgence of several endemic viruses in Catalonia (Spain) was noted during the early summer of 2021.ObjectivesIn this study, we investigated whether the circulation of non-SARS-CoV-2 respiratory viruses in Catalonia, assessed by Microbiological Reporting System of Catalonia (MRSC) and the Epidemiological Surveillance Network of Catalonia, was affected by the strict lockdown measures, as well as, the implication of the Coronavirus Disease 19 (COVID-19) de-escalation process in the late season outbreaks registered during the 2020-2021 season.Study designA retrospective comparison of epidemic patterns in the respiratory viruses' incidence, using regional public health surveillance data from MRSC, was performed between weeks 26/2016 to week 27/2021. Data were expressed as the weekly total number of test positivity for individual viruses. A segmented negative binomial regression model was conducted, with two parameters included (level and trend) for each segment of the time series (2020 pre-lockdown, 2020 post-lockdown and 2021). Results were reported as a unit changed in the strict lockdown.ResultsA total of 51588 confirmed cases of the different respiratory viruses were included in the analysis, the majority were influenza cases (63.7%). An immediate reduction in the weekly number of cases was observed in 2020 after the COVID-19 outbreak for human adenovirus virus (HAdV) (β2 = -2.606; P ConclusionsOur data not only provides evidence that occurrence of different respiratory virus infections was affected by the strict lockdown taken against SARS-CoV-2 but it also shows a late resurgence of seasonal respiratory viruses' cases during the 2020-2021 season following the relaxation of COVID-19-targeted non-pharmaceutical interventions.

Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.

The COVID-19 pandemic drastically affected many areas and contexts of today's society, including school and family. Several studies focused on the worldwide effects of school closures on students' learning outcomes, context, and well-being. However, the data emerging from these studies are often inconsistent and fragmentary, highlighting the need of a comprehensive analysis of the phenomenon. This need is especially urgent for the countries with the most severe school closure, like Italy. This systematic review aims to collect the opinions of parents, teachers, and students on: other dimensions of Italian primary school students affected by school closures, beyond academic performance; hypothetical agreement between the opinions of parents, teachers, and students regarding the different effects of school closures on Italian primary school students; possible differences between the effects of school closures on Italian primary school students and the students in other countries. Our search was conducted using PRISMA 2020 guidelines on Web of Science, Pubmed, Scopus, and EBSCOHost. The results obtained from 34 articles revealed a strong concern on the part of all stakeholders involved in learning during the pandemic, with evident negative effects for Italian school students. The constraint on distance learning led to a drastic change in everyone's routine, and a negative emotional change on the part of young students. Parents and teachers generally considered distance learning to be ineffective for the education of their children and students; they encountered technical-practical difficulties in the use of electronic devices for participation in school activities; overall learning deficits on the part of students, especially in mathematics, as confirmed by INVALSI results were also found. The investigation reveals a condition of shared emotional and academic performance difficulty, and a further challenging circumstance for students previously at risk of marginalization. Further research in this field is paramount to identify new and adequate recovery strategies.

Prochlorococcus marinus, the smallest picocyanobacterium, comprises multiple clades occupying distinct niches, currently across tropical and sub-tropical oligotrophic ocean regions, including Oxygen Minimum Zones. Ocean warming may open growth-permissive temperatures in new, poleward photic regimes, along with expanded Oxygen Minimum Zones. We used ocean metaproteomic data on current Prochlorococcus marinus niches, to guide testing of Prochlorococcus marinus growth across a matrix of peak irradiances, photoperiods, spectral bands and dissolved oxygen. MED4 from Clade HLI requires greater than 4 h photoperiod, grows at 25 μmol O2 L-1 and above, and exploits high cumulative diel photon doses. MED4, however, relies upon an alternative oxidase to balance electron transport, which may exclude it from growth under our lowest, 2.5 μmol O2 L-1, condition. SS120 from clade LLII/III is restricted to low light under full 250 μmol O2 L-1, shows expanded light exploitation under 25 μmol O2 L-1, but is excluded from growth under 2.5 μmol O2 L-1. Intermediate oxygen suppresses the cost of PSII photoinactivation, and possibly the enzymatic production of H2O2 in SS120, which has limitations on genomic capacity for PSII and DNA repair. MIT9313 from Clade LLIV is restricted to low blue irradiance under 250 μmol O2 L-1, but exploits much higher irradiance under red light, or under lower O2 concentrations, conditions which slow photoinactivation of PSII and production of reactive oxygen species. In warming oceans, range expansions and competition among clades will be governed not only by light levels. Short photoperiods governed by latitude, temperate winters, and depth attenuation of light, will exclude clade HLI (including MED4) from some habitats. In contrast, clade LLII/III (including SS120), and particularly clade LLIV (including MIT9313), may exploit higher light niches nearer the surface, under expanding OMZ conditions, where low O2 relieves the stresses of oxidation stress and PSII photoinhibition.

Objective To determine the concordance and statistical precision in gait velocity in people with multiple sclerosis (pwMS), measured with FeetMe® (insoles with pressure and motion sensors) compared with GAITRite® (classic reference system of gait analysis) in the timed 25-Feet Walk test (T25WT). Methods This observational, cross-sectional, prospective, single center study was conducted between September-2018 and April-2019 in pwMS aged 18–55 years, with Expanded Disability Status Scale (EDSS) 0–6.5 and relapse free ≥30 days at baseline. Primary endpoint was gait velocity. Secondary endpoints were ambulation time, cadence, and stride length assessment, while the correlation between gait variables and the clinical parameters of MS subjects was assessed as an exploratory endpoint. Results A total of 207 MS subjects were enrolled, of whom, 205 were considered in primary analysis. Most subjects were women (66.8%) and had relapsing-remitting MS (RRMS) (82.9%), with overall mean (standard deviation [SD]) age of 41.5 (8.0) year and EDSS 3.1 (2.0). There was a statistically significant (p0.830) in gait velocity, ambulation time and cadence assessment between FeetMe® and GAITRite®. Conclusions Agreement between devices was strong (ICC≥0.800). FeetMe® is the first validated wearable medical device that allows gait monitoring in MS subjects, being potentially able to assess disease activity, progression, and treatment response.

