Search Results for: Le sigarette light sono più pericolose di quelle normali

This Viewpoint discusses human germline genome editing (GGE) in light of changes in the landscape around biomedical technology over the last 10 years, considering ethical, legal, and social issues and in particular whether GGE holds future therapeutic value.

Introduction
Pain accounts for approximately 80% of emergency department admissions. While intravenous morphine titration is commonly used for severe pain, non-invasive alternatives that bypass intravenous access are needed. Nebulised fentanyl, combined with pupillometry for objective monitoring of opioid impregnation, may offer a rapid and safe alternative for pain management.

Methods and analysis
This phase I, open-label, randomised, exploratory, crossover, single-centre prospective controlled trial will employ pharmacokinetic–pharmacodynamic (PK–PD) modelling to assess the variability in bioavailability of nebulised fentanyl administered via intranasal route versus facial aerosol. 20 healthy volunteers will receive three repeated administrations of fentanyl over two visits. At each visit, blood samples (n=11) will be collected for fentanyl quantification by liquid chromatography–tandem mass spectrometry, and pupillary unrest in ambient light (PUAL) measurements (n=9) will be recorded. The resulting data will be analysed using Monolix 2024R1 to model PK–PD relationships, perform Monte Carlo simulations and determine the optimal dosing and timing required to achieve a reduction of more than 30% in PUAL, while also evaluating safety, comfort and tolerance.

Ethics and dissemination
The study has been approved by the Ethic Committee Île-de-France VII (approval reference number: 000216, February 2024) and will be conducted in accordance with the Declaration of Helsinki. Informed consent will be obtained from all participants. Study findings will be disseminated through peer-reviewed publications, conference presentations and appropriate data-sharing platforms to support further research and clinical application.

Trial registration number
This trial is registered at ClinicalTrials.gov (Identifier: NCT06281951).

Introduction
Social accountability is a key value and aspirational goal of many medical institutions. While much has been studied on social accountability in the context of medical education and institutions, less research has examined how social accountability influences research. In light of this absence, the objective of our scoping review is to research the following questions: (1) What characterises socially accountable research (SAR), and how is it expressed and experienced? (2) How do language, positionality, and worldview influence SAR?, and (3) What structures and considerations are necessary to support successful SAR in local and global contexts?

Methods and analysis
To answer the above research questions, the Arksey and O’Malley, Levac et al, Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and Joanna Briggs Institute (JBI) guidelines will be followed. The search strategy was adapted and applied to MEDLINE, Embase, ERIC, and CINAHL databases. A total of n=5289 eligible articles were identified. Articles were excluded if they were published before 1995, were in a language other than English, or were duplicates, leaving n=2840 articles for title/abstract screening.

Ethics and dissemination
Ethical approval is not required to complete this study. We will take an integrated knowledge translation approach. Throughout the project, results will be disseminated to knowledge users (ie, consultations, following Arksey and O’Malley). Our findings will be presented to the larger academic community, policymakers, and healthcare practitioners through presentations, reports, newsletters, and an online repository.

Trial registration number
Open Science Framework 16 July 2024. osf.io/mvhnu.

This cohort study evaluates the distribution of serum free light chains and free light chain ratios in individuals with preserved kidney function and proposes revised reference intervals and a new definition of light chain monoclonal gammopathy of undetermined significance.

In JAMA Internal Medicine, Luchsinger et al describe the results of a prespecified secondary analysis of the GRADE clinical trial on cognitive performance. The GRADE trial randomized 3721 patients with type 2 diabetes using metformin at baseline to add either a long-acting insulin, a sulfonylurea, a glucagon-like peptide-1 (GLP-1) agonist, or a dipeptidyl peptidase-4 inhibitor. At 4 years following randomization, cognitive performance was not different between treatment groups across 3 validated cognitive tests. However, worsened glycemic control was associated with modestly lower cognitive test scores. These findings provide important data for clinicians, particularly in light of recent lay press and scientific enthusiasm about GLP-1 agonists for dementia prevention.

