An analysis of the immune compartment within bovine adipose tissue.

Adipose tissue (AT) has wide functions as an active endocrine organ acting as a site of nutrient storage and thermogenesis. Recently it has been identified as having a key role in murine and human immunity and inflammation. Type 1 or type 2 immune responses and their respective cytokines have been linked to white or brown AT, respectively. Most dramatic is the involvement of type-2 innate lymphoid cells (ILC2s) in stimulating eosinophil recruitment via interleukin (IL)-13 which in turn stimulates alternative macrophage activation via IL-4/IL-13. Recruited leukocytes are capable of influencing the cellular composition and function of adipose tissue and present a route to combat human obesity, however these processes are poorly understood in ruminants. Here we have characterised the resident leukocytes populations within bovine mesenteric AT (MAT) and subcutaneous AT (SAT), compared with the corresponding mesenteric lymph node (MLN). Concurring with related studies, we find bovine AT has its own resident leukocyte populations where eosinophils and neutrophils dominate. Importantly the proportion of eosinophils or neutrophils corresponded to the adipocyte size found in both depots. Further exploration of this area may have important implications on the food production industry or could be applied to improve the course of pathogenesis during disease

The Lifestyle Information and Intervention Preferences of Teenage and Young Adult Cancer Survivors: A Qualitative Study

Background: Little is currently known about how best to promote healthy lifestyle choices among teenage and young adult (TYA) cancer survivors. Such data gathered from a patient-centered perspective are instrumental for the development of health behavior change interventions for young people with cancer. Objective: This study aimed to explore the lifestyle information needs of TYA cancer survivors and their preferences regarding lifestyle information and intervention delivery. Lifestyle behaviors of interest were physical activity, diet, smoking, alcohol consumption, and sun safety. Methods: A total of 13 TYA cancer survivors (mean age, 22.9 years) participated in 10 individual interviews and 1 focus group (n = 3). Each interview and focus group followed the same semistructured interview guide, which was designed to explore young peoples’ motivation behind leading a healthy lifestyle, their past experience of searching for lifestyle information, and their preferences relating to lifestyle information delivery. Results: Three core themes emerged: cancer as a catalyst to lifestyle behavior change, factors influencing health behavior change, and health behavior information preferences. Social support emerged as facilitator of both health behavior change and self-efficacy. Conclusion: Young people with cancer want age-appropriate lifestyle information on a range of topics delivered in multiple formats at various time points. Implications for Practice: Health professionals working with TYA cancer survivors should address young peoples’ lifestyle information needs throughout the cancer care pathway and support young people to foster the confidence to make, and sustain, positive lifestyle behavior changes

Study of Foaming Properties and Effect of the Isomeric Distribution of Some Anionic Surfactants

Using different reaction conditions of photosulfochlorination of n-dodecane, two samples of anionic surfactants of sulfonate type are obtained. Their micellar behavior has been already reported and the relationship between their isomeric distribution and their chemical structures and micellar behaviors have been more thoroughly explored. In this investigation, we screened the foaming properties (foaming power and foam stability) by a standardized method very similar to the Ross–Miles foaming tests to identify which surfactants are suitable for applications requiring high foaming, or, alternatively, low foaming. The results obtained for the synthesized surfactants are compared to those obtained for an industrial sample of secondary alkanesulfonate (Hostapur 60) and to those of a commercial sample of sodium dodecylsulfate used as reference for anionic surfactants. The foam formation and foam stability of aqueous solutions of the two samples of dodecanesulfonate are compared as a function of their isomeric distribution. These compounds show good foaming power characterized in most cases by metastable or dry foams. The highest foaming power is obtained for the sample rich in primary isomers which also produces foam with a relatively high stability. For the sample rich in secondary isomers we observe under fixed conditions a comparable initial foam height but the foam stability turns out to be low. This property is interesting for applications requiring low foaming properties such as dishwashing liquid for machines. The best results are observed near and above the critical micellar concentrations and at 25 C for both the samples

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

Exercise-induced improvements in liver fat and endothelial function are not sustained 12 months following cessation of exercise supervision in non-alcoholic fatty liver disease (NAFLD).

AIMS: Supervised exercise reduces liver fat and improves endothelial function, a surrogate of cardiovascular disease risk, in non-alcoholic fatty liver disease (NAFLD). We hypothesised that after a 16-week supervised exercise program, patients would maintain longer-term improvements in cardiorespiratory fitness, liver fat and endothelial function. MATHERIALS AND METHODS: Ten NAFLD patients [5/5 males/females, age 51±13years, BMI 31±3 kg.m(2) (mean±s.d.)] underwent a 16-week supervised moderate-intensity exercise intervention. Biochemical markers, cardiorespiratory fitness (VO2peak), subcutaneous, visceral and liver fat (measured by magnetic resonance imaging and spectroscopy respectively) and brachial artery flow-mediated dilation (FMD) were assessed at baseline, after 16 weeks supervised training and 12-months after ending supervision. RESULTS: Despite no significant change in body weight, there were significant improvements in VO2peak [6.5 ml.kg(-1).min(-1) (95% CI 2.8, 10.1); P=0.003], FMD [2.9% (1.5, 4.2); P=0.001], liver transaminases (P0.05) and liver fat [1.4% (-13.0, 15.9); P=0.83] were not significantly different from baseline. CONCLUSIONS: Twelve months following cessation of supervision, exercise-mediated improvements in liver fat and other cardiometabolic variables had reversed with cardiorespiratory fitness at baseline levels. Maintenance of high cardiorespiratory fitness and stability of body weight are critical public health considerations for the treatment of NAFLD.International Journal of Obesity accepted article preview online, 21 July 2016. doi:10.1038/ijo.2016.123

Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma.

