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Introduction: Systematic reviews are an important knowledge synthesis tool for critical care medicine clinicians and researchers. With new literature available each day, reviewers must balance identifying all relevant literature against timely synthesis. We therefore sought to apply capture-mark-recapture, a novel methodology, to estimate the population of articles available for a systematic review of effective patient rounding practices in critical care medicine. Methods: Capture-mark-recapture was applied retrospectively to estimate the population of articles available for a systematic review of 4 bibliographic databases. All research studies (no methodology restrictions) of patient rounding practices in critical care medicine were included. Estimates of article population size were calculated for search of the bibliographic databases, selection of articles for fulltext review, and selection of articles for inclusion in the systematic review. Results: Capture-mark-recapture estimated a population of 28 839 articles (95% confidence interval [CI], 12 393-70 990) for search of the bibliographic databases, 169 articles (95% CI, 152-202) for fulltext review, and 48 articles (95% CI, 39-131) for inclusion in the systematic review. These estimates suggest that our search identified 15% (4462/28 839) of the population of potentially available articles for the search of the bibliographic databases, 79% (133/169) of articles for full-text review, and 79% (38/48) of articles for inclusion in the systematic review. Conclusions: The capture-mark-recapture technique can be applied to systematic reviews in critical care medicine with heterogeneous study methodologies to estimate the population of articles available. Capture-mark-recapture may help clinicians who use systematic reviews to estimate search completeness and researchers who perform systematic reviews to develop more efficient literature search strategies. [ABSTRACT FROM AUTHOR]

Objectives: Moderate daily mocha pot coffee intake has been associated with better mood and cognition in patients with mild vascular cognitive impairment (VCI). Similarly, moderate red wine consumption has shown protective effects on cognitive disorders, including Alzheimer's disease and vascular dementia. The aim of this study was to explore the synergistic relation between red wine and coffee intake on mood and cognitive status in mild VCI patients at risk for dementia. Methods: A total of 300 non-demented older patients with mild VCI were asked for coffee and red wine consumption and administered with the 17-items Hamilton Depression Rating Scale (HDRS), the Mini Mental State Examination (MMSE), and the Stroop Color-Word Interference Test (Stroop T), as well as the Activities of Daily Living (ADL) and the Instrumental ADL to measure their mood status, cognitive performance, and functional independence. Linear regression models were used to test the association between variables. Results: Moderate wine drinkers tended to show the best Stroop T score at any level of coffee consumption; conversely, heavy wine consumers performed worse at the Stroop T, especially in patients reporting high coffee intake. Moderate drinkers of both coffee and wine showed the lowest HDRS scores. Finally, a progressive increase in MMSE score was evident with increasing coffee consumption, which peaks when combined with a moderate wine consumption. Conclusions: Daily mocha pot coffee and red wine intake seem to be synergistically associated with global cognition, executive functioning, and mood status in patients with mild VCI; the association was not linear, resulting in a protective direction for moderate intake and detrimental for heavy consumption. Future studies are needed to further corroborate the present findings and the potential long-term protective effects of these dietary compounds over time.

Abstract Background Little is known about what happens when patients and caregivers are involved in an academic setting as co-teachers and how healthcare professionals approach a new model of partnership-based teaching. This study aimed to explore the learning and behavioural patterns of a group of healthcare professionals who were learning to teach with patients and caregivers as co-teachers in a post-graduate course. Methods A focused ethnographic study involving 11 health professionals was conducted. Data were collected through participatory observation during the course, individual semi-structured interviews, and a follow-up focus group. Taxonomic analysis was performed. Results Three categories were identified: ‘group’, ‘role of narration’ and ‘applying co-teaching with patients and caregivers ’. Specifically, heterogeneity, absence of hierarchies, and balanced relationships characterised the group dynamic and promoted partnership. Narration played a key role both in learning and in healthcare professionals’ relationship with patients and caregivers and promoted emotional skills and self-awareness. Project planning and lessons simulations were essential aspects of the implementation process. Conclusions This focused ethnography helped further understanding of the context of a specific project involving patients and caregivers as co-teachers in healthcare professional education. The development of emotional skills and self-awareness are the main learning patterns of co-teaching, and interprofessionalism and balanced relationships are the basis of the behavioural patterns. These patterns facilitated the involvement of patients and caregivers in health education.

Background Systematic reviews (SRs) are being published at an accelerated rate. Decision-makers may struggle with comparing and choosing between multiple SRs on the same topic. We aimed to understand how healthcare decision-makers (eg, practitioners, policymakers, researchers) use SRs to inform decision-making and to explore the potential role of a proposed artificial intelligence (AI) tool to assist in critical appraisal and choosing among SRs.Methods We developed a survey with 21 open and closed questions. We followed a knowledge translation plan to disseminate the survey through social media and professional networks.Results Our survey response rate was lower than expected (7.9% of distributed emails). Of the 684 respondents, 58.2% identified as researchers, 37.1% as practitioners, 19.2% as students and 13.5% as policymakers. Respondents frequently sought out SRs (97.1%) as a source of evidence to inform decision-making. They frequently (97.9%) found more than one SR on a given topic of interest to them. Just over half (50.8%) struggled to choose the most trustworthy SR among multiple. These difficulties related to lack of time (55.2%), or difficulties comparing due to varying methodological quality of SRs (54.2%), differences in results and conclusions (49.7%) or variation in the included studies (44.6%). Respondents compared SRs based on the relevance to their question of interest, methodological quality, and recency of the SR search. Most respondents (87.0%) were interested in an AI tool to help appraise and compare SRs.Conclusions Given the identified barriers of using SR evidence, an AI tool to facilitate comparison of the relevance of SRs, the search and methodological quality, could help users efficiently choose among SRs and make healthcare decisions.

The safety profile of baricitinib (BARI), a Janus kinase inhibitor broadly used for the treatment of rheumatoid arthritis (RA), includes asymptomatic laboratory abnormalities, such as an increase in creatine kinase (CK). Data from randomized controlled trials suggest that concomitant myalgia is rare in RA and does not lead to drug discontinuation. We describe the case of a 68-year-old Caucasian female with longstanding, multi-failure RA who started BARI and achieved disease remission. However, she developed a symptomatic CK increase, as well as a parallel increase in total cholesterol, low-density lipoprotein, and triglycerides. Dechallenge-rechallenge demonstrated a plausible relationship between the clinical/laboratory abnormalities and BARI. In fact, when the drug was withdrawn, CK returned to normal and myalgia disappeared, whereas symptoms returned and CK levels increased when BARI was restarted. BARI may be rarely associated with symptomatic CK elevation, and this may pose clinical challenges, particularly for patients with multi-failure RA who achieved good disease control with BARI but required drug discontinuation due to intolerance.

Abstract Translational research for the evaluation of physical activity habits and lifestyle modifications based on nutrition and exercise has recently gained attention. In this study, we evaluated the effects of serum samples obtained before and after a 12-week home-based lifestyle intervention based on nutrition and exercise in breast cancer survivors in terms of modulation of the tumorigenic potential of breast cancer cells. The home-based lifestyle intervention proposed in this work consisted of educational counselling on exercise and nutritional behaviors and in 12 weeks of structured home-based exercise. Triple-negative breast cancer cell line MDA-MB-231 was cultured in semi-solid medium (3D culture) with sera collected before (PRE) and after (POST) the lifestyle intervention program. Spheroid formation was evaluated by counting cell colonies after 3 weeks of incubation. Results show a slight but significant reduction of spheroid formation induced by serum collected POST in comparison to those obtained PRE. Moreover, statistical analyses aimed to find physiologic and metabolic parameters associated with 3D cell proliferation revealed the proliferative inducer IGF-1 as the only predictor of cell tumorigenic potential. These results highlight the importance of lifestyle changes for cancer progression control in a tertiary prevention context. Translational research could offer a useful tool to identify metabolic and physiological changes induced by exercise and nutritional behaviors associated with cancer progression and recurrence risk.

