Search Results for: Scoperte le cause biologiche della depressione

We read with interest the Australian inflammatory bowel disease (IBD) consensus statements for pregnancy by Laube et al, which highlights that patients with IBD in the active stage have reduced fertility with unclear reasons.1 IBD, encompassing ulcerative colitis (UC) and Crohn’s disease (CD), involves gut microbiota and metabolites as key players in its development.2 A recent study revealed ovarian impairment in CD, while polycystic ovary syndrome (PCOS) is a common cause of ovarian dysfunction and infertility in women.3 4 Mounting evidence supported an association between gut microbiota and ovarian function,5 and our recent work revealed that gut microbiota was involved in the pathogenesis of PCOS.6 7 Therefore, we speculated that IBD may induce PCOS by disrupting gut microbiota, leading to alterations in plasma metabolites. Initially, we performed a phenome-wide Mendelian randomisation (MR) analysis based on…

Alcohol-associated liver disease (ALD) is a leading cause of chronic liver disease and liver-related mortality worldwide. The progression of ALD can range from simple fatty liver (steatosis) to severe liver damage, including alcohol-associated hepatitis (AH), liver fibrosis or cirrhosis, and hepatocellular carcinoma.1 Research over the past few decades has shown that the mechanisms behind the development of ALD are complex, involving multiple cellular factors and interactions between different organs. At the cellular level, alcohol and its metabolites, such as acetaldehyde, can lead to the production of reactive oxygen species, increase in endoplasmic reticulum stress, mitochondrial damage and megamitochondria formation, impaired autophagy-lysosomal functions, and the accumulation of Mallory-Denk bodies resulting in hepatocyte death and degeneration, as well as increased infiltration of immune cells, particularly neutrophils with high IL-8 expression.1 2 Consequently, these changes also contribute to an increased ductular reaction (DR) and cholestasis, fibrosis,…

Introduction
Severe perinatal asphyxia at term or near term remains a critical public health issue, associated with high risks of neonatal death and hypoxic-ischaemic encephalopathy (HIE). Despite improved clinical guidelines, suboptimal care persists in many cases, and previous audits have demonstrated that up to 50% of asphyxia cases could be associated with suboptimal care. OptiNeoCare is a French study which aims to assess the prevalence and determinants of suboptimal obstetric and neonatal care and evaluate its potential impact on neonatal outcomes.

Materials and methods
This prospective, population-based observational study will include newborns ≥36 weeks’ gestation with severe perinatal asphyxia across 12 French perinatal networks (213 maternity units). Inclusion criteria comprise neonatal death or moderate/severe HIE with confirmed biochemical markers of asphyxia. Data will be collected prospectively from labour wards, transport teams and neonatal intensive care units using an electronic case report form, and the in-situ team will be invited to complete a morbi-mortality review (MMR). Approximately 336 cases will be included over 12 months, with 25% randomly selected for confidential enquiry by two experts. The quality of care will be assessed based on a structured classification of medical errors (diagnostic, therapeutic, preventive and systemic) by a panel of experts including an obstetrician or midwife and a paediatrician. Root cause analysis will identify determinants of suboptimal care. A concordance analysis will compare findings from MMRs and confidential enquiries. Statistical analysis will include multivariable logistic regression to explore associations between care quality and neonatal outcomes.

Ethics and dissemination
Ethical approval was granted by the Ethics Committee for Research in Obstetrics and Gynaecology. Informed non-opposition is required from participants. Results will be shared with participating centres, healthcare professionals and through scientific dissemination.

Trial registration number
ClinicalTrials.gov ID: NCT06322732.

Objectives
To review the available evidence of screening for atherosclerosis in adults in a primary prevention setting with coronary artery calcium scoring (CACS) on the impact on cardiovascular (CV) risk factor control, health behaviour and clinical events.

Design
Systematic review, reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources
We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials through 22 January 2025.

Eligibility criteria
We included randomised controlled trials (RCTs) and prospective cohorts, without language restrictions, comparing adults without cardiovascular diseases undergoing CACS to a control group that either did not undergo CACS or where the participants and physicians were blinded to its result. Outcomes included changes in CV risk factor control, CV therapy, changes in health behaviour at follow-up and clinical events (all-cause and CV mortality and non-fatal CV events).

Data extraction and synthesis
Two independent reviewers extracted data and assessed the risk of bias. Due to substantial heterogeneity among the included studies, a quantitative analysis was not possible.

