Background. The aim of the study is to compare the current two endovenous thermal ablation methods by examining the effects on the visual analog scale (VAS) and the short form-36® quality of life index. Methods. Ninety-six patients who underwent unilateral endovenous thermal ablation of great saphenous vein were included. ClosureFast™ catheters were used in the RFA group and 1470 nm radial fiber laser catheters were used in the EVLA group. Results. The RFA group consisted of 41 patients and the EVLA group consisted of 55 patients. The preoperative baseline characteristics of both groups were similar. On the day of operation, VAS values were in the RFA group and in the EVLA group (). Comparisons of short form-36 parameters in both groups showed them to be similar except the pain detected at postoperative 1st week ( for RFA, for EVLA, ). Conclusion. Results in postprocedural quality of life were found to be similar in both of the techniques. However, in terms of postoperative pain, radiofrequency ablation is still superior to the 1470 nm radial fiber laser catheters.
http://ift.tt/2hDJmJx
Τετάρτη 15 Νοεμβρίου 2017
Effects of Two Current Great Saphenous Vein Thermal Ablation Methods on Visual Analog Scale and Quality of Life
Predictive QSAR modeling study on berberine derivatives with hypolipidemic activity
Abstract
Berberine (BBR) isolated from a Chinese herb, is identified as a new cholesterol-lowering small molecule, and hundreds of berberine derivatives have been obtained for optimization of their hypolipidemic activities in recent years. However, so far there is no available quantitative structure-activity relationship (QSAR) model used for the development of novel BBR analogs with hypolipidemic activities, mainly due to lack of lipid-lowering molecular mechanisms and target identification of BBR. In this paper, the tactics using ligand efficiency indices instead of pIC50 as the activity could be adopted for the development of BBR QSAR models. A series of 59 BBR derivatives with hypolipidemic activities have been studied and split randomly into three sets of training and test sets. Statistical quality of most building models shows obviously robust. Best calculated model that employ LLE indice as the activity (Model 6) has the following statistical parameters: for training set R2 = 0.984, Q2 = 0.981, RMSE = 0.1160, and for test set R2 = 0.989, RMSE = 0.0067. This model would be used for the development of novel BBR analogues with lipid-lowering activities as a hit discovery tool.
This article is protected by copyright. All rights reserved.
59 berberine (BBR) derivatives with hypolipidemic activity were split into three training and test sets. Four ligand efficiency indices (BEI, LLE, SEI, and LELP) instead of the negative logarithm of ten of half maximal inhibitory concentration (pIC50) as the activity could be used for the development of BBR quantitative structure-activity relationship (QSAR) models. The predictive potency of most built models were robust.
http://ift.tt/2zMDoKV
Synthesis, molecular modeling and biological evaluation of 4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides towards acetylcholinesterase, carbonic anhydrase I and II enzymes
Abstract
In the present study, 4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides were synthesized and inhibition effects on AChE, hCA I and hCA II were evaluated. Ki values of the compounds towards hCA I were in the range of 24.2±4.6-49.8±12.8 nM while they were in the range of 37.3±9.0-65.3±16.7 nM towards hCA II. Ki values of the Acetazolamide were 282.1±19.7 nM and 103.60±27.6 nM towards both isoenzymes, respectively. The compounds inhibited AChE with Ki in the range of 22.7±10.3-109.1±27.0 nM, whereas the Tacrine had Ki value of 66.5±13.8 nM. Electronic structure calculations at M06-L/6-31+G(d,p)//AM1 level and molecular docking studies were also performed to enlighten inhibition mechanism and to support experimental findings. Results obtained from calculations of molecular properties showed that the compounds obey drug likeness properties. The experimental and computational findings obtained in the present study might be useful in the design of novel inhibitors against hCA I, hCA II, and AChE.
This article is protected by copyright. All rights reserved.
4-[5-Aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides TP1-10 were synthesized and biological activities were evaluated on AChE, hCA I and hCA II enzymes. The compounds had demonstrated their inhibitory activities at nanomolar concentrations on AChE, hCA I and hCA II enzymes. The experimrntal and computational findings obtained in the present study might be useful in the design of novel inhibitors against hCA I, hCA II and AChE.
http://ift.tt/2iXMzAa
Designing Ethical Trials of Germline Gene Editing
The recent announcement that researchers have successfully used the CRISPR (clustered regularly interspaced short palindromic repeats) gene-editing technique to correct a mutation that leads to hypertrophic cardiomyopathy in human embryos is the latest reminder of the urgency of the social and…
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Compelling Reasons for Repairing Human Germlines
Under normal circumstances, if you combined sperm half of which carried a dominant disease allele with unaffected oocytes, only 50% of the resulting human embryos would be expected to have unaffected copies of the gene in question. Researchers Ma, Mitalipov, and colleagues recently reported that…
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Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer; A JSMO - ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS
http://ift.tt/2ikKvTq
Economic evaluation of an e-mental health intervention for patients with retinal exudative diseases who receive intraocular anti-VEGF injections (E-PsEYE): protocol for a randomised controlled trial
Introduction
Because of the great potential of vascular endothelial growth factor inhibitors (anti-VEGF) for retinal exudative diseases, an increased number of patients receives this treatment. However, during this treatment, patients are subjected to frequent invasive intravitreal injections, and the effects on reversing the process of vision loss are uncertain, which may have negative consequences for patients' mental health. One in three patients experience at least mild symptoms of depression/anxiety. To support patients in dealing with these symptoms, an e-mental health intervention (called E-PsEYE) has been developed. E-PsEYE is based on cognitive–behavioural therapy (CBT) and contains nine modules. A stepped-care model with three steps will be used to deliver the intervention: (1) providing information and psychoeducation, (2) when symptoms of depression/anxiety persist, guided CBT is offered and supported by social workers from low vision rehabilitation services and (3) when symptoms still persist, patients are referred to their general practitioner.
Methods and analysisAn economic evaluation from a healthcare and societal perspective will be conducted alongside a multicentre randomised controlled trial in two parallel groups to evaluate whether E-PsEYE is cost-effective in comparison with usual care. Participants (n=174) will be 50 years or older, have retinal exudative diseases, receive anti-VEGF treatment and have mild symptoms of depression/anxiety (assessed prior to randomisation). Main outcome measures are: depression (Patient Health Questionnaire-9), anxiety (Hospital Anxiety and Depression Scale-Anxiety) and quality-adjusted life-years (determined with the Health Utility Index-3 and the EuroQol-5 dimensions). Five measurements take place: at baseline and after 3, 6, 9 and 12 months.
Ethics and disseminationThe study has been approved by the Medical Ethics Committee of the VU University Medical Centre Amsterdam. It will provide new and essential information on the cost-effectiveness of an innovative intervention for a vulnerable population. Outcomes will be disseminated through peer-reviewed publications and conference presentations.
Trial registrationhttp://ift.tt/13oTAKm, identifier: NTR6337.
http://ift.tt/2ARY30r
Knowledge, attitudes and intention regarding mHealth in generation Y: evidence from a population based cross sectional study in Chakaria, Bangladesh
Background and objectives
mHealth offers a new opportunity to ensure access to qualified healthcare providers. Therefore, to better understand its potential in Bangladesh, it is important to understand how young people use mobile phones for healthcare. Here we examine the knowledge, attitudes and intentions to use mHealth services among young population.
DesignPopulation based cross sectional household survey.
