Dynamic properties of noise and Her6 levels are optimized by miR-9, allowing the decoding of the Her6 oscillator

This work was supported by a Wellcome Trust Senior Research Fellowship to NP (106185/Z/14/Z).Noise is prevalent in biology and has been widely quantified using snapshot measurements. This static view obscures our understanding of dynamic noise properties and how these affect gene expression and cell state transitions. Using a CRISPR/Cas9 Zebrafish her6::Venus reporter combined with mathematical and in vivo experimentation, we explore how noise affects the protein dynamics of Her6, a basic helix‐loop‐helix transcriptional repressor. During neurogenesis, Her6 expression transitions from fluctuating to oscillatory at single‐cell level. We identify that absence of miR‐9 input generates high‐frequency noise in Her6 traces, inhibits the transition to oscillatory protein expression and prevents the downregulation of Her6. Together, these impair the upregulation of downstream targets and cells accumulate in a normally transitory state where progenitor and early differentiation markers are co‐expressed. Computational modelling and double smFISH of her6 and the early neurogenesis marker, elavl3, suggest that the change in Her6 dynamics precedes the downregulation in Her6 levels. This sheds light onto the order of events at the moment of cell state transition and how this is influenced by the dynamic properties of noise. Our results suggest that Her/Hes oscillations, facilitated by dynamic noise optimization by miR‐9, endow progenitor cells with the ability to make a cell state transition.Publisher PDFPeer reviewe

Tobacco Use, Exposure to Secondhand Smoke, and Training on Cessation Counseling Among Nursing Students: Cross-Country Data from the Global Health Professions Student Survey (GHPSS), 2005–2009

The Nursing Global Health Professions Student Survey (GHPSS) has been conducted in schools in 39 countries and the Gaza Strip/West Bank (identified as “sites” for the remainder of this paper). In half the sites, over 20% of the students currently smoked cigarettes, with males having higher rates than females in 22 sites. Over 60% of students reported having been exposed to secondhand smoke in public places in 23 of 39 sites. The majority of students recognized that they are role models in society, believed they should receive training on counseling patients to quit using tobacco, but few reported receiving any formal training. Tobacco control efforts must discourage tobacco use among health professionals, promote smoke free workplaces, and implement programs that train health professionals in effective cessation-counseling techniques

Глобальне опитування дорослих щодо вживання тютюну (GATS): звіт за результатами дослідження: Україна, 2010

Tobacco use is a major preventable cause of premature death and disease worldwide, presently causing over 5 million deaths each year and expected to cause over 8 million deaths yearly by 2030. Within the European Region, tobacco is responsible for approximately 1.6 million deaths a year. The World Health Organization (WHO) Tobacco Free Initiative (TFI) aims to reduce the global burden of disease and death caused by tobacco, thereby protecting present and future generations from the devastating health, social, environmental, and economic consequences of tobacco consumption and exposure to tobacco smoke. This will be accomplished by providing global policy leadership -- promoting the WHO Framework Convention on Tobacco Control (FCTC), as well as the MPOWER package of tobacco policies as a key entry point to the WHO FCTC. Within the European Region, 46 countries and the European Community have ratified the Treaty. Ukraine ratified the WHO FCTC in 2006. In August 2006, the WHO and the United States Centers for Disease Control and Prevention (CDC) convened an expert consultation to discuss adult tobacco surveillance and made recommendations for the development of a standard survey protocol. The Global Adult Tobacco Survey (GATS) enables countries to collect data on key tobacco control measures in the adult population. The aim of the GATS is to collect data on tobacco use and tobacco control measures using a standardized questionnaire, sample design, and data collection/management procedures among adults aged 15 years and older. Results from the GATS will assist countries in the formulation, tracking and implementation of effective tobacco control interventions, and countries will be able to compare results of their survey with results from other countries implementing the GATS.Вживання тютюну – основна причина передчасних смертей та хвороб в усьому світі, яким людство здатне запобігти. На сьогоднішній день від вживання тютюну щороку гине понад 5 мільйонів людей; очікується, що до 2030 року ця цифра зросте до 8 мільйонів смертей щорічно. У Європейському регіоні тютюн винен у смерті близько 1,6 мільйона людей на рік. Ініціатива "Звільнення від тютюну" (Tobacco Free Initiative (TFI)) Всесвітньої Організації Охорони Здоров’я (ВООЗ) покликана зменшити глобальний тягар хвороб і смертей, спричинених вживанням тютюну, таким чином захищаючи теперішні та майбутні покоління від шкідливих наслідків куріння для здоров’я, негативних соціальних, економічних та екологічних наслідків, пов’язаних із вживанням тютюну та впливом тютюнового диму. Цієї мети буде досягнуто через глобальне стратегічне лідерство – просування Рамкової конвенції ВООЗ із боротьби проти тютюну, так само як і через комплекс антитютюнових заходів MPOWER, що є ключовим інструментом реалізації Рамкової конвенції. У Європейському регіоні Конвенцію ратифікували 46 країн та Європейське співтовариство. Україна ратифікувала Рамкову конвенцію ВООЗ із боротьби проти тютюну 2006 року. У серпні 2006 року ВООЗ і Центри з контролю та профілактики захворювань США (ЦКПЗ) скликали експертну нараду, аби обговорити питання нагляду за вживанням тютюну серед дорослого населення й виробити рекомендації щодо розроблення стандартизованої програми опитування. "Глобальне опитування дорослого населення щодо вживання тютюну" (The Global Adult Tobacco Survey – GATS) дає країнам змогу зібрати дані щодо ключових антитютюнових заходів серед дорослого населення. Мета проекту GATS – збір даних щодо вживання тютюну і заходів контролю над тютюном із використанням стандартизованих анкети, дизайну вибірки й процедур збору та обробки даних серед населення віком 15 років і старші. Результати проекту GATS допоможуть країнам у розробленні, відстеженні і втіленні ефективних заходів контролю над тютюном, і країни матимуть змогу порівняти свої результати із результатами інших країн, які беруть участь у проекті.Bloomberg Global Initiative to reduce tobacco us