It is well documented that patients affected by rheumatoid arthritis (RA) have distinct susceptibility to the different biologic DMARDs available on the market, probably because of the many facets of the disease. Monocytes are deeply involved in the pathogenesis of RA and we therefore evaluated and compared the transcriptomic profile of monocytes isolated from patients on treatment with methotrexate alone or in combination with tocilizumab, anti-TNFα or abatacept and from healthy donors. Whole-genome transcriptomics yielded a list of regulated genes by Rank Product statistics and DAVID was then used for functional annotation enrichment analysis. Last, data were validated by qRT-PCR. Abatacept, tocilizumab and anti-TNFa cohorts were separately compared with methotrexate, leading to the identification of 78, 6, and 436 differentially expressed genes, respectively. The upper-most ranked genes were related to inflammatory processes and immune responses. Such an approach draws the genomic profile of monocytes in treated RA patients and lays the basis for finding gene signature for tailored therapeutic choices.

Intimate partner violence (IPV) during pregnancy, a condition as common as obstetrics conditions like gestational diabetes, is associated with maternal and neonatal complications. Systematic detection of IPV is not well established in antenatal screening probably because the effectiveness of protective interventions has not been evaluated. E-health interventions may be beneficial among mothers exposed to IPV. Prior to performing a full-scale effectiveness trial for such an intervention, a pilot study is required to assess the feasibility of randomising a sufficiently large number of women exposed to IPV during pregnancy. The eIPV trial is a randomised pilot study nested within a cohort of consenting mothers who screen positive for IPV in the first antenatal visit at

IntroductionCare for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374).Study designRegistry-based cohort study including only people with rare head and neck cancers.Objectivesto help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care.MethodsSettings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present.ResultsThe registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.

BackgroundPost-exposure prophylaxis (PEP) for pertussis is recommended for household contacts of pertussis cases in the United States within 21 days of exposure, but data on PEP effectiveness for prevention of secondary cases in the setting of widespread pertussis vaccination are limited. We implemented a multi-state evaluation of azithromycin PEP use and effectiveness among household contacts.MethodsCulture- or PCR-confirmed pertussis cases were identified through surveillance. Household contacts were interviewed within 7 days of case report and again 14-21 days later. Interviewers collected information on exposure, demographics, vaccine history, prior pertussis diagnosis, underlying conditions, PEP receipt, pertussis symptoms, and pertussis testing. A subset of household contacts provided nasopharyngeal and blood specimens during interviews.ResultsOf 299 household contacts who completed both interviews, 12 (4%) reported not receiving PEP. There was no evidence of higher prevalence of cough or pertussis symptoms among contacts who did not receive PEP. Of 168 household contacts who provided at least one nasopharyngeal specimen, four (2.4%) were culture or PCR positive for B. pertussis; three of these received PEP prior to their positive test result. Of 156 contacts with serologic results, 14 (9%) had blood specimens that were positive for IgG anti-pertussis toxin (PT) antibodies; all had received PEP.ConclusionsVery high PEP uptake was observed among household contacts of pertussis patients. Although the number of contacts who did not receive PEP was small, there was no difference in prevalence of pertussis symptoms or positive laboratory results among these contacts compared with those who did receive PEP.

IntroductionWe are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.MethodsFollowing a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).ResultsSufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (pConclusionOur experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.

Linking routinely collected healthcare administrative data is a valuable method for conducting research on morbidity outcomes, but linkage quality and accuracy needs to be assessed for bias as the data were not collected for research. The aim of this study was to describe the rates of linking data on children with and without congenital anomalies to regional or national hospital discharge databases and to evaluate the quality of the matched data. Eleven population-based EUROCAT registries participated in a EUROlinkCAT study linking data on children with a congenital anomaly and children without congenital anomalies (reference children) born between 1995 and 2014 to administrative databases including hospital discharge records. Odds ratios (OR), adjusted by region, were estimated to assess the association of maternal and child characteristics on the likelihood of being matched. Data on 102,654 children with congenital anomalies were extracted from 11 EUROCAT registries and 2,199,379 reference children from birth registers in seven regions. Overall, 97% of children with congenital anomalies and 95% of reference children were successfully matched to administrative databases. Information on maternal age, multiple birth status, sex, gestational age and birthweight were >95% complete in the linked datasets for most regions. Compared with children born at term, those born at ≤27 weeks and 28–31 weeks were less likely to be matched (adjusted OR 0.23, 95% CI 0.21–0.25 and adjusted OR 0.75, 95% CI 0.70–0.81 respectively). For children born 32–36 weeks, those with congenital anomalies were less likely to be matched (adjusted OR 0.78, 95% CI 0.71–0.85) while reference children were more likely to be matched (adjusted OR 1.28, 95% CI 1.24–1.32). Children born to teenage mothers and mothers ≥35 years were less likely to be matched compared with mothers aged 20–34 years (adjusted ORs 0.92, 95% CI 0.88–0.96; and 0.87, 95% CI 0.86–0.89 respectively). The accuracy of linkage and the quality of the matched data suggest that these data are suitable for researching morbidity outcomes in most regions/countries. However, children born preterm and those born to mothers aged

The urgent need to remediate ocean acidification has brought attention to the ability of marine macrophytes (seagrasses and seaweeds) to take up carbon dioxide (CO2) and locally raise seawater pH via primary production. This physiological process may represent a powerful ocean acidification mitigation tool in coastal areas. However, highly variable nearshore environmental conditions pose uncertainty in the extent of the amelioration effect. We developed experiments in aquaria to address two interconnected goals. First, we explored the individual capacities of four species of marine macrophytes (Ulva lactuca, Zostera marina, Fucus vesiculosus and Saccharina latissima) to ameliorate seawater acidity in experimentally elevated pCO2. Second, we used the most responsive species (i.e., S. latissima) to assess the effects of high and low water residence time on the amelioration of seawater acidity in ambient and simulated future scenarios of climate change across a gradient of irradiance. We measured changes in dissolved oxygen, pH, and total alkalinity, and derived resultant changes to dissolved inorganic carbon (DIC) and calcium carbonate saturation state (Ω). While all species increased productivity under elevated CO2, S. latissima was able to remove DIC and alter pH and Ω more substantially as CO2 increased. Additionally, the amelioration of seawater acidity by S. latissima was optimized under high irradiance and high residence time. However, the influence of water residence time was insignificant under future scenarios. Finally, we applied predictive models as a function of macrophyte biomass, irradiance, and residence time conditions in ambient and future climatic scenarios to allow projections at the ecosystem level. This research contributes to understanding the biological and physical drivers of the coastal CO2 system.