Abstract The current global pandemic of COVID-19 is characterized by waves of infection due to the emergence of new SARS-CoV-2 variants carrying mutations on the Spike (S) protein gene. Since autumn 2020 many Variants of Concern (VOC) have been reported: Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1, Delta/B.1.617.2, Omicron/B.1.1.529, and sublineages. Surveillance of genomic variants is currently based on whole-genome sequencing (WGS) of viral genomes on a random fraction of samples positive to molecular tests. WGS involves high costs, extended analysis time, specialized staff, and expensive instruments compared to a PCR-based test. To rapidly identify the VOCs in positive samples, six assays based on real-time PCR and high-resolution melting (HRM) were designed on the S gene and applied to 120 oro/nasopharyngeal swab samples collected from October 2020 to June 2022 (106 positive and 14 negative samples). Overall, the assays showed 100% specificity and sensitivity compared with commercial PCR tests for COVID-19. Moreover, 104 samples out of 106 (98.1%) were correctly identified as follows: 8 Wuhan (wild type), 12 Alpha, 23 Delta, 46 Omicron BA.1/BA.1.1, 15 Omicron BA.2/BA.4/BA.5. With our lab equipment, about 10 samples can be processed every 3 h at the cost of less than € 10 ($ 10.60) per sample, including RNA extraction. The implementation of this approach could help local epidemiological surveillance and clinical decision-making.

Background Rating of perceived exertion (RPE) is considered a valid method for prescribing prolonged aerobic steady-state exercise (SSE) intensity due to its association with physiological indicators of exercise intensity, such as oxygen uptake (V̇O2) or heart rate (HR). However, these associations between psychological and physiological indicators of exercise intensity were found during graded exercise tests (GXT) but are currently used to prescribe SSE intensity even though the transferability and validity of the relationships found during GXT to SSE were not investigated. The present study aims to verify whether (a) RPE-HR or RPE-V̇O2 relations found during GXTs are valid during SSEs, and (b) the duration and intensity of SSE affect these relations. Methods Eight healthy and physically active males (age 22.6 ± 1.2 years) were enrolled. On the first visit, pre-exercise (during 20 min standing) and maximal (during a GXT) HR and V̇O2 values were measured. Then, on separate days, participants performed 4 SSEs on the treadmill by running at 60% and 80% of the HR reserve (HRR) for 15 and 45 min (random order). Individual linear regressions between GXTs’ RPE (dependent variable) and HRR and V̇O2 reserve (V̇O2R) values (computed as the difference between maximal and pre-exercise values) were used to predict the RPE associated with %HRR (RPEHRR) and %V̇O2R (RPEV̇O2R) during the SSEs. For each relation (RPE-%HRR and RPE-%V̇O2R), a three-way factorial repeated measures ANOVA (α = 0.05) was used to assess if RPE (dependent variable) was affected by exercise modality (i.e., RPE recorded during SSE [RPESSE] or GXT-predicted), duration (i.e., 15 or 45 min), and intensity (i.e., 60% or 80% of HRR). Results The differences between RPESSE and GXT-predicted RPE, which were assessed by evaluating the effect of modality and its interactions with SSE intensity and duration, showed no significant differences between RPESSE and RPEHRR. However, when RPESSE was compared with RPEV̇O2R, although modality or its interactions with intensity were not significant, there was a significant (p = 0.020) interaction effect of modality and duration yielding a dissociation between changes of RPESSE and RPEV̇O2R over time. Indeed, RPESSE did not change significantly (p = 0.054) from SSE of 15 min (12.1 ± 2.0) to SSE of 45 min (13.5 ± 2.1), with a mean change of 1.4 ± 1.8, whereas RPEV̇O2R decreased significantly (p = 0.022) from SSE of 15 min (13.7 ± 3.2) to SSE of 45 min (12.4 ± 2.8), with a mean change of −1.3 ± 1.5. Conclusion The transferability of the individual relationships between RPE and physiological parameters found during GXT to SSE should not be assumed as shown by the results of this study. Therefore, future studies modelling how the exercise prescription method used (e.g., RPE, HR, or V̇O2) and SSE characteristics (e.g., exercise intensity, duration, or modality) affect the relationships between RPE and physiological parameters are warranted.

This study aimed to compare the mechanical (lifting velocity and maximum number of repetitions), physiological (muscular activation, lactate, heart rate, and blood pressure), and psychological (rating of perceived exertion) responses to upper-body pushing exercises performed wearing a sports elastomeric garment or a placebo garment. Nineteen physically active young adults randomly completed two training sessions that differed only in the sports garment used (elastomeric technology or placebo). In each session, subjects performed one set of seated shoulder presses and another set of push-ups until muscular failure. The dependent variables were measured immediately after finishing the set of each exercise. Compared to the placebo garment, the elastomeric garment allowed participants to obtain greater muscular activation in the pectoralis major (push-ups: p = 0.04, d = 0.49; seated shoulder press: p < 0.01, d = 0.64), triceps brachialis (push-ups, p < 0.01, d = 0.77; seated shoulder press: p < 0.01, d = 0.65), and anterior deltoid (push-ups: p < 0.01, d = 0.72; seated shoulder press: p < 0.01, d = 0.83) muscles. Similarly, participants performed more repetitions (push-ups: p < 0.01; d = 0.94; seated shoulder press: p = 0.03, d = 0.23), with higher movement velocity (all p ≤ 0.04, all d ≥ 0.47), and lower perceived exertion in the first repetition (push-ups: p < 0.01, d = 0.61; seated shoulder press: p = 0.05; d = 0.76) wearing the elastomeric garment compared to placebo. There were no between-garment differences in most cardiovascular variables (all p ≥ 0.10). Higher diastolic blood pressure was only found after the seated shoulder press wearing the elastomeric garment compared to the placebo (p = 0.04; d = 0.49). Finally, significantly lower blood lactate levels were achieved in the push-ups performed wearing the elastomeric garment (p < 0.01; d = 0.91), but no significant differences were observed in the seated shoulder press (p = 0.08). Overall, the findings of this study suggest that elastomeric technology integrated into a sports garment provides an ergogenic effect on mechanical, physiological, and psychological variables during the execution of pushing upper-limb resistance exercises.

Abstract Cognitive control is a core feature of several mental disorders. A recent account poses that health problems may derive from proactive forms of cognitive control that maintain stress representation over time. The working hypothesis of the present study is that psychological distress is caused by the tendency to select a particular maladaptive self-regulation strategy over time, namely perseverative thinking, rather than by transient stimulus–response patterns. To test this hypothesis, we asked 84 women to carry out a battery of standardized questionnaires regarding their tendency to undertake perseverative thinking and their level of psychological distress, followed by cognitive tasks measuring the tendency to use proactive versus reactive control modality and disinhibition. Through a series of mediation analyses, we demonstrate that the tendency to use proactive control correlates with psychological distress and that this relation is mediated by perseverative thinking. Moreover, we show that the relation between low inhibitory control and psychological stress is more strongly mediated by perseverative thinking than impulsiveness, a classical construct that focuses on more transient reactions to stimuli. The present results underline the importance of considering psychological distress as the consequence of a maladaptive way of applying control over time, rather than the result of a general deficit in cognitive control abilities.

