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Abstract Background Facioscapulohumeral dystrophy (FSHD) is a myopathy characterized by the loss of repressive epigenetic features affecting the D4Z4 locus (4q35). The assessment of DNA methylation at two regions (DUX4-PAS and DR1) of D4Z4 locus proved to be an effective method to detect epigenetic signatures compatible with FSHD. The present study aims at validating the employment of this method into clinical practice and improving the protocol by refining the classification thresholds of 4qA/4qA patients. To this purpose, 218 subjects with clinical suspicion of FSHD collected in 2022–2023 were analyzed. Each participant underwent in parallel the traditional FSHD molecular testing (D4Z4 sizing) and the proposed methylation assay. The results provided by both analyses were compared to evaluate the concordance and calculate the performance metrics of the methylation test. Results Among the 218 subjects, the 4q variant type distribution was 54% 4qA/4qA, 43% 4qA/4qB and 3% 4qB/4qB. The methylation analysis was performed only on carriers of at least one 4qA allele. After refining the classification threshold, the test reached the following performance metrics: sensitivity = 0.90, specificity = 1.00 and accuracy = 0.93. These results confirmed the effectiveness of the methylation assay in identifying patients with genetic signature compatible with FSHD1 and FSHD2 based on their DUX4-PAS and DR1 profile, respectively. The methylation data were also evaluated with respect to the clinical information. Conclusions The study confirmed the ability of the method to accurately identify methylation profiles compatible with FSHD genetic signatures considering the 4q genotype. Moreover, the test allows the detection of hypomethylated profiles in asymptomatic patients, suggesting its potential application in identifying preclinical conditions in patients with positive family history and FSHD genetic signatures. Furthermore, the present work emphasizes the importance of interpreting methylation profiles considering the patients’ clinical data.

Objective: Researchers collaborated with undergraduate minority students to quantitatively and qualitatively investigate college students' mental health during the first year of the COVID-19 pandemic. Participants: Participants were two convenience samples of diverse college students surveyed in June (n = 128; M age = 21.7, SD = 1.7) and December (n = 242; M age = 20.3, SD = 1.7) of 2020. Methods: This study administered items from the California Health Interview Survey and open-ended qualitative items via Qualtrics. Results: Across both waves, students reported significant mental health challenges and psychological distress. Students surveyed in December were three to four times more likely to report depression and anxiety. Female and older students reported heightened odds of mental health challenges. Qualitative findings elaborated on contributing factors. Conclusion: During the pandemic, college students have experienced pronounced mental health challenges, potentially exacerbated by academic, professional, relational, and environmental stressors and uncertainty.

OBJETIVO: Estabelecer um modelo experimental de cultura primária de melanoma metastático por punção aspirativa por agulha fina (PAAF). MÉTODOS: Duas culturas primárias de células de melanoma metastático através de PAAF foram desenvolvidas a partir de pacientes submetidos à excisão de lesões metastáticas e identificadas por imunohistoquímica utilizando os marcadores S-100 e MB-45, específicos para melanoma. RESULTADOS: O diagnóstico da cultura foi confirmado através da imunohistoquímica. A técnica oferece vantagens como pequena morbidade e invasibilidade, além do mais, a mesma lesão pode ser puncionada seqüencialmente durante o tratamento do doente. CONCLUSÃO: O estabelecimento de cultura primária de melanoma metastático a partir de punção aspirativa por agulha fina mostrou-se uma técnica viável.

Introdução: Os pacientes com queimaduras extensas apresentam imunossupressão por longo período, além de perda da barreira da pele, uso de dispositivos invasivos e tempo de internação prolongado, tornando-os mais suscetíveis às infecções relacionadas à assistência à saúde (IRAS). Objetivo: Avaliar o perfil microbiológico e os principais microrganismos isolados nas IRAS identificadas em pacientes internados em uma unidade de tratamento de queimaduras. Método: Estudo de coorte realizado em hospital de ensino na cidade de São Paulo, no período de janeiro de 2020 a dezembro de 2023, na unidade de tratamento de queimaduras, composta por seis leitos de enfermaria e quatro de UTI. Resultados: Foram internados 450 pacientes no período, totalizando 9858 pacientes-dia. Nesse período, foram notificados 109 casos de IRAS (11,05 IRAS/1000 paciente-dia), sendo a infecção da área queimada a mais prevalente (32,1%), seguida de infecção primária de corrente sanguínea com e sem dispositivo (29,4%) e pneumonia associada à ventilação mecânica (13,8%). Entre os patógenos identificados temos: 71,1% (n = 86) Gram-negativos; 23,1% (n = 28) Gram-positivos e 5,8% (n = 7) fungos. Os microrganismos mais prevalentes foram: Acinetobacter baumannii (19,8%, n = 24); Klebsiella pneumoniae (19,8%, n = 24); Pseudomonas aeruginosa (19,8%, n = 24); Staphylococcus aureus (9,1%, n = 11) e Enterococcus faecalis (5,7%, n = 7). Em relação ao perfil de sensibilidade, os Gram-negativos apresentaram resistência aos carbapenêmicos em 51,2% (n = 44) e a polimixina B em 15,1% (n = 13). Entre os Gram-positivos, 72,7% (n = 8) dos Staphylococcus aureus foram resistentes à oxacilina. Conclusão: As infecções de área queimada e primária de corrente sanguínea com e sem dispositivo são as mais prevalentes em pacientes queimados, sendo causadas principalmente por Gram-negativos. Acinetobacter baumannii, Klebsiella pneumoniae e Pseudomonas aeruginosa foram os microrganismos com maior incidência, com resistência aos carbapenêmicos em mais da metade dos casos. S. aureus tiveram alta taxa de resistência à oxacilina.

