The association of appendicular lean mass and grip strength with low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein particle diameter: a Mendelian randomization study of the UK Biobank cohort

Reduced muscle mass and reduced strength are frequently associated with both alterations in blood lipids and poorer cardiometabolic outcomes in epidemiological studies; however, a causal association cannot be determined from such observations. Two-sample Mendelian randomization (MR) was applied to assess the association of genetically determined appendicular lean mass (ALM) and handgrip strength (HGS) with serum lipid particle diameter.Methods and resultsMendelian randomization was implemented using summary-level data from the largest genome-wide association studies on ALM (n = 450 243), HGS (n = 223 315), and lipoprotein [low-density lipoprotein (LDL), very LDL (VLDL), and high-density lipoprotein (HDL)] particle diameters (n = 115 078). Inverse variance-weighted (IVW) method was used to calculate the causal estimates. Weighted median-based method, MR-Egger, and leave-one-out method were applied as sensitivity analysis. Greater ALM had a statistically significant positive effect on HDL particle diameter (MR-Egger: β = 0.055, SE = 0.031, P = 0.081; IVW: β = 0.068, SE = 0.014, P < 0.001) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β = −0.114, SE = 0.039, P = 0.003; IVW: β = −0.081, SE = 0.017, P < 0.001). Similarly, greater HGS had a statistically significant positive effect on HDL particle diameter (MR-Egger: β = 0.433, SE = 0.184, P = 0.019; IVW: β = 0.121, SE = 0.052, P = 0.021) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β = −0.416, SE = 0.163, P = 0.011; IVW: β = −0.122, SE = 0.046, P = 0.009). There was no statistically significant effect of either ALM or HGS on LDL particle diameter.ConclusionThere were potentially causal associations between both increasing ALM and HGS and increasing HDL particle size and decreasing VLDL particle size. These causal associations may offer possibilities for interventions aimed at improving cardiovascular disease risk profile

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Impact of COVID-19 lockdown restrictions on cardiac rehabilitation participation and behaviours in the United Kingdom

BACKGROUND: COVID-19 lockdown measures led to the suspension of centre-based cardiac rehabilitation (CR). We aimed to describe the impact of lockdown on CR behaviours and perceptions of efficacy in a sample of CR participants. METHODS: An online survey was conducted amongst CR participants from May to October 2020, COVID-19-related lockdown restrictions. Anthropometric data, participant-determined levels of motivation and self-perceived efficacy, CR practices etc., pre- and post-lockdown, were collected. RESULTS: The probability of practicing CR in public gyms and hospitals decreased 15-fold (47.2% pre-, 5.6% post-lockdown; OR[95% CI] 0.065[0.013; 0.318], p < 0.001), and 34-fold (47.2% pre, 2.8% post; OR[95% CI] 0.029[0.004; 0.223], p < 0.001), respectively. Amongst participants, 79.5% indicated that their CR goals had changed and were 78% less likely to engage in CR for socialization after lockdown (47.2% pre, 16.7% post; OR[95% CI] 0.220[0.087; 0.555]; p = 0.002). The probability of receiving in-person supervision decreased by 90% (94.4% pre, 16.7% post; OR[95% CI] 0.011[0.002; 0.056]), while participants were almost 7 times more likely to use online supervision (11.1% pre, 44.4% post; OR[95% CI] 6.824[2.450; 19.002]) (both p < 0.001). Fifty percent indicated that their enjoyment of CR was lower than before lockdown and 27.8% reported they would be less likely to continue with CR in the newer format. CONCLUSIONS: Lockdown was associated with considerable changes in how CR was practiced, motivation levels and willingness to continue with CR. Further research is warranted to develop and improve strategies to implement in times when individuals cannot attend CR in person and not only during pandemics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13102-022-00459-5

Self-reported sleep duration, white blood cell counts and cytokine profiles in European adolescents: the HELENA study

BACKGROUND: Sleep patterns face important changes during adolescence. This can have implications for the immune system, which is regulated by the sleep-wake cycle; however, most studies relating sleep and immune system have been conducted on adults. OBJECTIVE: To study the relationships between sleep duration, immune cell counts, and cytokines in European adolescents participating in the HELENA Cross-Sectional Study. METHODS: Adolescents (12.5-17.5 years; n = 933; 53.9% girls) were grouped according to self-reported sleep duration into <8, 8-8.9 and ≥9 h/night. Blood samples were collected in the morning after an overnight fast to analyze counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, the lymphocyte subsets CD3(+), CD4(+), CD8(+), CD45RA(+), CD45RO(+), CD3(-)CD16(+)56(+) and CD19(+), and concentrations of cortisol, CRP, IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α and IFN-γ. Pro-/anti-inflammatory and Th1/Th2 cytokine ratios were calculated. Immune parameters were correlated to sleep duration and compared between the three groups. RESULTS: Sleep duration was negatively associated with cortisol levels and WBC, neutrophil, monocyte, CD4(+) and CD4(+)CD45RO(+) counts; in girls it is also negatively associated with IL-5 and IL-6 levels. The 8-8.9 h/night group presented the highest IL-4 values and the lowest pro-/anti-inflammatory and Th1/Th2 cytokine ratios. CONCLUSION: A sleep duration of 8-8.9 h/night was associated with a healthier immune profile in our adolescents.status: publishe

