No more than "half prevention": A qualitative study on psychosocial determinants of Covid-19 vaccination acceptance.

Vaccine hesitancy represents a major barrier to achieving Covid-19 vaccination coverage, including in Italy, where the vaccination rates suggest that Covid-19 vaccination has not been fully integrated into people's routine immunization schedules. While quantitative studies have generated ample data on factors influencing vaccination decisions, rarely was an overall picture of people's actual views and experiences with Covid-19 vaccines provided. To address this gap, this qualitative study aimed to explore, from a psychosocial perspective, the relationships between perceptions of Covid-19 vaccines, traditional vaccines, and general approaches to prevention. Following a Grounded Theory approach, we interviewed 25 Italian adults from different socioeconomic and working backgrounds. Findings revealed that, despite a generally positive attitude towards Covid-19 vaccines, they were often regarded as providing only partial protection-a "half prevention"-against the disease rather than a definitive preventive measure. In this sense, a gap emerged between the overall notion of prevention and the specific representations associated with Covid-19 vaccines. Therefore, to increase vaccination acceptance, interventions should prioritize the reduction of such a gap by promoting the idea that vaccination against Covid is, in all respects, a safe and effective preventive tool. This requires fostering a credible knowledge system and building trustful relationships among community members and stakeholders involved in the vaccination campaign, including general practitioners, healthcare professionals, and political authorities.

Proteinuria and hematuria as early signs of renal involvement in juvenile idiopathic arthritis.

Objectives: To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA). Methods: A total of 40 pediatric patients, 20 (50%) with JIA and 20 (50%) healthy control subjects, were studied, and performed the renal function on 24-h collection and the 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we compared renal function and blood pressure trends between the groups of JIA patients with different disease activities. Results: No statistically significant differences were observed between patients with JIA and healthy children in terms of glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tubular reabsorption of phosphate (TRP), and calcium-creatinine urine ratio (CaU/CrU). In contrast, we observed significantly higher values in JIA patients than in controls for the presence of hematuria (p < 0.0001) and proteinuria (p < 0.0001). Compared to the control group there were significantly higher values of hematuria and proteinuria/day in both groups of JIA patients with low disease activity (respectively, p = 0.0001 and p = 0.0002) and moderate disease activity (respectively p = 0.0001 and p = 0.0012). Systolic and diastolic dipping were significantly reduced in patients with JIA compared with healthy controls (p < 0.0001 and p < 0.0001, respectively). Conclusions: Our study showed that children with JIA, already in the early stages of the disease, have higher values of hematuria and proteinuria, which are early warning signs of nephropathy. Therefore, detailed screening of renal function and pressure monitoring in patients are necessary to monitor their evolution over time.

Combined exome and whole transcriptome sequencing identifies a de novo intronic SRCAP variant causing DEHMBA syndrome with severe sleep disorder.

Rare heterozygous variants in exons 33-34 of the SRCAP gene are associated with Floating-Harbor syndrome and have a dominant-negative mechanism of action. At variance, heterozygous null alleles falling in other parts of the same gene cause developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (DEHMBA) syndrome. We report an 18-year-old man with DEHMBA syndrome and obstructive sleep apnea, who underwent exome sequencing (ES) and whole transcriptome sequencing (WTS) on peripheral blood. Trio analysis prioritized the de novo heterozygous c.5658+5 G > A variant. WTS promptly demostrated four different abnormal transcripts affecting >40% of the reads, three of which leading to a frameshift. This study demonstrated the efficacy of a combined ES-WTS approach in solving undiagnosed cases. We also speculated that sleep respiratory disorder may be an underdiagnosed complication of DEHMBA syndrome.

Arginine methylation of SM-LIKE PROTEIN 4 antagonistically affects alternative splicing during Arabidopsis stress responses.