Poison frogs bioaccumulate alkaloids for chemical defense from their arthropod diet. Although many alkaloids are accumulated without modification, some poison frog species can metabolize pumiliotoxin (PTX 251D) into the more potent allopumiliotoxin (aPTX 267A). Despite extensive research characterizing the chemical arsenal of poison frogs, the physiological mechanisms involved in the sequestration and metabolism of individual alkaloids remain unclear. We first performed a feeding experiment with the Dyeing poison frog (Dendrobates tinctorius) to ask if this species can metabolize PTX 251D into aPTX 267A and what gene expression changes are associated with PTX 251D exposure in the intestines, liver, and skin. We found that D. tinctorius can metabolize PTX 251D into aPTX 267A, and that PTX 251D exposure changed the expression level of genes involved in immune system function and small molecule metabolism and transport. To better understand the functional significance of these changes in gene expression, we then conducted a series of high-throughput screens to determine the molecular targets of PTX 251D and identify potential proteins responsible for metabolism of PTX 251D into aPTX 267A. Although screens of PTX 251D binding human voltage-gated ion channels and G-protein coupled receptors were inconclusive, we identified human CYP2D6 as a rapid metabolizer of PTX 251D in a cytochrome P450 screen. Furthermore, a CYP2D6-like gene had increased expression in the intestines of animals fed PTX, suggesting this protein may be involved in PTX metabolism. These results show that individual alkaloids can modify gene expression across tissues, including genes involved in alkaloid metabolism. More broadly, this work suggests that specific alkaloid classes in wild diets may induce physiological changes for targeted accumulation and metabolism.

Activity-regulated cytoskeleton-associated protein (Arc) is a multidomain protein of retroviral origin with a vital role in the regulation of synaptic plasticity and memory formation in mammals. However, the mechanistic and structural basis of Arc function is poorly understood. Arc has an N-terminal domain (NTD) involved in membrane binding and a C-terminal domain (CTD) that binds postsynaptic protein ligands. In addition, the NTD and CTD both function in Arc oligomerisation, including assembly of retrovirus-like capsids involved in intercellular signalling. To obtain new tools for studies on Arc structure and function, we produced and characterised six high-affinity anti-Arc nanobodies (Nb). The CTD of rat and human Arc were both crystallised in ternary complexes with two Nbs. One Nb bound deep into the stargazin-binding pocket of Arc CTD and suggested competitive binding with Arc ligand peptides. The crystallisation of the human Arc CTD in two different conformations, accompanied by SAXS data and molecular dynamics simulations, paints a dynamic picture of the mammalian Arc CTD. The collapsed conformation closely resembles Drosophila Arc in capsids, suggesting that we have trapped a capsid-like conformation of the human Arc CTD. Our data obtained with the help of anti-Arc Nbs suggest that structural dynamics of the CTD and dimerisation of the NTD may promote the formation of capsids. Taken together, the recombinant high-affinity anti-Arc Nbs are versatile tools that can be further developed for studying mammalian Arc structure and function, as well as mechanisms of Arc capsid formation, both in vitro and in vivo. For example, the Nbs could serve as a genetically encoded tools for inhibition of endogenous Arc interactions in the study of neuronal function and plasticity.

PurposeIn recent decades, educators have pushed to implementing active learning techniques that can advance students' competences. Universities are increasingly required to develop knowledge measured in terms of grades (hard skills) and inter-personal, social, and communication abilities (soft skills). Nevertheless, within the field of active learning, educators often focus on how these techniques can improve students' hard skills and their satisfaction. Few have analysed whether and how these techniques might improve students' soft skills. Moreover, among these few studies, the majority has analysed hard and soft skills separately, measuring whether different active learning techniques may or may not improve them. Virtually no one has studied whether students' hard and soft skills can converge or diverge in an active learning format. This study allows us to understand the relations between these two sets of variables, for example, whether an improvement (or deterioration) in the hard skills corresponds to an improvement (or deterioration) in the soft skills, and vice versa.MethodIn our experiment, we analyse the impact of a specific active learning format, such as the Flipped Classroom (FC), on both students' hard and soft skills, by comparing it with a traditional class integrated with other active learning techniques, such as presentations, debates, and teamwork activities. First, we use Pearson correlations to measure the relation between students' hard skills, understood in terms of grades, and a set of soft skills, such as critical thinking, self-efficacy, teamwork, and perception of learning. Second, we use canonical correlations to analyse whether hard and soft skills converge or diverge in an FC format, in comparison with a traditional teaching format integrated with the other active learning techniques.Results and conclusionsOur main finding is that the FC per se neither improves nor worsens students' performance in terms of hard and soft skills.

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

BackgroundCongenital anomalies are a leading cause of childhood morbidity, but little is known about the long-term outcomes.ObjectiveTo quantify the burden of disease in childhood for children with congenital anomalies by assessing the risk of hospitalisation, the number of days spent in hospital and proportion of children with extended stays (≥10 days).MethodsEuropean population-based record-linkage study in 11 regions in eight countries including children with congenital anomalies (EUROCAT children) and without congenital anomalies (reference children) living in the same regions. The children were born between 1995 and 2014 and were followed to their tenth birthday or 31/12/2015. European meta-analyses of the outcome measures were performed by two age groups, Results99,416 EUROCAT children and 2,021,772 reference children were linked to hospital databases. Among EUROCAT children, 85% (95%-CI: 79-90%) were hospitalised in the first year and 56% (95%-CI: 51-61%) at ages 1-4 years, compared to 31% (95%-CI: 26-37%) and 25% (95%-CI: 19-31%) of the reference children. Median length of stay was 2-3 times longer for EUROCAT children in both age groups. The percentages of children with extended stays (≥10 days) in the first year were 24% (95%-CI: 20-29%) for EUROCAT children and 1% (95%-CI: 1-2%) for reference children. The median length of stay varied greatly between congenital anomaly subgroups, with children with gastrointestinal anomalies and congenital heart defects having the longest stays.ConclusionsChildren with congenital anomalies were more frequently hospitalised and median length of stay was longer. The outlook improves after the first year. Parents of children with congenital anomalies should be informed about the increased hospitalisations required for their child's care and the impact on family life and siblings, and they should be adequately supported.