Abstract Background Haemophilia A carries a substantial healthcare burden, affecting health-related quality of life (HRQoL). The Cost of Haemophilia in Men: a Socioeconomic Survey II (CHESS II), a retrospective real-world study, characterised the burden of haemophilia and its impact on HRQoL and work productivity. The current analysis explored the impact of bleeding events on HRQoL and work productivity in Europe. This analysis focused on data collected from males aged 18 to 64 years with haemophilia A without inhibitors who were receiving replacement factor products or a monoclonal antibody and were not participating in a clinical trial at the time of study recruitment. Descriptive statistics were analysed using scores from EuroQoL’s EQ-5D-5L index and EQ-VAS analogue scale and the Work Productivity and Activity Index Specific Health Problem (WPAI:SHP) percentage scores stratified by the number of annual bleeding events (ABs) 0, 1, 2, 3–4, or ≥ 5. Results Of 918 males with haemophilia A in CHESS II, 318 met inclusion criteria and had data available for HRQoL measures; mean age (SD) was 33.8 (12.1) years and 96% were White. Mean (SD) ABs of 2.7 (2.9) occurred over the preceding 12 months: 20% had 3 or 4 ABs; 17% had ≥ 5 ABs. Mean EQ-5D-5L index scores for patients with 0, 1, 2, 3–4, or ≥ 5 ABs were 0.92, 0.76, 0.76, 0.71, and 0.56, respectively. Mean (SD) EQ-VAS scores were 86.9 (13.6), with 0 ABs versus 69.5 (19.1) for 3 or 4 ABs and 61.2 (17.2) for ≥ 5 ABs. Mean percentage of overall work productivity loss on the WPAI:SHP questionnaire ranged from 9.70 to 0 ABs to 47.65 for ≥ 5 ABs. Conclusions In this European sample of adult men with haemophilia A, HRQoL and work productivity scores were lower among those reporting more AB events. Bleeding burden appears to affect HRQoL and productivity; however, this cross-sectional analysis limits the ability to draw firm conclusions on causality.

Abstract Background During the CoronaVIrus-19 (COVID-19) pandemic, nursing education has been dramatically transformed and shaped according to the restrictions imposed by national rules. Restoring educational activities as delivered in the pre-pandemic era without making a critical evaluation of the transformations implemented, may sacrifice the extraordinary learning opportunity that this event has offered. The aim of this study was to identify a set of recommendations that can guide the Italian nursing education to move forward in the post-pandemic era. Methods A qualitative descriptive design was undertaken in 2022–2023 and reported here according to the COnsolidated criteria for REporting Qualitative research guidelines. A network was established of nine Italian universities offering a bachelor’s degree in nursing for a total of 6135 students. A purposeful sample of 37 Faculty Members, 28 Clinical Nurse Educators and 65 Students/new graduates were involved. A data collection was conducted with a form including open-ended questions concerning which transformations in nursing education had been implemented during the pandemic, which of these should be maintained and valued, and what recommendations should address the transition of nursing education in the post-pandemic era. Results Nine main recommendations embodying 18 specific recommendations have emerged, all transversally influenced by the role of the digital transformation, as a complementary and strengthening strategy for face-to-face teaching. The findings also suggest the need to rethink clinical rotations and their supervision models, to refocus the clinical learning aims, to pay attention towards the student community and its social needs, and to define a pandemic educational plan to be ready for unexpected, but possible, future events. Conclusions A multidimensional set of recommendations emerged, shaping a strategic map of action, where the main message is the need to rethink the whole nursing education, where digitalization is embodied. Preparing and moving nursing education forward by following the emerged recommendations may promote common standards of education and create the basis on for how to deal with future pandemic/catastrophic events by making ready and prepared the educational systems.

BackgroundMASLD is a prevalent chronic liver condition with substantial clinical implications. This study aimed to assess the effectiveness of three new, elastography-based, scoring systems for advanced fibrosis ≥F3 (Agile 3+), cirrhosis F4 (Agile 4), and fibrotic NASH: NASH + NAS ≥4 + F≥2 (FAST score), in a cohort of biopsy-proven NAFLD meeting MASLD criteria. Our secondary aim was to compare their diagnostic performances with those of other fibrosis prediction tools: LSM-VCTE alone, and common, easily available scores (FIB-4 or APRI).MethodsSingle-center, retrospective study, on consecutive patients with baseline laboratory tests, liver biopsy, and reliable LSM-VCTE measurements. The discrimination between tests was evaluated by analyzing the AUROCs. Dual cut-off approaches were applied to rule-out and rule-in ≥F3, F4 and fibrotic NASH. We tested previously reported cut-off values and provided our best thresholds to achieve Se ≥85%, Se ≥90%, and Sp ≥90%, Sp ≥95%.ResultsAmong 246 patients, 113 (45.9%) were women, and 75 (30.5%) presented diabetes. Agile 3+ and Agile 4 demonstrated excellent performance in identifying ≥F3 and F4, achieving AUROCs of 0.909 and 0.968, while the FAST score yielded acceptable results in distinguishing fibrotic NASH. When compared to FIB-4 and LSM-VCTE, both Agile 3+ and Agile 4 performed better than FIB-4 and had a similar performance to LSM-VCTE, but with higher diagnostic accuracy, hence reducing the grey zone.ConclusionAgile 3+ and Agile 4 are reliable, non-invasive tests for identifying advanced fibrosis or cirrhosis in MASLD patients, while FAST score demonstrates moderate performance in identifying fibrotic NASH.

Introduction Pain is a multidimensional experience that varies among individuals and has a significant impact on their health. A biopsychosocial approach is recommended for effective pain management; however, health professionals’ education is weak on this issue. Patient involvement is a promising didactic methodology in developing a more holistic perspective, however there is a lack of reliable evidence on this topic. The aim of the present study is to evaluate the effectiveness of patient involvement in pain education in undergraduate medicine and nursing students.Methods and analysis An open-label randomised controlled trial including qualitative data will be conducted. After an introductory lesson, each student will be randomly assigned to the intervention group, which includes an educational session conducted by a patient–partner along with an educator, or to the control group in which the session is exclusively conducted by an educator. Both sessions will be carried out according to the Case-Based Learning approach. Primary outcomes will be students’ knowledge, attitudes, opinions and beliefs about pain management, whereas the secondary outcome will be students’ satisfaction. The Pain Knowledge and Attitudes (PAK) and Chronic Pain Myth Scale (CPMS) will be administered preintervention and postintervention to measure primary outcomes. Students’ satisfaction will be measured by a questionnaire at the end of the session. Two focus groups will be conducted to evaluate non-quantifiable aspects of learning.Ethics and dissemination The protocol of this study was approved by the independent Area Vasta Emilia Nord ethics committee.Adherence to The Declaration of Helsinki and Good Clinical Practice will ensure that the rights, safety and well-being of the participants in the study are safeguarded, as well as data reliability. The results will be disseminated through scientific publications and used to improve the educational offer. A version of the anonymised data set will be released for public access.Trial registration Trial was not registered on ClinicalTrials.gov as the interventions being compared only concern educational programmes and the outcomes considered do not refer to any clinical dimension.

Abstract Many factors regulate scar formation, which yields a modified extracellular matrix (ECM). Among ECM components, microfibril-associated proteins have been minimally explored in the context of skin wound repair. Microfibril-associated protein 5 (MFAP5), a small 25 kD serine and threonine rich microfibril-associated protein, influences microfibril function and modulates major extracellular signaling pathways. Though known to be associated with fibrosis and angiogenesis in certain pathologies, MFAP5’s role in wound healing is unknown. Using a murine model of skin wound repair, we found that MFAP5 is significantly expressed during the proliferative and remodeling phases of healing. Analysis of existing single-cell RNA-sequencing data from mouse skin wounds identified two fibroblast subpopulations as the main expressors of MFAP5 during wound healing. Furthermore, neutralization of MFAP5 in healing mouse wounds decreased collagen deposition and refined angiogenesis without altering wound closure. In vitro, recombinant MFAP5 significantly enhanced dermal fibroblast migration, collagen contractility, and expression of pro-fibrotic genes. Additionally, TGF-ß1 increased MFAP5 expression and production in dermal fibroblasts. Our findings suggest that MFAP5 regulates fibroblast function and influences scar formation in healing wounds. Our work demonstrates a previously undescribed role for MFAP5 and suggests that microfibril-associated proteins may be significant modulators of wound healing outcomes and scarring.