Non-randomised feasibility study testing a primary care intervention to promote engagement in an online health community for adults with troublesome asthma: protocol

Introduction: In the UK, approximately 4.3 million adults have asthma, with one-third experiencing poor asthma control, affecting their quality of life, and increasing their healthcare use. Interventions promoting emotional/behavioural self-management can improve asthma control and reduce comorbidities and mortality. Integration of online peer support into primary care services to foster self-management is a novel strategy. We aim to co-design and evaluate an intervention for primary care clinicians to promote engagement with an asthma online health community (OHC). Our protocol describes a ‘survey leading to a trial’ design as part of a mixed-methods, non-randomised feasibility study to test the feasibility and acceptability of the intervention. Methods and analysis: Adults on the asthma registers of six London general practices (~3000 patients) will be invited to an online survey, via text messages. The survey will collect data on attitudes towards seeking online peer support, asthma control, anxiety, depression, quality of life, information on the network of people providing support with asthma and demographics. Regression analyses of the survey data will identify correlates/predictors of attitudes/receptiveness towards online peer support. Patients with troublesome asthma, who (in the survey) expressed interest in online peer support, will be invited to receive the intervention, aiming to reach a recruitment target of 50 patients. Intervention will involve a one-off, face-to-face consultation with a practice clinician to introduce online peer support, sign patients up to an established asthma OHC, and encourage OHC engagement. Outcome measures will be collected at baseline and 3 months post intervention and analysed with primary care and OHC engagement data. Recruitment, intervention uptake, retention, collection of outcomes, and OHC engagement will be assessed. Interviews with clinicians and patients will explore experiences of the intervention. Ethics and dissemination: Ethical approval was obtained from a National Health Service Research Ethics Committee (reference: 22/NE/0182). Written consent will be obtained before intervention receipt and interview participation. Findings will be shared via dissemination to general practices, conference presentations and peer-reviewed publications. Trial registration number: NCT05829265

Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2

SATB2-Associated syndrome (SAS) is an autosomal dominant, multisystemic, neurodevelopmental disorder due to alterations in SATB2 at 2q33.1. A limited number of individuals with 2q33.1 contiguous deletions encompassing SATB2 (ΔSAS) have been described in the literature. We describe 17 additional individuals with ΔSAS, review the phenotype of 33 previously published individuals with 2q33.1 deletions (n = 50, mean age = 8.5 ± 7.8 years), and provide a comprehensive comparison to individuals with other molecular mechanisms that result in SAS (non-ΔSAS). Individuals in the ΔSAS group were often underweight for age (20/41 = 49%) with a progressive decline in weight (95% CI = −2.3 to −1.1, p \u3c 0.0001) and height (95% CI = −2.3 to −1.0, p \u3c 0.0001) Z-score means from birth to last available measurement. ΔSAS individuals were often noted to have a broad spectrum of facial dysmorphism. A composite image of ΔSAS individuals generated by automated image analysis was distinct as compared to matched controls and non-ΔSAS individuals. We also present additional genotype–phenotype correlations for individuals in the ΔSAS group such as an increased risk for aortic root/ascending aorta dilation and primary pulmonary hypertension for those individuals with contiguous gene deletions that include COL3A1/COL5A2 and BMPR2, respectively. Based on these findings, we provide additional care recommendations for individuals with ΔSAS variants