Setting and participantsA total of 4909 respondents, aged 18 years and above, under the Chakaria Health and Demographic Surveillance System (HDSS) area, were interviewed during the period November 2012 to April 2013.
MethodsParticipants younger than 30 years of age were defined as young (or generation Y). To examine the level of knowledge about and intention towards mHealth services in generation Y compared with their older counterparts, the percentage of the respective outcome measure from a 2x2 contingency table and adjusted odds ratio (aOR), which controls for potential confounders such as mobile ownership, sex, education, occupation and socioeconomic status, were estimated. The aOR was estimated using both the Cochran–Mantel–Haenszel approach and multivariable logistic regression models controlling for confounders.
ResultsGeneration Y had significantly greater access to mobile phones (50%vs40%) and better knowledge about its use for healthcare (37.8%vs27.5%;aOR 1.6 (95% CI1.3 to 2.0)). Furthermore, the level of knowledge about two existing mHealth services in generation Y was significantly higher compared with their older counterparts, with aOR values of 3.2 (95% CI 2.6 to 5.5) and 1.5 (95% CI 1.1 to 1.8), respectively. Similarly, generation Y showed significantly greater intention towards future use of mHealth services compared with their older counterparts (aOR 1.3 (95% CI 1.1 to 1.4)). The observed associations were not modified by sociodemographic factors.
ConclusionThere is a greater potential for mHealth services in the future among young people compared with older age groups. However, given the low overall use of mHealth, appropriate policy measures need to be formulated to enhance availability, access, utilisation and effectiveness of mHealth services.
http://ift.tt/2ARY0lh
A randomised controlled trial of a duodenal-jejunal bypass sleeve device (EndoBarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes mellitus
Introduction
The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum. The non-surgical and reversible nature of these devices represents an attractive therapeutic option for patients with obesity and T2DM by potentially improving glycaemic control and reducing their weight.
Methods and analysisIn this multicentre, randomised, controlled, non-blinded trial, male and female patients aged 18–65 years with a body mass index 30–50 kg/m2 and inadequately controlled T2DM on oral antihyperglycaemic medications (glycosylated haemoglobin (HbA1c) 58–97 mmol/mol) will be randomised in a 1:1 ratio to receive either the EndoBarrier device (n=80) for 12 months or conventional medical therapy, diet and exercise (n=80). The primary outcome measure will be a reduction in HbA1c by 20% at 12 months. Secondary outcome measures will include percentage weight loss, change in cardiovascular risk factors and medications, quality of life, cost, quality-adjusted life years accrued and adverse events. Three additional subgroups will investigate the mechanisms behind the effect of the EndoBarrier device, looking at changes in gut hormones, metabolites, bile acids, microbiome, food hedonics and preferences, taste, brain reward system responses to food, eating and addictive behaviours, body fat content, insulin sensitivity, and intestinal tissue gene expression.
Trial registration numberISRCTN30845205, ClinicalTrials.gov Identifier NCT02459561.
http://ift.tt/2im6pps
Antibiotic use and bacterial complications following upper respiratory tract infections: a population-based study
Objectives
To investigate if use of antibiotics was associated with bacterial complications following upper respiratory tract infections (URTIs).
DesignEcological time-trend analysis and a prospective cohort study.
SettingPrimary, outpatient specialist and inpatient care in Stockholm County, Sweden. All analyses were based on administrative healthcare data on consultations, diagnoses and dispensed antibiotics from January 2006 to January 2016.
Main outcome measuresEcological time-trend analysis: 10-year trend analyses of the incidence of URTIs, bacterial infections/complications and respiratory antibiotic use. Prospective cohort study: Incidence of bacterial complications following URTIs in antibiotic-exposed and non-exposed patients.
ResultsThe utilisation of respiratory tract antibiotics decreased by 22% from 2006 to 2015, but no increased trend for mastoiditis (p=0.0933), peritonsillar abscess (p=0.0544), invasive group A streptococcal disease (p=0.3991), orbital abscess (p=0.9637), extradural and subdural abscesses (p=0.4790) and pansinusitis (p=0.3971) was observed. For meningitis and acute ethmoidal sinusitis, a decrease in the numbers of infections from 2006 to 2015 was observed (p=0.0038 and p=0.0003, respectively), and for retropharyngeal and parapharyngeal abscesses, an increase was observed (p=0.0214). Bacterial complications following URTIs were uncommon in both antibiotic-exposed (less than 1.5 per 10 000 episodes) and non-exposed patients (less than 1.3 per 10 000 episodes) with the exception of peritonsillar abscess after tonsillitis (risk per 10 000 tonsillitis episodes: 32.4 and 41.1 in patients with no antibiotic treatment and patients treated with antibiotics, respectively).
ConclusionsBacterial complications following URTIs are rare, and antibiotics may lack protective effect in preventing bacterial complications. Analyses of routinely collected administrative healthcare data can provide valuable information on the number of URTIs, antibiotic use and bacterial complications to patients, prescribers and policy-makers.
http://ift.tt/2ASD91a
Dynamic treatment selection and modification for personalised blood pressure therapy using a Markov decision process model: a cost-effectiveness analysis
Objective
Personalised medicine seeks to select and modify treatments based on individual patient characteristics and preferences. We sought to develop an automated strategy to select and modify blood pressure treatments, incorporating the likelihood that patients with different characteristics would benefit from different types of medications and dosages and the potential severity and impact of different side effects among patients with different characteristics.
Design, setting and participantsWe developed a Markov decision process (MDP) model to incorporate meta-analytic data and estimate the optimal treatment for maximising discounted lifetime quality-adjusted life-years (QALYs) based on individual patient characteristics, incorporating medication adjustment choices when a patient incurs side effects. We compared the MDP to current US blood pressure treatment guidelines (the Eighth Joint National Committee, JNC8) and a variant of current guidelines that incorporates results of a major recent trial of intensive treatment (Intensive JNC8). We used a microsimulation model of patient demographics, cardiovascular disease risk factors and side effect probabilities, sampling from the National Health and Nutrition Examination Survey (2003–2014), to compare the expected population outcomes from adopting the MDP versus guideline-based strategies.
Main outcome measuresCosts and QALYs for the MDP-based treatment (MDPT), JNC8 and Intensive JNC8 strategies.
ResultsCompared with the JNC8 guideline, the MDPT strategy would be cost-saving from a societal perspective with discounted savings of US$1187 per capita (95% CI 1178 to 1209) and an estimated discounted gain of 0.06 QALYs per capita (95% CI 0.04 to 0.08) among the US adult population. QALY gains would largely accrue from reductions in severe side effects associated with higher treatment doses later in life. The Intensive JNC8 strategy was dominated by the MDPT strategy.
ConclusionsAn MDP-based approach can aid decision-making by incorporating meta-analytic evidence to personalise blood pressure treatment and improve overall population health compared with current blood pressure treatment guidelines.
http://ift.tt/2yKYAzs
Antenatal care services and its implications for vital and health outcomes of children: evidence from 193 surveys in 69 low-income and middle-income countries
Objectives
Antenatal care (ANC) is an essential part of primary healthcare and its provision has expanded worldwide. There is limited evidence of large-scale cross-country studies on the impact of ANC offered to pregnant women on child health outcomes. We investigate the association of ANC in low-income and middle-income countries with short- and long-term mortality and nutritional child outcomes.
SettingWe used nationally representative health and welfare data from 193 Demographic and Health Surveys conducted between 1990 and 2013 from 69 low-income and middle-income countries for women of reproductive age (15–49 years), their children and their respective household.
