Effects of conjugated linoleic acid on myogenic and inflammatory responses in a human primary muscle and tumor coculture model

The antiproliferative and anti-inflammatory properties of conjugated linoleic acid (CLA) make it a potentially novel treatment in chronic inflammatory muscle wasting disease, particularly cancer cachexia. Human primary muscle cells were grown in coculture with MIA PaCa-2 pancreatic tumor cells and exposed to varying concentrations of c9,t11 and t10,c12 CLA. Expression of myogenic (Myf5, MyoD, myogenin, and myostatin) and inflammatory genes (CCL-2, COX-2, IL-8, and TNF-) were measured by real-time PCR. The t10,c12 CLA isomer, but not the c9,t11 isomer, significantly decreased MIA PaCa-2 proliferation by between 15% and 19%. There was a marked decrease in muscle MyoD and myogenin expression (78% and 62%, respectively), but no change in either Myf5 or myostatin, in myotubes grown in coculture with MIA PaCa-2 cells. CLA had limited influence on these responses. A similar pattern of myogenic gene expression changes was observed in myotubes treated with TNF- alone. Several-fold significant increases in CCL-2, COX-2, IL-8, and TNF- expression in myotubes were observed with MIA PaCa-2 coculture. The c9,t11 CLA isomer significantly decreased basal expression of TNF- in myotubes and could ameliorate its tumor-induced rise. The study provides insight into the anti-inflammatory and antiproliferative actions of CLA and its application as a therapeutic agent in inflammatory disease states.<br /

What do people do with porn? qualitative research into the consumption, use and experience of pornography and other sexually explicit media

This article reviews qualitative research into the consumption of pornography and other sexually explicit media emerging from a range of subject areas. Taking a critique of quantitative methods and a focus on measuring sexual effects and attitudes as a starting point, it considers the proposition that qualitative work is more suited to an examination of the complex social, cultural and political constructions of sexuality. Examining studies into the way men, women and young people see, experience, and use explicit media texts, the article identifies the key findings that have emerged. Qualitative work shows that sexuality explicit media texts are experienced and understood in a variety of ways and evoke strong and often contradictory reactions, not all of which are represented in public debates about pornography. These texts function in a range of different ways, depending on context; as a source of knowledge, a resource for intimate practices, a site for identity construction, and an occasion for performing gender and sexuality. The article reviews these studies and their findings, identifying what they suggest about directions for future research, both in terms of developing methodology and refining approaches to sexuality and media consumption.</p

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports

Effect of menopausal symptom treatment options on palpitations: a systematic review

This systematic review provides an overview of the effects of menopausal symptom treatment options on palpitations, defined as feelings of missed or exaggerated heart beats, reported by perimenopausal and postmenopausal women. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searches were conducted in PubMed, CINAHL and PsycINFO to identify articles meeting pre-specified inclusion criteria. Of 670 unique articles identified, 37 were included in the review. Treatments included drug therapies and non-drug therapies. Palpitations were studied as an outcome in 89% of articles and as an adverse effect in 11%. Articles provided mostly level II/III evidence due to their design and/or small sample sizes. Based on available evidence, no therapies can be fully recommended for clinical practice. Only some hormonal agents (e.g. estradiol) can be recommended with caution based on some positive evidence for reducing palpitation prevalence or severity. However, other drug therapies (e.g. moxonidine, atenolol), dietary supplementary treatments (e.g. isoflavones, Rheum rhaponticum, sage), cognitive-behavioral intervention and auricular acupressure cannot be recommended given the existing evidence. Additional well-designed randomized controlled treatment trials focusing on palpitations during the menopause transition as an inclusion criteria and outcome are needed to advance the field

A randomised feasibility study of EPA and Cox-2 inhibitor (Celebrex) versus EPA, Cox-2 inhibitor (Celebrex), Resistance Training followed by ingestion of essential amino acids high in leucine in NSCLC cachectic patients - ACCeRT Study

<p>Abstract</p> <p>Background</p> <p>Cancer cachexia is a syndrome of progressive weight loss. Non-small cell lung cancer patients experience a high incidence of cachexia of 61%. Research into methods to combat cancer cachexia in various tumour sites has recently progressed to the combination of agents.</p> <p>The combination of the anti-cachectic agent Eicosapentaenoic acid (EPA) and the cyclo-oxygenase-2 (COX-2) inhibitor celecoxib has been tested in a small study with some benefit. The use of progressive resistance training (PRT) followed by the oral ingestion of essential amino acids (EAA), have shown to be anabolic on skeletal muscle and acceptable in older adults and other cancer groups.</p> <p>The aim of this feasibility study is to evaluate whether a multi-targeted approach encompassing a resistance training and nutritional supplementation element is acceptable for lung cancer patients experiencing cancer cachexia.</p> <p>Methods/Design</p> <p>Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) is an open label, prospective, randomised controlled feasibility study with two parallel arms. All patients will be treated with EPA and the COX-2 inhibitor celecoxib on an outpatient basis at the study site. In the experimental group patients will participate in PRT twice a week, followed by the ingestion of essential amino acids high in leucine. A total of 21 patients are planned to be enrolled. Patients will be randomised using 1:2 ratio with 7 patients enrolled into the control arm, and 14 patients into the treatment arm. The primary endpoint is the acceptability of the above multi-targeted approach, determined by an acceptability questionnaire.</p> <p>Discussion</p> <p>To our knowledge ACCeRT offers for the first time the opportunity to investigate the effect of stimulating the anabolic skeletal muscle pathway with the use of PRT along with EAA alongside the combination of EPA and celecoxib in this population.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2040">ACTRN12611000870954</a></p