As internationalization of higher education has become more prevalent, the search for approaches to support quality learning within multicultural classrooms has become critical. In this study, we presented a blended and collaborative learning (BCL) method and discussed its potential as a viable learning approach for graduate classrooms with culturally-diverse students. We first discussed implementation of a BCL approach in a multicultural graduate course, then explored learnings gained from the BCL experience in terms of three interdependent Community of Inquiry elements: teaching, cognitive, and social presences, and in terms of its implementation in a multicultural setting.

BackgroundCardio-vascular disease and depression are thought to be closely related, due to shared risk factors. The aim of the study was to determine the association between cardio-vascular risk (CVR) factors and depressive status in a population (55-75 years) with metabolic syndrome (MetS) from the PREDIMED-Plus trial.Methods and findingsParticipants were classified into three groups of CVR according to the Framingham-based REGICOR function: (1) low (LR), (2) medium (MR) or (3) high/very high (HR). The Beck Depression Inventory-II (BDI-II) was used to assess depressive symptoms at baseline and after 2 years. The association between CVR and depressive status at baseline (n = 6545), and their changes after 2 years (n = 4566) were evaluated through multivariable regression models (logistic and linear models). HR women showed higher odds of depressive status than LR [OR (95% CI) = 1.78 (1.26, 2.50)]. MR and HR participants with total cholesterol ConclusionsImproving cardiovascular health could prevent the onset of depression in the elderly. Diabetes and total cholesterol in individuals at high CVR, may play a specific role in the precise response. International Standard Randomized Controlled Trial (ISRCTN89898870).

The ability to acquire chemical defenses through the diet has evolved across several major taxa. Chemically defended organisms may need to balance chemical defense acquisition and nutritional quality of prey items. However, these dietary preferences and potential trade-offs are rarely considered in the framework of diet-derived defenses. Poison frogs (Family Dendrobatidae) acquire defensive alkaloids from their arthropod diet of ants and mites, although their dietary preferences have never been investigated. We conducted prey preference assays with the Dyeing Poison frog (Dendrobates tinctorius) to test the hypothesis that alkaloid load and prey traits influence frog dietary preferences. We tested size preferences (big versus small) within each of four prey groups (ants, beetles, flies, and fly larvae) and found that frogs preferred interacting with smaller prey items of the fly and beetle groups. Frog taxonomic prey preferences were also tested as we experimentally increased their chemical defense load by feeding frogs decahydroquinoline, an alkaloid compound similar to those naturally found in their diet. Contrary to our expectations, overall preferences did not change during alkaloid consumption, as frogs across groups preferred fly larvae over other prey. Finally, we assessed the protein and lipid content of prey items and found that small ants have the highest lipid content while large fly larvae have the highest protein content. Our results suggest that consideration of toxicity and prey nutritional value are important factors in understanding the evolution of acquired chemical defenses and niche partitioning.

Prochlorococcus marinus, the smallest picocyanobacterium, comprises multiple clades occupying distinct niches, currently across tropical and sub-tropical oligotrophic ocean regions, including Oxygen Minimum Zones. Ocean warming may open growth-permissive temperatures in new, poleward photic regimes, along with expanded Oxygen Minimum Zones. We used ocean metaproteomic data on current Prochlorococcus marinus niches, to guide testing of Prochlorococcus marinus growth across a matrix of peak irradiances, photoperiods, spectral bands and dissolved oxygen. MED4 from Clade HLI requires greater than 4 h photoperiod, grows at 25 μmol O2 L-1 and above, and exploits high cumulative diel photon doses. MED4, however, relies upon an alternative oxidase to balance electron transport, which may exclude it from growth under our lowest, 2.5 μmol O2 L-1, condition. SS120 from clade LLII/III is restricted to low light under full 250 μmol O2 L-1, shows expanded light exploitation under 25 μmol O2 L-1, but is excluded from growth under 2.5 μmol O2 L-1. Intermediate oxygen suppresses the cost of PSII photoinactivation, and possibly the enzymatic production of H2O2 in SS120, which has limitations on genomic capacity for PSII and DNA repair. MIT9313 from Clade LLIV is restricted to low blue irradiance under 250 μmol O2 L-1, but exploits much higher irradiance under red light, or under lower O2 concentrations, conditions which slow photoinactivation of PSII and production of reactive oxygen species. In warming oceans, range expansions and competition among clades will be governed not only by light levels. Short photoperiods governed by latitude, temperate winters, and depth attenuation of light, will exclude clade HLI (including MED4) from some habitats. In contrast, clade LLII/III (including SS120), and particularly clade LLIV (including MIT9313), may exploit higher light niches nearer the surface, under expanding OMZ conditions, where low O2 relieves the stresses of oxidation stress and PSII photoinhibition. [ABSTRACT FROM AUTHOR]

Herein we report the design and the synthesis of a library of new and more hydrophilic bisindole analogues based on our previously identified antileishmanial compound URB1483 that failed the preliminary in vivo test. The novel bisindoles were phenotypically screened for efficacy against Leishmania infantum promastigotes and simultaneously for toxicity on human macrophage-like THP-1 cells. Among the less toxic compounds, eight bisindoles showed IC50 below 10 μM. The most selective compound 1h (selectivity index = 10.1, comparable to miltefosine) and the most potent compound 2c (IC50 = 2.7 μM) were tested for their efficacy on L. infantum intracellular amastigotes. The compounds also demonstrated their efficacy in the in vitro infection model, showing IC50 of 11.1 and 6.8 μM for 1h and 2c, respectively. Moreover, 1h showed a better toxicity profile than the commercial drug miltefosine. For all these reasons, 1h could be a possible new starting point for hydrophilic antileishmanial agents with low cytotoxicity on human macrophage-like cells. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic drastically affected many areas and contexts of today's society, including school and family. Several studies focused on the worldwide effects of school closures on students' learning outcomes, context, and well-being. However, the data emerging from these studies are often inconsistent and fragmentary, highlighting the need of a comprehensive analysis of the phenomenon. This need is especially urgent for the countries with the most severe school closure, like Italy. This systematic review aims to collect the opinions of parents, teachers, and students on: other dimensions of Italian primary school students affected by school closures, beyond academic performance; hypothetical agreement between the opinions of parents, teachers, and students regarding the different effects of school closures on Italian primary school students; possible differences between the effects of school closures on Italian primary school students and the students in other countries. Our search was conducted using PRISMA 2020 guidelines on Web of Science, Pubmed, Scopus, and EBSCOHost. The results obtained from 34 articles revealed a strong concern on the part of all stakeholders involved in learning during the pandemic, with evident negative effects for Italian school students. The constraint on distance learning led to a drastic change in everyone's routine, and a negative emotional change on the part of young students. Parents and teachers generally considered distance learning to be ineffective for the education of their children and students; they encountered technical-practical difficulties in the use of electronic devices for participation in school activities; overall learning deficits on the part of students, especially in mathematics, as confirmed by INVALSI results were also found. The investigation reveals a condition of shared emotional and academic performance difficulty, and a further challenging circumstance for students previously at risk of marginalization. Further research in this field is paramount to identify new and adequate recovery strategies. [ABSTRACT FROM AUTHOR]