Arabidopsis (Arabidopsis thaliana) PROTEIN ARGININE METHYLTRANSFERASE5 (PRMT5) post-translationally modifies RNA-binding proteins by arginine (R) methylation. However, the impact of this modification on the regulation of RNA processing is largely unknown. We used the spliceosome component, SM-LIKE PROTEIN 4 (LSM4), as a paradigm to study the role of R-methylation in RNA processing. We found that LSM4 regulates alternative splicing (AS) of a suite of its in vivo targets identified here. The lsm4 and prmt5 mutants show a considerable overlap of genes with altered AS raising the possibility that splicing of those genes could be regulated by PRMT5-dependent LSM4 methylation. Indeed, LSM4 methylation impacts AS, particularly of genes linked with stress response. Wild-type LSM4 and an unmethylable version complement the lsm4-1 mutant, suggesting that methylation is not critical for growth in normal environments. However, LSM4 methylation increases with abscisic acid and is necessary for plants to grow under abiotic stress. Conversely, bacterial infection reduces LSM4 methylation, and plants that express unmethylable-LSM4 are more resistant to Pseudomonas than those expressing wild-type LSM4. This tolerance correlates with decreased intron retention of immune-response genes upon infection. Taken together, this provides direct evidence that R-methylation adjusts LSM4 function on pre-mRNA splicing in an antagonistic manner in response to biotic and abiotic stress.

The circadian clock and thermal regulation in plants: novel insights into the role of positive circadian clock regulators in temperature responses.

The impact of rising global temperatures on crop yields is a serious concern, and the development of heat-resistant crop varieties is crucial for mitigating the effects of climate change on agriculture. To achieve this, a better understanding of the molecular basis of the thermal responses of plants is necessary. The circadian clock plays a central role in modulating plant biology in synchrony with environmental changes, including temperature fluctuations. Recent studies have uncovered the role of transcriptional activators of the core circadian network in plant temperature responses. This expert view highlights key novel findings regarding the role of the RVE and LNK gene families in controlling gene expression patterns and plant growth under different temperature conditions, ranging from regular diurnal oscillations to extreme stress temperatures. These findings reinforce the essential role of the circadian clock in plant adaptation to changing temperatures and provide a basis for future studies on crop improvement.

Users' Experience of Public Cancer Screening Services: Qualitative Research Findings and Implications for Public Health System.

Following the One Health approach, designing multidimensional strategies to orient healthcare in promoting health and preventive processes has become paramount. In particular, in the prevention domain, cancer screening attendance is still unsatisfactory in many populations and requires specific consideration. To this end, following a research-intervention logic, this study aims to investigate the experiences and meanings that users of public cancer screening services associate with prevention, particularly participation in the screenings. The experiences of 103 users (96 females; Mage = 54.0; SD = 1.24) of public cancer screening programs in the Campania region (Italy) were collected through interviews. The data collected were analysed following the Grounded Theory Methodology, supported by the software Atlas.ti 8.0. The text material was organised into eight macro-categories: Health and Body; Relationship with Cancer and Diseases; Health Facilities and Health Providers; The Affective Determinants of Cancer Screening Participation; Partners and Children; Physical Sensations and Emotions in the Course of Action; Protective Actions; Promotion and Dissemination. The core category was named Family and Familiarity. Respondents perceived prevention as an act of care for the family and themselves. Our findings support a shift from the idea of taking care of personal health as an individual matter toward considering it as a community issue, according to which resistance to act is overcome for and through the presence of loved ones. The results of this study contribute to a deeper understanding of the perspectives of southern Italian users on participation in cancer screening, and provide important insights to guide future actions to promote these public programmes based primarily on the emerging theme of family and familiarity related to screening programs.

Hereditary coagulation factor XI deficiency: a rare or neglected disease? Results from a retrospective, single-centre cohort in northern Italy.

To examine real-life clinical data regarding hereditary factor XI (FXI) deficiency from a secondary care centre. Retrospective review of clinical records for every FXI:C 0.7 IU/ml or less reported from 2012 to 2020. Seventy-nine patients were included. Six (7.6%) had a severe deficiency (FXI:C <0.2 IU/ml). Only 55 (69.6%) patients were referred to the Haemostasis Centre. Among them, six (15%) were subsequently not identified at increased haemorrhagic risk before a surgical/obstetrical procedure. Thirty-three (41.8%) experienced at least one bleeding event, minor (25 patients) and/or major (16 patients). Minor bleedings were predominantly spontaneous and more frequent in women, major events were mainly provoked. No correlation was found between FXI:C and risk of bleeding ( P  = 0.9153). Lower FXI:C, but not a positive bleeding history, was related with higher likelihood of being referred to the Haemostasis Centre ( P  = 0.0333). Hereditary FXI deficiency prevalence is likely underestimated, real-life clinical practices outside reference centres could be suboptimal.

Therapeutic Approach to Post-Transplant Recurrence of Hepatocellular Carcinoma: Certainties and Open Issues.

Hepatocellular carcinoma (HCC) is a growing indication for liver transplantation (LT). Careful candidate selection is a prerequisite to keep post-LT recurrence rates within acceptable percentages. In the pre-LT period, various types of locoregional treatments and/or systemic therapies can be used for bridging or downstaging purposes. In this context, one of the factors limiting the possibility of treatment is the degree of functional liver impairment. In the LT subject, no widely accepted indications are available to guide treatment of disease recurrence and heterogeneity exists between transplant centers. Improved liver function post LT makes multiple therapeutic strategies theoretically feasible, but patient management is complicated by the need to adjust immunosuppressive therapy and to assess potential toxicities and drug-drug interactions. Finally, there is controversy and uncertainty about the use of recently introduced immunotherapeutic drugs, mainly due to the risk of organ rejection. In this paper, we will review the most recent available literature on the management of post-transplant HCC recurrence, discussing evidence and controversies.

Ceftazidima/avibactam frente a otros antimicrobianos para el tratamiento de bacteriemias por Enterobacterales productores de carbapenemasa KPC: datos de la vida real en un hospital universitario de Argentina / Ceftazidime/avibactam versus other antibiotics for the treatment of KPC carbapenemase-producing Enterobacterales bacteremia: real-life data from a university hospital in Argentina

INTRODUCCIÓN: Las bacteriemias por Enterobacterales productores de carbapenemasa KPC (EPC-KPC) presentan una mortalidad elevada y opciones terapéuticas limitadas. OBJETIVOS: Describir y comparar la evolución de los pacientes con bacteriemia por EPC-KPC tratados con ceftazidima/avibactam (CA) frente a otros antimicrobianos (OA). PACIENTES Y MÉTODOS: Estudio prospectivo y retrospectivo de casos y controles. Se incluyeron pacientes adultos con bacteriemia por EPC-KPC, con una proporción entre casos tratados con CA y controles tratados con OA. de 1:2. Se analizaron variables clínicas, epidemiológicas y de evolución. RESULTADOS: Se incluyeron 48 pacientes (16 CA y 32 OA). Los casos se encontraban más frecuentemente neutropénicos (50 vs.16%, p = 0,012); asimismo, presentaron medianas de score de APACHE II más altas y de score de Pitt más bajas. El 65% de la cohorte total presentó un foco clínico y Klebsiellapneumoniae fue el microorganismo más frecuentemente aislado. Los casos recibieron una mayor proporción de tratamiento antimicrobiano empírico adecuado (81 vs. 53%, p = 0,05). La antibioterapia dirigida en casos y controles fue combinada en 38 y 91%, p = 0,009. Los casos presentaron menor mortalidad al día 7 y al día 30 relacionada a infección (0 vs. 22%, p = 0,04 y 0 vs. 34%, p = 0,008). Solo los controles desarrollaron shock, ingresaron a la unidad de cuidados intensivos y presentaron bacteriemia de brecha. CONCLUSIÓN: CA mostró beneficio clínico frente a OA para el tratamiento de pacientes con bacteriemia por EPC-KPC.

BACKGROUND: KPC-producing Enterobacterales bacteremia (KPCCPE) is associated with a high mortality rate and limited therapeutic options. AIM: To describe and compare the outcome of patients with KPC-CPE bacteremia treated with ceftazidime/avibactam (CA) versus other antibiotics (OA). METHODS: Prospective and retrospective cases and control study performed in adult patients with KPC-CPE bacteremia, with a 1:2 ratio between cases treated with CA. and controls treated with OA. Clinical, epidemiological, and outcome variables were analyzed. RESULTS: Forty-eight patients (16 CA and 32 OA) were included. Cases were more frequently neutropenic (50 vs. 16%, p = 0.012), presented higher median APACHE II score and lower Pitt score. Of the total cohort, 65% had a clinical source, and Klebsiella pneumoniae was the most frequently isolated microorganism. Cases received more adequate empirical antibiotic treatment (81 vs. 53%, p = 0.05). Targeted antibiotic therapy in cases and controls was combined in 38 and 91%, p = 0.009. Cases had a lower 7-day mortality and 30-day infection-related mortality (0 vs. 22%, p = 0.04 and 0 vs. 34%, p = 0.008). Only controls developed shock, were admitted to the intensive care unit, and had breakthrough bacteremia. CONCLUSION: CA. showed clinical benefit over OA in the treatment of patients with EPC-KPC bacteremia.