In the United States, autistic individuals experience disproportionate physical and mental health challenges relative to non-autistic individuals, including higher rates of co-occurring and chronic conditions and lower physical, social, and psychological health-related quality of life. The Autism Intervention Research Network on Physical Health (AIR-P) is an interdisciplinary, multicenter research network for scientific collaboration and infrastructure that aims to increase the life expectancy and quality of life for autistic individuals, with a focus on underserved or vulnerable populations. The current paper describes the development of the AIR-P Research Agenda. Development of the research agenda involved an iterative and collaborative process between the AIR-P Advisory Board, Steering Committee, and Autistic Researcher Review Board. The methodology consisted of 3 phases: (1) ideation and design, (2) literature review and synthesis; and (3) network engagement. Six core research priorities related to the health of autistic individuals were identified: (1) primary care services and quality, (2) community-based lifestyle interventions, (3) health systems and services, (4) gender, sexuality, and reproductive health, (5) neurology, and (6) genetics. Specific topics within each of these priorities were identified. Four cross-cutting research priorities were also identified: (1) neurodiversity-oriented care, (2) facilitating developmental transitions, (3) methodologically rigorous intervention studies, and (4) addressing health disparities. The AIR-P Research Agenda represents an important step forward for enacting large-scale health-promotion efforts for autistic individuals across the lifespan. This agenda will catalyze autism research in historically underrepresented topic areas while adopting a neurodiversity-oriented approach to health-promotion.

Obituary for Franco Fido

Chronic hepatitis B (HBV), alongside hepatitis D virus (HDV) super-/co-infection and chronic hepatitis C (HCV), are major contributors to cirrhosis, end-stage liver disease, hepatocellular carcinoma (HCC), and liver-related mortality. Despite significant progress in antiviral treatments and HBV vaccination, viral hepatitis remains a global health burden. Vulnerable populations, such as those experiencing homelessness, migrants, and economically disadvantaged groups, are disproportionately impacted by these infections, often facing barriers to care and exclusion from traditional health systems. This leads to undiagnosed cases and ongoing transmission, undermining global efforts to eliminate HBV and HCV by 2030, as outlined by the World Health Organization (WHO). Recent studies highlight the importance of tailored interventions to address health inequalities. For instance, on-site community-based screening initiatives targeting marginalized groups have shown promise, achieving higher linkage to care rates without monetary incentives. These approaches not only enhance diagnosis but also facilitate integration into healthcare systems, addressing both public health and social disparities. This review underscores the need for targeted strategies to promote the early detection and management of HBV and HCV in underserved populations. Such efforts are critical to advancing the WHO's elimination goals, improving health outcomes, and addressing the broader social determinants of health. [ABSTRACT FROM AUTHOR]

ObjectiveHepatitis B virus (HBV) infection causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Furthermore, about 20% of the patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV), polyarteritis nodosa, non-rheumatoid arthritis, glomerulonephritis and non-Hodgkin lymphoma. This review analyzed literature data on clinical manifestations of HBV-related CV and the impact of antiviral therapy with analoques nucleotide.MethodsA PubMed search was performed to select eligible studies in the literature, up to July 2022.ResultsSome studies have analyzed clinical manifestations in HBV-related CV and have investigated the role of antiviral therapy with nucleotides analogues (NAs). Clinical manifestations of CV vary from mild to moderate (purpura, asthenia and arthralgias) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, and non-Hodking lymphoma). NAs therapy leads to suppression of HBV-DNA; therefore, it is capable of producing clinical response in the majority of patients with mild to moderate symptoms.ConclusionAntiviral therapy with NAs is the first choice for HBV suppression and control of mild to moderate disease. In severe vasculitis (glomerulonephritis, progressive peripheral neuropathy and leg ulcers), rituximab alone or with plasma-exchange is always indicated in combination with antiviral therapy.