In Reply We read with great interest the letter by Dr Yu et al shedding light on sex and age disparities of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). While we agree with the authors that comparing the incidence rates and trends based on sex and age is of value, the aim of our prior study was not to conduct a head-to-head comparison between different populations. In light of the increasing recognition and familiarity of GEP-NETs by clinicians in the US, our recent epidemiologic analysis aimed to evaluate the national burden of GEP-NETs and to statistically demonstrate the significant increase in GEP-NETs across most gastrointestinal organs while highlighting variations between organs and populations. Our goal was to provide an updated and comprehensive epidemiological understanding of the burden of GEP-NETs using a nationally representative database that covers around 98% of the US population.

In light of a continuing public health emergency resulting from dramatic increases in drug-related deaths during the past 25 years, the seemingly impenetrable wall of universal prohibition laws criminalizing, among other things, possession and use of psychoactive drugs (other than alcohol and cannabis) has begun to fracture as the more traditional drug policy stance has been reevaluated to try to stem a seemingly never-ending and increasing casualty rate, especially in North America, but also internationally. As highlighted in the Table, beginning with Portugal’s decriminalization of all formerly illicit substances in 2001, to Oregon’s state-level emulation of the Portuguese model in the US, and more recently in the Canadian province of British Columbia (BC), a variety of new policy ideas and public health strategies have been implemented and tested with varying degrees of success.

Chronic gastrointestinal (GI) diseases, including functional, inflammatory, and neoplastic conditions, are rising globally, partly due to modern lifestyles. The circadian rhythm, regulated by the central clock in the hypothalamus and synchronized with peripheral clocks in the gastrointestinal organs, orchestrates GI functions in response to environmental cycles. This clock is influenced by cues such as light, sleep, and eating times. The circadian machinery prepares the host to cope with environmental conditions to adjust cellular and organ function accordingly.

Introduction
Communication challenges are among the main barriers for people with intellectual disabilities in accessing palliative care. They include inadequate skills among staff and difficulties with confirming understanding and around the presentation and assessment of symptoms. In-depth analysis of interactions between people with an intellectual disability and staff may shed light on these communicative challenges as well as facilitators. However, no studies have closely analysed the interactions between people with an intellectual disability and professionals within palliative care settings.

Methods and analysis
This protocol describes a pilot study assessing the feasibility and acceptability of conducting a Conversation Analysis study involving video-recording palliative care conversations between people with intellectual disabilities and professionals.
Three conversations between patients with an intellectual disability, their companions and palliative care staff will be video recorded in a UK hospice. Recordings will be transcribed and analysed using Conversation Analysis. Communication phenomena of interest and worth further exploration will be identified in collaboration with key stakeholders.

Ethics and dissemination
The study received a favourable opinion by a UK research ethics committee in February 2025. All participants must provide informed consent to take part in the study. It will be carefully assessed that potential participants with an intellectual disability have capacity to consent to take part. Accessible study information materials for participants with an intellectual disability are available (ie, easy-read and video).
Study findings will be disseminated in academic papers and conference presentations. Progress and findings will also be shared via social media and with relevant groups of people with intellectual disabilities, family carers, service providers and academics.

Introduction
Depression and anxiety are highly prevalent mental health conditions that significantly affect quality of life and cause societal burdens. However, their detection and diagnosis rates remain low owing to the limitations of the current screening methods. With rapid technological advancements and the proliferation of consumer-grade wearable devices and smartphones, their integration into digital phenotyping research has enabled the unobtrusive screening for depression and anxiety in natural settings. The Smartphone and Wearable Assessment for Real-Time Screening of Depression and Anxiety study aims to develop prediction algorithms to identify individuals at risk for depressive and anxiety disorders, as well as those with mild-to-severe levels of either condition or both. By collecting comprehensive data using smartphones and smartwatches, this study aims to facilitate the translation of artificial intelligence-based early detection research into clinical impact, thereby potentially enhancing patient care through more accurate and timely interventions.