ParticipantsThe analytical sample consisted of 752 635 observations for neonatal mortality, 574 675 observations for infant mortality, 400 426 observations for low birth weight, 501 484 observations for stunting and 512 424 observations for underweight.
Main outcomes and measuresOutcome variables are neonatal and infant mortality, low birth weight, stunting and underweight.
ResultsAt least one ANC visit was associated with a 1.04% points reduced probability of neonatal mortality and a 1.07% points lower probability of infant mortality. Having at least four ANC visits and having at least once seen a skilled provider reduced the probability by an additional 0.56% and 0.42% points, respectively. At least one ANC visit is associated with a 3.82% points reduced probability of giving birth to a low birth weight baby and a 4.11 and 3.26% points reduced stunting and underweight probability. Having at least four ANC visits and at least once seen a skilled provider reduced the probability by an additional 2.83%, 1.41% and 1.90% points, respectively.
ConclusionsThe currently existing and accessed ANC services in low-income and middle-income countries are directly associated with improved birth outcomes and longer-term reductions of child mortality and malnourishment.
http://ift.tt/2ARXJPh
What is the relationship between physical activity and cardiovascular risk factors in stroke survivors post completion of rehabilitation? Protocol for a longitudinal study
Introduction
Physical activity (PA) can modify cardiovascular and other health risks in people with stroke, but we know little about long-term PA in this group. This study aims to describe PA levels and investigate relationships between PA, cardiovascular risk factors, mobility and participant characteristics (eg, age, mood and fatigue) in the 2 years following rehabilitation discharge after first stroke.
Methods and analysisThis is a longitudinal observational study with follow-up at 6, 12 and 24 months after rehabilitation discharge. Inclusion criteria are broad; excluding only those with previous stroke, palliative diagnosis, living more than 2 hours from the centre or admitted less than 5 days.
The primary outcome of interest is duration of moderate to vigorous PA (min/day) measured by the Sensewear MF Armband (SWAB). Secondary outcomes include other PA measures measured with the SWAB; cardiovascular risk factors (eg, systolic blood pressure, fasting lipid profile and smoking status), mobility (10 m walk test), the Hospital Anxiety and Depression Scale and the Fatigue Severity Scale. All outcomes, except blood tests, are gathered at each time point.
The target sample size is 77. We will explore associations between PA levels, cardiovascular risk factors, mobility and participant characteristics at baseline compared with 6, 12 and 24 months using random-effects regression modelling.
The long-term PA of stroke survivors is largely unknown. We hope to identify factors that influence PA and cardiovascular risk in this population, which may help health professionals target the stroke survivors most at risk and implement appropriate treatment, preventative strategies and education.
Ethics and disseminationApproval was granted from Alfred Hospital and La Trobe University Research Ethics Committees. The study results will be disseminated in a number of ways including journal publication and international conference presentations.
Trial registration numberhttp://ift.tt/2ilV5JH
Unequal cluster sizes in stepped-wedge cluster randomised trials: a systematic review
Objectives
To investigate the extent to which cluster sizes vary in stepped-wedge cluster randomised trials (SW-CRT) and whether any variability is accounted for during the sample size calculation and analysis of these trials.
SettingAny, not limited to healthcare settings.
ParticipantsAny taking part in an SW-CRT published up to March 2016.
Primary and secondary outcome measuresThe primary outcome is the variability in cluster sizes, measured by the coefficient of variation (CV) in cluster size. Secondary outcomes include the difference between the cluster sizes assumed during the sample size calculation and those observed during the trial, any reported variability in cluster sizes and whether the methods of sample size calculation and methods of analysis accounted for any variability in cluster sizes.
ResultsOf the 101 included SW-CRTs, 48% mentioned that the included clusters were known to vary in size, yet only 13% of these accounted for this during the calculation of the sample size. However, 69% of the trials did use a method of analysis appropriate for when clusters vary in size. Full trial reports were available for 53 trials. The CV was calculated for 23 of these: the median CV was 0.41 (IQR: 0.22–0.52). Actual cluster sizes could be compared with those assumed during the sample size calculation for 14 (26%) of the trial reports; the cluster sizes were between 29% and 480% of that which had been assumed.
ConclusionsCluster sizes often vary in SW-CRTs. Reporting of SW-CRTs also remains suboptimal. The effect of unequal cluster sizes on the statistical power of SW-CRTs needs further exploration and methods appropriate to studies with unequal cluster sizes need to be employed.
http://ift.tt/2ARXzHF
Benefits and risks of Iron interventions in children (BRISC): protocol for a three-arm parallel-group randomised controlled field trial in Bangladesh
Introduction
Anaemia is a major global health problem affecting about 43% of preschool children globally and 60% of 6–24-month-old children in rural Bangladesh, half of which is attributed to iron deficiency (ID). Although WHO recommends universal supplementation with iron or home fortification with iron-containing multiple micronutrient powders (MMPs) to children under 2 years, evidence for benefits of these interventions on childhood development (a key rationale for these interventions) and harms (especially infection) remains limited. This study aims to evaluate the impact of iron or MMPs supplementation compared with placebo on (a) children's development, (b) growth, (c) morbidity from infections and (d) haematological and iron indices.
Methods and analysisThis study is a three-arm, blinded, double-dummy, parallel-group, placebo-controlled superiority trial using stratified individual block randomisation. The trial will randomise 3300 children aged 8–9 months equally to arm 1: iron syrup (12.5 mg elemental iron), placebo MMPs; arm 2: MMPs (including 12.5 mg elemental iron), placebo syrup; and arm 3: placebo syrup, placebo MNPs. Children will receive interventions for 3 months based on WHO recommendations and then be followed up for 9 months post intervention. The primary outcome is cognitive composite score measured by Bayley III. Secondary outcomes include motor and language composite score by Bayley III, behaviour rating using selected items from Wolke's rating scales and BSID-II behaviour ratings, temperament, growth, haemoglobin, anaemia and iron status, and infectious morbidity. Outcomes will be measured at baseline, at the end of 3-month intervention and after 9 months postintervention follow-up.
Ethics and disseminationThe trial has been approved by the Ethical Review Committee of icddr,b (Dhaka, Bangladesh) and the Melbourne Health Human Research Ethics Committee (Melbourne, Australia). Results of the study will be disseminated through scientific publications, presentations at international meetings and policy briefs to key stakeholders.
Trial registration numberACTRN12617000660381;Pre-results.
WHO Universal Trial NumberU1111-1196-1125.
http://ift.tt/2yL45yk
Preventing type 2 diabetes: systematic review of studies of cost-effectiveness of lifestyle programmes and metformin, with and without screening, for pre-diabetes
Objective
Explore the cost-effectiveness of lifestyle interventions and metformin in reducing subsequent incidence of type 2 diabetes, both alone and in combination with a screening programme to identify high-risk individuals.
DesignSystematic review of economic evaluations.
Data sources and eligibility criteriaDatabase searches (Embase, Medline, PreMedline, NHS EED) and citation tracking identified economic evaluations of lifestyle interventions or metformin alone or in combination with screening programmes in people at high risk of developing diabetes. The International Society for Pharmaco-economics and Outcomes Research's Questionnaire to Assess Relevance and Credibility of Modelling Studies for Informing Healthcare Decision Making was used to assess study quality.
