INCOME, WEALTH, AND THE ECONOMIC WELL-BEING OF FARM HOUSEHOLDS

Agricultural policy is rooted in the 1930s notion that providing transfers of money to the farm sector translates into increased economic well-being of farm families. This report shows that changes in income for the farm sector or for any particular group of farm businesses do not necessarily reflect changes confronting farm households. Farm households draw income from various sources, including off-farm work, other businesses operated, and increasingly nonfarm investments. Likewise, focus on a single indicator of well-being, like income, overlooks other indicators such as the wealth held by the household and the level of consumption expenditures for health care, food, housing, and other items. Using an expanded definition of economic well-being, we show that farm households as a whole are relatively better off than the average U.S. household, but that about 6 percent remain economically disadvantaged relative to the rest of the population.Consumption, farm households, income, wealth, well-being, off-farm employment, Consumer/Household Economics,

Assessment of PULP score in predicting 30-day perforated duodenal ulcer morbidity, and comparison of its performance with Boey and ASA, a retrospective study

Background: /aim: Scores commonly employed to risk stratify perforated peptic ulcer patients include ASA (American Society of Anesthesiologists), Boey and peptic ulcer perforation score (PULP). However, few studies assessed and compared the accuracy indices of these three scores in predicting post PPU repair 30-day morbidity. We assessed accuracy indices of PULP, and compared them to Boey and ASA in predicting post perforated duodenal (PDU) ulcer repair 30-day morbidity. Methods: Retrospective chart review of all PDU patients (perforated duodenal ulcers only) at the largest two hospitals in Qatar (N = 152). Data included demographic, clinical, laboratory, operative, and post repair 30-day morbidity. Area under the Curve (AUC), sensitivity and specificity were computed for each of the 3 scores. Multivariate logistic regression assessed the accuracy indices of each score. Results: All patients were males (M age 37.41 years). Post PDU repair 30-day morbidity was 10.5% (16 morbidities). Older age, higher ASA (?3), Boey (?1) or PULP (?8) scores, shock on admission and preoperative comorbidities; and conversely, lower hemoglobin and albumin were all positively significantly associated with higher post PDU 30-day morbidity. PULP displayed the largest AUC (72%), and was the only score to significantly predict 30-day morbidity. The current study is the first to report the sensitivity and specificity of these three scores for post PDU repair 30-day morbidity; and first to assess accuracy indices for PULP in predicting post PDU repair 30-day morbidity. Conclusion: PULP score had the largest AUC and was the only score to significantly predict post PDU repair 30-day morbidity.Scopu

Investigating self-reported efficacy of lifestyle medicine approaches to tackle erectile dysfunction: a cross-sectional eSurvey based study

Background: Erectile dysfunction (ED) is the most common sexual dysfunction in men. Some types of ED are amenable to treatment using lifestyle medicine approaches with or without pharmacotherapy. Aim: Investigate self-reported efficacy of lifestyle medicine approaches to tackle ED. Methods: A cross-sectional online survey of 1177 community dwelling adults explored the prevalence and methods used to tackle ED in the community setting. We examined differences between participants with and without ED. Variables associated with ED in univariable analyses were included in a multivariable logistic regression to identify variables independently associated with the condition. Outcomes: Self-reported measure: perceived effectiveness of lifestyle medicine interventions to tackle ED. Results: Most respondents (76.5%) had experienced ED, and this was associated with having a long-term condition, taking anti-hypertensive medication, hypercholesterolaemia and obesity. Medication was the most common management strategy overall (65.9%), followed by stress management (43.5%) and weight loss (40.4%). Over half (53.9%) did not use any lifestyle modification strategies to tackle ED. Only 7.0% of ED sufferers received a mental health assessment and 29.2% received other tests (e.g., blood test, medical imaging) by GPs. Cardiovascular training was identified as the best rated strategy by its users (37.8%). Supplements (35.1%) and weight training/physical activity (32.6%) were also positively rated. Clinical implications Structured education to general practitioners and community dwelling adults about the impact of lifestyle behaviour modification and how this could influence the appearance or trajectory of ED could help improve personal choice when tackling ED. Strengths and limitations: To our knowledge, this is the first study to collect eSurvey responses from community dwelling adults to gauge their reliance and perceived effectiveness of lifestyle medicine approaches to tackle ED. The principal limitation was the lack of follow-up, and not recording other information including lifestyle factors such as nutrition, smoking, and the use of alcohol and recreational drugs, which may have enabled a fuller exploration of the factors that could influence the primary outcome measures examined. Conclusion: Despite the high prevalence of ED, there is not enough awareness in the community setting about effective and low-cost lifestyle medicine strategies, including cardiovascular training and the use of supplements and weight training, to help tackle this common condition