Methods and analysis
This cross-sectional observational study will enrol up to 2500 participants (at least 1000) aged 19-59 years from South Korea via social media outreach and clinical referrals. The eligible participants must use a compatible smartphone. Each participant will be followed up for 4 weeks. Data will be collected using a custom-developed smartphone application called PixelMood. Active data collection will include daily, weekly and monthly self-report questionnaires incorporating validated scales, such as the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Passive data from smartphones include information on physical activity, location, ambient light and smartphone usage patterns. Optionally, participants using the Apple Watch or Galaxy Watch devices can provide additional data on physiological responses and sleep health. The primary outcome will be the development of machine-learning algorithms to predict depression and anxiety based on these digital biomarkers. We will employ various machine-learning techniques, including random forest, support vector machine and deep-learning models. The secondary outcomes will include the association between digital biomarkers and clinical measures, and the feasibility and acceptability of data collection methods. Various features characterising mobile usage behaviours, physical/social activity, sleep patterns, resting physiological states and circadian rhythms will be exploited to serve as potential digital phenotyping markers. Advanced machine-learning and deep-learning techniques will be applied to multimodal data for model generation.

Ethics and dissemination
This study protocol was reviewed and approved by the Institutional Review Board of the Korea University Anam Hospital (approval number: 2023AN0506). The results of this study will be disseminated via multiple channels. The findings will be presented at local, national and international conferences in relevant fields, such as psychiatry, psychology and digital health. Manuscripts detailing the study results will be submitted to peer-reviewed journals for publication.

Trial registration number
The present study was registered with the Clinical Research Information Service (CRIS, https://cris.nih.go.kr; identifier: KCT0009183).

Stroke, Ahead of Print. BACKGROUND:Poststroke depression (PSD) affects ≈33% of individuals 1 year after a stroke. Blood-brain barrier (BBB) dysfunction in the nucleus accumbens (NAc), a hub for emotional processing, reward, and mood regulation, has been linked to stress-induced depressive-like behaviors in male mice. Neurovascular alterations were also observed in postmortem tissue samples from men with a diagnosis of major depression. Thus, we aimed to investigate if BBB changes in the NAc could contribute to PSD pathophysiology.METHODS:Stereotaxic injection of ET-1 (endothelin-1), a potent vasoconstrictor, was performed in the NAc of male mice to create a focal brain stroke, and then, infarct size and localization were assessed and quantified. We subsequently evaluated transcriptomic and morphological effects of the infarct on BBB-related genes and cells in the NAc, particularly those known to be altered after stress exposure in mice or human depression. BBB integrity was assessed with a dextran dye, and magnetic resonance imaging scans were conducted before versus after the injection of Gadovist, a contrast agent. Last, a battery of behavioral tests related to depressive- and anxiety-like behaviors was performed to determine if an infarct in the NAc is sufficient to induce a PSD-like phenotype.RESULTS:Following ET-1 injection, ≈50% of the total lesion was observed in the NAc leading to BBB hyperpermeability in this brain area. BBB gene expression was impacted by ET-1, and also surgery alone and profiles were differentially regulated throughout time up to 14 days. Gliosis in the NAc was observed with increased reactivity of astrocytes and microglia. The effect of ET-1 on PSD-like symptoms was limited. However, body weight, sociability, and activity were affected by surgery with a more pronounced impact of ET-1 on social interactions compared with naive animals.CONCLUSIONS:While no clear PSD phenotype was observed following an ET-1–induced stroke in the NAc of male mice, our study shed light on the technical complexity of focal lesions in deep brain structures, an understudied phenomenon occurring in humans. We provide technical insights for the development of a mouse model of deep brain lesions, characterize its impact at molecular, cellular, and behavioral levels, and highlight the need to control for vascular alterations when performing stroke surgeries.