Results27 studies were included; all had evaluated lifestyle interventions and 12 also evaluated metformin. Primary studies exhibited considerable heterogeneity in definitions of pre-diabetes and intensity and duration of lifestyle programmes. Lifestyle programmes and metformin appeared to be cost effective in preventing diabetes in high-risk individuals (median incremental cost-effectiveness ratios of £7490/quality-adjusted life-year (QALY) and £8428/QALY, respectively) but economic estimates varied widely between studies. Intervention-only programmes were in general more cost effective than programmes that also included a screening component. The longer the period evaluated, the more cost-effective interventions appeared. In the few studies that evaluated other economic considerations, budget impact of prevention programmes was moderate (0.13%–0.2% of total healthcare budget), financial payoffs were delayed (by 9–14 years) and impact on incident cases of diabetes was limited (0.1%–1.6% reduction). There was insufficient evidence to answer the question of (1) whether lifestyle programmes are more cost effective than metformin or (2) whether low-intensity lifestyle interventions are more cost effective than the more intensive lifestyle programmes that were tested in trials.
ConclusionsThe economics of preventing diabetes are complex. There is some evidence that diabetes prevention programmes are cost effective, but the evidence base to date provides few clear answers regarding design of prevention programmes because of differences in denominator populations, definitions, interventions and modelling assumptions.
http://ift.tt/2AOTfsB
Qualitative evaluation of a deferred consent process in paediatric emergency research: a PREDICT study
Background
A challenge of conducting research in critically ill children is that the therapeutic window for the intervention may be too short to seek informed consent prior to enrolment. In specific circumstances, most international ethical guidelines allow for children to be enrolled in research with informed consent obtained later, termed deferred consent (DC) or retrospective consent. There is a paucity of data on the attitudes of parents to this method of enrolment in paediatric emergency research.
ObjectivesTo explore the attitudes of parents to the concept of DC and to expand the knowledge of the limitations to informed consent and DC in these situations.
MethodChildren presenting with uncomplicated febrile seizures or bronchiolitis were identified from three separate hospital emergency department databases. Parents were invited to participate in a semistructured telephone interview exploring themes of limitations of prospective informed consent, acceptability of the DC process and the most appropriate time to seek DC. Transcripts underwent inductive thematic analysis with intercoder agreement, using Nvivo 11 software.
ResultsA total of 39 interviews were conducted. Participants comprehended the limitations of informed consent under emergency circumstances and were generally supportive of DC. However, they frequently confused concepts of clinical care and research, and support for participation was commonly linked to their belief of personal benefit.
ConclusionParticipants acknowledged the requirement for alternatives to prospective informed consent in emergency research, and were supportive of the concept of DC. Our results suggest that current research practice seems to align with community expectations.
http://ift.tt/2A1ZIDr
Impact of informal caregiving on older adults physical and mental health in low-income and middle-income countries: a cross-sectional, secondary analysis based on the WHOs Study on global AGEing and adult health (SAGE)
Objectives
A high proportion of care stemming from chronic disease or disability in low-income and middle-income countries is provided by informal caregivers. The goal of this study was to determine the level of burden experienced by these caregivers, explore associated factors and assess whether caregivers' and non-caregivers' health differed.
Design and settingThis cross-sectional study was a secondary analysis of data on caregivers' burden, health and health risk factors in Ghana, India and the Russian Federation collected as part of the WHO's Study on global AGEing and adult health (SAGE) Wave 1.
ParticipantsCaregivers in Ghana (n=143), India (n=490) and Russia (n=270) completed the measures.
Outcome measuresFactors associated (ie, demographics and caregiving profile variables) with burden were explored among caregivers. Then, quality of life (QOL), perceived stress, depression, self-rated health (SRH) and health risk factors were compared between caregivers and matched non-caregivers (1:2).
ResultsThe largest caregiving subgroups were spouses and adult children. Caregivers mostly cared for one person and provided financial, social/emotional and/or physical support, but received little support themselves. Burden level ranged from 17.37 to 20.03. Variables associated with burden were mostly country-specific; however, some commonality for wealth, type of care and caregiving duration was noted. Caregivers with a moderate or high level of burden reported lower QOL and higher perceived stress than those experiencing low burden. Caregivers reported lower QOL and SRH than non-caregivers.
ConclusionGiven the lack of support received and consequences of the burden endured by caregivers, policy and programme initiatives are needed to ensure that caregivers in low- and middle-income countries can fulfil their role without compromising their own health.
http://ift.tt/2zEOWlT
Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment
Introduction
Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%–15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery. A rigorous comparative effectiveness trial in the USA that is sufficiently large and pragmatic to incorporate usual variations in care and measures the patient experience is needed to determine whether antibiotics are as good as appendectomy.
ObjectivesThe Comparing Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial for acute appendicitis aims to determine whether the antibiotic treatment strategy is non-inferior to appendectomy.
Methods/AnalysisCODA is a randomised, pragmatic non-inferiority trial that aims to recruit 1552 English-speaking and Spanish-speaking adults with imaging-confirmed appendicitis. Participants are randomised to appendectomy or 10 days of antibiotics (including an option for complete outpatient therapy). A total of 500 patients who decline randomisation but consent to follow-up will be included in a parallel observational cohort. The primary analytic outcome is quality of life (measured by the EuroQol five dimension index) at 4 weeks. Clinical adverse events, rate of eventual appendectomy, decisional regret, return to work/school, work productivity and healthcare utilisation will be compared. Planned exploratory analyses will identify subpopulations that may have a differential risk of eventual appendectomy in the antibiotic treatment arm.
Ethics and disseminationThis trial was approved by the University of Washington's Human Subjects Division. Results from this trial will be presented in international conferences and published in peer-reviewed journals.
Trial registration numberNCT02800785.
http://ift.tt/2AJNg7C
Lipid profiles and determinants of total cholesterol and hypercholesterolaemia among 25-74 year-old urban and rural citizens of the Yangon Region, Myanmar: a cross-sectional study
Objective
The first is to estimate the prevalence of dyslipidaemia (hypercholesterolaemia, hypertriglyceridaemia, high low-density lipoprotein (LDL) level and low high-density lipoprotein (HDL) level), as well as the mean levels of total cholesterol, triglyceride, LDL and HDL, in the urban and rural Yangon Region, Myanmar. The second is to investigate the association between urban-rural location and total cholesterol.
DesignTwo cross-sectional studies using the WHO STEPS methodology.
SettingBoth the urban and rural areas of the Yangon Region, Myanmar.
ParticipantsA total of 1370 men and women aged 25–74 years participated based on a multistage cluster sampling. Physically and mentally ill people, monks, nuns, soldiers and institutionalised people were excluded.
ResultsCompared with rural counterparts, urban dwellers had a significantly higher age-standardised prevalence of hypercholesterolaemia (50.7% vs 41.6%; p=0.042) and a low HDL level (60.6% vs 44.4%; p=0.001). No urban-rural differences were found in the prevalence of hypertriglyceridaemia and high LDL. Men had a higher age-standardised prevalence of hypertriglyceridaemia than women (25.1% vs 14.8%; p<0.001), while the opposite pattern was found in the prevalence of a high LDL (11.3% vs 16.3%; p=0.018) and low HDL level (35.3% vs 70.1%; p<0.001).
