Active surveillance for favorable-risk prostate cancer: Is there a greater psychological impact than previously thought? A systematic, mixed studies literature review.

OBJECTIVE: Active surveillance (AS) allows men with favorable-risk prostate cancer to avoid or postpone active treatment and hence spares potential adverse effects for a significant proportion of these patients. Active surveillance may create an additional emotional burden for these patients. The aim of the review was to determine the psychological impact of AS to inform future study in this area and to provide recommendations for clinical practice. METHODS: Studies were identified through database searching from inception to September 2015. Quantitative or qualitative noninterventional studies published in English that assessed the psychological impact of AS were included. The Mixed Methods Appraisal Tool was used to assess methodological quality. RESULTS: Twenty-three papers were included (20 quantitative and 3 qualitative). Quantitatively, the majority of patients do not report psychological difficulties; however, when appropriateness of study design is considered, the conclusion that AS has minimal impact on well-being may not be accurate. This is due to small sample sizes, inappropriately timed baseline, and inappropriate/lack of comparison groups. In addition, a mismatch in outcome was noted between the outcome of quantitative and qualitative studies in uncertainty, with qualitative studies indicating a greater psychological impact. CONCLUSIONS: Because of methodological concerns, many quantitative studies may not provide a true account of the burden of AS. Further mixed-methods studies are necessary to address the limitations highlighted and to provide clarity on the impact of AS. Practitioners should be aware that despite findings of previous reviews, patients may require additional emotional support

Unravelling the metabolic impact of SBS-associated microbial dysbiosis: Insights from the piglet short bowel syndrome model

peer-reviewedLiver disease is a major source of morbidity and mortality in children with short bowel syndrome (SBS). SBS-associated microbial dysbiosis has recently been implicated in the development of SBS-associated liver disease (SBS-ALD), however the pathological implications of this association have not been explored. In this study high-throughput sequencing of colonic content from the well-validated piglet SBS-ALD model was examined to determine alterations in microbial communities, and concurrent metabolic alterations identified in urine samples via targeted mass spectrometry approaches (GC-MS, LC-MS, FIA-MS) further uncovered impacts of microbial disturbance on metabolic outcomes in SBS-ALD. Multi-variate analyses were performed to elucidate contributing SBS-ALD microbe and metabolite panels and to identify microbe-metabolite interactions. A unique SBS-ALD microbe panel was clearest at the genus level, with discriminating bacteria predominantly from the Firmicutes and Bacteroidetes phyla. The SBS-ALD metabolome included important alterations in the microbial metabolism of amino acids and the mitochondrial metabolism of branched chain amino acids. Correlation analysis defined microbe-metabolite clustering patterns unique to SBS-ALD and identified a metabolite panel that correlates with dysbiosis of the gut microbiome in SBS

Inferring copy number and genotype in tumour exome data

Background: Using whole exome sequencing to predict aberrations in tumours is a cost effective alternative to whole genome sequencing, however is predominantly used for variant detection and infrequently utilised for detection of somatic copy number variation. Results: We propose a new method to infer copy number and genotypes using whole exome data from paired tumour/normal samples. Our algorithm uses two Hidden Markov Models to predict copy number and genotypes and computationally resolves polyploidy/aneuploidy, normal cell contamination and signal baseline shift. Our method makes explicit detection on chromosome arm level events, which are commonly found in tumour samples. The methods are combined into a package named ADTEx (Aberration Detection in Tumour Exome). We applied our algorithm to a cohort of 17 in-house generated and 18 TCGA paired ovarian cancer/normal exomes and evaluated the performance by comparing against the copy number variations and genotypes predicted using Affymetrix SNP 6.0 data of the same samples. Further, we carried out a comparison study to show that ADTEx outperformed its competitors in terms of precision and F-measure. Conclusions: Our proposed method, ADTEx, uses both depth of coverage ratios and B allele frequencies calculated from whole exome sequencing data, to predict copy number variations along with their genotypes. ADTEx is implemented as a user friendly software package using Python and R statistical language. Source code and sample data are freely available under GNU license (GPLv3) at http://adtex.sourceforge.net/