Abstract Background Metabolic syndrome (MetS) is a cluster of atherosclerotic risk factors that increases cardiovascular risk. MetS has been associated with periodontitis, but the contribution of single MetS components and any possible sexual dimorphism in this relation remain undetermined. Methods Using the third National Health and Nutrition Examination Survey (NHANES III), we performed a nested cross-sectional study to test whether individuals aged > 30 years undergoing periodontal evaluation (population) exposed to ≥ 1 MetS component (exposure) were at increased risk of bleeding/non-bleeding periodontal diseases (outcome) compared to nonexposed individuals, propensity score matched for sex, age, race/ethnicity, and income (controls). The association between MetS components combinations and periodontal diseases was explored overall and across subgroups by sex and smoking. Periodontal health status prediction based on MetS components was assessed. Results In total, 2258 individuals (n. 1129/group) with nested clinical-demographic features were analyzed. Exposure was associated with gingival bleeding (+ 18% risk for every unitary increase in MetS components, and triple risk when all five were combined), but not with stable periodontitis; the association was specific for women, but not for men, irrespective of smoking. The only MetS feature with significant association in men was high BP with periodontitis. CRP levels significantly increased from health to disease only among exposed women. MetS components did not substantially improve the prediction of bleeding/non-bleeding periodontal disease. Conclusion The observed women-specific association of gingival bleeding with single and combined MetS components advances gender and precision periodontology. Further research is needed to validate and expand these findings.

Hereditary spherocytosis (HS) is the most common, nonimmune, hereditary, chronic hemolytic anemia after hemoglobinopathies. The genetic defects in membrane function causing HS lead to perturbation of the RBC metabolome, with altered glycolysis. In mice genetically lacking protein 4.2 (4.2–/–; Epb42), a murine model of HS, we showed increased expression of pyruvate kinase (PK) isoforms in whole and fractioned RBCs in conjunction with abnormalities in the glycolytic pathway and in the glutathione (GSH) system. Mitapivat, a PK activator, metabolically reprogrammed 4.2–/– mouse RBCs with amelioration of glycolysis and the GSH cycle. This resulted in improved osmotic fragility, reduced phosphatidylserine positivity, amelioration of RBC cation content, reduction of Na/K/Cl cotransport and Na/H-exchange overactivation, and decrease in erythroid vesicles release in vitro. Mitapivat treatment significantly decreased erythrophagocytosis and beneficially affected iron homeostasis. In mild-to-moderate HS, the beneficial effect of splenectomy is still controversial. Here, we showed that splenectomy improves anemia in 4.2–/– mice and that mitapivat is noninferior to splenectomy. An additional benefit of mitapivat treatment was lower expression of markers of inflammatory vasculopathy in 4.2–/– mice with or without splenectomy, indicating a multisystemic action of mitapivat. These findings support the notion that mitapivat treatment should be considered for symptomatic HS.

Scientific evidence suggests a relation between dietary factors and sleep. Several studies show that higher adherence to the Mediterranean diet is associated with better sleep quality, but the relation with chronotype has been only recently explored. The aim of this study was to better understand the relation between chronotype and Mediterranean diet adherence. For this purpose, an analysis of 1936 adults (age 18–90 y) living in Italy was performed to investigate the association between chronotype (assessed with a short form of the morningness-eveningness questionnaire) and adherence to the Mediterranean diet (assessed through a 110-item food frequency questionnaire and the Medi-Lite literature-based Mediterranean adherence score). A multivariate logistic regression analysis was conducted to calculate odds ratios (OR) and 95 % confidence intervals (CIs) describing the association between chronotypes and high adherence to the Mediterranean diet (>14 points). Moreover, a systematic review of other observational studies published so far was performed. Individuals reporting having intermediate (n = 614) and evening (n = 173) chronotypes were less likely to have high adherence to the Mediterranean diet compared to morning chronotype (OR = 0.28, 95 % CI: 0.18, 0.42 and OR = 0.08, 95 % CI: 0.03, 0.27, respectively). When the analysis was conducted in subgroups of age, the results were similar in mid-age (>50 y) participants (for intermediate and evening chronotypes, OR = 0.21, 95 % CI: 0.10, 0.43 and OR = 0.92, 95 % CI: 0.01, 0.69, respectively) while the association with high adherence to the Mediterranean diet of evening compared to morning chronotype lost significance in older (>60 y) participants (for intermediate and evening chronotypes, OR = 0.27, 95 % CI: 0.09, 0.82 and OR = 0.22, 95 % CI: 0.02, 1.92, respectively). Out of 10 studies (date range of publication 2020–2022) included in the systematic review, there was a general consistence of findings showing higher adherence to the Mediterranean diet among morning chronotypes, although few studies reported null results. In conclusion, current evidence suggests that an intermediate and evening chronotype could be associated with lower adherence to a Mediterranean diet, but the association could be modified by other factors when considering older individuals.

Introduction The objective is to investigate the effect of antimicrobial photodynamic therapy (aPDT) mediated by erythrosine and a blue light-emitting diode (LED) in the reduction of bacteria in dental biofilm.Methods and analysis This clinical trial will be conducted with 30 patients who have biofilm, but without the presence of periodontal pockets, and who are being treated at the Dental Clinic of Universidade Metropolitana de Santos. A split-mouth model will be used (n=30), with group 1 control (conventional treatment) and group 2 (conventional treatment and aPDT). The bicarbonate jet will be used to remove dental biofilm in both groups. The treatment will be carried out in one session. aPDT will be performed before cleaning/prophylaxis, only in group 2. Participants will rinse with the photosensitiser erythrosine (diluted to 1 mM) for 1 min of pre-irradiation time, so that the drug can stain all the bacterial biofilm. Then, the D-2000 LED (DMC) will be applied, emitting at a wavelength of ʎ=470 nm, radiant power of 1000 mW, irradiance of 0.532 W/cm2 and radiant exposure of 63.8 J/cm2. Irradiation will be performed until the biofilm of the cervical region is illuminated for 2 min/point (4 cm2). The microbiological examination will be performed from samples of supragingival biofilm collected from the gingival sulcus. Collection will be performed in each experimental site before irradiation, immediately after the irradiation procedure and after the prophylaxis. Colony-forming units will be counted and the data will be submitted for statistical analysis for comparison of pretreatment and post-treatment results and between groups (conventional X aPDT).Ethics and dissemination This study has been approved by the Ethics Committee of Universidade Metropolitana de Santos under process number 66984123.0.0000.5509. Results will be published in peer-reviewed journals and will be presented at conferences.Trial registration number NCT05805761.