Socioeconomic factors are associated with folate and vitamin B-12 intakes and related biomarkers concentrations in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study

Because socioeconomic factors (SEFs) may influence dietary quality and vitamin intakes, this study aimed to examine associations between socioeconomic factors and folate and vitamin B-12 intakes as well as their related biomarkers in the Healthy Lifestyle in Europe by Nutrition in Adolescence study. Vitamin intakes were obtained from two 24-hour recalls in 2253 participants (47% males). Vitamin B biomarkers were assessed in a subsample of 977 participants (46% males). Socioeconomic factors were assessed by questionnaire, and 1-way analysis of covariance and linear regression analysis were applied. For males and females, mean intakes of folate were 211.19 and 177.18 mu g/d, and for vitamin B-12, 5.98 and 4.54 mu g/d, respectively. Levels of plasma folate, red blood cell folate, serum B-12, and holotranscobalamin were 18.74, 807.19, 330.64, and 63.04 nmol/L in males, respectively, and 19.13, 770.16, 377.9, and 65.63 nmol/L in females, respectively. Lower folate intakes were associated with several SEFs, including maternal and paternal education in both sexes. Regarding folate biomarkers, lower plasma folate intakes were associated with single/shared care in males and with lower paternal occupation in females. Lower vitamin B-12 intakes were associated with almost all the studied SEFs, except paternal occupation in both sexes. In females, when considering vitamin B-12 biomarkers, lower plasma vitamin B-12 was associated with lower maternal education and occupation, and lower holotranscobalamin was associated with lower maternal education and lower paternal occupation. In conclusion, from the set of socioeconomic determinants studied in a sample of European adolescents, maternal education and paternal occupation were more consistently associated with folate and vitamin B-12 intakes and biomarkers concentrations

Nivelación de Lenguaje - HU24 - 201702

Descripción: Nivelación de Lenguaje es un curso de formación general, de carácter práctico, dirigido a estudiantes de primeros ciclos. Esta asignatura busca desarrollar habilidades de redacción prácticas, aterrizadas en un correlato real de escritura determinado: un correo electrónico, una publicación de Facebook, etc. Para ello, el curso se orienta a afianzar las habilidades relacionadas con la organización del texto, así como los conocimientos básicos sobre la normativa de la lengua española. Lo aprendido en esta asignatura ofrecerá al estudiante las herramientas lingüísticas básicas idóneas para desarrollarse con suficiencia en una redacción cotidiana, en un comentario en sus redes sociales o en un examen de algún curso. Propósito: El curso desarrolla la competencia de Comunicación Escrita, en el nivel 1; es decir, el estudiante es capaz de construir mensajes coherentes y sólidos que se adecúan a la situación y propósito comunicativo. Este desarrollo le permite la generación y construcción de nuevas ideas, lo cual es relevante para su vida académica y profesional. La actual sociedad de la información y el conocimiento, caracterizada por la disrupción, la innovación y la complejidad en las formas de comunicación mediadas por la tecnología, enfrenta al estudiante y al profesional a nuevos retos en las maneras de comunicar aquello que conoce y que construye. En este escenario, la competencia comunicativa escrita adquiere protagonismo como herramienta para transmitir el conocimiento creado. El curso se alinea con esta exigencia, pues contribuye a que el estudiante responda exitosamente a las demandas comunicativas del contexto académico, y a que el egresado pueda desenvolverse idóneamente en el campo profesional y laboral

Dietary lipid intake only partially influences variance in serum phospholipid fatty acid composition in adolescents: impact of other dietary factors

The present study aimed to assess the correlation between food and fatty acid (FA) intake and the serum phospholipid (PL) FA status in European adolescents and explored the percentage of variation in serum PL FA that could be attributed to dietary habits. Participants included 528 adolescents recruited in the HELENA Study. Dietary intake was assessed by two, self-administered, non-consecutive 24-h recalls. PL FA concentrations were measured in fasting venous serum samples. Reduced rank regressions were applied to examine the combined effect of food intakes. Results indicated that the variance in serum PL FA in adolescents, that could be explained by diet varied from 7.0 % for MUFA to 14.2 % for n-3FA. The variance in the long-chain n-3FA was mainly explained by fish intake but also by coffee and tea consumption. In conclusion this study indicated that dietary intake influences the serum PL FA status to a limited amount but that also other factors interfere. However, dietary intake is important as it is among those factors that could be modified. Furthermore, the results suggest that the overall dietary habits should be considered instead of only the consumption of single foods or nutrients, as the medium of the food or concomitant intake of foods and nutrients might interact and as such influence absorption or metabolism