[Human monkeypox: epidemiological and clinical characteristics of a series of cases]. / Viruela símica humana: características epidemiológicas y clínicas de una serie de casos.

INTRODUCTION: Monkeypox It is a zoonotic disease. The etiologic agent is the monkeypox virus. Since January 1, 2022, monkeypox cases have been reported to the World Health Organization (WHO) in 110 Member States across 6 WHO regions. METHODS: The present work is a descriptive-observational-retrospective cohort in the first instance, and prospective at the end, where the epidemiological characteristics, clinical presentation and complications collected by telephone call on day 28, are described 75 patients diagnosed with monkeypox, confirmed by RT-PCR (corresponding to 7% of the cases reported in Argentina). It was developed between July 12, 2022 and October 6, 2022. RESULTS: The affected population was entirely cisgender men, 70 (93.3%) identified as men who have sex with men (MSM). Fifty-one (68%) were co-infected with HIV, 50 (98%) were receiving ART. All patients presented mucocutaneous manifestations. The rash manifested with a variety of lesions: papular, vesicular, and pustular. In 26 (44.1%) the systemic symptoms presented prior to the appearance of the rash, being the increase in body temperature the most frequent. Thirty-four (45.3%) of the patients reported some complication, with proctitis being the most frequent followed by penile edema. Sequelae were observed in 40 (53.3%), the most frequent being skin scars. CONCLUSION: In this case series we were able to observe mostly mild symptoms, with anogenital lesions being the most frequent clinical presentation. The presence of sequelae, the social and emotional impact of this disease make a multidisciplinary approach necessary.

Introducción: Es una enfermedad zoonótica cuyo agente etiológico es el virus de la viruela símica. Desde el 1 de enero de 2022, se han notificado casos de viruela símica a la Organización Mundial de la Salud (OMS) en 110 Estados Miembros en las 6 regiones de la OMS. Métodos: El presente trabajo es un estudio observacional descriptivo de cohorte retrospectivo en primera instancia, y prospectivo al final, donde se describen las características epidemiológicas, la presentación clínica, y las complicaciones recabadas mediante llamado telefónico al día 28 en 75 pacientes con diagnóstico de viruela símica confirmado por RT-PCR (correspondientes al 7% de los casos notificados en Argentina). Fue desarrollado entre el 12 de julio de 2022 y el 6 de octubre de 2022. Resultados: La población afectada fue en su totalidad hombres cisgénero, 70 (93.3%) identificados como hombres que tienen sexo con hombres (HSH). Cincuenta y uno (68%) estaban coinfectados con HIV, 50 (98%) estaban recibiendo TARV. Todos los pacientes presentaron manifestaciones mucocutáneas. El exantema se manifestó con variedad de lesiones: papulares, vesiculares y pustulosas. En 26 (44.1%) los síntomas sistémicos se presentaron previos a la aparición del exantema, siendo el aumento de la temperatura corporal el más frecuente. Treinta y cuatro (45.3%) de los pacientes reportaron alguna complicación, siendo la proctitis la más frecuente seguida por edema de pene. Se observaron secuelas en 40 (53.3%), siendo la más frecuente las cicatrices cutáneas. Conclusión: En esta serie de casos pudimos observar mayormente cuadros leves, siendo las lesiones anogenitales la presentación clínica más frecuente. La presencia de secuelas, el impacto social y emocional de esta enfermedad hacen necesario un enfoque multidisciplinario.

Unearthed opium: development of a UHPLC-MS/MS method for the determination of Papaver somniferum alkaloids in Daunian vessels.