Results
We identified seven RCTs and one observational study, with participants ranging from 56 to 43 447 with a total of 51 554. Populations were heterogeneous with a mean age range of 42–64 years, % women ranging from 21% to 100% and mean baseline CACS from 1.37 to >100 Agatston units. Interventions following CACS were also heterogeneous, ranging from simply communicating results to participants to initiating statin therapy for detectable CACS. One RCT demonstrated improvement regarding blood pressure (BP) (n=2137; change in systolic BP: CACS: –5 mm Hg; control: –7 mm Hg; p=0.02), several an improvement in blood lipids between groups (five studies, n=3693; eg, low-density lipoprotein (LDL) cholesterol: range –6.0 to –4.9 mg/dL). Results regarding CV medication (seven studies, n=51 104) were more discrepant, with some studies showing a decrease and others an increase in indication for or usage of CV medication. Three trials (n=3338) investigated adherence to CV medication, with only one showing increased adherence to statins (CACS: 63.3%; control: 45.6%; p=0.03). Five trials (n=3692) investigated behavioural changes, with one showing an increased motivation to change lifestyle (CACS: 94%; control: 62.8%; p=0.002) and another a higher adherence in self-reported physical activity (CACS: 96%; control: 59%; p

Objectives
Elevated left ventricular end-diastolic pressure (LVEDP) in ST-segment elevation myocardial infarction (STEMI) has been studied in patients who received thrombolysis or who were treated early in the primary percutaneous coronary intervention (PCI) era; LVEDP was found to be a predictor of adverse outcomes in these retrospective post hoc analyses. The aim of the current analysis is to assess the prognostic value of the elevated LVEDP in STEMI patients undergoing primary PCI in current contemporary practice.

Design
Prospective, single-centre study.

Participants
Our study enrolled STEMI patients with elevated LVEDP undergoing primary PCI at John Hunter Hospital, Newcastle, Australia.

Primary outcome measure
The primary endpoint was the combination of 12-month all-cause mortality and heart failure admissions, comparing different quartiles of LVEDP.

Results
A total of 997 patients underwent primary PCI at our hospital during the 5-year study period (age: 64±13 years, males: 73%; n=728) from 1 January 2015 to 31 December 2019. The median LVEDP for the whole cohort was 27 mm Hg (IQR: 22–31 mm Hg). The median LVEDP was 17 mm Hg (IQR: 13–18 mm Hg) and 33 mm Hg (IQR: 30–36 mm Hg) for 1st and 4th quartiles respectively (p

In un mondo sempre più dominato dagli smartphone e dai tablet, il benessere mentale degli adolescenti potrebbe pagare un prezzo molto alto. Una nuova ricerca dell’Università di Pittsburgh, pubblicata su…

Objectives
To evaluate how insurance influences the risk of a dementia diagnosis among a large, diverse cohort of US civilian adults with traumatic brain injury (TBI) over a 22-year period.

Design
This is a retrospective cohort study involving individuals diagnosed with TBI.

Setting
The study used the Merative MarketScan Research Database, specifically drawing from the Commercial Claims and Encounters, Medicare Supplemental and Medicaid databases, from 2000 to 2022 in the USA. These databases provide comprehensive insights into healthcare services received by enrollees, including inpatient and outpatient services, outpatient prescription claims, clinical utilisation records and healthcare expenditures.

Participants
267 473 adults aged 55 and older who were diagnosed with a TBI between 1 January 2000 and 31 December 2022. Individuals with unknown TBI severity and dementia claims 2 years preceding TBI were excluded. TBI and dementia diagnoses were identified using International Classification of Disease 9th and 10th editions codes from inpatient and outpatient admission records.

Interventions
None.

Primary and secondary outcome measures
We compared the incidence of all-cause dementia across different insurance types to assess potential disparities in diagnosis following TBI. Cox proportional hazards models, with age as the time scale, were used to study the association between insurance type and dementia diagnosis following a TBI. Models were adjusted for key demographic variables, medical comorbidities and psychiatric conditions to account for potential confounding.

Results
Of the 267 473 individuals with TBI, 12.7% were diagnosed with dementia over a mean follow-up period of 40 months (SD of 42 months). Dementia incidence differed significantly by insurance type, with 18.2% for Medicaid recipients, 17.3% for Medicare beneficiaries and only 2.3% among individuals with commercial insurance. The adjusted HR for dementia was notably higher among individuals enrolled on Medicaid (HR 2.9, 95% CI: 2.8 to 3.1) and Medicare (HR 2.1, 95% CI: 2.0 to 2.2), when compared with those with commercial insurance.

Conclusions
Individuals with TBI covered by Medicaid and Medicare are significantly more likely to be diagnosed with dementia, with a 2.9-fold and 2.1-fold increase risk, respectively, compared with those with commercial insurance. Addressing insurance-related disparities in dementia diagnosis is crucial for building a more equitable healthcare system. It is essential that individuals with TBI cases, regardless of their insurance type, have access to comprehensive care and preventive interventions to achieve the best possible long-term outcomes.