A Systematic Review of Palpitations Prevalence by Menopausal Status

Purpose of the Review The purpose was to systematically review evidence on the prevalence of palpitations by menopausal stage. Palpitations are a feeling of missed, irregular, or exaggerated heart beats. Recent Findings Carefully delineated search, screening, and data extraction strategies resulted in five articles for review. Articles offered cross-sectional findings from menopausal symptom surveys from five countries between 1974 and 2011 with clinic- and community-based samples of premenopausal, perimenopausal, and postmenopausal women. Reported studies were good (n = 2) to fair (n = 3) quality with low (n = 2) to moderate (n = 3) bias. Menopausal palpitations were not the focus of any study but were assessed as a single item of heart racing, pounding, or discomfort over the past 2 weeks, month, or year. Palpitations prevalence rates by menopausal stage were 3.7 to 40.2% premenopausal, 20.1 to 40.2% perimenopausal, and 15.7 to 54.1% postmenopausal. Three of five articles showed that compared with premenopausal and postmenopausal women, palpitation prevalence was significantly higher among perimenopausal and surgically postmenopausal women. Summary Good-quality evidence on palpitation prevalence by menopausal stage is limited but suggests that physiological changes of menopause may play a role in this symptom. Measurement varied, suggesting a need to standardize the assessment of menopausal palpitations. The review findings suggest a strong need for clinicians and researchers to collaborate to standardize documentation of menopausal palpitations across the menopause transition

Review of menopausal palpitations measures

Palpitations are reported commonly by women around the time of menopause as skipped, missed, irregular, and/or exaggerated heartbeats or heart pounding. However, much less is known about palpitations than other menopausal symptoms such as vasomotor symptoms. The objective of this review was to integrate evidence on menopausal palpitations measures. Keyword searching was done in PubMed, CINAHL, and PsycINFO for English-language, descriptive articles containing data on menopause and palpitations and meeting other pre-specified inclusion criteria. Of 670 articles, 110 met inclusion criteria and were included in the review. Results showed that 11 different measures were used across articles, with variability within and between measures. Inconsistencies in the wording of measurement items, recall periods, and response options were observed even when standardized measures were used. Most measures were limited to assessing symptom presence and severity. Findings suggest that efforts should be undertaken to (1) standardize conceptual and operational definitions of menopausal palpitations and (2) develop a patient-friendly, conceptually clear, psychometrically sound measure of menopausal palpitations

Towards access for all: 1st Working Group Report for the Global Gene Therapy Initiative (GGTI)

The gene and cell therapy field saw its first approved treatments in Europe in 2012 and the United States in 2017 and is projected to be at least a $10B USD industry by 2025. Despite this success, a massive gap exists between the companies, clinics, and researchers developing these therapeutic approaches, and their availability to the patients who need them. The unacceptable reality is a geographic exclusion of low-and middle-income countries (LMIC) in gene therapy development and ultimately the provision of gene therapies to patients in LMIC. This is particularly relevant for gene therapies to treat human immunodeficiency virus infection and hemoglobinopathies, global health crises impacting tens of millions of people primarily located in LMIC. Bridging this divide will require research, clinical and regulatory infrastructural development, capacity-building, training, an approval pathway and community adoption for success and sustainable affordability. In 2020, the Global Gene Therapy Initiative was formed to tackle the barriers to LMIC inclusion in gene therapy development. This working group includes diverse stakeholders from all sectors and has set a goal of introducing two gene therapy Phase I clinical trials in two LMIC, Uganda and India, by 2024. Here we report on progress to date for this initiative

The role of zinc in the anti-tumour and anti-cachectic activity of D-myo-inositol 1,2,6-triphosphate

Background: D-myo-inositol-1,2,6-triphosphate (a-trinositol, AT) is a polyanionic molecule capable of chelating divalent metal ions with anti-tumour and anti-cachectic activity in a murine model. Methods: To investigate the role of zinc in this process, mice bearing cachexia-inducing MAC16 tumour were treated with AT, with or without concomitant administration of ZnSO4. Results: At a dose of 40mgkg-1, AT effectively attenuated both weight loss and growth of the MAC16 tumour, and both effects were attenuated by co-administration of Zn2+. The concentration of zinc in gastrocnemius muscle increased with increasing weight loss, whereas administration of AT decreased the levels of zinc in plasma, skeletal muscle and tumour, which were restored back to control values after administration of ZnSO4. Conclusion: These results suggest that zinc is important in both tumour growth and cachexia in this animal model