IntroductionBesides affecting physical health, Oropharyngeal Dysphagia (OD) entails limitations in daily activities and social participation for both patients and their informal caregivers. The identification of OD-related needs is crucial for designing appropriate person-centered interventions.AimsTo explore and map the literature investigating the care needs related to OD management of adult persons with OD and their informal caregivers during the last 20 years.MethodsA scoping review was conducted and reported following PRISMA guidelines. Five electronic databases and reference lists of eligible publications were searched for original works in English or Italian, published between January 2000 and February 2021. Two independent raters assessed studies' eligibility and extracted data; a third rater resolved disagreements. Extracted care needs were analyzed using a Best fit framework synthesis approach.ResultsOut of 2,534 records preliminarily identified, 15 studies were included in the review and 266 care needs were extracted. All studies were conducted in Western countries. Research methods primarily consisted of qualitative interviews and focus groups (14 studies, 93.3%); head and neck cancer was the most frequent cause of patients' dysphagia (8 studies, 53.3%); caregivers' perspective was seldom investigated (5 studies, 33.3%). Both patients and caregivers primarily reported social (N = 77; 28.9%) and practical (N = 67; 25.2%) needs, followed by informational (N = 55; 20.7%) and psychological (N = 54; 20.3%) ones. Only patients reported physical needs (N = 13; 4.9%), while spiritual needs were not cited.ConclusionsThe recurrence of personal and social needs besides physical ones highlighted the manifold impact of OD on patients' and caregivers' lives. Larger and more focused studies are required in order to design tools and interventions tailored to patients' and caregivers' needs.

Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies such as anti-Sm. Studies in patients with SLE and murine models of lupus reveal that the most critical anti-Sm autoantibodies are predominantly direct against D1(83–119), D2, and B´/B epitopes. Objectives The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D183-119, D2, B´/B, and B´/BCOOH in co-vaccination with IFN-γ or IL-10 in a murine model of lupus induced by pristane. Material and methods To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D183-119, D2, B´/B, B´/BCOOH, IFN-γ, or IL-10. Lupus was induced by 0.5 mL of pristane via intraperitoneal in BALB/c female mice. Immunoprecipitation with K562 cells was metabolically labeled with 35S and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-γ from splenocytes supernatants. Proteinuria was assessed monthly, and lupus nephritis was evaluated by immunofluorescence, and electron microscopy. Results The prophylactic co-vaccination with D2/IL-10 reduced the expression of kidney damage observed by electron microscopy, direct immunofluorescence, and H & E, along with reduced level of anti-nRNP/Sm antibodies (P = 0.048). Conclusion The prophylactic co-vaccination of IL-10 with D2 in pristane-induced lupus ameliorates the renal damage maybe by acting as prophylactic DNA tolerizing therapy.

Bats are highly gregarious animals, displaying a large spectrum of social systems with different organizational structures. One important factor shaping sociality is group stability. To maintain group cohesion and stability, bats often rely on vocal communication. The Honduran white bat, Ectophylla alba, exhibits an unusual social structure compared to other tent-roosting species. This small white-furred bat lives in perennial stable mixed-sex groups. Tent construction requires several individuals and, as the only tent roosting species so far, involves both sexes. The bats´ social system and ecology render this species an interesting candidate to study social behaviour and vocal communication. In our study, we investigated the social behaviour and vocalizations of E. alba in the tent by observing two stable groups, including pups, in the wild. We documented 16 different behaviours, among others play and fur chewing, a behaviour presumably used for scent-marking. Moreover, we found 10 distinct social call types in addition to echolocation calls, and for seven call types we were able to identify the corresponding broad behavioural context. Most of the social call types were affiliative, including two types of contact calls, maternal directive calls, pup isolation calls and a call type related to the fur-chewing behaviour. In sum, this study entails an ethogram and describes the social vocalizations of a tent-roosting phyllostomid bat, providing the basis for further in-depth studies about the sociality and vocal communication in E. alba.

Ultrasound is considered a safe and non-invasive tool in regenerative medicine and has been used in the clinic for more than twenty years for applications in bone healing after the approval of the Exogen device, also known as low-intensity pulsed ultrasound (LIPUS). Beyond its effects on bone health, LIPUS has also been investigated for wound healing of soft tissues, with positive results for various cell processes including cell proliferation, migration and angiogenesis. As LIPUS has the potential to treat chronic skin wounds, we sought to evaluate the effects produced by a conventional therapeutic ultrasound device at low intensities (also considered LIPUS) on the migration capacity of mouse and human skin mesenchymal precursors (s-MPs). Cells were stimulated for 3 days (20 minutes per day) using a traditional ultrasound device with the following parameters: 100 mW/cm2 with 20% duty cycle and frequency of 3 MHz. At the parameters used, ultrasound failed to affect s-MP proliferation, with no evident changes in morphology or cell groupings, and no changes at the cytoskeletal level. Further, the migration and invasion ability of s-MPs were unaffected by the ultrasound protocol, and no major changes were detected in the gene/protein expression of ROCK1, integrin β1, laminin β1, type I collagen and transforming growth factor β1. Finally, RNA-seq analysis revealed that only 10 genes were differentially expressed after ultrasound stimulation. Among them, 5 encode for small nuclear RNAs and 2 encode for proteins belonging to the nuclear pore complex. Considering the results overall, while the viability of s-MPs was not affected by ultrasound stimulation and no changes were detected in proliferation/migration, RNA-seq analysis would suggest that s-MPs do respond to ultrasound. The use of 100 mW/cm2 intensity or conventional therapeutic ultrasound devices might not be optimal for the stimulation the properties of cell populations. Future studies should investigate the potential application of ultrasound using variations of the tested parameters.