Background
Human papillomavirus (HPV) is the most common cause of cervical cancer in women. However, among adolescent boys, initial exposure to HPV is associated with a higher risk of developing oropharyngeal and oral cancers compared with girls. Notably, the incidence of oropharyngeal cancer has been rising sharply in high-income countries, yet HPV vaccination coverage among adolescent boys remains suboptimal. Therefore, understanding the perceptions of adolescent boys and their parents regarding HPV vaccination in high-income countries is crucial for the development of effective public health strategies.

Objectives
This scoping review aims to explore the perceptions of adolescent boys and their parents regarding HPV vaccination and investigate the facilitating factors and barriers influencing HPV vaccination.

Methods and analysis
The method framework of Arksey and O’Malley, the Joanna Briggs Institute, as well as the recommendations of Levac will be used to conduct the scoping review. This scoping review will be reported in accordance with the PRISMA extension for scoping reviews checklist. A systematic literature search will be performed on Ovid-MEDLINE, CINAHL, Cochrane CENTRAL, Ovid-Embase, PsycINFO and Web of Science. Two reviewers will independently perform the study selection and data extraction. Identified studies will be extracted using a customised extraction template on Covidence and analysed descriptively using narrative synthesis. The review commenced in April 2024 and will be completed in July 2025.

Ethics and dissemination
Formal ethical approval is not required, as primary data will not be collected for this study. The findings will be disseminated through publication in a peer-reviewed journal.

Registration
This protocol has been registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/M5NH2).

Conferma da Izs Teramo, nei giorni scorsi 2 casi su cornacchie

Annals of Internal Medicine, Ahead of Print.

This JAMA Patient Page describes hantavirus infection and the syndromes it can cause, as well as treatment options and prevention measures.

Despite a significant decline in colorectal cancer (CRC) incidence and mortality over the past several decades in the US, CRC remains the second leading cause of cancer deaths. Most of these deaths could be prevented if the 42% of Americans aged 45 to 75 years who are not up to date with screening would participate. There is strong evidence supporting screening with lower intestinal endoscopy (ie, colonoscopy or flexible sigmoidoscopy) or repeated rounds of occult blood–based stool screening tests. These screening tests are effective in detecting cancer at early, curable stages as well as preventing cancer through detection and removal of advanced precancerous lesions, including adenomas and serrated colorectal lesions. Despite public awareness campaigns, organized screening (eg, programmatic mailed stool-based tests), and patient decision aids and navigation, participation is suboptimal, and closing the screening gap remains elusive. This gap may result from reluctance to complete screening due to inconvenience, discomfort, embarrassment, aversion to handling stool, or fear of complications. The ideal CRC screening test would be noninvasive and acceptable to those being screened, be highly sensitive for both early cancer and advanced precancerous lesions, have excellent specificity, and be widely accessible. All of the currently available CRC screening test options fall short of this ideal in at least 1 way, limiting their effectiveness. Thus, there is an ongoing search for more agreeable screening test options.

This cohort study evaluates whether discontinuation of antipsychotic medication after hospital discharge, compared with antipsychotic medication continuation, is associated with reduced risk of rehospitalization and all-cause mortality among older adults with hospitalization-related delirium.

Introduction
Sleep disturbance is prevalent in pregnancy and can result in significant adverse outcomes for women and their infants. Numerous clinical trials of various nonpharmacotherapies for preventing or treating sleep disturbances have been conducted previously; however, previous systematic reviews with direct comparisons have failed to demonstrate the best options for different kinds of treatments. This systematic review and network meta-analysis (NMA) aims to explore the comparative efficacy and acceptability of nonpharmacological interventions for sleep disturbances in pregnancy and to assist clinical decision-making through ranking interventions concerning critical clinical outcomes.

Methods and analysis
We will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Two reviewers will systematically search five major bibliographic databases (PubMed, Embase, Cochrane Library, Web of Science and Cumulative Index to Nursing and Allied Health Literature) and registries for published and unpublished randomised controlled trials (RCTs) of any nonpharmacological interventions for sleep disturbances from inception to 24 June 2025. To ensure the search is up to date, we will also perform an updated search up to the time of final analysis submission. Primary outcomes will consider efficacy (the overall mean change of any predefined sleep disturbances, including sleep quality, sleep duration and sleep-specific symptoms) and acceptability (all-cause discontinuation). The risk of bias of each included RCT will be assessed using the Cochrane Risk of Bias 2.0 Tool (RoB2). Traditional pairwise meta-analyses and NMAs will be performed to compare the efficacy and acceptability of different nonpharmacological interventions. Surface under the cumulative ranking curve for the outcomes of interest will be used to rank the competing interventions. The Grading of Recommendations, Assessment, Development and Evaluation system will be used to assess the quality of evidence associated with the main results.