Compared with rural inhabitants, urban dwellers had higher age-standardised mean levels of total cholesterol (5.31 mmol/L, SE: 0.044 vs 5.05 mmol/L, 0.068; p=0.009), triglyceride (1.65 mmol/L, 0.049 vs 1.38 mmol/L, 0.078; p=0.017), LDL (3.44 mmol/L, 0.019 vs 3.16 mmol/L, 0.058; p=0.001) and lower age-standardised mean levels of HDL (1.11 mmol/L, 0.010 vs 1.25 mmol/L, 0.012; p<0.001). In linear regression, the total cholesterol was significantly associated with an urban location among men, but not among women.
ConclusionThe mean level of total cholesterol and the prevalence of hypercholesterolaemia were alarmingly high in men and women in both the urban and rural areas of Yangon Region, Myanmar. Preventive measures to reduce cholesterol levels in the population are therefore needed.
http://ift.tt/2zGQmfD
Correction: Interpretation of CIs in clinical trials with non-significant results: systematic review and recommendations
Gewandter JS, McDermott MP, Kitt RA, et al. Interpretation of CIs in clinical trials with non-significant results: systematic review and recommendations. BMJ Open 2017;7:e017288. doi: 10.1136/bmjopen-2017-017288.
In the Abstract, the following list should include the British Medical Journal:
"Design Systematic review of RCT reports published in 2014 in Annals of Internal Medicine, New England Journal of Medicine, JAMA, JAMA Internal Medicine and The Lancet (n=247)."
http://ift.tt/2imKD4V
Menopausal hormone therapy and colorectal cancer: a linkage between nationwide registries in Norway
Objectives
With the present study, we aimed to investigate the association between menopausal hormone therapy (HT) and risk of colorectal cancer (CRC).
SettingCohort study based on the linkage of Norwegian population-based registries.
ParticipantsWe selected 466822 Norwegian women, aged 55–79, alive and residing in Norway as of 1 January 2004, and we followed them from 2004 to 2008. Each woman contributed person-years at risk as non-user, current user and/or past HT user.
Outcome measuresThe outcome of interest was adenocarcinoma of the colorectal tract, overall, by anatomic site and stage at diagnosis. Incidence rate ratios (RRs) with 95% CIs were estimated by Poisson regression and were used to evaluate the association between HT and CRC incidence.
ResultsDuring the median follow-up of 4.8 years, 138 655 (30%) women received HT and 3799 (0.8%) incident CRCs occurred. Current, but not past, use of HT was associated with a lower risk of CRC (RR 0.88; 95% CI 0.80 to 0.98). RRs for localised, regionally advanced and metastatic CRC were 1.13 (95% CI 0.91 to 1.41), 0.81 (95% CI 0.70 to 0.94) and 0.79 (95% CI 0.62 to 1.00), respectively. RRs for current use of oestrogen therapy (ET) were 0.91 (95% CI 0.80 to 1.04) while RR for current use of combined oestrogen–progestin therapy (EPT) was 0.85 (95% CI 0.70 to 1.03), as compared with no use of HT. The same figures for ET and EPT in oral formulations were 0.83 (95% CI 0.68 to 1.03) and 0.86 (95% CI 0.71 to 1.05), respectively.
ConclusionsIn our nationwide cohort study, HT use lowered the risk of CRC, specifically the most advanced CRC.
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What are older smokers attitudes to quitting and how are they managed in primary care? An analysis of the cross-sectional English Smoking Toolkit Study
Objectives
To investigate whether age is associated with access to smoking cessation services.
DesignData from the Smoking Toolkit Study 2006–2015, a repeated multiwave cross-sectional household survey (n=181 157).
SettingEngland.
ParticipantsPast-year smokers who participated in any of the 102 waves stratified into age groups.
Outcome measuresAmount smoked and nicotine dependency, self-reported quit attempts and use of smoking cessation interventions. Self-report of whether the general practitioner (GP) raised the topic of smoking and made referrals for pharmacological support (prescription of nicotine replacement therapies (NRTs)) or other support (counselling or support groups).
ResultsOlder smokers (75+ years) were less likely to report that they were attempting to quit smoking or seek help from a GP, despite being less nicotine-dependent. GPs raised smoking as a topic equally across all age groups, but smokers aged 70+ were more likely not to be referred for NRT or other support (ORs relative to 16–54 years; 70–74 years 1.27, 95% CI 1.03 to 1.55; 75–79 years 1.87, 95% CI 1.43 to 2.44; 80+ years 3.16, 95% CI 2.20 to 4.55; p value for trend <0.001).
ConclusionsOur findings suggest that there are potential missed opportunities in facilitating smoking cessation in older smokers. In this large population-based study, older smokers appeared less interested in quitting and were less likely to be offered support, despite being less addicted to nicotine than younger smokers. It is unclear whether this constitutes inequitable access to services or reflects informed choices by older smokers and their GPs. Future research is needed to understand why older smokers and GPs do not pursue smoking cessation. Service provision should consider how best to reduce these variations, and a stronger effectiveness evidence base is required to support commissioning for this older population so that, where appropriate, older smokers are not missing out on smoking cessation therapies and the health benefits of cessation at older ages.
http://ift.tt/2zGQcox
'When it goes back to my normal I suppose: a qualitative study using online focus groups to explore perceptions of 'control among people with eczema and parents of children with eczema in the UK
Objective
To inform the development of a core outcome set for eczema by engaging with people with eczema and parents of children with eczema to understand their experiences and understanding of the concept 'eczema control'.
Design37 participants took part in a total of six semi-structured online focus groups held in a typed chatroom with 5–7 participants per group. Three groups involved adults with eczema and three groups involved parents of children with eczema. Framework analysis was used for data analysis.
SettingA community-based sample was recruited from across the UK via social media and email.
Participants19 adults aged 17–61 years (15/19 female, 16/19 white) and 18 parents of children with eczema aged 9 months–17 years (9/18 female, 18/19 white).
ResultsFour main themes were identified:(1) 'Commonalities and differences in the experiences of control': a reduction in symptoms such as itch and sleep loss characterised eczema control, but what level was acceptable differed across participants;(2) 'Eczema control goes beyond the skin': psychological factors, social factors, the constant scratching and the impact on everyday activities are a variety of ways an individual can be impacted;(3) 'Stepping up and down of treatment': participants' stepped-up treatment in response to loss of control, but several factors complicated this behaviour. Control needed to be maintained after stepped-up treatment ended to be acceptable; and (4) 'How to measure control': self-report was generally preferred to allow frequent measurements and to capture unobservable features. Although most thought their eczema needed to be measured frequently, many also felt that this was not always realistic or desirable.
Conclusions'Eczema control' is a complex experience for people with eczema and parents of children with the condition. These experiences could have important implications on how long-term control should be measured in eczema clinical trials and clinical practice.
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Prevalence of pregnancy-related pelvic girdle pain and associated factors in Australia: a cross-sectional study protocol
Introduction
Pregnancy-related pelvic girdle pain (PPGP) is a common musculoskeletal disorder. Women with PPGP report difficulty performing everyday functional activities, such as standing and walking. However, the magnitude of the problem remains unknown in Australia. It is important to determine how many women are affected by this condition and the factors associated with PPGP as this will direct healthcare services to being able to better manage women during pregnancy. Thus, this study aims to determine the prevalence of PPGP and associated factors in a Western Sydney population.
Methods and analysisThis study is a cross-sectional study to be conducted at a single hospital in Australia. Participants will be over 18 years of age, between 14 and 38 weeks gestation and recruited randomly from all pregnant women attending antenatal care. Participants will have anthropomorphic measures recorded, such as height and body weight, and be asked to complete questionnaires about their current pregnancy, sociodemographic information, ethnoculture, occupational factors and participation in functional activities. The classification of PPGP will be made as per the published guidelines and will include a physical examination.