IntroductionAdvances in the operational mode of the cerebellum indicate a role in sequencing and predicting non-social and social events, crucial for individuals to optimize high-order functions, such as Theory of Mind (ToM). ToM deficits have been described in patients with remitted bipolar disorders (BD). The literature on BD patients’ pathophysiology reports cerebellar alterations; however, sequential abilities have never been investigated and no study has previously focused on prediction abilities, which are needed to properly interpret events and to adapt to changes.MethodsTo address this gap, we compared the performance of BD patients in the euthymic phase with healthy controls using two tests that require predictive processing: a ToM test that require implicit sequential processing and a test that explicitly assesses sequential abilities in non-ToM functions. Additionally, patterns of cerebellar gray matter (GM) alterations were compared between BD patients and controls using voxel-based morphometry.ResultsImpaired ToM and sequential skills were detected in BD patients, specifically when tasks required a greater predictive load. Behavioral performances might be consistent with patterns of GM reduction in cerebellar lobules Crus I-II, which are involved in advanced human functions.DiscussionThese results highlight the importance of deepening the cerebellar role in sequential and prediction abilities in patients with BD.

IntroductionHepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV specificity. These cells display an atypical CD21low phenotype and functional exhaustion evidenced by unresponsiveness to BCR and Toll-like receptor 9 (TLR9) stimuli. Although antiviral therapy is effective on MC vasculitis, pathogenic B cell clones persist long thereafter and can cause virus-independent disease relapses.MethodsClonal B cells from patients with HCV-associated type 2 MC or healthy donors were stimulated with CpG or heath-aggregated IgG (as surrogate immune complexes) alone or in combination; proliferation and differentiation were then evaluated by flow cytometry. Phosphorylation of AKT and of the p65 NF-kB subunit were measured by flow cytometry. TLR9 was quantified by qPCR and by intracellular flow cytometry, and MyD88 isoforms were analyzed using RT-PCR.DiscussionWe found that dual triggering with autoantigen and CpG restored the capacity of exhausted VH1-69pos B cells to proliferate. The signaling mechanism for this BCR/TLR9 crosstalk remains elusive, since TLR9 mRNA and protein as well as MyD88 mRNA were normally expressed and CpG-induced phosphorylation of p65 NF-kB was intact in MC clonal B cells, whereas BCR-induced p65 NF-kB phosphorylation was impaired and PI3K/Akt signaling was intact. Our findings indicate that autoantigen and CpG of microbial or cellular origin may unite to foster persistence of pathogenic RF B cells in HCV-cured MC patients. BCR/TLR9 crosstalk might represent a more general mechanism enhancing systemic autoimmunity by the rescue of exhausted autoreactive CD21low B cells.

The literature on social cognition abilities in bipolar disorder (BD) is controversial about the occurrence of theory of mind (ToM) alterations. In addition to other cerebral structures, such as the frontal and limbic areas, the processing of socially relevant stimuli has also been attributed to the cerebellum, which has been demonstrated to be involved in the above-mentioned disorder. Nevertheless, the cerebellar contribution to ToM deficits in bipolar patients needs to be elucidated further. To this aim, two tests assessing different components of ToM were used to evaluate the ability to appreciate affective and mental states of others in 17 individuals with a diagnosis of BD type 1 (BD1) and 13 with BD type 2 (BD2), both in the euthymic phase, compared to healthy matched controls. Cerebellar gray matter (GM) volumes were extracted and compared between BD1 and controls and BD2 and controls by using voxel-based morphometry. The results showed that BD1 patients were compromised in the cognitive and advanced components of ToM, while the BD2 ToM profile resulted in a more widespread compromise, also involving affective and automatic components. Both overlapping and differing areas of cerebellar GM reduction were found. The two groups of patients presented a pattern of GM reduction in cerebellar portions that are known to be involved in the affective and social domains, such as the vermis and Crus I and Crus II. Interestingly, in both BD1 and BD2, positive correlations were detected between lower ToM scores and decreased volumes in the cerebellum. Overall, BD2 patients showed a more compromised ToM profile and greater cerebellar impairment than BD1 patients. The different patterns of structural abnormalities may account for the different ToM performances evidenced, thus leading to divergent profiles between BD1 and BD2.

Introdução: Embora o tratamento do câncer de cabeça e pescoço tenha evoluído nos últimos anos, ainda é um desafio preservar e restaurar a simetria facial após o mesmo, comprometendo significativamente a qualidade de vida dos pacientes. Em cirurgia reconstrutiva, o enxerto de gordura autóloga vem sendo usado para tratar defeitos de volume e de contorno. O objetivo é revisar os efeitos do enxerto de gordura em pacientes com radiodermite, devido ao tratamento radioterápico de câncer de cabeça e pescoço. Métodos: Revisão de literatura nas bases PubMed e SciELO, buscando estudos publicados nos últimos 20 anos nas línguas portuguesa, inglesa ou espanhola. Foram utilizados os descritores "adipose tissue", "transplantation", "neoplasms", "head and neck neoplasms" e "radiotherapy"; e os termos não descritores "fat grafting", "fat transplantation" e "fat graft". Resultados: De 212 artigos encontrados, apenas 7 estavam em conformidade aos critérios de elegibilidade. Conclusão: A revisão sugere que a lipoenxertia em reconstrução oncológica de cabeça e pescoço é um tratamento seguro e permite otimizar os resultados estéticos e funcionais. Faltam estudos prospectivos para melhor definição de técnicas e de resultados.