Flowering of kiwifruit (Actinidia deliciosa) is reduced by long photoperiods

Mature kiwifruit (Actinidia deliciosa ‘Hayward’) vines grown under standard orchard management were exposed to 16-h photoperiods from the longest day in summer until after leaf fall in autumn. Photoperiod extension was achieved with tungsten halogen lamps that produced 2–8 µmols m–2 s–1 photosynthetically active radiation. Long day treatments did not affect fruit dry matter or fruit weight at harvest during the growing season that the treatments were applied or during the following growing season. However, flowering was reduced by 22% during the spring following treatment application. As this reduction in flowering was not accompanied by a decrease in budbreak, the long day effect is not consistent with a delay in the onset of winter chilling. It is suggested therefore, that the observed reduction in flowering may be because of a diminution of floral evocation

ANALYSIS OF THE DIURNAL EXPRESSION PATTERNS OF THE TOMATO CHLOROPHYLL alb BINDING PROTEIN GENES. INFLUENCE OF LIGHT and CHARACTERIZATION OF THE GENE FAMILY *

Steady-state mRNA levels of the chlorophyll alb binding ( cab ) proteins oscillate substantially during a diurnal cycle in tomato leaves. This accumulation pattern is also observed in complete darkness, supporting the hypothesis that the expression of cab genes is at least partially regulated by an endogenous rhythm (“biological clock”). The amplitude of the cab mRNA accumulation is dependent on the duration of illumination and the circadian phase in which light was applied to the tomato plants. These results at the molecular level correlate well with the photoperiodic phenomenon. The characterization of the expression pattern of individual members of the cab gene family was attempted. Distinct primer extension products were detected using specific oligonucleotides homologous to the cab 1, cab 4, cab 5 and cab 8 genes. Based on this analysis the transcription start sites of these genes were determined to be between position -70 and -9 upstream of the ATG codon. During the diurnal cycle the cab 1 and cab 4 genes exhibit the same expression pattern; no transcripts detected at 3 and 6 a.m., maximum mRNA levels were measured at noon and decreasing levels in the afternoon.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74852/1/j.1751-1097.1990.tb01752.x.pd

Investigating the Psychological Impact of Active Surveillance or Active Treatment in Newly Diagnosed Favorable-Risk Prostate Cancer Patients: A 9 month Longitudinal Study

Objective This study aimed to explorethe psychological impact of favorable-risk prostate cancer (PCa) and associated treatment (Active Surveillance (AS) or Active Treatment (AT)), comparing prevalence and temporal variability of generalized anxiety, PCa-specific anxiety, and depression symptoms. Methods PCa patients were recruited at diagnosis prior to treatment decision-making and completed questionnaires assessing anxiety (STAI-6; MAX-PC) and depression symptoms (CES-D) at four timepoints for 9-months. Non-cancer controls were recruited via university staff lists and community groups. Results were analyzed using analysis of variance. Results Fifty-four PCa (AS n=11, AT n=43) and fifty-three non-cancer participants were recruited. The main effect of time or treatment group were not statistically significant for CES-D scores (p>0.05). The main effect of treatment on STAI-6 scores was significant (F(2,73)=4.678, p=0.012) with AS patients reporting highest STAI-6 scores (T1 M=36.56; T2 M=36.89, T3 M=38.46; T4 M=38.89). There was a significant main effect for time since diagnosis on MAX-PC (F(3,123)=3.68, p=0.01), AS patient scored higher than AT at all timepoints (T1 M=10.33 v 10.78; T2 M=11.11 v 11.30; T3 M=13.44 v 10.55; T4 M=11.33 v 8.88), however both groups declined overall with time. Conclusions Men undergoing AS had significantly higher anxiety symptoms than AT and non-cancer participants, contradicting previous literature. This may be due to perceived inactivity of AS relative to traditional narratives of cancer treatment. Participant experiences appear to be less favorable relative to other international centers. Recommendations for future research and clinical practice include the need to improve diagnosis and treatment information provision particularly for lower-risk patients

