Patients are asking about e-cigarettes. What do we tell them?

Provides an overview of what e-cigarettes are and who is using them. Considers the safety, quality and efficacy of e-cigarettes. Outlines the current and proposed legislation on e-cigarettes. Suggests advice for health professionals to give patients about e-cigarettes. Lists the questions to consider when deciding whether to permit or prohibit use of e-cigarettes on premises. Abstract E-cigarettes are electronic devices that deliver vaporised nicotine liquid into the lungs. Since the introduction of e-cigarettes in 2004, the market in the UK has rapidly expanded and increasingly people are asking health professionals about them. This article gives an overview of e-cigarettes, their use, their regulatory status and evidence for their safety, quality and efficacy. Advice about e-cigarettes for dental health professionals to give patients is provided, as well as the five questions, proposed by Action on Smoking and Health, to consider when deciding whether to permit or prohibit use of e-cigarettes on premises

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: Evidence for genetic and environmental heterogeneity in the developing brain.

Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD. © 2007 Elsevier Inc. All rights reserved

Middle to late Pleistocene palaeoecological reconstructions and palaeotemperature estimates for cold/cool stage deposits at Whittlesey, eastern England

Fossiliferous beds in a complex sequence of late Middle to Late Pleistocene deposits at Whittlesey, eastern England, provided a rare opportunity for a multidisciplinary study of the palaeoecology of cool/cold stage deposits from different glacial stages. The fossiliferous sediments investigated form part of the River Nene 1st Terrace. Three of the four fossil assemblages investigated pre-date the last interglacial stage (Ipswichian/Eemian/marine oxygen isotope stage (MIS) 5e), whereas the other dates to part of the MIS 3 interstadial complex (Middle Devensian/Weichselian). Pollen, plant macrofossil, molluscan, coleopteran, ostracod, foraminifera and vertebrate data are available to a greater or lesser extent for each cool/cold stage assemblage, and they broadly present the same ecological picture for each one: a continuum from low-energy permanent to non-permanent aquatic habitats through marshland with associated waterside taxa, together with flood influxes of fluvial, riparian and ruderal taxa. Although each fossil assemblage records cool/cold climatic conditions, to a greater or lesser extent, these conditions are more apparent in the insect and ostracod faunas. In comparison with results published for the Last Glacial Maximum (LGM) stadial in The Netherlands, palaeotemperature estimates based on ranges of mutual agreement between independent coleopteran and ostracod methods for the three pre-Ipswichian/Eemian assemblages indicate minimum mean July air temperatures that are from +1° to +3 °C warmer, but January values that embrace the −8 °C estimate for the LGM. There is, however, a disparity between the coleopteran and ostracod palaeotemperature estimates for the Middle Devensian/Weichselian fossil assemblage, which are based on two different sample stratigraphic levels; the lower, coleopteran assemblage is indicative of very cool, continental climates, whereas the stratigraphically slightly higher ostracod assemblage suggests a climatic amelioration. Lack of numerical age-estimates prevents a robust stratigraphical interpretation, but the youngest pre-Ipswichian/Eemian fossil assemblage could date to the MIS 7–6 transition, at a time when cooling possibly preceded glacially driven sea-level fall. It is apparent from the rich coleopteran data that some continental cold-indicator taxa also appeared in pre-Ipswichian/Eemian cold stages and therefore assignment of continental cold-indicator taxa to particular Devensian/Weichselian intervals should be undertaken with care

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research

Long-range Angular Correlations On The Near And Away Side In P-pb Collisions At √snn=5.02 Tev

7191/Mar294

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding: UK Research and Innovation and National Institute for Health Research

New insights into the immediate outcome of collagenase injections for Dupuytren’s contracture

Collagenase clostridium histolyticum is now established as an effective and safe option to treat patients with a single joint affected with Dupuytren's contracture. We have extended its use to natatory and combined cords. In a prospective consecutive series of 298 cords in 237 patients, the mean total extension loss improved in cords crossing the metacarpophalangeal joint from 46° to 1°, in cords crossing the proximal interphalangeal joint from 56° to 7°, in natatory cords from 130° to 25° and in combined cords from 102° to 16°. The immediate correction of combined cords and natatory cords was less reliable than that obtained in cords crossing the metacarpophalangeal joint or proximal interphalangeal joint. Less severe pre-intervention contractures tended to correct better. We found a high complication rate, which may cause alarm. A total of 21% developed skin splits, with the risk of skin splits generally increasing with more severe pre-injection deformity. Blood blisters were only encountered after manipulation of the more severe contractures. A total of 23 patients (8%) had a spontaneous rupture and 57 patients (19%) had a partial spontaneous rupture. Only 4.9% needed a second injection. We noticed a learning curve, with seven of the first 20 cords (35%) needing a second injection to achieve a satisfactory correction and then only seven (2.5%) in the res