Introduction: The analysis of organic residue in ancient vessels to investigate early-age civilization habits is an important archeological application that needs advanced analytical methods. However, these procedures should meet inherent requisites such as low sampling invasiveness and high sensitivity for trace analysis. This study deals with the development of advanced analytical methods for the detection of opium alkaloids in ceramic vessels and its first application to the study of Daunian pots dating back to the VIII-IV sec BC. Methods: All the stages of the analytical procedure, from sampling to analysis, were carefully optimized. Concerning sampling, the traditional scraping approach was compared with a swabbing strategy which permitted minimizing sample encroachment. Extraction was based on pressurized liquid extraction or ultrasound-assisted liquid extraction, followed by dispersive liquid-liquid microextraction, which allowed concentration enrichment. On the other hand, a UHPLC-MS/MS method was specifically developed and validated to obtain reliable data. Some Daunian pots, belonging to the Ceci-Macrini private archeological collection, were selected for sample withdrawal as their iconography could suggest opium usage. Results: Several of the analyzed samples resulted positive to thebaine and less frequently to morphine and codeine; furthermore, 70% of the analyzed items tested positive for at least one opium alkaloid. Positive findings were common to all the samples collected in the pots, suggesting that scraping and swabbing provided comparable results and validating this unusual sampling strategy. All samples were additionally analyzed by UHPLC-HRMS to further improve the confidence level of the identified compounds. The obtained results shed new light on the hypothesis of opium usage by the ancient Daunian civilization. Furthermore, this study provided suitable analytical tools for further investigations on the same topic, with a good level of confidence in the quality of the results.

Antiphospholipid Syndrome: State of the Art of Clinical Management.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder clinically characterized by recurrent arterial and venous thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies. Currently, treatment is mainly focused on anticoagulation, but therapies targeting mechanisms involved in APS autoimmune pathogenesis could play an important role in specific settings. An evidence-based therapeutic approach is limited by the broad clinical spectrum of the syndrome and the nature of a "rare disease" that makes it difficult to carry out well-designed prospective studies. Vitamin K antagonists (AVK), notably warfarin, are the standard treatment for preventing recurrent venous thrombosis and perhaps also arterial thrombosis. Direct oral anticoagulants (DOACs) are not recommended at least in patients with triple positivity APS. Treatment options for the prevention of pregnancy complications in obstetric APS, as combined use of aspirin and heparin, low-dose prednisolone, hydroxychloroquine, intravenous immunoglobulin (IVIG), may improve pregnancy outcome. The catastrophic antiphospholipid syndrome (CAPS) is the most severe form of APS with acute multiple organ involvement and small vessel thrombosis. Glucocorticoids, heparin, plasma exchange or IVIG, rituximab, or eculizumab must be added to concurrent treatment of precipitating factors (e.g. infections) as rescue therapies. Finally, it has been observed that SARS COV2 infection may produce vascular complications mimicking the clinical and pathophysiological features of APS and particularly of CAPS. From this point of view, attention has been focused on the "protective" role of anticoagulant therapy in preventing thrombotic complication when these clinical conditions coexist.

Viruela símica humana: características epidemiológicas y clínicas de una serie de casos / Human monkeypox: epidemiological and clinical charac teristics of a series of cases

Resumen Introducción : Es una enfermedad zoonótica cuyo agente etiológico es el virus de la viruela símica. Desde el 1 de enero de 2022, se han notificado casos de viruela símica a la Organización Mundial de la Salud (OMS) en 110 Estados Miembros en las 6 regiones de la OMS. Métodos : El presente trabajo es un estudio observa cional descriptivo de cohorte retrospectivo en primera instancia, y prospectivo al final, donde se describen las características epidemiológicas, la presentación clínica, y las complicaciones recabadas mediante llamado telefó nico al día 28 en 75 pacientes con diagnóstico de viruela símica confirmado por RT-PCR (correspondientes al 7% de los casos notificados en Argentina). Fue desarrollado entre el 12 de julio de 2022 y el 6 de octubre de 2022. Resultados : La población afectada fue en su totalidad hombres cisgénero, 70 (93.3%) identificados como hom bres que tienen sexo con hombres (HSH). Cincuenta y uno (68%) estaban coinfectados con HIV, 50 (98%) esta ban recibiendo TARV. Todos los pacientes presentaron manifestaciones mucocutáneas. El exantema se mani festó con variedad de lesiones: papulares, vesiculares y pustulosas. En 26 (44.1%) los síntomas sistémicos se presentaron previos a la aparición del exantema, siendo el aumento de la temperatura corporal el más frecuente. Treinta y cuatro (45.3%) de los pacientes reportaron algu na complicación, siendo la proctitis la más frecuente se guida por edema de pene. Se observaron secuelas en 40 (53.3%), siendo la más frecuente las cicatrices cutáneas. Conclusión : En esta serie de casos pudimos observar mayormente cuadros leves, siendo las lesiones anogeni tales la presentación clínica más frecuente. La presencia de secuelas, el impacto social y emocional de esta enfer medad hacen necesario un enfoque multidisciplinario.

