Holidays, celebrations, and commiserations: measuring drinking during feasting and fasting to improve national and individual estimates of alcohol consumption

BACKGROUND: Accurate measures of alcohol consumption are critical in assessing health harms caused by alcohol. In many countries, there are large discrepancies between survey-based measures of consumption and those based on alcohol sales. In England, surveys measuring typical alcohol consumption account for only around 60% of alcohol sold. Here, using a national survey, we measure both typical drinking and atypical/special occasion drinking (i.e., feasting and fasting) in order to develop more complete measures of alcohol consumption. METHODS: A national random probability telephone survey was implemented (May 2013 to April 2014). Inclusion criteria were resident in England and aged 16 years or over. Respondents (n = 6,085) provided information on typical drinking (amounts per day, drinking frequency) and changes in consumption associated with routine atypical days (e.g., Friday nights) and special dinking periods (e.g., holidays) and events (e.g., weddings). Generalized linear modelling was used to identify additional alcohol consumption associated with atypical/special occasion drinking by age, sex, and typical drinking level. RESULTS: Accounting for atypical/special occasion drinking added more than 120 million UK units of alcohol/week (~12 million bottles of wine) to population alcohol consumption in England. The greatest impact was seen among 25- to 34-year-olds with the highest typical consumption, where atypical/special occasions added approximately 18 units/week (144 g) for both sexes. Those reporting the lowest typical consumption (≤1 unit/week) showed large relative increases in consumption (209.3%) with most drinking associated with special occasions. In some demographics, adjusting for special occasions resulted in overall reductions in annual consumption (e.g., females, 65 to 74 years in the highest typical drinking category). CONCLUSIONS: Typical drinking alone can be a poor proxy for actual alcohol consumption. Accounting for atypical/special occasion drinking fills 41.6% of the gap between surveyed consumption and national sales in England. These additional units are inevitably linked to increases in lifetime risk of alcohol-related disease and injury, particularly as special occasions often constitute heavy drinking episodes. Better population measures of celebratory, festival, and holiday drinking are required in national surveys in order to adequately measure both alcohol consumption and the health harms associated with special occasion drinking

Crosstalk between cilia and autophagy: implication for human diseases

Macroautophagy/autophagy is a self-degradative process necessary for cells to maintain their energy balance during development and in response to nutrient deprivation. Autophagic processes are tightly regulated and have been found to be dysfunctional in several pathologies. Increasing experimental evidence points to the existence of an interplay between autophagy and cilia. Cilia are microtubule-based organelles protruding from the cell surface of mammalian cells that perform a variety of motile and sensory functions and, when dysfunctional, result in disorders known as ciliopathies. Indeed, selective autophagic degradation of ciliary proteins has been shown to control ciliogenesis and, conversely, cilia have been reported to control autophagy. Moreover, a growing number of players such as lysosomal and mitochondrial proteins are emerging as actors of the cilia-autophagy interplay. However, some of the published data on the cilia-autophagy axis are contradictory and indicate that we are just starting to understand the underlying molecular mechanisms. In this review, the current knowledge about this axis and challenges are discussed, as well as the implication for ciliopathies and autophagy-associated disorders

Under-reporting of foetal alcohol spectrum disorders: an analysis of hospital episode statistics

<p>Abstract</p> <p>Background</p> <p>Internationally, 0.97 per 1,000 live births are affected by foetal alcohol syndrome (FAS). However, prevalence intelligence has been limited in the UK, hindering the development of appropriate services. This analysis compares hospital admissions over time, between regions and with alcohol-related admissions for adult females to assess whether established patterns (such as the North experiencing elevated harms) can be identified.</p> <p>Methods</p> <p>A retrospective analysis of hospital admissions data (April 2002 to March 2008) for foetal alcohol spectrum disorder (FASD)-related conditions: foetal alcohol syndrome (dysmorphic) (n = 457); foetus and newborn affected by maternal use of alcohol (n = 157); maternal care for (suspected) damage to foetus from alcohol (n = 285); and 322,161 women admitted due to alcohol-related conditions.</p> <p>Results</p> <p>Whilst the rate of admission for alcohol-related conditions in women aged 15-44 years increased significantly by 41% between 2002/03 and 2007/08 (p < 0.0001), no such increases were seen in the numbers of FASD-related conditions (all p < 0.05). Established regional rates of admission for alcohol-related conditions in women aged 15-44 years old were not associated with admission for FASD-related conditions.</p> <p>Conclusions</p> <p>It would be expected that the North West and North East regions, known to have higher levels of alcohol harm would have higher levels of FASD-related conditions. However, this was not reflected in the incidence of such conditions, suggesting under-reporting. With incomplete datasets, intelligence systems are severely limited, hampering efforts to develop targeted interventions. Improvements to intelligence systems, practitioner awareness and screening are essential in tackling this.</p

