Randomized Phase II Trial of Exercise, Metformin, or Both on Metabolic Biomarkers in Colorectal and Breast Cancer Survivors.

Background: Observational data support inverse relationships between exercise or metformin use and disease outcomes in colorectal and breast cancer survivors, although the mechanisms underlying these associations are not well understood.

Methods: In a phase II trial, stage I-III colorectal and breast cancer survivors who completed standard therapy were randomly assigned to structured exercise or metformin or both or neither for 12 weeks. The primary outcome was change in fasting insulin levels; secondary outcomes included changes in other blood-based energetic biomarkers and anthropometric measurements.

Purified oleocanthal and ligstroside protect against mitochondrial dysfunction in models of early Alzheimer's disease and brain ageing.

As components of the Mediterranean diet (MedDiet) olive polyphenols may play a crucial role for the prevention of Alzheimer's disease (AD). Since mitochondrial dysfunction is involved in both, brain ageing and early AD, effects of 10 different purified phenolic secoiridoids (hydroxytyrosol, tyrosol, oleacein, oleuroside, oleuroside aglycon, oleuropein, oleocanthal, ligstroside, ligstroside aglycone and ligustaloside B) and two metabolites (the plant metabolite elenolic acid and the mammalian metabolite homovanillic acid) were tested in very low doses on mitochondrial function in SH-SY5Y-APP cells - a cellular model of early AD. All tested secoiridoids significantly increased basal adenosine triphosphate (ATP) levels in SY5Y-APP cells.

Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans.

Background: Dietary protein ingestion stimulates muscle protein synthesis by providing amino acids to the muscle. The magnitude and duration of the postprandial increase in muscle protein synthesis rates are largely determined by dietary protein digestion and amino acid absorption kinetics.

Objective: We assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans.

Correction to: Increased DNA Damage and Apoptosis in CDKL5-Deficient Neurons.

The original version of this article unfortunately contained error in Fig. 5a to where a panel is missing.

No Association Between Vitamin D Supplementation and Risk of Colorectal Adenomas or Serrated Polyps in a Randomized Trial.

Background & Aims: The effects of vitamin D on risk of colorectal cancer precursors are not clear. We examined the influence of vitamin D supplementation on risk of colorectal adenomas and serrated polyps in a prespecified ancillary study of a large-scale prevention trial (the vitamin D and omegA-3 trial, VITAL) of individuals who were free of cancer and cardiovascular disease at enrollment.

Methods: In VITAL trial, 25,871 adults with no history of cancer or cardiovascular disease (12,786 men 50 years or older and 13,085 women 55 years or older) were randomly assigned to groups given daily dietary supplements (2000 IU vitamin D and 1 g marine n-3 fatty acid) or placebo.

The green tea polyphenol epigallocatechin-3-gallate (EGCG) restores CDKL5-dependent synaptic defects in vitro and in vivo.

CDKL5 deficiency disorder (CDD) is a rare X-linked neurodevelopmental disorder that is characterised by early-onset seizures, intellectual disability, gross motor impairment, and autistic-like features. CDD is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene that encodes a serine/threonine kinase with a predominant expression in the brain. Loss of CDKL5 causes neurodevelopmental alterations in vitro and in vivo, including defective dendritic arborisation and spine maturation, which most likely underlie the cognitive defects and autistic features present in humans and mice.

Increased DNA Damage and Apoptosis in CDKL5-Deficient Neurons.

Mutations in the CDKL5 gene, which encodes a serine/threonine kinase, causes a rare encephalopathy, characterized by early-onset epilepsy and severe intellectual disability, named CDKL5 deficiency disorder (CDD). In vitro and in vivo studies in mouse models of Cdkl5 deficiency have highlighted the role of CDKL5 in brain development and, in particular, in the morphogenesis and synaptic connectivity of hippocampal and cortical neurons. Interestingly, Cdkl5 deficiency in mice increases vulnerability to excitotoxic stress in hippocampal neurons.

Physical activity compared to adiposity and risk of liver-related mortality: Results from two prospective, nationwide cohorts.

Background & Aims: Obesity in adulthood has been associated with increased risk of liver-related mortality. Whether higher levels of physical activity counteract the excess risk conferred by obesity remains unknown. We simultaneously evaluated the long-term impact of physical activity and adiposity on liver-related mortality, within 2 nationwide populations.

Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data.

Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation.

Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer.

Fusobacterium nucleatum (F. nucleatum), which has been associated with colorectal carcinogenesis, can impair anti-tumour immunity, and actively invade colon epithelial cells. Considering the critical role of autophagy in host defence against microorganisms, we hypothesised that autophagic activity of tumour cells might influence the amount of F.

Endogenous sex hormones and colorectal cancer survival among men and women.

Although previous studies have suggested a potential role of sex hormones in the etiology of colorectal cancer (CRC), no study has yet examined the associations between circulating sex hormones and survival among CRC patients. We prospectively assessed the associations of prediagnostic plasma concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone and sex hormone-binding globulin (SHBG) with CRC-specific and overall mortality among 609 CRC patients (370 men and 239 postmenopausal women not taking hormone therapy at blood collection) from four U.S.

On-site blood culture incubation shortens the time to knowledge of positivity and microbiological results in septic patients.

Introduction: To determine whether on-site incubation of blood cultures at the intensive care unit (ICU) improves not only the time to incubation but also time to positivity, time to knowledge of positivity and time to results (identification and antibiotic susceptibility testing).