Background The incidence of high-grade anal intraepithelial lesions (HSILs) has increased in recent years among men who have sex with men with human immunodeficiency virus (HIV). This work evaluated the validity of the human papilloma virus viral load (HPV-VL) versus cytological and qualitative HPV results to detect HSILs. Methods From May 2017 to January 2020, 93 men who have sex with men and HIV were included in an anal cancer screening program from the Infectious Diseases Unit at a tertiary-care hospital in Alicante (Spain). The gold-standard for the screening of anal HSILs is the anal biopsy using high-resolution anoscopy. The diagnostic methods compared against gold-standard were HPV-16-VL, HPV-18-VL, and HPV-16-18-VL co-testing, anal cytology, and qualitative HPV detection. The receiver operating characteristic (ROC) curve and cut-off points for HPV-VL were calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen’s Kappa coefficient (κ) were also calculated. Results The mean patient age was 44.6 ± 9.5 years. All of them received antiretroviral treatment, 96.8% had an HIV viral load of 6.2 copies/cell was detected in the HSIL biopsy samples (p = 0.007), showing a sensitivity of 100% and a specificity of 46.2%. HPV-18-VL and HPV16-18-VL co-testing showed a sensitivity of 75% and 76.9% and a specificity of 72.7% and 61.3%, respectively. The highest PPV was 50% obtained with the cytology and HPV-18-VL. The HPV-16-VL showed a NPV of 100%, followed by 88.9% in the HPV-18-VL and 87% in the abnormal cytology. Cohen’s Kappa coefficient were: HPV-18-VL (κ = 0.412), abnormal cytology (κ = 0.353) and HPV-16-VL (κ = 0.338). Conclusions HPV-VL testing improved the detection sensitivity but not the specificity for HSIL biopsies compared to anal cytology and the qualitative detection of HPV. In men who have sex with men and HIV the HPV-VL could be an useful tool for diagnosis of HSILs in anal cancer screening programs. Further studies will be needed to evaluate the clinical implications of HPV-VL in these programs.

Objetivo: Analizar los antecedentes de formación, conductas y conocimientos sobre salud bucodental infantil en un grupo de pediatras en formación y recientemente graduados. Materiales y métodos: Estudio descriptivo mediante la aplicación de una encuesta anónima de 18 ítems, autoadministrada, enviada en forma virtual a estudiantes y graduados de un posgrado de Pediatría de la Universidad Maimónides en la Ciudad Autónoma de Buenos Aires, Argentina. Resultados: Se obtuvieron 60 respuestas. El 80 % de los participantes fueron mujeres, en su mayoría sin hijos, pertenecientes a los 3 años de formación del posgrado o con menos de 2 años de experiencia. El 78,90 % no consigna habitualmente la información del estado de salud bucodental en la historia clínica del paciente. Un 72 % de los encuestados fallaron en determinar la prevalencia de la caries dental con relación a otras patologías de la infancia. También se encontraron errores de concepto en cuanto a la etiología de la caries. Un 67,20 % no había recibido hasta el momento ninguna capacitación en salud bucodental; los que la habían recibido refirieron que esta había sido insuficiente. La autopercepción para llevar adelante acciones de prevención fue poco homogénea, y se identificaron dificultades para el reconocimiento temprano de lesiones. Un 60 % tuvo dificultades para establecer la cantidad adecuada de pasta dental que un niño debe utilizar y tampoco se sintió capacitado para dar recomendaciones sobre la técnica correcta del cepillado. Asimismo, en la muestra no se observó un criterio correcto y uniforme para la primera visita del niño sano al odontopediatra. Conclusiones: Al igual que lo manifestado por otros autores, se encuentran deficiencias en la formación y, por ende, en la autopercepción de los pediatras en formación y recientemente graduados en temas relacionados con la salud bucodental. A pesar de las dificultades reconocidas por los participantes, hubo consenso en la importancia del rol del pediatra en la prevención de la salud bucodental y en el impacto de esta en la calidad de vida del niño.

Abstract Objective: to evaluate the incompleteness of Mortality Information System (Sistema de Informações sobre Mortalidade - SIM) data on deaths from external causes (ECs) in the state of Rio Grande do Sul, Brazil, 2000-2019. Methods: This was an ecological study, using SIM data on all deaths from external causes and, specifically, from transport accident, homicides, suicides and falls; the analysis of the trend of incompleteness was performed by means of Prais-Winsten regression, with a 5% significance level. Results: A total of 146,882 deaths were evaluated; sex (0.1%), place of death (0.1%) and age (0.4%) showed the lowest incompleteness in 2019; the proportion of incompleteness showed a decreasing trend for the place of death and schooling, an increasing trend for marital status and a stable trend for age and race/skin color, among all types of death evaluated. Conclusion: the variables analyzed reached a high degree of completion; with the exception of marital status and schooling, for which unsatisfactory scores persisted for deaths from ECs, both total and by subgroups.

ABSTRACT Introduction COVID-19 is associated with endothelial activation and systemic inflammation; consequently, statins can be used in its treatment as they have anti-inflammatory, antithrombotic, and profibrinolytic properties and may interfere with COVID-19 viral entry into cells through disruption of cell membrane lipid rafts. Objective We performed a meta-analysis of randomized clinical trials that compared statin therapy to placebo or to standard care in adult patients hospitalized for COVID-19. Methods We searched the MEDLINE, EMBASE, and Cochrane Library databases for all-cause mortality, hospitalization duration, and admission to the intensive care unit. Results Of the 228 studies reviewed, four studies were included, with a total of 1,231 patients, of whom 610 (49.5%) were treated with statins. There was no significant difference in all-cause mortality (odds ratio [OR] 0.96; 95% confidence interval [95%CI]: 0.61-1.51; p=0.86; I2=13%), duration of hospitalization (mean difference [MD] 0.21; 95%CI: -1.74-2.16; p=0.83; I2=92%), intensive care unit admission (OR= 3.31; 95%CI: 0.13-87.1; p=0.47; I2=84%), need for mechanical ventilation (OR= 1.03; 95%CI: 0.36-2.94; p=0.95; I2=0%), or increase in liver enzyme levels (OR= 0.58; 95%CI: 0.27-1.25; p=0.16; I2=0%) between patients treated with or without statin therapy. Conclusion Our findings suggest that in adult patients hospitalized with COVID-19, statin therapy results in no difference in clinical outcomes when compared to outcomes by placebo or standard of care. Prospero database registration: (www.crd.york.ac.uk/prospero) under the number CRD42022338283.

Abstract Deep-habitat cetaceans are generally difficult to study, leading to a limited knowledge of their population. This paper assesses the differential distribution patterns of three deep-habitat cetaceans (Sperm whale—Physeter macrocephalus, Risso’s dolphin—Grampus griseus & Cuvier’s beaked whale—Ziphius cavirostris). We used data of 842 opportunistic sightings of cetaceans in the western Mediterranean sea. We inferred environmental and spatio-temporal factors that affect their distribution. Binary logistic regression models were generated to compare the presence of deep-habitat cetaceans with the presence of other cetacean species in the dataset. Then, the favourability function was applied, allowing for comparison between all the models. Sperm whale and Risso’s dolphin presence was differentially favoured by the distance to towns in the eastern part of the western Mediterranean sea. The differential distribution of sperm whale was also influenced by the stability of SST, and that of the Risso’s dolphin by lower mean salinity and higher mean Chlorophyll A concentration. When modelling the three deep-habitat cetaceans (including Cuvier’s beaked whale), the variable distance to towns had a negative influence on the presence of any of them more than it did to other cetaceans, being more favourable far from towns, so this issue should be further investigated.

Healthy successful aging with preserved mental and cognitive health is expected to be one of the most important challenges of the growing old population globally. Studies investigating these multi-dimensional aspects of senescence are important to identify potential targets for early prevention. The aim of this study was to investigate the relation between adherence to the Mediterranean diet and mental and cognitive health, quality of life, and successful aging in middle-age and older adults living in Sicily, southern Italy. Data from a sample of 883 individuals was collected including information on food intake (through a 110-item food frequency questionnaire), sleep quality (through the Pittsburgh sleep quality index) depressive symptoms (through the Center for the Epidemiological Studies of Depression Short Form), quality of life (through the Manchester Short Assessment of Quality of Life), cognitive status (through the Short Portable Mental Status Questionnaire), and overall successful aging (through the Successful Aging Index). Multivariate logistic regression analyses were conducted to assess the association between adherence to the Mediterranean diet and the outcomes investigated. After adjustment for potential confounding factors, individuals in the highest quartile of adherence to the Mediterranean diet were less likely to have cognitive impairment (OR = 0.19, 95 % CI: 0.04, 0.86), depressive symptoms (OR = 0.19, 95 % CI: 0.08, 0.46) and more likely to have good quality of life (OR = 14.04, 95 % CI: 6.81, 28.93); significant results were also found for individuals in the third quartile of Mediterranean diet adherence and good sleep quality (OR = 1.65, 95 % CI: 1.03, 2.64). Moreover, individuals in the highest quartile of adherence were more likely to have a successful aging (OR = 1.65, 95 % CI: 1.01, 2.68). In conclusion, this study supports the hypothesis that adherence to the Mediterranean diet provides a positive trajectory toward a healthy successful aging, with major potential benefits toward mental and cognitive health.

Objectives To better define the spectrum of new-onset post-COVID-19 and post-COVID-19 vaccine inflammatory rheumatic diseases (IRD) from a large multicentric observational study.Methods Consecutive cases of IRD encountered during a 12-month period and satisfying one of the following inclusion criteria: (a) onset of the rheumatic manifestations within 4 weeks from SARS-CoV-2 infection or (b) onset of the rheumatic manifestations within 4 weeks from the administration of one of the COVID-19 vaccines ws recruited.Results The final analysis cohort comprised 267 patients, of which 122 (45.2%) in the post-COVID-19 and 145 (54.8%) in the postvaccine cohort. Distribution of IRD categories differed between the two cohorts: the post-COVID-19 cohort had a higher percentage of patients classified as having inflammatory joint diseases (IJD, 52.5% vs 37.2%, p=0.013) while the post-vaccine cohort had a higher prevalence of patients classified as polymyalgia rheumatica (PMR, 33.1% vs 21.3%, p=0.032). No differences were detected in the percentage of patients diagnosed with connective tissue diseases (CTD 19.7% vs 20.7%, p=0.837) or vasculitis (6.6% vs 9.0%, p=0.467). Despite the short follow-up period, IJD and PMR patients’ response to first-line therapy was favourable, with both groups achieving a drop in baseline disease activity scores of ~30% and ~70% respectively.Conclusion Our article reports the largest cohort published to date of new-onset IRD following SARS-CoV-2 infection or COVID-19 vaccines. Although causality cannot be ascertained, the spectrum of possible clinical manifestations is broad and includes IJD, PMR, CTD and vasculitis.

Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort.Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets.Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud’s phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1–16.5) than lcSSc (2 years, IQR 0–7), and dcSSc (1 year, IQR 0–3) (p

Abstract Cardiovascular disease is the leading cause of death worldwide. New therapeutic strategies are aimed to modulate the athero-inflammatory process that partially orchestrates underlying vascular damage. Peripheral blood circulating cells include different immune cells with a central role in the development of the atherogenic inflammatory response. The anti-aging protein α-Klotho has been related to protective effects against CVD. KL is expressed in monocytes, macrophages, and lymphocytes where it exerts anti-inflammatory effects. In this work, we analyse the relationships of the levels of inflammatory markers with the expression of the KL gene in PBCCs and with the serum levels of soluble KL in atherosclerotic vascular disease. For this, we conducted a cross-sectional single-center case–control study including a study group of 76 CVD patients and a control group of 16 cadaveric organ donors without medical antecedent or study indicating CVD. Vascular artery fragments and whole blood and serum samples were obtained during elective or organ retrieval surgery. Serum levels of sKL, TNFα and IL10, and gene expression levels of KL, TNF, IL10, NFKB1, DNMT1, and DNMT3A in PBCCs were measured. In these cells, we also determined KL promoter methylation percentage. Histological and immunohistochemical analyses were employed to visualize atherosclerotic lesions and to measure IL10 and TNFα levels in vascular fragments. Patients with CVD presented higher values of proinflammatory markers both at systemic and in the vasculature and in the PBCCs, compared to the control group. In PBCCs, CVD patients also presented lower gene expression levels of KL gene (56.4% difference, P < 0.001), higher gene expression levels of DNMT1 and DNMT3A (P < 0.0001, for both) and a higher methylation status of in the promoter region of KL (34.1 ± 4.1% vs. 14.6 ± 3.4%, P < 0.01). In PBCCs and vasculature, KL gene expression correlated inversely with pro-inflammatory markers and directly with anti-inflammatory markers. sKL serum levels presented similar associations with the expression levels of pro- and anti-inflammatory markers in PBCCs. The differences in KL expression levels in PBCCs and in serum sKL levels with respect to control group was even greater in those CVD patients with macroscopically observable atheromatous plaques. We conclude that promoter methylation-mediated downregulation of KL gene expression in PBCCs is associated with the pro-inflammatory status in atherosclerotic vascular disease.

Abstract It is crucial to control the tuning and improve the emission of a quantum emitter at the nanoscale. We report multiple Fano resonances in metallic nanostructures on an Er3+-doped tellurite glass. Periodic nanoslits were fabricated with a focused gallium ion beam on a gold thin film deposited on the tellurite glass. Is proposed a coupling function with Fano line-shape form, and the asymmetric parameter q for each resonance wavelength in the 515 to 535 nm region was calculated. This asymmetric resonance effect is a consequence of the quantum interaction between the continuum state, generated in the nanostructure, and the Stark splits of the $$^2$$ 2 H $$_{11/2}$$ 11 / 2 state.

Abstract Background Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare genetic diseases characterized by inadequate bile secretion that requires substantial ongoing care, though little research is published in this area. We report health-related quality of life (HRQoL) and work productivity outcomes from the retrospective, cross-sectional PICTURE study investigating the burden of PFIC on caregivers. Information from caregivers of patients with PFIC 1 or 2 in Germany, the United Kingdom and the United States from September 2020 to March 2021 was included. Results The PICTURE study sample comprised HRQoL responses from 22 PFIC caregivers. Patients were on average 8.2 years old; most caregivers were 30–49 years old (68%) and mothers (77%). Median CarerQoL-7D score was 67.7/100; mean CarerQoL-VAS score for general happiness was 5.7/10 (SD 2.1). Most caregivers reported fulfilment in their caregiving responsibilities, but problems with mental and physical health, finances, and relationships. When stratified by patient’s PFIC type, mean CarerQoL-7D and CarerQoL-VAS scores suggested worse HRQoL outcomes with PFIC2 versus PFIC1 (59.4 vs. 71.2, and 5.3 vs. 6.5, respectively). Additionally, more caregivers reported impact on sleep in the PFIC2 versus PFIC1 subgroup (93% vs. 75%). When stratified by history of PFIC-related surgeries, mean CarerQoL-7D and VAS scores were higher among those whose children had no specified surgeries (67.7 vs. 59.0/100 and 6.2 vs. 5.2/10, respectively). Nearly all caregivers reported an impact of caregiving responsibilities on sleeping (86%) and on personal relationships (82%). No caregivers reported having formal care support. Most caregivers were employed (73%); a third reported mean productivity loss of 12.9 days (SD 19.3) over the last 3 months, and a mean of 2.8 (SD 9.5) missed years of employment during their career. A higher number of workdays were missed by PFIC 2 caregivers compared to PFIC1 over last 3 months (16 days vs. 3 days). Conclusions The PICTURE study has demonstrated the prevalent, comprehensive, and meaningful burden that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL including mental and physical health, productivity, career prospects, sleep, relationships and finances.