Abstract Introduction : Monkeypox It is a zoonotic disease. The etiologic agent is the monkeypox virus. Since January 1, 2022, monkeypox cases have been reported to the World Health Organization (WHO) in 110 Member States across 6 WHO regions. Methods : The present work is a descriptive-ob servational-retrospective cohort in the first instance, and prospective at the end, where the epidemiological characteristics, clinical presentation and complications collected by telephone call on day 28, are described 75 patients diagnosed with monkeypox, confirmed by RT-PCR (corresponding to 7% of the cases reported in Argentina). It was developed between July 12, 2022 and October 6, 2022. Results : The affected population was entirely cis gender men, 70 (93.3%) identified as men who have sex with men (MSM). Fifty-one (68%) were co-infected with HIV, 50 (98%) were receiving ART. All patients presented mucocutaneous manifestations. The rash manifested with a variety of lesions: papular, vesicular, and pustular. In 26 (44.1%) the systemic symptoms presented prior to the appearance of the rash, being the increase in body temperature the most frequent. Thirty-four (45.3%) of the patients reported some complication, with proctitis being the most frequent followed by penile edema. Se quelae were observed in 40 (53.3%), the most frequent being skin scars. Conclusion: In this case series we were able to ob serve mostly mild symptoms, with anogenital lesions being the most frequent clinical presentation. The pres ence of sequelae, the social and emotional impact of this disease make a multidisciplinary approach necessary.

Efficacy of Burosumab Every 2 Weeks in an Adult with X-Linked Hypophosphatemia: Should We Learn from Children?

X-linked hypophosphatemia is a genetic condition that leads to fibroblast-growth-factor 23 (FGF23) increase, causing phosphate renal wasting. Since 2018, burosumab, an anti-FGF23 antibody, has been used for this disease with different dosage in children and adults. We report the case of burosumab administration every 2 weeks, as usually done in children. We retrospectively evaluated parathormone (PTH), alkaline phosphatase, serum phosphate, tubular reabsorption of phosphate (TRP), and 25OH vitamin D every 2 weeks in a 29-year-old man with nephrocalcinosis and tertiary hyperparathyroidism who did not respond to standard treatment with burosumab nor to maximum dosage and was treated with burosumab 90 mg every 2 weeks. His serum phosphate and TRP increased with this regimen compared with 4 weeks frequency (respectively 1.74 ± 0.26 mg/dL vs. 2.3 ± 0.19 mg/dL [p 0.0004] and 71.3% ± 4.8% vs. 83.9% ± 7.9% [p 0.01]) with decrease in PTH (183 ± 24.7 pg/mL vs. 109 ± 12.2 pg/mL [p 0.04]). Burosumab may be a good choice in adult patients with X-linked hypophosphatemia; new data are needed regarding the increase in dosage and/or frequency of administration as usually done in children, to achieve disease control.

Solar clock and school start time effects on adolescents' chronotype and sleep: A review of a gap in the literature.

Circadian rhythms are entrained by external factors such as sunlight and social cues, but also depend on internal factors such as age. Adolescents exhibit late chronotypes, but worldwide school starts early in the morning leading to unhealthy sleep habits. Several studies reported that adolescents benefit from later school start times. However, the effect of later school start time on different outcomes varies between studies, and most previous literature only takes into consideration the social clock (i.e. local time of school starting time) but not the solar clock (e.g. the distance between school start time and sunrise). Thus, there is an important gap in the literature: when assessing the effect of a school start time on chronotype and sleep of adolescents at different locations and/or seasons, the solar clock might differ and, consistently, the obtained results. For example, the earliest school start time for adolescents has been suggested to be 08:30 hours, but this school start time might correspond to different solar times at different times of the year, longitudes and latitudes. Here, we describe the available literature comparing different school start times, considering important factors such as geographic position, nationality, and the local school start time and its distance to sunrise. Then, we described and contrasted the relative role of both social and solar clocks on the chronotype and sleep of adolescents. As a whole, we point and discuss a gap in literature, suggesting that both clocks are relevant when addressing the effect of school start time on adolescents' chronotype and sleep.