Use of fake identification to purchase alcohol amongst 15-16 year olds: a cross-sectional survey examining alcohol access, consumption and harm

<p>Abstract</p> <p>Background</p> <p>Despite legislation and enforcement activities to prevent underage access to alcohol, underage individuals continue to be able to access alcohol and to do so at levels which put them at significant risk of alcohol-related harm.</p> <p>Methods</p> <p>An opportunistic survey of 15-16 year olds (n = 9,833) across North West England was used to examine alcohol consumption, methods of access and related harms experienced (such as regretted sex). Associations between these were analysed using chi square and logistic regression techniques.</p> <p>Results</p> <p>Over a quarter (28.3%) of 15-16 year old participants who drank reported having bought their own alcohol. One seventh (14.9%) of these owned at least one form of fake identification for which by far the most common purchase method was online. Logistic regression analyses showed that those who owned fake identification were significantly more likely to be male (AOR = 2.0; 95% CI = 1.7-2.5; P < 0.001) and to receive a higher personal weekly income (comparing those who received > £30 with those who received ≤ £10: AOR = 3.7; 95% CI = 2.9-4.9; P < 0.001). After taking into account differences in demographic characteristics and personal weekly income, ownership of fake identification was significantly associated with binge drinking (AOR = 3.5, 95% CI = 2.8-4.3; P < 0.001), frequent drinking (AOR = 3.0, 95% CI = 2.5-3.7; P < 0.001) and public drinking (AOR = 3.3, 95% CI = 2.5-4.1; P < 0.001) compared with those who did not own fake identification. Further, those who reported owning fake identification were significantly more likely to report experiencing a variety of alcohol-related harms such as regretted sex after drinking (chi square, all P < 0.001).</p> <p>Conclusions</p> <p>Young people (aged 15-16 years) who have access to fake identification are at a particularly high risk of reporting hazardous alcohol consumption patterns and related harm. Owning fake identification should be considered a risk factor for involvement in risky drinking behaviours. Information on these hazards should be made available to schools and professionals in health, social and judicial services, along with advice on how to best to work with those involved.</p

Novel Missense Mutation A789V in IQSEC2 underlies X-Linked intellectual disability in the MRX78 family

Disease gene discovery in neurodevelopmental disorders, including X-linked intellectual disability (XLID) has recently been accelerated by next-generation DNA sequencing approaches. To date, more than 100 human X chromosome genes involved in neuronal signaling pathways and networks implicated in cognitive function have been identified. Despite these advances, the mutations underlying disease in a large number of XLID families remained unresolved. We report the resolution of MRX78, a large family with six affected males and seven affected females, showing X-linked inheritance. Although a previous linkage study had mapped the locus to the short arm of chromosome X (Xp11.4-p11.23), this region contained too many candidate genes to be analyzed using conventional approaches. However, our X-chromosome exome resequencing, bioinformatics analysis and inheritance testing revealed a missense mutation (c.C2366T, p.A789V) in IQSEC2, encoding a neuronal GDP-GTP exchange factor for Arf family GTPases (ArfGEF) previously implicated in XLID. Molecular modeling of IQSEC2 revealed that the A789V substitution results in the insertion of a larger side-chain into a hydrophobic pocket in the catalytic Sec7 domain of IQSEC2. The A789V change is predicted to result in numerous clashes with adjacent amino acids and disruption of local folding of the Sec7 domain. Consistent with this finding, functional assays revealed that recombinant IQSEC2A789V was not able to catalyze GDP-GTP exchange on Arf6 as efficiently as wild-type IQSEC2. Taken together, these results strongly suggest that the A789V mutation in IQSEC2 is the underlying cause of XLID in the MRX78 family