Anabolic androgenic steroid abuse in the United Kingdom: An update

© 2020 The British Pharmacological Society. This is the peer reviewed version of the following article: Mullen, C, Whalley, BJ, Schifano, F, Baker, JS. Anabolic Androgenic Steroid Abuse in the United Kingdom; An Update The increasing popularity of anabolic androgenic steroids. Br J Pharmacol. 2020, which has been published in final form at https://doi.org/10.1111/bph.14995. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Anabolic androgenic steroids (AASs) are prescribed for medical conditions related to low testosterone. Abuse of AASs has surged as they become recognised as potent image enhancement drugs. The primary goal of most abusers is to obtain a more attractive outward appearance. Abuse is complex. There are a vast range of AAS substances illegally available, the nature of their true composition is difficult to evaluate. Users follow dosing patterns which incorporate a number of different AASs, in addition to other pharmaceutical substances believed to complement the desired physical effects or manage unwanted effects. Animal work and medical case reports suggest potential to cause serious hepatotoxicity, plus possible neurotoxicity, nephrotoxicity and damage to the cardiovascular and reproductive systems. As the long-term AASs users reach maturity, further controlled experimentation, with larger sample sizes, is required. Data gathering should be directed towards the most vulnerable group of AAS users, females and adolescent boys.Peer reviewedFinal Accepted Versio

RNA sequencing supports distinct reactive oxygen species-mediated pathways of apoptosis by high and low size mass fractions of Bay leaf (Lauris nobilis) in HT-29 cells

Anti-proliferative and pro-apoptotic effects of Bay leaf (Laurus nobilis) in mammalian cancer and HT-29 adenocarcinoma cells have been previously attributed to effects of polyphenolic and essential oil chemical species. Recently, we demonstrated differentiated growth-regulating effects of high (HFBL) versus low molecular mass (LFBL) aqueous fractions of bay leaf and now confirm by comparative effects on gene expression, that HFBL and LFBL suppress HT-29 growth by distinct mechanisms. Induction of intra-cellular lesions including DNA strand breakage by extra-cellular HFBL, invoked the hypothesis that iron-mediated reactive oxygen species with capacity to penetrate cell membrane, were responsible for HFBL-mediated effects, supported by equivalent effects of HFBL in combination with γ radiation. Activities of HFBL and LFBL were interpreted to reflect differentiated responses to iron-mediated reactive oxygen species (ROS), occurring either outside or inside cells. In the presence of LFBL, apoptotic death was relatively delayed compared with HFBL. ROS production by LFBL mediated p53-dependent apoptosis and recovery was suppressed by promoting G1/S phase arrest and failure of cellular tight junctions. In comparison, intra-cellular anti-oxidant protection exerted by LFBL was absent for extra-cellular HFBL (likely polysaccharide-rich), which potentiated more rapid apoptosis by producing DNA double strand breaks. Differentiated effects on expression of genes regulating ROS defense and chromatic condensation by LFBL versus HFBL, were observed. The results support ferrous iron in cell culture systems and potentially in vivo, can invoke different extra-cellular versus intra-cellular ROS-mediated chemistries, that may be regulated by exogenous, including dietary species

Role of Histone Acetylation in the Stimulatory Effect of Valproic Acid on Vascular Endothelial Tissue-Type Plasminogen Activator Expression

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BRAF Mutations in Advanced Cancers: Clinical Characteristics and Outcomes