Methods: This observational single-centre study in ICU patients with severe sepsis and septic shock investigated the impact of blood culture incubation immediately on-site at the ICU (ICU group) by comparison with traditional processing in a remote laboratory (LAB group) on different time intervals of blood culture diagnostics from obtaining blood to clinician notification of final result. The effect of on-site incubation was evaluated in Kaplan-Meier estimates for the time to positivity, time to knowledge of positivity and time to microbiological results and a linear mixed model was built.

Postexercise cooling impairs muscle protein synthesis rates in recreational athletes.

Key Points: Protein ingestion and cooling are strategies employed by athletes to improve postexercise recovery and, as such, to facilitate muscle conditioning. However, whether cooling affects postprandial protein handling and subsequent muscle protein synthesis rates during recovery from exercise has not been assessed. We investigated the effect of postexercise cooling on the incorporation of dietary protein-derived amino acids into muscle protein and acute postprandial (hourly) as well as prolonged (daily) myofibrillar protein synthesis rates during recovery from resistance-type exercise over 2 weeks.

Effect of Supplementation With Marine ω-3 Fatty Acid on Risk of Colorectal Adenomas and Serrated Polyps in the US General Population: A Prespecified Ancillary Study of a Randomized Clinical Trial.

Importance: Marine ω-3 fatty acid has been suggested to protect against colorectal cancer.

Objective: To assess the effect of daily marine ω-3 fatty acid supplementation on the risk of colorectal cancer precursors, including conventional adenomas and serrated polyps.

Design, Setting, And Participants: This study was a prespecified ancillary study of the placebo-controlled randomized clinical trial VITAL (Vitamin D and Omega-3 Trial).

When Wounds Are Good for You: The Regenerative Capacity of Fractional Resurfacing and Potential Utility in Chronic Wound Prevention.

Fractional resurfacing involves producing arrays of microinjuries on the skin, by thermal or mechanical means, to trigger tissue regeneration. Originally developed for cosmetic enhancement, fractional resurfacing induces a broad array of improvements in the structural and functional qualities of the treated skin and is especially effective at returning defective skin to a more normal state. In addition to fascinating questions about the nature of this remarkable regenerative capacity, there may be potential utility in ulcer prevention by halting or even reversing the progressive decline in overall skin quality that usually precedes chronic wound development.

Shared Genetic Etiology of Obesity-Related Traits and Barrett's Esophagus/Adenocarcinoma: Insights from Genome-Wide Association Studies.

Background: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits.

In Vivo Reflectance Confocal Microscopy of Gold Microparticles Deposited in the Skin. A Case Report on Cutaneous Chrysiasis.

Cutaneous chrysiasis is gold deposition in the dermis, described after parenteral administration of gold salts or after topical exposure to gold-containing materials. Gold microparticles (GMPs) have versatile therapeutic effects and are increasingly used in medicine. This case report describes the development of a blue-gray macule following the facial application of GMPs and laser treatment of acne vulgaris.

Medical Etiologies of Secondary Psychosis in Children and Adolescents.

This is an updated review of child and adolescent somatic disorders associated with psychosis/psychotic symptoms, organized into neurologic, infectious, genetic, inborn errors of metabolism, autoimmune, rheumatologic, endocrine, nutritional, metabolic, and iatrogenic categories. When possible clinical manifestations or types of psychotic symptoms and proposed neuropathogenesis causing the neuropsychiatric symptoms are included. In some cases, the psychiatric symptoms may be the first presentation of the disease.

Dietary Intake of Branched-Chain Amino Acids and Risk of Colorectal Cancer.

Branched-chain amino acids (BCAA) are essential amino acids, and emerging evidence suggests that BCAAs may mediate pathways related to cancer progression, possibly due to their involvement in insulin metabolism. We investigated the association between dietary intake of BCAAs with colorectal cancer risk in three prospective cohorts: the Nurses' Health Study I [(NHS), number of participants () at baseline = 77,017], NHS II ( = 92,984), and the Health Professionals Follow-up Study [(HPFS) = 47,255]. Validated food frequency questionnaires were administered every 4 years and follow-up questionnaires on lifestyle biennially.

Night-Shift Work Duration and Risk of Colorectal Cancer According to and Expression.

Background: We hypothesized that the risk of colorectal cancer in night-shift workers might be different according to insulin receptor substrate status.

Methods: Among 77,470 eligible women having night work assessed in the Nurses' Health Study, we documented a total of 1,397 colorectal cancer cases, of which 304 or 308 had available data on and , respectively. We used duplication-method Cox proportional hazards regression analysis for competing risks to calculate HRs and 95% confidence intervals (CI) for each colorectal cancer subtype.

An MCMC computational approach for a continuous time state-dependent regime switching diffusion process.

State-dependent regime switching diffusion processes or hybrid switching diffusion (HSD) processes are hard to simulate with classical methods which leads us to adopt a Markov chain Monte Carlo (MCMC) Bayesian approach very convenient to estimate complicated models such as the HSD one. In the HSD, the diffusion component is dependent on the switching discrete hidden regimes and the transition rates of the regime switching are dependent on the diffusion observations. Since in reality phenomena are only observed in discrete times, data imputation is called for to create more observations so as to have good approximations for the density of the diffusion process.

Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity.

Immunotherapy has transformed cancer treatment. However, current immunotherapy modalities face various limitations. In the present study, we developed multiplexed activation of endogenous genes as an immunotherapy (MAEGI), a new form of immunotherapy that elicits antitumor immunity through multiplexed activation of endogenous genes in tumors.

Plasma 25-Hydroxyvitamin D Levels and Survival in Patients with Advanced or Metastatic Colorectal Cancer: Findings from CALGB/SWOG 80405 (Alliance).

Purpose: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic colorectal cancer.

Experimental Design: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic colorectal cancer participating in a randomized phase III clinical trial of first-line chemotherapy plus biologic therapy.