BACKGROUND: Sunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are both approved for advanced renal cell carcinoma (RCC) as first-line and second-line therapy, respectively. In the clinics, sunitinib treatment is limited by the emergence of acquired resistance, leading to a switch to second-line treatment at progression, often based on everolimus. No data have been yet generated on programmed alternating sequential strategies combining alternative use of sunitinib and everolimus before progression. Such strategy is expected to delay the emergence of acquired resistance and improve tumour control. The aim of our study was to assess the changes in tumours induced by three different sequences administration of sunitinib and everolimus. METHODS: In human Caki-1 RCC xenograft model, sunitinib was alternated with everolimus every week, every 2 weeks, or every 3 weeks. Effects on necrosis, hypoxia, angiogenesis, and EMT status were assessed by immunohisochemistry and immunofluorescence. RESULTS: Sunitinib and everolimus programmed sequential regimens before progression yielded longer median time to tumour progression than sunitinib and everolimus monotherapies. In each group of treatment, tumour growth control was associated with inhibition of mTOR pathway and changes from a mesenchymal towards an epithelial phenotype, with a decrease in vimentin and an increase in E-cadherin expression. The sequential combinations of these two agents in a RCC mouse clinical trial induced antiangiogenic effects, leading to tumour necrosis. CONCLUSIONS: In summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent

Does hypoglycemia following a glucose challenge test identify a high risk pregnancy?

<p>Abstract</p> <p>Objective</p> <p>An association between maternal hypoglycemia during pregnancy with fetal growth restriction and overall perinatal mortality has been reported. In a retrospective pilot study we found that hypoglycemia was linked with a greater number of special care/neonatal intensive care unit admissions and approached significance in the number of women who developed preeclampsia. That study was limited by its retrospective design, a narrow patient population and the inability to perform multivariate analysis because of the limitations in the data points collected. This study was undertaken to compare the perinatal outcome in pregnancies with hyoglycemia following a glucose challenge test (GCT) to pregnancies with a normal GCT.</p> <p>Methods</p> <p>Obstetric patients (not pre-gestational diabetics or gestational diabetes before 24 weeks were eligible. Women with a 1 hour glucose ≤ 88 mg/dL (4.8 m/mol) following a 50-gram oral GCT were matched with the next patient with a 1 hour glucose of 89–139 mg/dL. Pregnancy outcomes were evaluated.</p> <p>Results</p> <p>Over 22 months, 436 hypoglycemic patients and 434 normal subjects were identified. Hypoglycemia was increased in women < 25 (p = 0.003) and with pre-existing medical conditions (p < 0.001). Hypoglycemia was decreased if pre-pregnancy BMI ≥ 30 (p = 0.008).</p> <p>Preeclampsia/eclampsia was more common in hypoglycemic women. (OR = 3.13, 95% CI 1.51 – 6.51, p = 0.002) but not other intrapartum and perinatal outcomes.</p> <p>Conclusion</p> <p>Hypoglycemic patients are younger, have reduced pre-pregnancy weight, lower BMIs, and are more likely to develop preeclampsia than normoglycemic women.</p

Development of a highly sensitive liquid biopsy platform to detect clinically-relevant cancer mutations at low allele fractions in cell-free DNA.

INTRODUCTION: Detection and monitoring of circulating tumor DNA (ctDNA) is rapidly becoming a diagnostic, prognostic and predictive tool in cancer patient care. A growing number of gene targets have been identified as diagnostic or actionable, requiring the development of reliable technology that provides analysis of multiple genes in parallel. We have developed the InVision™ liquid biopsy platform which utilizes enhanced TAm-Seq™ (eTAm-Seq™) technology, an amplicon-based next generation sequencing method for the identification of clinically-relevant somatic alterations at low frequency in ctDNA across a panel of 35 cancer-related genes. MATERIALS AND METHODS: We present analytical validation of the eTAm-Seq technology across two laboratories to determine the reproducibility of mutation identification. We assess the quantitative performance of eTAm-Seq technology for analysis of single nucleotide variants in clinically-relevant genes as compared to digital PCR (dPCR), using both established DNA standards and novel full-process control material. RESULTS: The assay detected mutant alleles down to 0.02% AF, with high per-base specificity of 99.9997%. Across two laboratories, analysis of samples with optimal amount of DNA detected 94% mutations at 0.25%-0.33% allele fraction (AF), with 90% of mutations detected for samples with lower amounts of input DNA. CONCLUSIONS: These studies demonstrate that eTAm-Seq technology is a robust and reproducible technology for the identification and quantification of somatic mutations in circulating tumor DNA, and support its use in clinical applications for precision medicine

The ethics of digital well-being: a multidisciplinary perspective

This chapter serves as an introduction to the edited collection of the same name, which includes chapters that explore digital well-being from a range of disciplinary perspectives, including philosophy, psychology, economics, health care, and education. The purpose of this introductory chapter is to provide a short primer on the different disciplinary approaches to the study of well-being. To supplement this primer, we also invited key experts from several disciplines—philosophy, psychology, public policy, and health care—to share their thoughts on what they believe are the most important open questions and ethical issues for the multi-disciplinary study of digital well-being. We also introduce and discuss several themes that we believe will be fundamental to the ongoing study of digital well-being: digital gratitude, automated interventions, and sustainable co-well-being