Domestic cattle were brought to Spain by early settlers and agricultural societies. Due to missing Neolithic sites in the Spanish region of Galicia, very little is known about this process in this region. We sampled 18 cattle subfossils from different ages and different mountain caves in Galicia, of which 11 were subject to sequencing of the mitochondrial genome and phylogenetic analysis, to provide insight into the introduction of cattle to this region. We detected high similarity between samples from different time periods and were able to compare the time frame of the first domesticated cattle in Galicia to data from the connecting region of Cantabria to show a plausible connection between the Neolithization of these two regions. Our data shows a close relationship of the early domesticated cattle of Galicia and modern cow breeds and gives a general insight into cattle phylogeny. We conclude that settlers migrated to this region of Spain from Europe and introduced common European breeds to Galicia.

Access to water for rural populations is vital not only for personal consumption and hygiene but also for food production, income generation and cultural practices. To deepening the understanding of this issue, this research addressed the access to water in a settlement of the Landless Workers Movement. The perspective of the Human Rights to Water and Sanitation was used as a theoretical framework, assessing how inadequate access to water impacts the quality of rural populations. A qualitative research was used, through participant observation and individual interviews with 12 rural workers, living at the Ulisses Oliveira settlement. The findings reflect that water is not sufficiently available to meet the community's social, economic and cultural needs and that such conditions can lead to a loss of identity. Therefore, access to water must be understood in the light of its political, social and cultural dimensions and the Human Rights to Water and Sanitation can be used as an instrument to public policies.

BackgroundViral hepatitis (hepatitis A, B, C, D and E) remains a public health problem in Peru, with a high disease burden. There are limited data on the prevalence of viral hepatitis at a national level, and none reported for over two decades. In this study, the prevalence rates of hepatitis A (HAV), B (HBV), C (HCV), D (HDV) and E virus (HEV) infections in the Peruvian population were determined to provide updated baseline data that would help guide the development of strategies aimed at reducing the transmission of viral hepatitis in Peru.MethodsWe conducted a cross-sectional, population-based study in the 25 regions of Peru. The study included participants of both sexes, aged 15-69 years, who had lived for >6 months in a specific region of Peru. Serum samples were analyzed by ELISA for anti-HAV (IgG), anti-HBs ≥10 mUI/ml, anti-HCV, anti-HDV and anti-HEV (IgG) antibodies, and by chemiluminescence for the HBV surface antigen (HBsAg) and antibodies against the core HBV antigen (anti-HBc IgM and IgG).ResultsIn a total of 5183 study participants, the prevalence rates of anti-HAV (IgG), HBsAg, total anti-HBc IgG, anti-HBs ≥10 mUI/ml, anti-HCV and anti-HEV (IgG) were 98.4% [95% confidence interval (CI) 98.0-98.7), 0.4% (95% CI 0.21-0.55), 10.1% (95% CI 9.4-11.0), 60% (95% CI 58.5-61.2), 0.1% (95% CI 0.02-0.25), and 14% (95% CI 13.1-15.0%), respectively. The prevalence of anti-HDV among HBsAg carriers was 15% (3/20).ConclusionsThe prevalence of HAV and HEV in the population aged 15-69 years in Peru is high, while the prevalence of HBV and HDV has changed from intermediate to low endemicity level and the prevalence of HCV is low. These findings would prove useful in the development of new strategies aimed at reducing the transmission of viral hepatitis in Peru, with a view to ultimately eliminating these infections in the future.

Global trade and climate change are re-shaping the distribution map of pandemic pathogens. One major emerging concern is Xylella fastidiosa, a tropical bacterium recently introduced into Europe from America. In last decades, X. fastidiosa was detected in several European countries. X. fastidiosa is an insect vector-transmitted bacterial plant pathogen associated with severe diseases in a wide range of hosts. X. fastidiosa through a tight coordination of the adherent biofilm and the planktonic states, invades the host systemically. The planktonic phase is correlated to low cell density and vessel colonization. Increase in cell density triggers a quorum sensing system based on mixture of cis 2-enoic fatty acids-diffusible signalling factors (DSF) that promote stickiness and biofilm. The lipidome profile of Olea europaea L. (cv. Ogliarola salentina) samples, collected in groves located in infected zones and uninfected zones was performed. The untargeted analysis of the lipid profiles of Olive Quick Decline Syndrome (OQDS) positive (+) and negative (-) plants showed a clustering of OQDS+ plants apart from OQDS-. The targeted lipids profile of plants OQDS+ and OQDS- identified a shortlist of 10 lipids that increase their amount in OQDS+ and X. fastidiosa positive olive trees. These lipid entities, provided to X. fastidiosa subsp. pauca pure culture, impact on the dual phase, e.g. planktonic ↔ biofilm. This study provides novel insights on OQDS lipid hallmarks and on molecules that might modulate biofilm phase in X. fastidiosa subsp. pauca.

BACKGROUND:Numerous studies have noted the presence of a dysexecutive component of the ALS-FTD. The most widely replicated result refers to the significantly reduced verbal fluency of ALS patients when compared to healthy people. As ALS patients have motor alterations that interfere with production, qualitative studies have the advantage of being independent of the degree of motor disability and revealing patients' cognitive state. This study examined the production differences between 42 ALS patients who presented with different degrees of dementia and motor impairment and 42 healthy people. Production processes were studied by extending the administration time of a letter fluency task to 2 minutes for the phonemic verbal fluency (PVF) and semantic verbal fluency (SVF) categories. This ensured that the qualitative aspects of verbal fluency were addressed, paying special attention to the new perseverations and intrusions, as well as any clinical correlates that may exist. RESULTS:The ALS patients produced a significantly lower number of responses in PVF (p = .017) and SVF (p = .008). The rest of the indicators for frontal lobe alteration also suggested the existence of a dysfunction. The most remarkable results were the number of intrusions on the PVF task, which was much higher in the ALS group (p = .002). However, the number of perseverations did not differ significantly. CONCLUSIONS:This study highlights the value of intrusions in addressing cognitive deterioration in ALS patients. This deterioration seems to be independent of the degree of motor impairment and of behavioural alterations. Therefore, the value of the intromissions on the verbal fluency task was highlighted as an indicator of a new cognitive alteration, which can be easily evaluated, even retrospectively.