BACKGROUND: Oncogenic BRAF mutations have been found in diverse malignancies and activate RAF/MEK/ERK signaling, a critical pathway of tumorigenesis. We examined the clinical characteristics and outcomes of patients with mutant (mut) BRAF advanced cancer referred to phase 1 clinic. METHODS: We reviewed the records of 80 consecutive patients with mutBRAF advanced malignancies and 149 with wild-type (wt) BRAF (matched by tumor type) referred to the Clinical Center for Targeted Therapy and analyzed their outcome. RESULTS: Of 80 patients with mutBRAF advanced cancer, 56 had melanoma, 10 colorectal, 11 papillary thyroid, 2 ovarian and 1 esophageal cancer. Mutations in codon 600 were found in 77 patients (62, V600E; 13, V600K; 1, V600R; 1, unreported). Multivariate analysis showed less soft tissue (Odds ratio (OR) = 0.39, 95%CI: 0.20-0.77, P = 0.007), lung (OR = 0.38, 95%CI: 0.19-0.73, p = 0.004) and retroperitoneal metastases (OR = 0.34, 95%CI: 0.13-0.86, p = 0.024) and more brain metastases (OR = 2.05, 95%CI: 1.02-4.11, P = 0.043) in patients with mutBRAF versus wtBRAF. Comparing to the corresponding wtBRAF, mutBRAF melanoma patients had insignificant trend to longer median survival from diagnosis (131 vs. 78 months, p = 0.14), while mutBRAF colorectal cancer patients had an insignificant trend to shorter median survival from diagnosis (48 vs. 53 months, p = 0.22). In melanoma, V600K mutations in comparison to other BRAF mutations were associated with more frequent brain (75% vs. 36.3%, p = 0.02) and lung metastases (91.6% vs. 47.7%, p = 0.007), and shorter time from diagnosis to metastasis and to death (19 vs. 53 months, p = 0.046 and 78 vs. 322 months, p = 0.024 respectively). Treatment with RAF/MEK targeting agents (Hazard ratio (HR) = 0.16, 95%CI: 0.03-0.89, p = 0.037) and any decrease in tumor size after referral (HR = 0.07, 95%CI: 0.015-0.35, p = 0.001) correlated with longer survival in mutBRAF patients. CONCLUSIONS: BRAF appears to be a druggable mutation that also defines subgroups of patients with phenotypic overlap, albeit with differences that correlate with histology or site of mutation

Chemically induced DNA hypomethylation in breast carcinoma cells detected by the amplification of intermethylated sites

INTRODUCTION: Compromised patterns of gene expression result in genomic instability, altered patterns of gene expression and tumour formation. Specifically, aberrant DNA hypermethylation in gene promoter regions leads to gene silencing, whereas global hypomethylation events can result in chromosomal instability and oncogene activation. Potential links exist between environmental agents and DNA methylation, but the destabilizing effects of environmental exposures on the DNA methylation machinery are not understood within the context of breast cancer aetiology. METHODS: We assessed genome-wide changes in methylation patterns using a unique methylation profiling technique called amplification of intermethylated sites (AIMS). This method generates easily readable fingerprints that represent the investigated cell line's methylation profile, based on the differential cleavage of DNA with methylation-specific isoschisomeric restriction endonucleases. RESULTS: We validated this approach by demonstrating both unique and reoccurring sites of genomic hypomethylation in four breast carcinoma cell lines treated with the cytosine analogue 5-azacytidine. Comparison of treated with control samples revealed individual bands that exhibited methylation changes, and these bands were excized and cloned, and the precise genomic location individually identified. In most cases, these regions of hypomethylation coincided with susceptible target regions previously associated with chromosome breakage, rearrangement and gene amplification. Similarly, we observed that acute benzopyrene exposure is associated with altered methylation patterns in these cell lines. CONCLUSION: These results reinforce the link between environmental exposures, DNA methylation and breast cancer, and support a role for AIMS as a rapid, affordable screening method to identify environmentally induced DNA methylation changes that occur in tumourigenesis

A New Perspective on Transcriptional System Regulation (TSR): Towards TSR Profiling

It has been hypothesized that the net expression of a gene is determined by the combined effects of various transcriptional system regulators (TSRs). However, characterizing the complexity of regulation of the transcriptome is a major challenge. Principal component analysis on 17,550 heterogeneous human microarray experiments revealed that 50 orthogonal factors (hereafter called TSRs) are able to capture 64% of the variability in expression in a wide range of experimental conditions and tissues. We identified gene clusters controlled in the same direction and show that gene expression can be conceptualized as a process influenced by a fairly limited set of TSRs. Furthermore, TSRs can be linked to biological functions, as we demonstrate a strong relation between TSR-related gene clusters and biological functionality as well as cellular localization, i.e. gene products of similarly regulated genes by a specific TSR are located in identical parts of a cell. Using 3,934 diverse mouse microarray experiments we found striking similarities in transcriptional system regulation between human and mouse. Our results give biological insights into regulation of the cellular transcriptome and provide a tool to characterize expression profiles with highly reliable TSRs instead of thousands of individual genes, leading to a >500-fold reduction of complexity with just 50 TSRs. This might open new avenues for those performing gene expression profiling studies

Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.

BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC). METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA. RESULTS: We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 μg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients. CONCLUSIONS: Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs