Dyerbunn7167

K

channels are of great interest to epilepsy research as mutations in their genes are found in humans with inherited epilepsy. At the level of cellular physiology, K+channels control neuronal intrinsic excitability and are the main contributors to membrane repolarization of active neurons. Recently, a genetically modified voltage-dependent K

channel has been patented as a remedy for epileptic seizures.

We review the role of potassium channels in excitability, clinical and experimental evidence for the association of potassium channelopathies with epilepsy, the targeting of K+channels by drugs, and perspectives of gene therapy in epilepsy with the expression of extra K+channels in the brain.

Control over K+conductance is of great potential benefit for the treatment of epilepsy. Nowadays, gene therapy affecting K+channels is one of the most promising approaches to treat pharmacoresistant focal epilepsy.

Control over K+ conductance is of great potential benefit for the treatment of epilepsy. Nowadays, gene therapy affecting K+ channels is one of the most promising approaches to treat pharmacoresistant focal epilepsy.Introduction Malformation of cortical development (MCD) is strongly associated with drug-resistant epilepsies for which surgery to remove epileptogenic lesions is common. Two notable technological advances in this field are identification of the underlying genetic cause and techniques in neuroimaging. These now question how presurgical evaluation ought to be approached for 'mTORpathies.'Area covered From review of published primary and secondary articles, the authors summarize evidence to consider focal cortical dysplasia (FCD), tuber sclerosis complex (TSC), and hemimegalencephaly (HME) collectively as MCD mTORpathies. The authors also consider the unique features of these related conditions with particular focus on the practicalities of using neuroimaging techniques currently available to define surgical targets and predict post-surgical outcome. Ultimately, the authors consider the surgical dilemmas faced for each condition.Expert opinion Considering FCD, TSC, and HME collectively as mTORpathies has some merit; however, a unified approach to presurgical evaluation would seem unachievable. Nevertheless, the authors believe combining genetic-centered classification and morphologic findings using advanced imaging techniques will eventually form the basis of a paradigm when considering candidacy for early surgery.

Friends and family members provide critical support to patients on the waitlist for deceased donor kidney transplantation. However, little is known about how best to support and engage them effectively to improve patient outcomes.

We conducted 5 focus groups with the family members of patients on the waitlist for a deceased donor kidney (n=23) to identify individual- and group-level targets for an intervention. Discussions encouraged participants to reflect on their support roles, experiences at the transplant evaluation, interactions with providers, knowledge of transplant options and expected outcomes. Transcripts of study sessions were coded using an iterative and inductive process.

The thematic analysis produced two main themes related to experiences providing care to patients on the waitlist for kidney transplantation. First, participants revealed that supporting a patient on the waitlist created challenges that reverberate through their entire social structure. Family members discussed frustrationage friends and family members in the care of kidney transplant candidates need to effectively address these challenges.Mitral valve repair is typically performed by implanting a ring-like device at the valve annulus to reshape the annulus and to improve leaflet coaptation. In most cases, some additional procedures are needed, including leaflet resection and artificial chordae implantation. However, artificial chordae implantation could be technically challenging and postoperative left ventricular remodeling could increase the risk of recurrent mitral regurgitation. We propose an innovative annular device made of chromo-cobalt, finalized not only to reshape the annulus but also to enable anchoring of leaflets to a fixed intraventricular structure. Durability evaluation of the device was tested by applying eight radial force vectors equally spaced along the ring and related fatigue analysis. To evaluate the efficacy of the mitral valvuloplasty using the tested ring, the device was implanted in five adult swine hearts. Functional analysis of the ring was performed by measuring left ventricular pressure and fluid volume loss, following implantation in normal and dysfunctional mitral valve leaflets. Both fatigue and functional analysis showed satisfactory and promising results in terms of durability and efficacy of mitral valve repair. Because of its favorable durability and functional characteristics this device appears promising and provides good results in terms of valve competence, thus avoiding both manipulations of papillary muscles and interference in left ventricular hemodynamics. However, an in vivo test is mandatory to fully understand the impact of the device on subvalvular apparatus.Organisational competitive procurement environment positively impacts prices while supply side factors also determine participation in bidding. With strong competition costs come down. Instances of low competition in equipment purchase in the apex tertiary care hospital led to this study aimed at determining procurement practices, competition in procurement and its determinants. Review of tender records for three financial years (2011-2014) was conducted to ascertain procurement practices and resulting competition. Sellers' perspective on factors determining participation was captured through a questionnaire. Although four bids per tender were received only two qualified technically emphasising need for broad based specifications. Both sellers and peer staff also feel that specifications are not broad based. Regression analysis showed that one unit increase in bid led to six per cent price reduction. Increase in number of equipment led to an increase in the number of bids received but no price decrease. Pre-bid meetings have no effect on the price offered. Quality of tender document and feasible demonstration are modifiable bidding factors. Procuring agencies need to be transparent to reflect an organisationally supported competitive environment. The future research directions are interventional studies on specifications, pre-bid meetings and increasing transparency.Background Despite the wide range of available treatment modalities a delay between the first outbreak of acne vulgaris and an effective treatment outcome is experienced by many patients. Considering the growing incentives to improve patient satisfaction and quality of care while reducing healthcare costs, insights into the structure, quality and accessibility of acne healthcare services beyond guidelines are therefore needed.Objective To provide insights into the structure, quality and accessibility of acne healthcare services.Methods A qualitative study was conducted according to the principles of 'situational analysis'. The Dutch acne healthcare system was taken as an illustrative example. Twenty-four semi-structured interviews were conducted among representatives of the 4 main Dutch professions providing acne care. All interviews were audiotaped, transcribed verbatim and analyzed.Results Multiple facilitators and barriers emerged from the interviews. Identified facilitators were care providers delivering personalized patient care and having a positive attitude toward formalized multidisciplinary care delivery. A lack of streamlined referral pathways and standardization in acne severity-assessment, financial aspects and unfamiliarity with the content and added value of other acne care professionals were identified as barriers. Further research is recommended to investigate how de-medicalisation, the gatekeepers role, and the impact of location and work setting influence the quality of and accessibility to care.Conclusions Identified facilitators and barriers and an overall positive attitude of care providers toward multidisciplinary care provision provides opportunities for the utilization of future guidelines involving streamlined referral pathways and good working arrangements between all acne care providing professions.