Ethics and disseminationEthical approval has been granted by the Human Research Ethics Committees of Westmead Hospital, Sydney, and Western Sydney University, Sydney. Dissemination of results will be via journal articles and conference presentations.
Trial registration numberhttp://ift.tt/2zFYsF9
Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study
Objectives
To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verify the effect of a polymorphism in the microRNA136 (MIR136) IL18RAP binding region.
DesignWe analysed samples from two Spanish cross-sectional studies, VALCAR (Spanish Mediterranean coast) and Hortega (Spanish centre). These studies aimed at analysing cardiovascular risk and development of cardiovascular disease in the general population. Both populations correspond to regions with different characteristics.
SettingFive IL18RAP single nucleotide polymorphisms were selected using the SYSNPs web tool and analysed by oligonucleotide ligation assay (SNPlex). For the MIR136 functional study, cells were transfected with plasmids containing different rs7559479 polymorphism alleles and analysed by luciferase reporter assays.
Participants1970 individuals (Caucasian, both genders): VALCAR (468) and Hortega (1502).
Resultsrs2293225, rs2272127 and rs7559479 showed the following associations: rs7559479 G allele correlated with a higher obesity risk (P=0.01; OR=1.82; 95% CI 1.15 to 2.87 for the VALCAR group; P=0.033; OR=1.35; 95% CI 1.03 to 1.79 for the Hortega population) and higher body mass index (BMI) values (P=0.0045; P=0.1 for VALCAR and Hortega, respectively); a significant association with obesity (P=0.0024, OR=1.44, 95% CI 1.14 to 1.82) and increased BMI values (P=0.008) was found when considering both populations together. rs2293225 T allele was associated with lower obesity risk (P=0.036; OR=0.60; 95% CI 0.35 to 0.96) and lower BMI values (P=0.0038; OR=1.41) while the rs2272127 G allele was associated with lower obesity risk (P=0.028; OR=0.66; 95% CI 0.44 to 0.97) only in the VALCAR population. A reporter assay showed that the presence of the A allele in rs7559479 was associated with increased MIR136 binding to IL18RAP.
ConclusionsOur results suggest that polymorphisms in IL18RAP influence susceptibility to obesity. We demonstrated that the A allele in rs7559479 increases MIR136 binding, which regulates IL-18 system activity.
http://ift.tt/2zEOiEZ
Midazolam Injection, USP, 2 mg/2 mL by Fresenius Kabi: Recall - Reports of Blister Packages Containing Syringes of Ondansetron Injection
Audience: Pharmacy, Surgery, Risk Manager ISSUE: Fresenius Kabi USA is voluntarily recalling Lot of Midazolam Injection, USP, 2 mg/2 mL packaged in a 2 mL prefilled single-use glass syringe to the hospital/user level. The product mislabeled as...
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Durvalumab in non-small-cell lung cancer patients: current developments
Future Oncology, Ahead of Print.
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Genotyping-by-Sequencing in Almond: SNP Discovery, Linkage Mapping and Marker Design
In crop plant genetics, linkage maps provide the basis for the mapping of loci that affect important traits and for the selection of markers to be applied in crop improvement. In outcrossing species such as almond [Prunus dulcis (Mill.) D.A. Webb], application of a double pseudo-testcross mapping approach to the F1 progeny of a bi-parental cross leads to the construction of a linkage map for each parent. Here, we report on the application of genotyping-by-sequencing to discover and map single-nucleotide polymorphisms in the almond cultivars 'Nonpareil' and 'Lauranne'. Allele-specific marker assays were developed for 309 tag pairs. Application of these assays to 231 'Nonpareil' x 'Lauranne' F1 progeny provided robust linkage maps for each parent. Analysis of phenotypic data for shell hardness demonstrated the utility of these maps for quantitative trait locus mapping. Comparison of these maps to the peach genome assembly confirmed high synteny and collinearity between the peach and almond genomes. The marker assays were applied to progeny from several other 'Nonpareil' crosses, providing the basis for a composite linkage map of 'Nonpareil'. Applications of the assays to a panel of almond clones and a panel of rootstocks used for almond production demonstrated the broad applicability of the markers and providing subsets of markers that could be used to discriminate among accessions. The sequence-based linkage maps and single nucleotide polymorphism assays presented here could be useful resources for the genetic analysis and genetic improvement of almond.
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RNA-Sequencing of Drosophila melanogaster Head Tissue on High Sugar and High Fat Diets
Obesity has been shown to increase risk for cardiovascular disease and type-2 diabetes. In addition, it has been implicated in aggravation of neurological conditions such as Alzheimer's. In the model organism Drosophila melanogaster, a physiological state mimicking diet-induced obesity can be induced by subjecting fruit flies to a solid medium disproportionately higher in sugar than protein or that has been supplemented with a rich source of saturated fat. These flies can exhibit increased circulating glucose levels, increased triglyceride content, insulin-like peptide resistance, and behavior indicative of neurological decline. We subjected flies to variants of the high-sugar diet, high-fat diet, or normal (control) diet, followed by a total RNA extraction from fly heads of each diet group for the purpose of Poly-A selected RNA-Sequencing. Our objective was to identify the effects of obesogenic diets on transcriptome patterns, how they differed between obesogenic diets, and identify genes that may relate to pathogenesis accompanying an obesity-like state. Gene ontology analysis indicated an overrepresentation of affected genes associated with immunity, metabolism, and hemocyanin in the high-fat diet group, and CHK, cell cycle activity, and DNA binding and transcription in the high-sugar diet group. Our results also indicate differences in the effects of the high-fat diet and high-sugar diet on expression profiles in head tissue of flies, despite the reportedly similar phenotypic impacts of the diets. The impacted genes, and how they may relate to pathogenesis in the Drosophila obesity-like state, warrant further experimental investigation.
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Correction to: Abstracts
Abstract
In Poster Sessions, the first-author name was missing from the authorship group originally listed for Abstract PS-13-001 (page S176), entitled "Gastric carcinoma with lymphoid stroma: Analysis of microsatellite instability and Epstein-Barr virus status". The correct authorship group is shown above.
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Correction to: Abstracts
Abstract
In Poster Sessions, the first-author name was missing from the authorship group originally listed for Abstract PS-01-004 (page S52), entitled "Clinicopathological features of microinvasive breast cancer". The correct authorship group is shown above.
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Correction to: Abstracts
Abstract
Due to an error with the registration system, the following abstract was regrettably omitted from the Poster Sessions. The abstract should have been included as PS-13-116 and displayed on page S199.
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Upregulation of Tyrosine Kinase FYN in Human Thyroid Carcinoma: Role in Modulating Tumor Cell Proliferation, Invasion, and Migration
Cancer Biotherapy & Radiopharmaceuticals Nov 2017, Vol. 32, No. 9: 320-326.
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Comparative In Vitro Study of 11C-Methionine and 11C-Deuterodeprenyl Uptake in Three Human Glioma Cell Lines
Cancer Biotherapy & Radiopharmaceuticals Nov 2017, Vol. 32, No. 9: 344-350.
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Carcinosarcoma of the ovary compared to ovarian high-grade serous carcinoma: impact of optimal cytoreduction and standard adjuvant treatment
Abstract
Objective
The purpose of this retrospective study was to compare the prognoses of women with ovarian carcinosarcoma (OCS) who had optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy to those of women with ovarian high-grade serous carcinoma (HGSC) treated in the same manner.