The maintenance of the deciduous tooth until its physiological exfoliation occurs is one of the main objectives of pediatric dentistry. Endodontic treatment in deciduous teeth resulting from carious or traumatic lesions with pulpal involvement is often necessary and we often find it difficult to perform it, due to the difficult control of the child, the internal anatomy of the root canals, and root resorptions. The non-instrumental endodontic treatment technique (NIET) associated with antimicrobial drugs has advantages such as shorter chair time and less complexity than the conventional technique in which root canal instrumentation is performed. The aim of this study is to carry out a controlled and randomized clinical trial to compare the effectiveness of (NIET) in primary teeth associated with the use of two obturator pastes. One hundred and twenty necrotic deciduous teeth of children aged between 3 and 6 years will be selected; and the teeth will be divided into two groups. In Group 1 and Group 2, root canals will not be instrumented, just irrigated and filled with the respective pastes, antibiotic (CTZ) and iodoform (Guedes-Pinto). Presence of fistula and mobility will be clinically evaluated. The evaluations will be carried out in both groups on the day of treatment and in periods of 1, 3 and 6 months after treatment. For the main outcome, the tooth will be the unit of analysis and the Kaplan-Meier test will be performed to estimate the survival rates of the included teeth. For comparison between the two groups, Student's t test or Mann-Whitney test will be performed, depending on the normality of the data. In addition, Poisson regression analyzes will be carried out, in order to allow the evaluation of the influence of some variables on the results. For all analyses, the significance value will be adjusted to 5%. Trial registration: NCT04587089 in ClinicalTrials.gov. Approval date: May 15, 2023.

IntroductionCoronavirus disease 2019 (COVID-19) pandemic has influenced health-care organization worldwide, including management of non-communicable diseases. The aim of this study was to determine the impact of COVID-19 pandemic on cardiac implantable electronic devices' (CIEDs) implantation rates in Croatia.MethodsA retrospective, observational, national study was conducted. The data on CIEDs' implantation rates from 20 Croatian implantation centres, between January 2018 and June 2021, were extracted from the national Health Insurance Fund registry. Implantation rates before and after COVID-19 pandemic started, were compared.ResultsThe overall numbers of CIED implantations in Croatia during COVID-19 pandemic were not different in comparison to 2 years pre-COVID-19 time (2618 vs. 2807, p = .081). The pacemaker implantation rates decreased significantly (by 45%) during April (122 vs. 223, p < .001) and May 2020 (135 vs. 244, p = .001), as well as during November 2020 (177 vs. 264, p = .003), but significantly increased during summer months 2020 comparing to 2018 and 2019 (737 vs. 497, pConclusionTo the authors best knowledge this is a first study including complete national data on CIED implantation rates and COVID-19 pandemic impact. A significant reduction in number of both pacemaker and ICD implants during specific months of the COVID-19 pandemic was determined. However, afterwards compensation in implants resulted in similar total number when the complete year was evaluated.

Information and communication technologies have significantly transformed the way advanced societies interact, produce, deliver services and consume resources. All walks of life are now touched by these technologies. However, compared to other areas of society, digital penetration is much lower in the development of and access to social services. The main objective of this paper was to find out what technological devices are used, how they are used and the way citizens interact with public bodies using technology to deliver social services. This has been part of a wider project on innovation in social services using participative methodologies centred on the development of local Hubs. The findings reveal a digital divide in technology-enabled access to social services that excludes the very people most in need of benefits and support.

BackgroundThis study aimed to identify a Relative Age Effect (RAE) among French young swimmers and apply corrective adjustment procedures to rebalance performances according to categories and events.Methods5,339,351 performances of French swimmers aged 10 to 18 were collected between 2000 and 2019. Birth quarters distribution was examined according to competitiveness level ('All', 'Top50%', 'Top25%' and 'Top10%'), event and age category. A linear relationship between the distribution of performances and calendar days provides a calibration coefficient allowing to rebalance performances by considering the effect of RAE for each event. Then, adjusted performances are recalculated using this coefficient, the initial performance and the relative age.ResultsProportion of swimmers born in the first quarter was higher than the proportion of those born in the last quarter for all events and strokes (p < 0.01). RAE increases with the competitiveness level for all events. Indeed, among 'All' 12 years old 50m freestyle swimmers, the proportion born in the first quarter is 30.9% vs 19.2% in the fourth quarter, while among the "Top10%", 47.5% were born in the first quarter vs 10.3% in the last one. (p-value < 0.01). In average, each day represents a gap of 0.008 second, resulting in a difference of almost 3 seconds over a year. This tool is validated by comparing swimmers who have performed at least twice in a season. It provides a day by day rebalancing method for all swimming events and age categories.ConclusionsRelative age effect is present among French young male and female swimmers, and is strengthened by competitiveness level. A new corrective adjustment procedure to rebalance performances considering categories and events is proposed and validated. By applying such a tool, we are able to reveal the full potential of swimmers and make it possible to compare them at the same relative age.

Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. A high prevalence of AA-amyloidosis has been reported in captive cheetahs and a horizontal transmission has been proposed. In domestic cats, AA-amyloidosis has been mainly described in predisposed breeds but only rarely reported in domestic short-hair cats. Aims of the study were to determine AA-amyloidosis prevalence in dead shelter cats. Liver, kidney, spleen and bile were collected at death in cats from 3 shelters. AA-amyloidosis was scored. Shedding of amyloid fibrils was investigated with western blot in bile and scored. Descriptive statistics were calculated. In the three shelters investigated, prevalence of AA-amyloidosis was 57.1% (16/28 cats), 73.0% (19/26) and 52.0% (13/25), respectively. In 72.9% of cats (35 in total) three organs were affected concurrently. Histopathology and immunofluorescence of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B = 0.026, CI95% = 0.007-0.046; p = 0.010). AA-amyloidosis was very frequent in shelter cats. Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease. In conclusion, AA-amyloidosis was very frequent in shelter cats and those staying longer had more deposits. The cat may represent a natural model of AA-amyloidosis.

BackgroundSex differences in vascular cognitive impairment (VCI) at risk for future dementia are still debatable. Transcranial magnetic stimulation (TMS) is used to evaluate cortical excitability and the underlying transmission pathways, although a direct comparison between males and females with mild VCI is lacking.MethodsSixty patients (33 females) underwent clinical, psychopathological, functional, and TMS assessment. Measures of interest consisted of: resting motor threshold, latency of motor evoked potentials (MEPs), contralateral silent period, amplitude ratio, central motor conduction time (CMCT), including the F wave technique (CMCT-F), short-interval intracortical inhibition (SICI), intracortical facilitation, and short-latency afferent inhibition, at different interstimulus intervals (ISIs).ResultsMales and females were comparable for age, education, vascular burden, and neuropsychiatric symptoms. Males scored worse at global cognitive tests, executive functioning, and independence scales. MEP latency was significantly longer in males, from both sides, as well CMCT and CMCT-F from the left hemisphere; a lower SICI at ISI of 3 ms from the right hemisphere was also found. After correction for demographic and anthropometric features, the effect of sex remained statistically significant for MEP latency, bilaterally, and for CMCT-F and SICI. The presence of diabetes, MEP latency bilaterally, and both CMCT and CMCT-F from the right hemisphere inversely correlated with executive functioning, whereas TMS did not correlate with vascular burden.ConclusionsWe confirm the worse cognitive profile and functional status of males with mild VCI compared to females and first highlight sex-specific changes in intracortical and cortico-spinal excitability to multimodal TMS in this population. This points to some TMS measures as potential markers of cognitive impairment, as well as targets for new drugs and neuromodulation therapies.