Circulation, Ahead of Print. BACKGROUND:The RhoA (Ras homolog family member A) signaling pathway is pivotal in regulating vascular smooth muscle cells (VSMCs) function and blood pressure homeostasis. Current inhibitors of the RhoA signaling pathway are limited in hypertension treatment, suffering from poor efficacy, insufficient specificity, and developmental challenges.METHODS:Cryo-electron microscopy (EM), proximity ligation assay (PLA), and site-directed mutagenesis were used to explore the mechanism of RhoA activity regulation. VSMC, hypertensive animal models,Trpv4-/-andArhgdiaf/fMyh11-CREERT2(smooth muscle–specific RhoGDI1 knockout) mice were used to investigate the role of the TRPV4 (transient receptor potential cation channel subfamily V member 4)–RhoA–RhoGDI1 (Rho GDP dissociation inhibitor 1) axis in hypertension.RESULTS:AH001 ((R)-1-(3-ethylphenyl) ethane-1,2-diol) was identified as a novel inhibitor of the RhoA signaling pathway. It targets the TRPV4–RhoA–RhoGDI1 axis to effectively sequester inactive RhoA–GDP in the plasma membrane and cytoplasm, which is distinct from typical RhoA inhibition modes. The cryo-EM structure of the TRPV4AH001–RhoA complex showed that AH001-bound TRPV4 adopts a closed state with RhoA in an inactive GDP-bound state. Functional studies further revealed that AH001 reduced the pool of active RhoA by enhancing TRPV4–RhoA binding and facilitating RhoGDI1–RhoA interaction in VSMC. This inhibition notably decreased both acute and long-term blood pressure and prevented vascular remodeling in Ang II–induced hypertensive mice and spontaneously hypertensive rats. However, these antihypertensive effects were weakened inTrpv4-/-andArhgdiaf/fMyh11-CREERT2mice. Additionally, AH001 effectively inhibited VSMC contraction via the RhoA/ROCK (Rho-associated protein kinase)/MYPT1 (myosin phosphatase target subunit 1)/MLC (myosin light chain 2) signaling pathway and suppressed VSMC phenotype switching to myofibroblasts through the RhoA/ROCK/LIMK1 (LIM domain kinase)/cofilin/MRTF-A (myocardin-related transcription factor A)/SRF (serum response factor) signaling cascade. TRPV4 and RhoGDI1 knockdown attenuated AH001’s inhibition of VSMC contraction and phenotypic switching to myofibroblasts.CONCLUSIONS:This study revealed a novel mode of RhoA signaling inhibition targeting the TRPV4–RhoA–RhoGDI1 axis, offering new insights for future antihypertensive drug development and proposing innovative strategies for targeting challenging Rho GTPases.

A scientific marvel, the process of DNA methylation in neurons plays a crucial role in memory formation and storage, influencing how synaptic connections are first established and later reinforced. Although this esoteric process might seem outright incredible to non-neurobiologists, in “A Blessing for Methylation,” the ingenuity of poetry becomes a useful entrée into grasping it. The brilliant opening couplet “memory/is physical” immediately bridges what might at first seem a yawning chasm between intangible humanity and hard science. The simplicity and elegance of the language throughout the poem evoke the fundamentally logical nature of the biochemical reactions that give rise to memory; the short lines with their frequent enjambment further contribute to an appreciation of the stepwise fashion in which such reactions occur. The poem also imparts a more ethereal sense of how such scientific mechanisms are translated into the wonder of our ability to remember, the last lines at once continuing the enacted metaphor of molecule-by-molecule, brick-by-brick building while surprising us with a luminous recollection of the speaker, a concrete neural product that seemingly miraculously transcends time. “… I/see my hand in/your hair again//not grey and wiry/but golden — it holds/the light like the sky//holds summer stars” arises from the cellular basis of neural plasticity evinced, surely, but also as a summative expression of a design even more astonishing and grand.