Parental knowledge of alcohol consumption : a cross sectional survey of 11-17 year old schoolchildren and their parents

Background: Developing timely and effective strategies for preventing alcohol misuse in young people is required in order to prevent related harms since, worldwide, alcohol consumption was associated with 320,000 deaths amongst 15–29 year olds in 2004. Providing guidance and advice to parents is essential if alcohol misuse is to be reduced. However, prevention of risky behaviours is hampered if parents are unaware of the risks involved. Methods: A cross-sectional school-based survey of parent–child dyads, simultaneously questioning 935 children aged 11–17 years old and their parent(s). Univariate and multivariate associations are reported between demography, alcohol behaviours and parental knowledge of their child’s alcohol consumption. Results: 41.1% (n = 384) of children reported drinking alcohol. Of these, 79.9% of their parents were aware of their child’s alcohol consumption. Children aged 11–14 years had over a twofold greater odds of consuming alcohol without parental knowledge compared with 15–17 year olds (AOR: 2.7, 95% CI: 1.3-5.7). Of parent–child dyads where the child reported consuming alcohol, 92.7% of parents reported that they had spoken to their child about alcohol at least once in the past three months, whereas 57.3% of their children reported that this had occurred. Children who consumed alcohol and whose parents did not know they drank alcohol were less likely to report having a parental discussion about alcohol in the last three months (AOR: 0.4, 95% CI: 0.1-1.0) or report lifetime receipt of at least one other parenting protective measure (AOR: 0.5, 95% CI: 0.2-0.9) compared with those children who drank alcohol with parental knowledge. Conclusions: Whilst only small numbers of young adolescents in our sample were drinking alcohol compared with older adolescents, those who did were more likely to do so without their parents’ knowledge. These two factors combined (drinking earlier and drinking without parental knowledge) could place children at risk of immediate harm. Further research is essential to identify whether public health strategies should be developed which could support parents to employ lifestyle parenting techniques even before the parent believes the child to be at risk

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine

Brief intervention to reduce risky drinking in pregnancy: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Risky drinking in pregnancy by UK women is likely to result in many alcohol-exposed pregnancies. Studies from the USA suggest that brief intervention has promise for alcohol risk reduction in antenatal care. However, further research is needed to establish whether this evidence from the USA is applicable to the UK. This pilot study aims to investigate whether pregnant women can be recruited and retained in a randomized controlled trial of brief intervention aimed at reducing risky drinking in women receiving antenatal care.</p> <p>Methods</p> <p>The trial will rehearse the parallel-group, non-blinded design and procedures of a subsequent definitive trial. Over 8 months, women aged 18 years and over (target number 2,742) attending their booking appointment with a community midwife (n = 31) in north-east England will be screened for alcohol consumption using the consumption questions of the Alcohol Use Disorders Identification Test (AUDIT-C). Those screening positive, without a history of substance use or alcohol dependence, with no pregnancy complication, and able to give informed consent, will be invited to participate in the trial (target number 120). Midwives will be randomized in a 1:1 ratio to deliver either treatment as usual (control) or structured brief advice and referral for a 20-minute motivational interviewing session with an alcohol health worker (intervention). As well as demographic and health information, baseline measures will include two 7-day time line follow-back questionnaires and the EuroQoL EQ-5D-3 L questionnaire. Measures will be repeated in telephone follow-ups in the third trimester and at 6 months post-partum, when a questionnaire on use of National Health Service and social care resources will also be completed. Information on pregnancy outcomes and stillbirths will be accessed from central health service records before the follow-ups. Primary outcomes will be rates of eligibility, recruitment, intervention delivery, and retention in the study population, to inform power calculations for a definitive trial. The health-economics component will establish how cost-effectiveness will be assessed, and examine which data on health service resource use should be collected in a main trial. Participants’ views on instruments and procedures will be sought to confirm their acceptability.</p> <p>Discussion</p> <p>The study will produce a full trial protocol with robust sample-size calculations to extend evidence on effectiveness of screening and brief intervention.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN43218782</p