A better alignment between chronotype and school timing is associated with lower grade retention in adolescents.

Schools start early in the morning all over the world, contrasting with adolescents' late chronotype. Interestingly, lower academic performance (i.e. grades or qualifications) was associated with later chronotypes. However, it is unclear whether it is a direct effect of chronotype or because students attend school too early to perform at their best. Moreover, little is known about how this affects students' academic success beyond their grades. To address this gap in knowledge, we studied how school timing and chronotype affect grade retention (i.e. repeat a year) in a unique sample of students randomly assigned to one of three different school timings (starting at 07:45, 12:40, or 17:20). Even when controlling for academic performance, we found that later chronotypes exhibit higher odds of grade retention only in the morning, but not in later school timings. Altogether, ensuring a better alignment between school timing and students' biological rhythms might enhance future opportunities of adolescents.

Specifications and validation of the ACMG/AMP criteria for clinical interpretation of sequence variants in collagen genes associated with joint hypermobility.

Deleterious variants in collagen genes are the most common cause of hereditary connective tissue disorders (HCTD). Adaptations of the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria are still lacking. A multidisciplinary team was set up for developing specifications of the ACMG/AMP criteria for COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL11A1, COL11A2 and COL12A1, associated with various forms of HCTD featuring joint hypermobility, which is becoming one of the most common reasons of referral for molecular testing in this field. Such specifications were validated against 209 variants, and resulted effective for classifying as pathogenic and likely pathogenic null alleles without downgrading of the PVS1 level of strength and recurrent Glycine substitutions. Adaptations of selected criteria reduced uncertainties on private Glycine substitutions, intronic variants predicted to affect the splicing, and null alleles with a downgraded PVS1 level of strength. Segregation and multigene panel sequencing data mitigated uncertainties on non-Glycine substitutions by the attribution of one or more benignity criteria. These specifications may improve the clinical utility of molecular testing in HCTD by reducing the number of variants with neutral/conflicting interpretations. Close interactions between laboratory and clinicians are crucial to estimate the a priori utility of molecular test and to improve medical reports.

Standardized nailfold capillaroscopy in children with rheumatic diseases: a worldwide study.

OBJECTIVES: To standardly assess and describe nailfold videocapillaroscopy (NVC) assessment in children and adolescents with juvenile rheumatic and musculoskeletal diseases (jRMD) vs healthy controls (HCs). MATERIAL AND METHODS: In consecutive jRMD children and matched HCs from 13 centres worldwide, 16 NVC images per patient were acquired locally and read centrally per international consensus standard evaluation of the EULAR Study Group on Microcirculation in Rheumatic Diseases. A total of 95 patients with JIA, 22 with JDM, 20 with childhood-onset SLE (cSLE), 13 with juvenile SSc (jSSc), 21 with localized scleroderma (lSc), 18 with MCTD and 20 with primary RP (PRP) were included. NVC differences between juvenile subgroups and HCs were calculated through multivariable regression analysis. RESULTS: A total of 6474 images were assessed from 413 subjects (mean age 12.1 years, 70.9% female). The quantitative NVC characteristics were significantly lower or higher in the following subgroups compared with HCs: for density: lower in jSSc, JDM, MCTD, cSLE and lSc; for dilations: higher in jSSc, MCTD and JDM; for abnormal shapes: higher in JDM and MCTD; for haemorrhages: higher in jSSc, MCTD, JDM and cSLE. The qualitative NVC assessment of JIA, lSc and PRP did not differ from HCs, whereas the cSLE and jSSc, MCTD, JDM and cSLE subgroups showed more non-specific and scleroderma patterns, respectively. CONCLUSIONS: This analysis resulted from a pioneering registry of NVC in jRMD. The NVC assessment in jRMD differed significantly from HCs. Future prospective follow-up will further elucidate the role of NVC in jRMD.