Methods
A multicenter, retrospective department database review was performed to identify patients with OCS at eight gynecologic oncology centers in Turkey. A total of 54 women with OCS who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy between 1999 and 2017 were included in this case–control study. Each case was matched to two women with ovarian HGSC who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy. The Kaplan–Meier method was used to generate survival data. Factors predictive of outcome were analysed using Cox proportional hazards models.
Results
Median disease-free survival (DFS) was 29 months [95% confidence interval (CI) 0–59, standard error (SE) 15.35] versus 27 months (95% CI 22.6–31.3, SE 2.22; p = 0.765) and median overall survival (OS) was 62 versus 82 months (p = 0.53) for cases and controls, respectively. For the entire cohort, the presence of ascites [hazard ratio (HR) 2.32; 95% CI 1.02–5.25, p = 0.04] and platinum resistance [HR 5.05; 95% CI 2.32–11, p < 0.001] were found to be independent risk factors for decreased OS.
Conclusion
DFS and OS rates of patients with OCS and HGSC seem to be similar whenever optimal cytoreduction is achieved and followed by platinum plus taxane combination chemotherapy.
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Polyglucosan myopathy and functional characterization of a novel GYG1 mutation
Objectives
Disorders of glycogen metabolism include rare hereditary muscle glycogen storage diseases with polyglucosan, which are characterized by storage of abnormally structured glycogen in muscle in addition to exercise intolerance or muscle weakness. In this study, we investigated the etiology and pathogenesis of a late-onset myopathy associated with glycogenin-1 deficiency.
Materials and methods
A family with two affected siblings, 64- and 66-year-olds, was studied. Clinical examination and whole-body MRI revealed weakness and wasting in the hip girdle and proximal leg muscles affecting ambulation in the brother. The sister had weakness and atrophy of hands and slight foot dorsiflexion difficulties. Muscle biopsy and whole-exome sequencing were performed in both cases to identify and characterize the pathogenesis including the functional effects of identified mutations.
Results
Both siblings demonstrated storage of glycogen that was partly resistant to alpha-amylase digestion. Both were heterozygous for two mutations in GYG1, one truncating 1-base deletion (c.484delG; p.Asp163Thrfs*5) and one novel missense mutation (c.403G>A; p.Gly135Arg). The mutations caused reduced expression of glycogenin-1 protein, and the missense mutation abolished the enzymatic function as analyzed by an in vitro autoglucosylation assay.
Conclusion
We present functional evidence for the pathogenicity of a novel GYG1 missense mutation located in the substrate binding domain. Our results also demonstrate that glycogenin-1 deficiency may present with highly variable distribution of weakness and wasting also in the same family.
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Oncogenic spiral by infectious pathogens: The cooperation of multiple factors in cancer development
Abstract
Chronic infection is one of the major causes of cancer, and there are several mechanisms for infection-mediated oncogenesis. Some pathogens encode gene products that behave like oncogenic factors, hijacking cellular pathways to promote the survival and proliferation of infected cells in vivo. Some of these viral oncoproteins trigger a cellular damage defense response leading to senescence; however, other viral factors hinder this suppressive effect, suggesting that cooperation of those viral factors is important for malignant transformation. Coinfection with multiple agents is known to accelerate cancer development in certain cases. For example, parasitic or bacterial infection is a risk factor for adult T-cell leukemia-lymphoma induced by human T-cell leukemia virus type 1, and Epstein-Barr virus and malaria are closely associated with endemic Burkitt lymphoma. Human immunodeficiency virus type 1 infection is accompanied by various types of infection-related cancer. These findings indicate that these oncogenic pathogens can cooperate to overcome host barriers against cancer development. In this review, the authors focus on the collaborative strategies of pathogens for oncogenesis from two different points of view: (1) the cooperation of two or more different factors encoded by a single pathogen, and (2) the acceleration of oncogenesis by coinfection with multiple agents.
This article is protected by copyright. All rights reserved.
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Comparative Transcriptomics of Seasonal Phenotypic Flexibility in Two North American Songbirds
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Understanding Evolutionary Impacts of Seasonality: An Introduction to the Symposium
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Genetic Decoupling of Thermal Hardiness across Metamorphosis in Drosophila melanogaster
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To Everything There Is a Season: Summer-to-Winter Food Webs and the Functional Traits of Keystone Species
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A Complex Lens for a Complex Eye
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Canalization of Seasonal Phenology in the Presence of Developmental Variation: Seed Dormancy Cycling in an Annual Weed
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Intracellular Recordings of Spectral Sensitivities in Stomatopods: a Comparison across Species
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Sensory Biology of Starfish—With Emphasis on Recent Discoveries in their Visual Ecology
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A Novel Display System Reveals Anisotropic Polarization Perception in the Motion Vision of the Butterfly Papilio xuthus
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The Preoptic Area and the RFamide-Related Peptide Neuronal System Gate Seasonal Changes in Chemosensory Processing
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Moving in Dim Light: Behavioral and Visual Adaptations in Nocturnal Ants
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Crustacean Larvae—Vision in the Plankton
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Resolving the Trade-off Between Visual Sensitivity and Spatial Acuity—Lessons from Hawkmoths
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Defining the Degree of Seasonality and its Significance for Future Research
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Insect Development, Thermal Plasticity and Fitness Implications in Changing, Seasonal Environments
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“Some Women Are Born Fighters”: Discursive Constructions of a Fighter’s Identity by Female Finnish Judo Athletes
Abstract
Martial arts and combat sports have been traditionally associated with masculinity, and a range of contradictory meanings have been attached to women's engagement and experiences. The present study draws on cultural praxis and feminist poststructuralist frameworks to explore how female martial artists are subjectified to dominant cultural discourses surrounding fighting and competition. Interviews with nine female judoka (judo athletes) were gathered in Finland and analyzed using Foucauldian Discourse Analysis (FDA). The FDA revealed that in female judoka talk, judo was constructed as a sport for all, but also as a male domain and a manly sport with fighting and competition as innate masculine qualities that are not learned. Two sets of wider, competing discourses provided the dominant structure for participants' constructions of judo: (a) a mass sport discourse versus an elite sport discourse and (b) a gender equality discourse versus a female biological inferiority discourse. Drawing on this discursive context and in seeking to make sense of their experiences, participants constructed a "naturally born fighter" identity. Although this might be an empowering identity for female judoka, it does not advance the agenda of gender equity in martial arts because it constructs "ordinary" women as biologically incapable of competitive judo. Our findings reveal that even in the relatively egalitarian culture of Finland, gender hierarchies persist in judo and that it is only by disrupting prevalent constructions of fighting and competitiveness as masculine that progress toward gender equity can be made.
http://ift.tt/2j03SAO
Microvascular insulin resistance in skeletal muscle and brain occurs early in the development of juvenile obesity in pigs
Background: Impaired microvascular insulin signaling may develop prior to overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signaling manifests in skeletal muscle (triceps), brain (prefrontal cortex) and corresponding vasculatures, and that depressed insulin-induced vasodilation is reversible with acute inhibition of protein kinase C beta (PKCβ). Methods and Results: Juvenile Ossabaw miniature swine (3.5-months of age) were divided into two groups: lean control (n=6) and obese (n=6). Obesity was induced by feeding the animals a high-fat/high-fructose corn syrup/high-cholesterol diet for 10-weeks. Juvenile obesity was characterized by excess body mass, hyperglycemia, physical inactivity (accelerometer) and marked lipid accumulation in the skeletal muscle, with no evidence of overt atherosclerotic lesions in athero-prone regions such as the abdominal aorta. Endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) vasomotor responses in the brachial and carotid arteries (wire myography) as well as in the skeletal muscle resistance and 2A pial arterioles (pressure myography) were unaltered, but insulin-induced microvascular vasodilation was impaired in the obese group. Blunted insulin-stimulated vasodilation, which was reversed with acute PKCβ inhibition (LY333-351), occurred alongside decreased tissue perfusion as well as reduced insulin-stimulated Akt signaling in the prefrontal cortex, but not the triceps. Conclusions: In the early stages of juvenile obesity development, the microvasculature and prefrontal cortex exhibit impaired insulin signaling. Such adaptations may underscore vascular and neurological derangements associated with juvenile obesity.
