Rationale, design and study protocol of the ‘Strong Families Start at Home’ feasibility trial to improve the diet quality of low-income, ethnically diverse children by helping parents improve their feeding and food preparation practices

There is an urgent need to create effective interventions that help parents establish a healthy diet among their children early in life, especially among low-income and ethnically and racially diverse families. U.S. children eat too few fruits, vegetables and whole grains, and too many energy dense foods, dietary behaviors associated with increased morbidity from chronic diseases. Parents play a key role in shaping children\u27s diets. Best practices suggest that parents should involve children in food preparation, and offer, encourage and model eating a variety of healthy foods. In addition, while parents help to shape food preferences, not all children respond in the same way. Certain child appetitive traits, such as satiety responsiveness (sensitivity to internal satiety signals), food responsiveness (sensitivity to external food cues), and food fussiness may help explain some of these differences. Prior interventions to improve the diet of preschool children have not used a holistic approach that targets the home food environment, by focusing on food quality, food preparation, and positive feeding practices while also acknowledging a child\u27s appetitive traits. This manuscript describes the rationale and design for a 6-month pilot randomized controlled trial, Strong Families Start at Home, that randomizes parents and their 2-to 5-year old children to either a home-based environmental dietary intervention or an attention-control group. The primary aim of the study is to explore the feasibility and acceptability of the intervention and evaluation and to determine the intervention\u27s preliminary efficacy on child diet quality, feeding practices, and availability of healthy foods in the home

Systematic comparison of the functional physico-chemical characteristics and biocidal activity of microbial derived biosurfactants on blood-derived and breast cancer cells

Hypothesis The cytotoxicity of biosurfactants on cell membranes may be influenced by composition of their hydrophilic head and hydrophobic tails. It is hypothesised that they form mixed micelles which exert a detergent-like effect that disrupts the plasma membrane. The functional physico-chemical and biocidal characteristics of four biosurfactants were concurrently investigated to determine which of their structural characteristics may be tuned for greater efficacy. Experiments Rhamnolipid-95, rhamnolipid-90, surfactin and sophorolipid were characterised using FTIR, LC-MS, HPLC, surface tension and critical micelle concentration. Their biocidal activity against HEK 293, MCF-7 and THP-1 cell lines were investigated by MTT assay, using doxorubicin as cytotoxic control. Growth curves were established for all cell lines using trypan blue (TB) and MTT assays, corresponding doubling time (DT) and growth rate were obtained and compared. Findings HEK 293 cell-line had the highest growth rate amongst the three cell lines. For TB assay, growth of HEK 293 > THP-1 and for MTT, HEK 293 > MCF-7 while the DT was in the order of THP-1 > MCF-7 > HEK 293. Sophorolipid showed anti-proliferative activity comparable to doxorubicin on THP-1 > MCF-7 > HEK 293. THP-1 showed high sensitivity to sophorolipid with IC50 of 10.50, 25.58 and 6.78 (μg/ml) after 24, 48 and 72 hr respectively. However, sophorolipid was cytotoxic from 24-72 hr on HEK 293 cell lines with IC50 of 21.53, 40.57 and 27.53 μg/ml respectively. Although, doxorubicin showed higher anti-proliferative activity than all biosurfactants, it had poorer selectivity index for the same time durations compared to the biosurfactants. This indicates that biosurfactants were more effective for slowing the growth of the tested cancer cell lines and hence may be potential candidates for use in human cancer therapy. Physico-chemical characteristics of the biosurfactants suggest that their mechanism of action may be due to activity on the cell membrane

SHORT syndrome due to a novel de novo mutation in PRKCE (Protein Kinase Cɛ) impairing TORC2-dependent AKT activation.