Ethics and dissemination
This review is a secondary analysis of published data and, therefore, does not require ethical approval. The results will be disseminated in a peer-reviewed journal.

PROSPERO registration number
CRD42024546340.

Introduction
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and mortality rates have continued to rise despite advancements in treatment. Six-monthly ultrasound surveillance is recommended by professional bodies for early detection of HCC in high-risk cohorts. However, surveillance rates remain poor; only 20% of patients attend for regular surveillance. Population health outreach strategies may be able to enhance surveillance rates by addressing patient-related barriers to engagement with healthcare. Using a co-design approach, we have developed outreach material in tandem with patients, with the aim of boosting HCC surveillance. VIGILANT aims to compare the effectiveness of bespoke mailed surveillance invitations with or without patient navigators (PNs) in improving attendance rates at surveillance appointments.

Methods and analysis
This is a two-arm randomised controlled trial that will recruit 652 participants. Participants will be patients with chronic liver disease or cirrhosis, who are eligible for HCC surveillance as defined by criteria from the National Institute for Health and Care Excellence and European Association for the Study of the Liver. Participants will be randomised (in a 1:1 ratio) to receive either (a) a mailed surveillance invitation or (b) a mailed invitation plus telephone call reminder from a PN 1 week prior to the appointment. The primary objective is to evaluate the impact of PNs and mailed invitations on attendance rates. Secondary objectives include rates of diagnosis of early-stage HCC among patients undergoing surveillance and cost-effectiveness of each arm.

Ethics and dissemination
Approval has been sought to conduct the research from Aberdeen Research Ethics Committee (REC Reference: 335338). The study is sponsored by Imperial College London and funded by RM Partners (West London Cancer Alliance). Study findings will be presented at medical conferences and published in peer-reviewed journals.

Trial registration number
NCT06635694.

Circulation, Ahead of Print. BACKGROUND:Pathological cardiac remodeling after myocardial infarction (MI) is a leading cause of heart failure and sudden death. The detailed mechanisms underlying the transition to heart failure after MI are not fully understood. Disruptions in the endoplasmic reticulum (ER)–mitochondria connectivity, along with mitochondrial dysfunction, are substantial contributors to this remodeling process. In this study, we aimed to explore the impact of mitochondrial tumor suppressor 1A (Mtus1A) on cardiac remodeling subsequent to MI and elucidate its regulatory role in ER-mitochondria interactions.METHODS:Single-nucleus RNA sequencing analysis was performed to delineate the expression patterns of Mtus1 in human cardiomyocytes under ischemic stress. MI models were induced in mice by left coronary artery ligation and replicated in vitro using primary neonatal rat ventricular myocytes exposed to oxygen glucose deprivation. Cardiac-specific deletion of Mtus1 was achieved by crossing floxed Mtus1 mice with the Myh6-MerCreMer mice. The impact of Mtus1A, a mitochondrial isoform of Mtus1, on cardiac function and the molecular mechanisms were investigated in both in vivo and in vitro settings. Mitochondria-associated ER membranes coupling levels were evaluated by transmission electron microscopy and live-cell imaging. Protein interactions involving Mtus1A were explored through immunoprecipitation–mass spectrometry, coimmunoprecipitation, and proximity ligation assay. The roles of Mtus1A and Fbxo7 (F-box protein 7) were validated in a murine MI model using adeno-associated virus serotype 9 (AAV9).RESULTS:Bioinformatics analysis revealed a significant downregulation of Mtus1 expression in human cardiomyocytes under ischemic conditions, indicating its potential role in stress response. The predominant isoform in murine cardiomyocytes, Mtus1A, showed reduced expression in the left ventricle of mice after MI, which is consistent with the decreased levels of its orthologs in heart tissues from patients with MI. Cardiac-specific knockout of Mtus1 in mice exacerbated cardiac dysfunction after MI. Both in vitro and in vivo studies demonstrated the vital role of Mtus1A in modulating mitochondria-associated ER membranes coupling and preserving mitochondrial function. Mechanistically, Mtus1A functions as a scaffold protein that maintains the formation of inositol 1,4,5-trisphosphate receptor 1 (IP3R1)–glucose-regulated protein 75 (Grp75)–voltage-dependent anion channel 1 (VDAC1) complex through its amino acid sequence 189-219. In addition, Mtus1A protein is stabilized by K6-linked ubiquitination through the E3 ubiquitin ligase Fbxo7. Mtus1A overexpression in mice mitigated MI-induced cardiac dysfunction and remodeling by maintaining ER-mitochondria connectivity.CONCLUSIONS:Our study demonstrates that Mtus1A is crucial for modulating MI-induced cardiac remodeling by preserving ER-mitochondria communication and ameliorating mitochondrial function in cardiomyocytes. Mtus1A may serve as a potential therapeutic target for treating heart failure after MI.