Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC

Does surgical procedure type impact postoperative pain and recovery in deep inferior epigastric artery perforator flap breast reconstruction?

Background: The deep inferior epigastric artery perforator (DIEP) flap is the commonest flap used for breast reconstruction after mastectomy. It is performed as a unilateral (based on one [unipedicled] or two [bipedicled] vascular pedicles) or bilateral procedure following unilateral or bilateral mastectomies. No previous studies have comprehensively analyzed analgesia requirements and hospital stay of these three forms of surgical reconstruction. Methods: A 7-year retrospective cohort study (2008–2015) of a single-surgeon’s DIEP-patients was conducted. Patient-reported pain scores, patient-controlled morphine requirements and recovery times were compared using non-parametric statistics and multivariable regression. Results: The study included 135 participants: unilateral unipedicled (n=84), unilateral bipedicled (n=24) and bilateral unipedicled (n=27). Univariate comparison of the three DIEP types showed a significant difference in 12-hour postoperative morphine requirements (P=0.020); bipedicled unilateral patients used significantly less morphine than unipedicled (unilateral) patients at 12 (P=0.005), 24 (P=0.020), and 48 (P=0.046) hours. Multivariable regression comparing these two groups revealed that both reconstruction type and smoking status were significant predictors for 12-hour postoperative morphine usage (P=0.038 and P=0.049, respectively), but only smoking, remained significant at 24 (P=0.010) and 48 (P=0.010) hours. Bilateral reconstruction patients’ mean hospital stay was 2 days longer than either unilateral reconstruction (P<0.001). Conclusions: Although all three forms of DIEP flap breast reconstruction had similar postoperative pain measures, a novel finding of our study was that bipedicled DIEP flap harvest might be associated with lower early postoperative morphine requirements. Bilateral and bipedicled procedures in appropriate patients might therefore be undertaken without significantly increased pain/morbidity compared to unilateral unipedicled reconstructions

QCD sum rules analysis of the rare radiative Bc -> D*_s gamma decay

In this work, the radiative Bc -> D*_s gamma decay is investigated in the framework of QCD sum rules. The transition form factors responsible for the decay are calculated. The branching ratio for this decay is estimated to be order of 10^-5 which can be measurable at LHC.Comment: 29 pages, Three Figures and two Table

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

The role of intrinsic muscle mechanics in the neuromuscular control of stable running in the guinea fowl

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66308/1/jphysiol.2009.171017.pd

Evaluation of metabolic syndrome in adults of Talca city, Chile

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.[Please see the Supplementary Note for acknowledgments.]This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.337

Metabolic syndrome: definitions and controversies

Metabolic syndrome (MetS) is a complex disorder defined by a cluster of interconnected factors that increase the risk of cardiovascular atherosclerotic diseases and diabetes mellitus type 2. Currently, several different definitions of MetS exist, causing substantial confusion as to whether they identify the same individuals or represent a surrogate of risk factors. Recently, a number of other factors besides those traditionally used to define MetS that are also linked to the syndrome have been identified. In this review, we critically consider existing definitions and evolving information, and conclude that there is still a need to develop uniform criteria to define MetS, so as to enable comparisons between different studies and to better identify patients at risk. As the application of the MetS model has not been fully validated in children and adolescents as yet, and because of its alarmingly increasing prevalence in this population, we suggest that diagnosis, prevention and treatment in this age group should better focus on established risk factors rather than the diagnosis of MetS

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation