Impaired glucose tolerance in adults with Duchenne and Becker muscular dystrophy

The aim of this study was to determine the response to an oral glucose tolerance test (OGTT) in adult males with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD), and to investigate whether body composition contributes to any variance in the glucose response. Twenty-eight adult males with dystrophinopathy (BMD, n = 13; DMD, n = 15) and 12 non-dystrophic controls, ingested 75 g oral anhydrous glucose solution. Fingertip capillary samples were assessed for glucose at 30-min intervals over 2-h post glucose ingestion. Fat free mass relative to body mass (FFM/BM) and body fat (BF%) was assessed using bioelectrical impedance. Vastus lateralis muscle anatomical cross sectional area (VL ACSA) was measured using B-mode ultrasonography. Blood glucose was higher in MD groups than control at 60, 90 and 120 min post ingestion of glucose. Compared to controls, FFM/BM and VL ACSA were lower in MD groups compared to controls (p < 0.001). Glucose tolerance values at 120 min were correlated with FFM/BM and BF% in the BMD group only. Our results suggest that glucose tolerance is impaired following OGTT in adult males with BMD and DMD. It is recommended that adults with BMD and DMD undertake routine glucose tolerance assessments to allow early detection of impaired glucose tolerance

The impact of surgery for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of treatment: A longitudinal, mixed methods study

© 2015 The Authors.Objective: To measure the long-term impact of surgical treatment for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of therapy. Methods: Prospective, longitudinal, mixed-methods study. Twenty-three women aged >18 years with a new diagnosis of vulval cancer were recruited. The EORTC QLQ C30, SF-36 and an electronic pelvic floor assessment questionnaire (ePAQ-PF) were administered at baseline (pre-treatment) and 3, 6, 9 and 12 months post-treatment. Mixed effects repeated measures models (all adjusted for age and BMI) were used to investigate changes over time and differences between cancer stage. Qualitative interviews were carried out with 11 of the women and analysed using a thematic approach. Results: Mean age was 59.9 years (SD=15.3; range=23.8-86.6 yrs). Mean BMI was 30.0 (SD=4.5; range=24.4-38.2). Sixteen women had early (Stage 1 to 2B), and seven women had advanced stage disease (Stage 3 to 4B). Questionnaire scores revealed that physical and social functioning, fatigue, pain and general sex life were significantly worse at 12 months than pre-treatment (p=< 0.05). Qualitative analysis revealed multiple treatment side effects which were perceived as severe and enduring. Women with advanced vulval cancer had significantly worse SF-36 mental health scores at 12 months compared to women with early stage disease (p=0.037). Conclusions: Surgery for vulval cancer has long-term implications which can be persistent 12 months post-treatment. High rates of morbidity relating to lymphoedema and sexual function re-enforce the need for specialist clinics to support women who suffer these complications

Observational study of the development and evaluation of a fertility preservation patient decision aid for teenage and adult women diagnosed with cancer: The Cancer, Fertility and Me research protocol

Introduction: Women diagnosed with cancer and facing potentially sterilising cancer treatment have to make time-pressured decisions regarding fertility preservation with specialist fertility services whilst undergoing treatment of their cancer with oncology services. Oncologists identify a need for resources enabling them to support women’s fertility preservation decisions more effectively; women report wanting more specialist information to make these decisions. The overall aim of the ‘Cancer, Fertility and Me’ study is to develop and evaluate a new evidence-based patient decision aid (ptDA) for women with any cancer considering fertility preservation to address this unmet need. Methods and analysis: This is a prospective mixed-method observational study including women of reproductive age (16 years +) with a new diagnosis of any cancer across two regional cancer and fertility centres in Yorkshire, UK. The research involves three stages. In Stage 1 the aim is to develop the ptDA using a systematic method of evidence synthesis and multidisciplinary expert review of current clinical practice and patient information. In Stage 2, the aim is to assess the face validity of the ptDA. Feedback on its content and format will be ascertained using both questionnaires and interviews with patients, user groups and key stakeholders. Finally, in Stage 3 the acceptability of using this resource when integrated into usual cancer care pathways at the point of cancer diagnosis and treatment planning will be evaluated. This will involve a quantitative and qualitative evaluation of the ptDA in clinical practice. Measures chosen include using count data of the ptDAs administered in clinics and accessed online, decisional and patient-reported outcome measures and qualitative feedback. Quantitative data will be analysed using descriptive statistics, paired sample t tests and confidence intervals; interviews will be analysed using thematic analysis. Ethics and dissemination: Research Ethics Committee approval (Ref: 16/EM/0122) and Health Research Authority approval (Ref: 194751) has been granted. Findings will be published in open access peer-reviewed journals, presented at conferences for academic and health professional audiences, with feedback to health professionals and program managers. The Cancer, Fertility and Me ptDA will be disseminated via a diverse range of open-access media, study and charity websites, professional organisations and academic sources. External endorsement will be sought from the International Patient Decision Aid Standards (IPDAS) Collaboration inventory of ptDAs and other relevant professional organisations e.g. the British Fertility Society. Trial registration number: NCT02753296 (www.clinicaltrials.gov); pre-results

Evaluating the Impact of a ‘Virtual Clinic’ on Patient Experience, Personal and Provider Costs of Care in Urinary Incontinence: A Randomised Controlled Trial.

Objective: To evaluate the impact of using a ‘virtual clinic’ on patient experience and cost in the care of women with urinary incontinence. Materials and Methods: Women, aged > 18 years referred to a urogynaecology unit were randomised to either (1) A Standard Clinic or (2) A Virtual Clinic. Both groups completed a validated, web-based interactive, patient-reported outome measure (ePAQ-Pelvic Floor), in advance of their appointment followed by either a telephone consultation (Virtual Clinic) or face-to-face consultation (Standard Care). The primary outcome was the mean ‘short-term outcome scale’ score on the Patient Experience Questionnaire (PEQ). Secondary Outcome Measures included the other domains of the PEQ (Communications, Emotions and Barriers), Client Satisfaction Questionnaire (CSQ), Short-Form 12 (SF-12), personal, societal and NHS costs. Results: 195 women were randomised: 98 received the intervention and 97 received standard care. The primary outcome showed a non-significant difference between the two study arms. No significant differences were also observed on the CSQ and SF-12. However, the intervention group showed significantly higher PEQ domain scores for Communications, Emotions and Barriers (including following adjustment for age and parity). Whilst standard care was overall more cost-effective, this was minimal (£38.04). The virtual clinic also significantly reduced consultation time (10.94 minutes, compared with a mean duration of 25.9 minutes respectively) and consultation costs compared to usual care (£31.75 versus £72.17 respectively), thus presenting potential cost-savings in out-patient management. Conclusions: The virtual clinical had no impact on the short-term dimension of the PEQ and overall was not as cost-effective as standard care, due to greater clinic re-attendances in this group. In the virtual clinic group, consultation times were briefer, communication experience was enhanced and personal costs lower. For medical conditions of a sensitive or intimate nature, a virtual clinic has potential to support patients to communicate with health professionals about their condition

Selection and validation of a set of reliable reference genes for quantitative sod gene expression analysis in C. elegans

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Laxative activities of Mareya micrantha (Benth.) Müll. Arg. (Euphorbiaceae) leaf aqueous extract in rats

<p>Abstract</p> <p>Background</p> <p><it>Mareya micrantha </it>(Benth.) Müll. Arg. (Euphorbiaceae) is a shrub that is commonly used in Côte d'Ivoire (West Africa) for the treatment of constipation and as an ocytocic drug. The present study was carried out to investigate the laxative activity of <it>Mareya micrantha </it>in albino's Wistar rats.</p> <p>Methods</p> <p>Rats were divided in 5 groups of 5 animals each, first group as control, second group served as standard (sodium picosulfate) while group 3, 4 and 5 were treated with leaf aqueous extract of <it>Mareya micrantha </it>at doses of 100, 200 and 400 mg/kg body weight (b.w.), <it>per os </it>respectively. The laxative activity was determined based on the weight of the faeces matter. The effects of the leaves aqueous extract of <it>Mareya micrantha </it>and castor oil were also evaluated on intestinal transit, intestinal fluid accumulation and ions secretion.</p> <p>Results</p> <p>Phytochemicals screening of the extract revealed the presence of flavonoids, alkaloids, tannins, polyphenols, sterols and polyterpenes. The aqueous extract of <it>Mareya micrantha </it>applied orally (100, 200 and 400 mg/kg; <it>p.o</it>.), produced significant laxative activity and reduced loperamide induced constipation in dose dependant manner. The effect of the extract at 200 and 400 mg/kg (<it>p.o</it>.) was similar to that of reference drug sodium picosulfate (5 mg/kg, <it>p.o</it>). The same doses of the extract (200 and 400 mg/kg, <it>p.o</it>.) produced a significant increase (p < 0.01) of intestinal transit in comparison with castor oil (2 mL) (p < 0.01). Moreover, the extract induced a significant enteropooling and excretion of Cl^-, Na⁺, K⁺and Ca²⁺in the intestinal fluid (p < 0.01).</p> <p>Conclusions</p> <p>The results showed that the aqueous extract of <it>Mareya micrantha </it>has a significant laxative activity and supports its traditional use in herbal medicine.</p

Targeted Deletion of HIF-1α Gene in T Cells Prevents their Inhibition in Hypoxic Inflamed Tissues and Improves Septic Mice Survival

Sepsis patients may die either from an overwhelming systemic immune response and/or from an immunoparalysis-associated lack of anti-bacterial immune defence. We hypothesized that bacterial superantigen-activated T cells may be prevented from contribution into anti-bacterial response due to the inhibition of their effector functions by the hypoxia inducible transcription factor (HIF-1alpha) in inflamed and hypoxic areas.Using the Cre-lox-P-system we generated mice with a T-cell targeted deletion of the HIF-1alpha gene and analysed them in an in vivo model of bacterial sepsis. We show that deletion of the HIF-1alpha gene leads to higher levels of pro-inflammatory cytokines, stronger anti-bacterial effects and much better survival of mice. These effects can be at least partially explained by significantly increased NF-kappaB activation in TCR activated HIF-1 alpha deficient T cells.T cells can be recruited to powerfully contribute to anti-bacterial response if they are relieved from inhibition by HIF-1alpha in inflamed and hypoxic areas. Our experiments uncovered the before unappreciated reserve of anti-bacterial capacity of T cells and suggest novel therapeutic anti-pathogen strategies based on targeted deletion or inhibition of HIF-1 alpha in T cells

Characterization of Clinically-Attenuated Burkholderia mallei by Whole Genome Sequencing: Candidate Strain for Exclusion from Select Agent Lists

is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microbial pathogens. genome. Therefore, the strain by itself is unlikely to revert naturally to its virulent phenotype. There were other genes present in one strain and not the other and vice-versa. was both avirulent in the natural host ponies, and did not possess T3SS associated genes may be fortuitous to advance biodefense research. The deleted virulence-essential T3SS is not likely to be re-acquired naturally. These findings may provide a basis for exclusion of SAVP1 from the Select Agent regulation or at least discussion of what else would be required for exclusion. This exclusion could accelerate research by investigators not possessing BSL-3 facilities and facilitate the production of reagents such as antibodies without the restraints of Select Agent regulation

Incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline-based chemotherapy with or without docetaxel

<p>Abstract</p> <p>Background</p> <p>To determine the incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline-based chemotherapy with or without docetaxel.</p> <p>Methods</p> <p>We studied the incidence and duration of amenorrhea induced by two chemotherapy regimens: (i) 6 cycles of 5-fluorouracil 500 mg/m², epirubicin 100 mg/m²and cyclophosphamide 500 mg/m²on day 1 every 3 weeks (6FEC) and (ii) 3 cycles of FEC 100 followed by 3 cycles of docetaxel 100 mg/m²on day 1 every 3 weeks (3FEC/3D). Reversible amenorrhea was defined as recovery of regular menses and, where available (101 patients), premenopausal hormone values (luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol) in the year following the end of chemotherapy.</p> <p>Results</p> <p>One hundred and fifty-four premenopausal patients were included: 84 treated with 6FEC and 70 with 3FEC/3D. The median age was 43.5 years (range: 28–58) in the 6FEC arm and 44 years (range: 29–53) in the 3FEC/3D arm. Seventy-eight percent of patients were treated in the context of the PACS 01 trial. The incidence of chemotherapy-induced amenorrhea at the end of chemotherapy was similar in the two groups: 93 % in the 6FEC arm and 92.8 % in the 3FEC/3D arm. However, in the year following the end of chemotherapy, more patients recovered menses in the 3FEC/3D arm than in the 6FEC arm: 35.5 % versus 23.7 % (p = 0.019). Among the 101 patients for whom hormone values were available, 43 % in the 3FEC/3D arm and 29 % in the 6FEC arm showed premenopausal levels one year after the end of chemotherapy (p < 0.01). In the 3FEC/3D group, there was a statistically significant advantage in disease-free survival (DFS) for patients who were still amenorrheic after one year, compared to patients who had recovered regular menses (p = 0.0017).</p> <p>Conclusion</p> <p>Our study suggests that 3FEC/3D treatment induces more reversible amenorrhea than 6FEC. The clinical relevance of these findings needs to be investigated further.</p

Hepatitis C Virus Infection in Guinea-Bissau: A Sexually Transmitted Genotype 2 with Parenteral Amplification?

BACKGROUND: Sub-Saharan Africa is the continent with the highest prevalence of Hepatitis C virus (HCV) infection. Genotype 2 HCV is thought to have originated from West Africa several hundred years ago. Mechanisms of transmission remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: To delineate mechanisms for HCV transmission in West Africa, we conducted a cross-sectional survey of individuals aged ≥50 years in Bissau, Guinea-Bissau. Dried blood spots were obtained for HCV serology and PCR amplification. Prevalence of HCV was 4.4% (47/1066) among women and 5.0% (27/544) among men. In multivariate analysis, the independent risk factors for HCV infection were age (baseline: 50–59 y; 60–69 y, adjusted odds ratio [AOR]: 1.67, 95% CI: 0.91–3.06; ≥70 y, AOR: 3.47, 95% CI: 1.89–6.39), belonging to the Papel, Mancanha, Balanta or Mandjako ethnic groups (AOR: 2.45, 95% CI:1.32–4.53), originating from the Biombo, Cacheu or Oio regions north of Bissau (AOR: 4.16, 95% CI: 1.18–14.73) and having bought or sold sexual services (AOR: 3.60, 95% CI: 1.88–6.89). Of 57 isolates that could be genotyped, 56 were genotype 2. CONCLUSIONS: Our results suggest that transmission of HCV genotype 2 in West Africa occurs through sexual intercourse. In specific locations and subpopulations, medical interventions may have amplified transmission parenterally