Passive Acoustic Monitoring (PAM) is a non-intrusive and cost-effective method capable of providing high-resolution, long-term information on the status and health of vocal populations and communities. To successfully monitor the same species over wide geographical and temporal scales, it is necessary to characterise the range of sound variability, as well as the consistency of sound features between populations. The meagre (Argyrosomus regius, Asso 1801) is an interesting case study because recent investigations suggest a wider vocal repertoire than previously described. In this study, meagre vocalizations were recorded and analysed from a variety of settings, ranging from rearing facilities to wild populations to provide a comprehensive characterisation of its vocal repertoire, while investigating the consistency of spawning sound features between populations. All sounds presented a similar acoustic structure in their basic unit (i.e. the pulse), while an important variability was found in the number of pulses; the meagre can emit sounds made of one single pulse or many pulses (up to more than 100). High level of overlap in the Principal Component Analysis made difficult to differentiate sound type clusters. Despite this, two sound types were identifiable: knocks (sounds from 1 to 3 pulses) and long grunts (sounds with more than 29 pulses). Discriminant Analysis carried out on PCA residuals showed that knock had the highest proportion of correct placement (92% of the observations correctly placed) followed by long grunts (80%). All other previously described sound types (intermediate grunt, short grunt and disturbance sounds) could not be separated and presented low levels of correct placement, suggesting that care should be taken when defining these as independent sound types. Finally, acoustic features consistency was found in meagre grunts emitted by different populations during spawning nights; statistical differences could be explained by recording settings and fish conditions. The results of this study provide important information for fostering PAM programs of wild meagre populations, while contributing to the discussion around the definition of fish sound types in vocal fish communities. Studies of this kind, which evaluate both variability and consistency of sound features, are of fundamental importance for maximising PAM efforts in the wild, at both the specific and the community level.

Background and aimsThis is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when β-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early β-cell damage.Materials and methodsWe performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis.ResultsWe demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early β-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk.ConclusionsRIAO level increases as the number of complications rises; RIAOs > 3.35 μg/ml is a predictor of changes in the current indicators of β-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children around the globe. Mexico City has one of the highest incidence rates of childhood leukemia worldwide with 49.5 cases per million children under the age of 15 which is similar to that reported for Hispanic populations living in the United States. In addition, it has been noted a dismal prognosis in Mexican and Hispanic ALL pediatric population. Although ALL, like cancer in general, has its origins in endogenous, exogenous, and genetic factors, several studies have shown that the immune system also plays a deterministic role in cancer development. Among various elements of the immune system, T lymphocytes and NK cells seem to dominate the immune response against leukemia. The aim of the present study was to perform a phenotypic and functional characterization of NK cells in ALL Mexican children at the moment of diagnosis and before treatment initiation. A case-control study was conducted by the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL). 41 cases were incident ALL children younger than 17 years old and residents of Mexico City. 14 controls were children without leukemia, matched by age and sex with cases. NK cell function was evaluated by degranulation assays towards K562 cells and SLAM-associated protein (SAP) expression was measured by intracellular staining. All assays were performed using peripheral blood mononuclear cells from controls and patients. The results indicate that NK mediated cytotoxicity, measured by CD107a degranulation assays in response to K562 cells, was reduced in ALL patients compared to controls. Interestingly, an impaired NK cell killing of target cells was not equally distributed among ALL patients. In contrast to patients classified as high-risk, standard-risk patients did not display a significant reduction in NK cell-mediated cytotoxicity. Moreover, patients presenting a leukocyte count ≥ 50,000xmm3 displayed a reduction in NK-cell mediated cytotoxicity and a reduction in SAP expression, indicating a positive correlation between a reduced SAP expression and an impaired NK cell-mediated citotoxicity. In the present study it was observed that unlike patients with standard-risk, NK cells from children presenting high-risk ALL, harbor an impaired cytotoxicity towards K562 at diagnosis. In addition, NK cell function was observed to be compromised in patients with a leukocyte count ≥50,000xmm3, where also it was noticed a decreased expression of SAP compared to patients with a leukocyte count

Many affected counties have had experienced a shortage of personal protective equipment (PPE) during the coronavirus disease (COVID-19) pandemic. We aimed to investigate the needs of healthcare professionals and the technical difficulties faced by them during the initial outbreak. A cross-sectional web-based survey was conducted among the healthcare workforce in the most populous cities from three Latin American countries in April 2020. In total, 1,082 participants were included. Of these, 534 (49.4%), 263 (24.3%), and 114 (10.5%) were physicians, nurses, and other professionals, respectively. At least 70% of participants reported a lack of PPE. The most common shortages were shortages in gown coverall suits (643, 59.4%), N95 masks (600, 55.5%), and face shields (569, 52.6%). Professionals who performed procedures that generated aerosols reported shortages more frequently (p

miRNAs regulate post-transcriptional gene expression in metazoans, and thus are involved in many fundamental cellular biological processes. Extracellular miRNAs are also found in most human biofluids including plasma. These circulating miRNAs constitute a long distance inter cellular communication system and are potentially useful biomarkers. High throughput technologies like microarrays are able to scan a complete miRNome providing useful detection scores that are underexplored. We proposed to answer how many and which miRNAs are detectable in plasma or extracellular vesicles as these questions have not yet been answered. We set out to address this knowledge gap by analyzing the mirRNome in plasma and corresponding extracellular vesicles (EVs) from 12 children affected by retinoblastoma (Rb) a childhood intraocular malignant tumor, as well as from 12 healthy similarly aged controls. We calculated an average of 537 detectable miRNAs in plasma and 625 in EVs. The most miRNA enriched compartment were EVs from Rb cases with an average of 656 detectable elements. Using hierarchical clustering with the detection scores, we generated broad detection mirnome maps and identified a plasma signature of 19 miRNAs present in all Rb cases that is able to discriminate cases from controls. An additional 9 miRNAs were detected in all the samples; within this group, miRNA-5787 and miRNA-6732-5p were highly abundant and displayed very low variance across all the samples, suggesting both are good candidates to serve as plasma references or normalizers. Further exploration considering participant's sex, allowed discovering 5 miRNAs which corresponded only to females and 4 miRNAs corresponding only to males. Target and pathway analysis of these miRNAs revealed hormonal function including estrogen, thyroid signaling pathways and testosterone biosynthesis. This approach allows a comprehensive unbiased survey of a circulating miRNome landscape, creating the possibility to define normality in mirnomic profiles, and to locate where in these miRNome profiles promising and potentially useful circulating miRNA signatures can be found.