Although the benefit of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) over chemotherapy in

mutation-positive (

m) non-small-cell lung cancer (NSCLC) has been demonstrated in clinical trials, the optimal treatment sequence remains unclear. The objective of our study was to evaluate the cost-effectiveness of dacomitinib in Sweden vs afatinib and osimertinib in first-line treatment of

m NSCLC.

A partitioned survival model was developed with three health states progression-free, post-progression, and death. Progression-free and overall survival curves were used to inform movements between states. Clinical data were taken from randomized trials, compared

a network meta-analysis (NMA). Utility data were taken from published studies and costs from national Swedish sources. The model used a 15-year time horizon and a Swedish healthcare payer perspective. Sensitivity and scenario analyses were performed.

The base-case analysis showed that dacomitinib accrued a tota and osimertinib.

Our model demonstrated that dacomitinib is cost-effective for first-line EGFRm NSCLC treatment in Sweden vs afatinib and osimertinib.

To determine the effects of dietary nitrate supplementation, in the form of red spinach extract (RSE), on adaptations to offseason training in collegiate athletes.

Sixteen Division I male baseball athletes (20.5 ± 1.7y, 90.4 ± 0.5 kg) enrolled in this study and were randomized into a RSE (

 = 8) or placebo (

 = 8; PL) group. Athletes completed an 11-week resistance training program during the offseason, which consisted of 2-3 workouts per week of upper and lower-body exercises and baseball-specific training. Athletes consumed a RSE (2 g; 180 mg nitrate) or PL supplement daily for the entire offseason training program. Pre and post-training, all athletes underwent one-repetition maximum (1RM) strength testing for the bench press and completed a Wingate anaerobic cycle test (WAnT). Body composition analysis was completed

a 4-compartment model, as well as muscle thickness (MT) measurement of the rectus femoris (RF) and vastus lateralis (VL)

ultrasonography. Resting heart rate and blood pressure (BP) following offseason training.

Idiopathic pulmonary fibrosis (IPF) is a type of progressive lung fibrosis disease. The survival time of diagnosed IPF patients is often only 2 years. Currently much evidence showed that the epithelial-mesenchymal transition (EMT) process is the main cause of the occurrence and development of IPF. LncRNA cardiac hypertrophy related factor (CHRF) was reported to be related with IPF development. Here we explored the functions and regulatory mechanisms of CHRF on EMT in IPF.

A549 cells were treated with transforming growth factor-β1 (TGF-β1) for 48 h to construct IPF cell model. CHRF and miR-146a expression were quantified using qPCR. The expression of L1 cell adhesion molecule (L1CAM) and EMT related indicators (E-cadherin, Vimentin, Slug and N-cadherin) were detected by qPCR and western blot. this website Dual luciferase reporter experiment was conducted to prove the molecular interaction of miR-146a and L1CAM, as well as CHRF and miR-146a.

CHRF and L1CAM expression were significantly upregulated and promoted the EMT process in A549 after treatment of TGF-β1.