New insights into early medieval Islamic cuisine : Organic residue analysis of pottery from rural and urban Sicily

Sicily, during the 9th-12th century AD, thrived politically, economically, and culturally under Islamic political rule and the capital of Palermo stood as a cultural and political centre in the Mediterranean Islamic world. However, to what extent the lifeways of the people that experienced these regimes were impacted during this time is not well understood, particularly those from lesser studied rural contexts. This paper presents the first organic residue analysis of 134 cooking pots and other domestic containers dating to the 9th -12th century in order to gain new insights into the culinary practices during this significant period. Ceramics from three sites in the urban capital of Palermo and from the rural town of Casale San Pietro were analysed and compared. The multi-faceted organic residue analysis identified a range of commodities including animal products, vegetables, beeswax, pine and fruit products in the ceramics, with a complex mixing of resources observed in many cases, across all four sites and ceramic forms. Alongside the identification of commodities and how they were combined, new light has been shed on the patterning of resource use between these sites. The identification of dairy products in calcite wares from the rural site of Casale San Pietro and the absence of dairy in ceramics from the urban centre of Palermo presents interesting questions regarding the role of rural sites in food consumption and production in Islamic Sicily. This is the first time organic residue analysis of ceramics has been used to explore foodways in a medieval multi-faith society and offers new pathways to the understanding of pottery use and resources that were prepared, consumed and combined, reflecting cuisine in different socio-economic environments within the pluralistic population of medieval Sicily

Tobacco use, exposure to secondhand smoke, and cessation counseling among medical students: cross-country data from the Global Health Professions Student Survey (GHPSS), 2005-2008

<p>Abstract</p> <p>Background</p> <p>GHPSS is a school-based survey that collects self-administered data from students in regular classroom settings. GHPSS produces representative data at the national or city level in each country. This study aims to investigate the prevalence of tobacco use, exposure to secondhand smoke, and cessation counseling among medical students using the GHPSS data.</p> <p>Methods</p> <p>The Global Health Professions Student Survey (GHPSS) was conducted among 3^rdyear medical students in 47 countries and the Gaza Strip/West Bank from 2005-2008 to determine the prevalence of tobacco use and amount of formal training in cessation counseling.</p> <p>Results</p> <p>In 26 of the 48 sites, over 20% of the students currently smoked cigarettes, with males having higher rates than females in 37 sites. Over 70% of students reported having been exposed to secondhand smoke in public places in 29 of 48 sites. The majority of students recognized that they are role models in society (over 80% in 42 of 48 sites), believed they should receive training on counseling patients to quit using tobacco (over 80% in 41 of 48 sites), but few reported receiving formal training (less than 40% in 46 of 48 sites).</p> <p>Conclusion</p> <p>Tobacco control efforts must discourage tobacco use among health professionals, promote smoke free workplaces, and implement programs that train medical students in effective cessation-counseling techniques.</p

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Sicily in transition : new research on early medieval Sicily, 2017-2018

Il testo che segue riguarda la nostra ricerca archeologica sulla Sicilia bizantina, islamica e normanno-sveva e in particolare riporta le ultime scoperte a Castronovo di Sicilia, che includono il riconoscimento di una chiesa del XII-XIII secolo sul Monte Kassar, la continuazione dello scavo a Casale San Pietro e una sintesi delle nuove ricognizioni nelle sue vicinanze. Quest’ultimo sito rimane il focus principale del Progetto ERC sictransit, ma in questa sede diamo anche conto dei primi risultati di un’indagine più ampia, che include una grossa quantità di reperti che provengono da tutta la Sicilia da siti scavati in precedenza (Fig 1). Questi reperti consistino in ceramiche, metalli e vetri assieme a resti umani, animali e vegetali, che vengono analizzati nei laboratori delle università partner del progetto: York, Roma e Lecce. I principali metodi scientifici applicati sono: analisi tipologiche, petrografiche e del contenuto organico delle ceramiche da cucina e da trasporto; degli isotopi stabili e del DNA antico sui resti umani e animali per determinare la dieta e l’ascendenza genetica; infine la identificazione tassonomica e la caratterizzazione isotopica degli insiemi di resti botanici per comprendere le loro relazioni con il clima e con le diverse fasi storiche. Sictransit combina quindi ricerche archeologiche, bioarcheologiche e biomolecolari in un unico progetto integrato. Gli obiettivi attesi sono stati suddivisi, per comodità e chiarezza, in tre principali aree di studio, vale a dire: agricoltura (e cibo), scambi e demografia. Infine concludiamo con una valutazione della ricerca svolta sul campo e delle prospettive di indagine dei tre laboratori