UV irradiation of skin regulates a murine model of Multiple Sclerosis

Objective: The prevalence of multiple sclerosis follows a latitude gradient, with increased disease at higher latitudes. Previous studies have focused on a vitamin D hypothesis; although recent evidence suggests that exposure to ultraviolet radiation (UVR) itself may be important. In this study, the effects of UVR on the development of experimental autoimmune encephalomyelitis (EAE) were examined. Methods: C57BL/6 mice were irradiated with a single erythemal dose of UVR (8 kJ/m2), or 4 daily sub-erythemal doses (1 kJ/m2), before sensitisation to myelin oligodendrocyte glycoprotein peptide. The UV irradiation protocols used do not increase 25-hydroxyvitamin D concentrations in serum of vitamin D-sufficient mice. The onset of EAE was recorded and mice were clinically monitored for 40 days. Results: A single dose of erythemal UVR (8 kJ/m2) significantly suppressed EAE onset and severity. Four daily exposures of sub-erythemal UVR (1 kJ/m2) also significantly delayed disease onset but was less effective than the erythemal dose. Conclusion: UV irradiation delayed the onset and reduced the severity of EAE. Continued administration of lower dose UVR following disease onset may be necessary to achieve similar results to a single higher dose delivered pre-sensitisation. Our results give further weight to suggestions that UVR exposure may delay MS onset and progression and UVB phototherapy may provide an option for treatment of MS

Atypical ductal hyperplasia: update on diagnosis, management, and molecular landscape

BackgroundAtypical ductal hyperplasia (ADH) is a common diagnosis in the mammographic era and a significant clinical problem with wide variation in diagnosis and treatment. After a diagnosis of ADH on biopsy a proportion are upgraded to carcinoma upon excision; however, the remainder of patients are overtreated. While ADH is considered a non-obligate precursor of invasive carcinoma, the molecular taxonomy remains unknown.Main textAlthough a few studies have revealed some of the key genomic characteristics of ADH, a clear understanding of the molecular changes associated with breast cancer progression has been limited by inadequately powered studies and low resolution methodology. Complicating factors such as family history, and whether the ADH present in a biopsy is an isolated lesion or part of a greater neoplastic process beyond the limited biopsy material, make accurate interpretation of genomic features and their impact on progression to malignancy a challenging task. This article will review the definitions and variable management of the patients diagnosed with ADH as well as the current knowledge of the molecular landscape of ADH and its clonal relationship with ductal carcinoma in situ and invasive carcinoma.ConclusionsMolecular data of ADH remain sparse. Large prospective cohorts of pure ADH with clinical follow-up need to be evaluated at DNA, RNA, and protein levels in order to develop biomarkers of progression to carcinoma to guide management decisions

Insufficient Sun Exposure Has Become a Real Public Health Problem.

This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer's disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. However, oral vitamin D supplementation has not been convincingly shown to prevent the above conditions; thus, serum 25(OH)D as an indicator of vitamin D status may be a proxy for and not a mediator of beneficial effects of sun exposure. New candidate mechanisms include the release of nitric oxide from the skin and direct effects of ultraviolet radiation (UVR) on peripheral blood cells. Collectively, this evidence indicates it would be wise for people living outside the tropics to ensure they expose their skin sufficiently to the sun. To minimize the harms of excessive sun exposure, great care must be taken to avoid sunburn, and sun exposure during high ambient UVR seasons should be obtained incrementally at not more than 5-30 min a day (depending on skin type and UV index), in season-appropriate clothing and with eyes closed or protected by sunglasses that filter UVR