Quarta regione per sigarette, ma 51% mangia fresco 3 volte al dì

Objectives
Adolescent health is critical for achieving Sustainable Development Goal 3, ‘health for all at all ages’. In sub-Saharan Africa (SSA), mining projects hold promise for social and economic development. Yet, the extent to which the health and well-being of adolescents are impacted by industrial mining is poorly understood. In this paper, we aim to investigate how adolescent health and well-being is perceived by key informants and caregivers in communities that have been affected by industrial mining projects in Mozambique.

Design and settings
A qualitative study was implemented from May–July 2022 in two rural districts in Mozambique’s northern and central regions. Both districts have large industrial mining projects: a coal mine in Moatize district and a mineral sands mine in Moma district.

Participants
A total of 21 key informant interviews (KIIs) were conducted with a range of stakeholders, including health professionals and civil society and private sector representatives. In addition, four focus group discussions (FGDs) were conducted with adolescents’ caregivers.

Results
Through the combined results from the KIIs and FGDs, four main health concerns affecting adolescents in mining areas were identified: sexually transmitted infections, respiratory tract infections, diarrhoeal diseases and malaria. Mining activities were perceived to exacerbate negative health effects and contribute to poor health outcomes among adolescents. Although mining companies invested in public infrastructure, most participants did not perceive this investment as a positive contribution to the health and well-being of adolescents.

Conclusion
Our study sheds light on the multifaceted challenges perceived by stakeholders that adolescents residing in mining communities in Mozambique face. Insufficient priority is given to effective interventions that specifically target adolescent health in the two study mining areas. In order to leave no one behind, as stipulated by the sustainable development agenda, more emphasis should be placed on the role and responsibility of mining companies in adequately addressing adolescents’ unique health needs in mining settings in SSA.

Introduction
Maintaining a satisfactory level of physical activity (PA) after cardiovascular rehabilitation in patients with coronary heart disease (CHD) is an important public health issue. However, more than half of patients do not maintain recommended levels of PA in the long term. There is growing interest in the use of cognitive-behavioural interventions that actively involve both health professionals and patients in education and research settings. We hypothesise that a personalised therapeutic education programme (PTEP) delivered by peers in collaboration with health professionals may help patients with CHD maintain appropriate levels of PA after participation in a cardiovascular rehabilitation programme (CRP).

Methods and analysis
We designed a prospective randomised controlled trial (the P-HEART-NER study) conducted jointly by health professionals and patients as experts or peers. The primary objective is to assess the impact of PTEP on objective levels of moderate to vigorous PA—measured by accelerometers—6 months after cessation of CRP. The secondary objectives are (1) to assess the impact of the intervention on light PA and sedentary time (also measured by accelerometry), (2) to evaluate changes in cardiovascular health indicators, including blood pressure, waist circumference and lipid profile, (3) to assess changes in motivation towards PA (using the Motivation Scale Towards Health-Oriented Physical Activity), PA self-efficacy (measured by the Exercise Confidence Survey) and quality of life (EQ-5D-5L). Patients will be enrolled at the end of a 4-week phase 2 CRP after a myocardial infarction. The intervention will consist of two teleconsultations and a group workshop at 2, 4 and 5 months, respectively, each jointly delivered by a peer and a health professional. The peers who will deliver the intervention will be patients who have participated in a phase 2 CRP with good compliance and who will be trained in motivational enhancement and cognitive behavioural therapies by health professionals and expert patients. The control group will not complete the PTEP.

Ethics and dissemination
Ethical approval was granted by the French regional ethics committee CPP Ile de France (Ref CPPIDF1-2023-DI36-Cat2). All participants will sign a written informed consent form. The results will be presented at conferences and published in peer-reviewed journals.

Trial registration number
NCT05927363.