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Maternal circadian rhythms and the programming of adult health and disease
The in utero environment is inherently rhythmic, with the fetus subjected to circadian changes in temperature, substrates and various maternal hormones. Meanwhile, the fetus is developing an endogenous circadian timing system, preparing for life in an external environment where light, food availability and other environmental factors change predictably and repeatedly every 24 hours. In humans, there are many situations that can disrupt circadian rhythms, including shift work, international travel, insomnias and circadian rhythm disorders (e.g., advanced/delayed sleep phase disorder), with a growing consensus that this chronodisruption can have deleterious consequences for an individual's health and wellbeing. However, the impact of chronodisruption during pregnancy on the health of both the mother and fetus is not well understood. In this review we outline circadian timing system ontogeny in mammals, and examine emerging research from animal models demonstrating long term negative implications for progeny health following maternal chronodisruption during pregnancy.
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Atypical G protein {beta}5 promotes cardiac oxidative stress, apoptosis, and fibrotic remodeling in response to multiple cancer chemotherapeutics
The clinical use of multiple classes of cancer chemotherapeutics is limited by irreversible, dose-dependent, and sometimes life-threatening cardiotoxicity. We report here that, though distinct in their mechanisms of action, doxorubicin, paclitaxel, and 5-FU all induce rapid and robust upregulation of atypical G protein Gβ5 in the myocardium, correlating with oxidative stress, myocyte apoptosis, and the accumulation of pro-inflammatory and pro-fibrotic cytokines. In ventricular cardiac myocytes (VCM), Gβ5 deficiency provided substantial protection against the cytotoxic actions of chemotherapeutics, including reductions in oxidative stress and simultaneous attenuation of ROS-dependent activation of the ATM and CaMKII pro-apoptotic signaling cascades. In addition, Gβ5 loss allowed for maintenance of Δψm, basal MCU, and mitochondrial Ca2+ levels, effects likely to preserve functional myocyte excitation-contraction coupling. Gβ5 knockdown also reduced chemotherapy-induced release of pro-inflammatory cytokines (e.g. TNFα), hypertrophic factors (e.g. ANP), and pro-fibrotic factors (e.g. TGFβ1) from both VCM and ventricular cardiac fibroblasts (VCF), with the most dramatic reductions occurring in co-cultured cells. Intracardiac injection of Gβ5-targeted shRNA allowed for heart specific protection against the damaging impact of chronic chemotherapy. These data suggest that Gβ5 facilitates the myofibroblast transition, the persistence of which contributes to pathological remodeling and heart failure. The convergence of Gβ5-mediated, ROS-dependent signaling pathways in both cell types represents a critical etiological factor in the pathogenesis of chemotherapy-induced cardiotoxicity.
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Rare Tumors in Kids May Respond to Tazemetostat [News in Brief]
EZH2 inhibitor shows some efficacy against INI1-deficient tumors.
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Wild Microbiome Stems Tumorigenesis in Lab Mice [News in Brief]
"Clean" lab animals given their wild counterparts' gut microbes are more resistant to colorectal cancer.
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Indolent T-lymphoblastic proliferation concomitant to acinic cell carcinoma mimicking T-lymphoblastic lymphoma: case report and literature review
Abstract
Aims
Indolent T-lymphoblastic proliferation (iT-LBP) is a non-clonal benign condition showing extrathymic proliferation of T-lymphoblasts positive for CD3, CD4, CD8, and TdT. Isolated iT-LBP has been observed, but the majority of iT-LBP have been seen in conjunction with other disorders including Castleman disease, hepatocellular carcinoma, follicular dendritic cell tumors, angioimmunoblastic T-cell lymphoma, myasthenia gravis, and acinic cell carcinoma (ACC). The clinical course of iT-LBP is indolent, and no therapy is usually required. A major concern is misdiagnosis for T-lymphoblastic lymphoma, and a correct diagnosis of iT-LBP often requires not only pathological analysis but also a cautious monitoring of the clinical course. The aim of this report is to broaden knowledge of this yet not well recognized entity to pathologists and physicians
Methods and Results
We report a case of iT-LBP concomitant to ACC, along with a literature review of all 14 cases of iT-LBP reported to date
Conclusions
iT-LBP should always be considered as a differential diagnosis of T-lymphoblastic lymphoma as the two disorders show extremely resembling traits.
This article is protected by copyright. All rights reserved.
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Epigenetic down-regulation of SOX2 is an independent poor prognostic factor for hypopharyngeal cancers
Abstract
Aims
We recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX2 expression had unique clinicopathological features and a dismal prognosis. The present study aimed to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal or oropharyngeal squamous cell carcinomas (HPSCCs or OPSCCs, respectively).
Methods and Results
The study cohort consisted of consecutive patients with HPSCC (n=130) and OPSCC (n=65) who underwent surgery without preoperative therapy. On immunostaining, SOX2 was almost entirely negative in 10/130 HPSCCs (8%) and 7/65 OPSCCs (11%). No significant differences were observed in clinicopathological features, including the p16 status, between SOX2-positive and SOX2-negative cancers. However, patients with SOX2-negative HPSCC had significantly worse overall and recurrence-free survivals than those with SOX2-positive cancer, while such prognostic relationship was not confirmed in patients with OPSCC. In a multivariate analysis, the loss of SOX2 expression appeared to be an independent poor prognostic factor for patients with HPSCC. In a sequencing analysis, no mutation was found in SOX2. Since SOX2 is known to contain an extensive CpG island before the transcription start site, methylation-specific PCR for the SOX2 promoter was performed. Methylated alleles were found in 9/10 SOX2-negative HPSCCs but none of SOX2-retained cases.
Conclusions
Similar to oesophageal cancers, a small subset (8%) of HPSCCs characteristically almost lacking SOX2 expression appeared to be aggressive neoplasms with high recurrence rates. Promoter hypermethylation was determined to be a major mechanism underlying epigenetic SOX2 silencing.
This article is protected by copyright. All rights reserved.
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Calcineurin inhibitor-induced complement system activation via ERK1/2 signalling is inhibited by SOCS-3 in human renal tubule cells
Abstract
One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations. Following knock-down and overexpression of SOCS-3, we found that SOCS-3 inhibits ERK1/-2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component-depleted conditions. In vivo, increased ERK1/-2 phosphorylation and SOCS-3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow-up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS-3 inhibits CNI-induced ERK1/-2 signalling, thereby blunting the negative control of C-system activation.
This article is protected by copyright. All rights reserved
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Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels
The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the ex...
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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