Background Latin America and the Caribbean Region are home to about 42 million Indigenous people, with about 900,000 living in Brazil. The little routinely collected population-level data from Indigenous communities in the region available shows stark inequities in health and well-being. There are 305 Indigenous ethnic groups, speaking 274 languages, spread across the remote national territory, who have endured long-lasting inequities related to poverty, poor health, and limited access to health care. Malnutrition and mental health are key concerns for young people. Building on our Indigenous communities-academic partnerships over the last two decades, we collaborated with young people from the Terena Indigenous ethnic group, village leaders, teachers, parents, and local health practitioners from the Polo Base (community health centres) to obtain their perspectives on important and feasible actions for a youth health promotion programme. Methods The report was conducted in the Tereré Village in Mato Grosso do Sul. Concept mapping, a participatory mixed method approach, was conducted in 7 workshops, 15 adults and 40 youths aged 9–17 years. Art-based concept mapping was used with 9 to 11 years old children (N = 20). Concept systems software was used to create concept maps, which were finalised during the workshops. Focused prompts related to factors that may influence the health and happiness of youths. The participatory method gave Terena youths a significant voice in shaping an agenda that can improve their health. Results Terena youths identified priority actions that clustered under ‘Family’, ‘School’, ‘Education’, ‘Socio-economic circumstances’, ‘Respect’ and ‘Sport’ in response to protecting happiness; and ‘Nutrition pattern’, ‘Physical activity’, ‘Local environment’, and ‘Well-being’ in response to having a healthy body. Through the participatory lens of concept mapping, youths articulated the interconnectedness of priority actions across these clusters such that behaviours (e.g. Nutrition pattern, drinking water, physical activity) and aspirations (being able to read, to have a good job) were recognised to be dependent on a wider ecology of factors (e.g. loss of eco-systems, parent-child relationships, student- teacher relationships, parental unemployment). In response to developing youth health, Terena adults suggested priority actions that clustered under ‘Relationships’, ‘Health issues’, ‘Prevention at Polo Base’, ‘Access to health care’, ‘Communication with young people’, ‘Community life’, ‘Raising awareness’ and ‘School support’. Their priorities reflected the need for structural transformative actions (e.g. Polo Base and school staff working together) and for embedding actions to protect Indigenous culture (e.g. integrating their cultural knowledge into training programmes). Conclusions Concept maps of Indigenous youths emphasised the need for a health promotion programme that engages with the structural and social determinants of health to protect their happiness and health, whilst those of adults emphasised the need to address specific health issues through preventative care via a school-Polo Base collaboration. Investment in a co-developed school-Polo-Base health promotion programme, with intersectoral engagement, has potential for making Indigenous health systems responsive to the inequalities of youth health, to yield dividends for healthy ageing trajectories as well as for the health of the next generation.

This study aimed to estimate prevalence of loneliness among older Brazilian adults over the first seven months of the COVID-19 pandemic and to identify the predictors of loneliness trajectories. Pre-pandemic data derived from face-to-face interviews of participants of the 2019-2020 Brazilian Longitudinal Study of Aging (ELSI-Brazil), which is a nationally representative study of community-dwelling individuals aged 50 years and over. Pandemic data were based on three rounds of telephone interviews among those participants, conducted from May to October 2020. Loneliness was measured by a single-item question, considering those who had at least two repeated measures. Explanatory variables included depression, living alone, leaving home in the last week, and virtual connectedness in the last month. Mixed-effects logistic regression was used to estimate odds ratios with their 95% confidence intervals (95%CI) and to investigate loneliness trajectories and their predictors. In total, 5,108 participants were included. The overall prevalence of loneliness in the pre-pandemic period was 33.1% (95%CI: 29.4-36.8), higher than the pandemic period (round 1: 23.6%, 95%CI: 20.6-26.9; round 2: 20.5%, 95%CI: 17.8-23.5; round 3: 20.6%, 95%CI: 17.1-24.6). A significant interaction (p ≤ 0.05) was evidenced only between depression and time; participants with depression showed a greater reduction in loneliness levels. Although loneliness levels in Brazil have decreased during the pandemic, this pattern is not present for all older adults. Individuals with depression had a more significant reduction, probably due to feeling closer to their social network members during the stay-at-home recommendations.

Abstract Functional connectivity (FC) of brain networks dynamically fluctuates during both rest and task execution. Individual differences in dynamic FC have been associated with several cognitive and behavioral traits. However, whether dynamic FC also contributes to sensorimotor representations guiding body-environment interactions, such as the representation of peripersonal space (PPS), is currently unknown. PPS is the space immediately surrounding the body and acts as a multisensory interface between the individual and the environment. We used an audio-tactile task with approaching sounds to map the individual PPS extension, and fMRI to estimate the background FC. Specifically, we analyzed FC values for each stimulus type (near and far space) and its across-trial variability. FC was evaluated between task-relevant nodes of two fronto-parietal networks (the Dorsal Attention Network, DAN, and the Fronto-Parietal Network, FPN) and a key PPS region in the premotor cortex (PM). PM was significantly connected to specific task-relevant nodes of the DAN and the FPN during the audio-tactile task, and FC was stronger while processing near space, as compared to far space. At the individual level, less PPS extension was associated with stronger premotor-parietal FC during processing of near space, while the across-trial variability of premotor-parietal and premotor-frontal FC was higher during the processing of far space. Notably, only across-trial FC variability captured the near-far modulation of space processing. Our findings indicate that PM connectivity with task-relevant frontal and parietal regions and its dynamic changes participate in the mechanisms that enable PPS representation, in agreement with the idea that neural variability plays a crucial role in plastic and dynamic sensorimotor representations.

Introduction To date, no pancreatic stump closure technique has been shown to be superior to any other in distal pancreatectomy. Although several studies have shown a trend towards better results in transection using a radiofrequency device (radiofrequency-assisted transection (RFT)), no randomised trial for this purpose has been performed to date. Therefore, we designed a randomised clinical trial, with the hypothesis that this technique used in distal pancreatectomies is superior in reducing clinically relevant postoperative pancreatic fistula (CR-POPF) than mechanical closures.Methods and analysis TRANSPAIRE is a multicentre randomised controlled trial conducted in seven Spanish pancreatic centres that includes 112 patients undergoing elective distal pancreatectomy for any indication who will be randomly assigned to RFT or classic stapler transections (control group) in a ratio of 1:1. The primary outcome is the CR-POPF percentage. Sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1−β), expected POPF in control group of 32%, expected POPF in RFT group of 10% and a clinically relevant difference of 22%. Secondary outcomes include postoperative results, complications, radiological evaluation of the pancreatic stump, metabolomic profile of postoperative peritoneal fluid, survival and quality of life. Follow-ups will be carried out in the external consultation at 1, 6 and 12 months postoperatively.Ethics and dissemination TRANSPAIRE has been approved by the CEIM-PSMAR Ethics Committee. This project is being carried out in accordance with national and international guidelines, the basic principles of protection of human rights and dignity established in the Declaration of Helsinki (64th General Assembly, Fortaleza, Brazil, October 2013), and in accordance with regulations in studies with biological samples, Law 14/2007 on Biomedical Research will be followed. We have defined a dissemination strategy, whose main objective is the participation of stakeholders and the transfer of knowledge to support the exploitation of activities.Registration details ClinicalTrials.gov Registry (NCT04402346).

The sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions, such as myopathies. Here, we investigated whether the nuclear receptor subfamily 1 group D member (NR1D1, also called REV-ERBα) regulates skeletal muscle SR calcium homeostasis. Our data demonstrate that NR1D1 deficiency in mice impaired sarco/endoplasmic reticulum calcium ATPase–dependent (SERCA-dependent) SR calcium uptake. NR1D1 acts on calcium homeostasis by repressing the SERCA inhibitor myoregulin through direct binding to its promoter. Restoration of myoregulin counteracted the effects of NR1D1 overexpression on SR calcium content. Interestingly, myoblasts from patients with Duchenne muscular dystrophy displayed lower NR1D1 expression, whereas pharmacological NR1D1 activation ameliorated SR calcium homeostasis and improved muscle structure and function in dystrophic mdx/Utr+/– mice. Our findings demonstrate that NR1D1 regulates muscle SR calcium homeostasis, pointing to its therapeutic potential for mitigating myopathy.