Recent studies aiming to facilitate mathematical skill development in primary school children have explored the electrophysiological characteristics associated with different levels of arithmetic achievement. The present work introduces an alternative EEG signal characterization using graph metrics and, based on such features, a classification analysis using a decision tree model. This proposal aims to identify group differences in brain connectivity networks with respect to mathematical skills in elementary school children. The methods of analysis utilized were signal-processing (EEG artifact removal, Laplacian filtering, and magnitude square coherence measurement) and the characterization (Graph metrics) and classification (Decision Tree) of EEG signals recorded during performance of a numerical comparison task. Our results suggest that the analysis of quantitative EEG frequency-band parameters can be used successfully to discriminate several levels of arithmetic achievement. Specifically, the most significant results showed an accuracy of 80.00% (α band), 78.33% (δ band), and 76.67% (θ band) in differentiating high-skilled participants from low-skilled ones, averaged-skilled subjects from all others, and averaged-skilled participants from low-skilled ones, respectively. The use of a decision tree tool during the classification stage allows the identification of several brain areas that seem to be more specialized in numerical processing.

Background: Following the low incidence rates of non-SARS-CoV-2 respiratory viruses registered during the strict lockdown enforced in the pandemic, a resurgence of several endemic viruses in Catalonia (Spain) was noted during the early summer of 2021. Objectives: In this study, we investigated whether the circulation of non-SARS-CoV-2 respiratory viruses in Catalonia, assessed by Microbiological Reporting System of Catalonia (MRSC) and the Epidemiological Surveillance Network of Catalonia, was affected by the strict lockdown measures, as well as, the implication of the Coronavirus Disease 19 (COVID-19) de-escalation process in the late season outbreaks registered during the 2020–2021 season. Study design: A retrospective comparison of epidemic patterns in the respiratory viruses' incidence, using regional public health surveillance data from MRSC, was performed between weeks 26/2016 to week 27/2021. Data were expressed as the weekly total number of test positivity for individual viruses. A segmented negative binomial regression model was conducted, with two parameters included (level and trend) for each segment of the time series (2020 pre-lockdown, 2020 post-lockdown and 2021). Results were reported as a unit changed in the strict lockdown. Results: A total of 51588 confirmed cases of the different respiratory viruses were included in the analysis, the majority were influenza cases (63.7%). An immediate reduction in the weekly number of cases was observed in 2020 after the COVID-19 outbreak for human adenovirus virus (HAdV) (β2 = -2.606; P <0.01), human parainfluenza virus (HPIV) (β2 = -3.023; P <0.01), influenza virus (IFV) (β2 = -1.259; P <0.01), but not for respiratory syncytial virus (RSV), where the number of cases remained unchanged. During 2020, a significant negative trend was found for RSV (β3 = -0.170, P <0.01), and a positive trend for HAdV (β3 = 0.075, P <0.01). During 2021, a significant reduction in the weekly number of cases was also observed for all respiratory viruses, and a borderline non-significant reduction for HPIV (β3 = -0.027; P = 0.086). Moreover, significant positive trends were found for each viral pathogen, except for influenza during 2020–2021 season, where cases remained close to zero. The respiratory viruses increased activity and their late season epidemic start particularly affected children under 6 years old. Conclusions: Our data not only provides evidence that occurrence of different respiratory virus infections was affected by the strict lockdown taken against SARS-CoV-2 but it also shows a late resurgence of seasonal respiratory viruses' cases during the 2020–2021 season following the relaxation of COVID-19-targeted non-pharmaceutical interventions. [ABSTRACT FROM AUTHOR]

INTRODUCTION:In the WHO European Region, endemic transmission of measles and rubella had been interrupted by 37 and 42 of the 53 member states (MSs), respectively, by 2018. Sixteen MSs are still endemic for measles, 11 for rubella and nine for both diseases, the latter including Italy. Elimination is documented by each country's National Verification Committee (NVC) through an annual status update (ASU). OBJECTIVE:By analysing data used to produce the ASUs, we aimed to describe the advances made by Italy towards elimination of measles and rubella. Moreover, we propose a set of major interventions that could facilitate the elimination process. METHODS:A total of 28 indicators were identified within the six core sections of the ASU form and these were evaluated for the period 2013-2018. These indicators relate to the incidence of measles/rubella; epidemiological investigation of cases; investigation of outbreaks; performance of the surveillance system; population immunity levels; and implementation of supplemental immunization activities (SIAs). RESULTS:From 2013 to 2018, epidemiological and laboratory analyses of measles cases in Italy improved substantially, allowing timely investigation in 2017 and 2018 of most outbreak and sporadic cases and identification of the majority of genotypic variants. Moreover, since 2017, vaccination coverage has increased significantly. Despite these improvements, several areas of concern emerged, prompting the following recommendations: i) improve outbreak monitoring; ii) strengthen the MoRoNet network; iii) increase the number of SIAs; iv) reinforce vaccination services; v) maintain regional monitoring; vi) design effective communication strategies; vii) foster the role of general practitioners and family paediatricians. CONCLUSIONS:The review of national ASUs is a crucial step to provide the NVC with useful insights into the elimination process and to guide the development of targeted interventions. Against this background, the seven recommendations proposed by the NVC have been shared with the Italian Ministry of Health and the Technical Advisory Group on measles and rubella elimination and have been incorporated into the new Italian Elimination Plan 2019-2023 as a technical aid to facilitate the achievement of disease elimination goals.