SHORT syndrome is a rare, recognizable syndrome resulting from heterozygous mutations in PIK3R1 encoding a regulatory subunit of phosphoinositide-3-kinase (PI3K). The condition is characterized by short stature, intrauterine growth restriction, lipoatrophy and a facial gestalt involving a triangular face, deep set eyes, low hanging columella and small chin. PIK3R1 mutations in SHORT syndrome result in reduced signaling through the PI3K-AKT-mTOR pathway. We performed whole exome sequencing for an individual with clinical features of SHORT syndrome but negative for PIK3R1 mutation and her parents. A rare de novo variant in PRKCE was identified. The gene encodes PKCε and, as such, the AKT-mTOR pathway function was assessed using phospho-specific antibodies with patient lymphoblasts and following ectopic expression of the mutant in HEK293 cells. Kinase analysis showed that the variant resulted in a partial loss-of-function. Whilst interaction with PDK1 and the mTORC2 complex component SIN1 was preserved in the mutant PKCε, it bound to SIN1 with a higher affinity than wild-type PKCε and the dynamics of mTORC2-dependent priming of mutant PKCε was altered. Further, mutant PKCε caused impaired mTORC2-dependent pAKT-S473 following rapamycin treatment. Reduced pFOXO1-S256 and pS6-S240/244 levels were also observed in the patient LCLs. To date, mutations in PIK3R1 causing impaired PI3K-dependent AKT activation are the only known cause of SHORT syndrome. We identify a SHORT syndrome child with a novel partial loss-of-function defect in PKCε. This variant causes impaired AKT activation via compromised mTORC2 complex function

Carbon Sequestration in Synechococcus Sp.: From Molecular Machines to Hierarchical Modeling

The U.S. Department of Energy recently announced the first five grants for the Genomes to Life (GTL) Program. The goal of this program is to "achieve the most far-reaching of all biological goals: a fundamental, comprehensive, and systematic understanding of life." While more information about the program can be found at the GTL website (www.doegenomestolife.org), this paper provides an overview of one of the five GTL projects funded, "Carbon Sequestration in Synechococcus Sp.: From Molecular Machines to Hierarchical Modeling." This project is a combined experimental and computational effort emphasizing developing, prototyping, and applying new computational tools and methods to ellucidate the biochemical mechanisms of the carbon sequestration of Synechococcus Sp., an abundant marine cyanobacteria known to play an important role in the global carbon cycle. Understanding, predicting, and perhaps manipulating carbon fixation in the oceans has long been a major focus of biological oceanography and has more recently been of interest to a broader audience of scientists and policy makers. It is clear that the oceanic sinks and sources of CO2 are important terms in the global environmental response to anthropogenic atmospheric inputs of CO2 and that oceanic microorganisms play a key role in this response. However, the relationship between this global phenomenon and the biochemical mechanisms of carbon fixation in these microorganisms is poorly understood. The project includes five subprojects: an experimental investigation, three computational biology efforts, and a fifth which deals with addressing computational infrastructure challenges of relevance to this project and the Genomes to Life program as a whole. Our experimental effort is designed to provide biology and data to drive the computational efforts and includes significant investment in developing new experimental methods for uncovering protein partners, characterizing protein complexes, identifying new binding domains. We will also develop and apply new data measurement and statistical methods for analyzing microarray experiments. Our computational efforts include coupling molecular simulation methods with knowledge discovery from diverse biological data sets for high-throughput discovery and characterization of protein-protein complexes and developing a set of novel capabilities for inference of regulatory pathways in microbial genomes across multiple sources of information through the integration of computational and experimental technologies. These capabilities will be applied to Synechococcus regulatory pathways to characterize their interaction map and identify component proteins in these pathways. We will also investigate methods for combining experimental and computational results with visualization and natural language tools to accelerate discovery of regulatory pathways. Furthermore, given that the ultimate goal of this effort is to develop a systems-level of understanding of how the Synechococcus genome affects carbon fixation at the global scale, we will develop and apply a set of tools for capturing the carbon fixation behavior of complex of Synechococcus at different levels of resolution. Finally, because the explosion of data being produced by high-throughput experiments requires data analysis and models which are more computationally complex, more heterogeneous, and require coupling to ever increasing amounts of experimentally obtained data in varying formats, we have also established a companion computational infrastructure to support this effort as well as the Genomes to Life program as a whole.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63164/1/153623102321112746.pd

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011