Association between Tetrodotoxin Resistant Channels and Lipid Rafts Regulates Sensory Neuron Excitability

PubMed ID: 22870192This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

There is insufficient evidence to recommend bremelanotide for hypoactive sexual desire disorder

An informed consent discussion for a patient with Hypoactive Sexual Desire Disorder

Management of Upper Aerodigestive Tract Bleeding in Patients on ECMO.

Introduction: Bleeding complications on Extracorporeal Membrane Oxygenation (ECMO) are often encountered. In a review of our own series, it was found that upper aero digestive tract bleeding was common and management was often difficult. We propose an algorithm to help manage upper aero digestive tract bleeding in the anticoagulated, ECMO patient. Hypothesis: Once an ECMO patient fails conservative management for upper aero digestive bleeding, more aggressive measures will prove successful, which will provide benefit to the patient. Methods: A retrospective chart review was performed of the patients who underwent venovenous or veno-arterial ECMO at our institution between July 2010 and July 2012. The patients that had upper aero digestive tract bleeding that required an Otolaryngology consultation were identified. They were further investigated to determine location of bleed and procedures performed to control the bleeding. Results: Among the 37 consecutive patients on ECMO, 11 (30%) had upper aero digestive tract bleeding events. Of these 11, 6 (55%) were secondary to an iatrogenic incident, such as placing a nasogastric tube or transesophageal echo probe. All 11 patients were treated at bedside with conservative management and 2 were treated in the operating room. 72.7 % of patients treated with conservative management required repeated procedures due to incomplete hemostasis, compared to 0% of patients once surgical intervention was complete. Conclusions: Approximately one third of the ECMO patients developed upper aero digestive tract bleeding. This bleeding should be controlled in a timely manner otherwise it may result in massive transfusions. Delaying intervention or conservative management may not be effective. We recommend surgical intervention if the initial conservative management failed and continued to bleed for more than 24-36 hours

Standards-based wireless sensor networks for power system condition monitoring

This paper assesses the industrial needs motivating interest in wireless monito ring within the power industry, and reviews applications of WSN technology for substation condition monitoring (Section 2). A key contribution is the identification of a set of technical requirements for substation - based WSNs, focused around security requi rements, robustness to RF noise, and other utility - specific concerns (Section 3). Section 4 comprehensively assesses the suitability of various IWSN protocols for substation environments, using these requirements. A case study implementation of one standar d, ISA100.11a, is reported in Section 5, along with deployment experience. The paper concludes by describing future research challenges for WSN protocols which are specific to this domain

Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis

Objectives: Obesity has been proposed as a risk factor for refractory rheumatoid arthritis (RA). We evaluated the impact of obesity on achieving clinical and imaging definitions of low disease activity. Methods: This study evaluated 470 patients with RA from GO-BEFORE and GO-FORWARD randomised clinical trials. Included patients had blinded clinical disease activity measures and MRI at baseline, 24 and 52 weeks. Synovitis, osteitis and total inflammation scores were determined using the RA MRI scoring system. Multivariable logistic regression analyses compared odds of achieving Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) remission, low component measures, or low MRI inflammation measures at 24 weeks in patients with obesity versus no obesity. Results: At 24 weeks, patients with obesity were significantly less likely to achieve DAS28(CRP) remission (OR 0.47; 95% CI 0.24 to 0.92, p=0.03). In contrast, patients with obesity had similar odds of achieving low synovitis (OR 0.94; 95% CI 0.51 to 1.72, p=0.84) and inflammation scores (OR 1.16; 95% CI 0.61 to 2.22, p=0.64) and greater odds of achieving low osteitis scores (OR 2.06; 95% CI 1.10 to 3.84, p=0.02) versus normal weight patients. Conclusions: Patients with RA and obesity have lower rates of DAS28 remission but similar rates of low MRI activity compared with patients without obesity, suggesting that obesity and its associated comorbidities can bias clinical disease activity measures. Trial registration number: NCT00361335 and NCT00264550; Post-results

Deletion of annexin 2 light chain p11 in nociceptors causes deficits in somatosensory coding and pain behavior

The S100 family protein p11 (S100A10, annexin 2 light chain) is involved in the trafficking of the voltage-gated sodium channel Na(V)1.8, TWIK-related acid-sensitive K+ channel (TASK-1), the ligand-gated ion channels acid-sensing ion channel 1a (ASIC1a) and transient receptor potential vanilloid 5/6 (TRPV5/V6), as well as 5-hydroxytryptamine receptor 1B (5-HT1B), a G-protein-coupled receptor. To evaluate the role of p11 in peripheral pain pathways, we generated a loxP-flanked (floxed) p11 mouse and used the Cre-loxP recombinase system to delete p11 exclusively from nociceptive primary sensory neurons in mice. p11-null neurons showed deficits in the expression of NaV1.8, but not of annexin 2. Damage-sensing primary neurons from these animals show a reduced tetrodotoxin-resistant sodium current density, consistent with a loss of membrane-associated NaV1.8. Noxious coding in wide-dynamic-range neurons in the dorsal horn was markedly compromised. Acute pain behavior was attenuated in certain models, but no deficits in inflammatory pain were observed. A significant deficit in neuropathic pain behavior was also apparent in the conditional-null mice. These results confirm an important role for p11 in nociceptor function

Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis

Objectives: Obesity has been proposed as a risk factor for refractory rheumatoid arthritis (RA). We evaluated the impact of obesity on achieving clinical and imaging definitions of low disease activity. Methods: This study evaluated 470 patients with RA from GO-BEFORE and GO-FORWARD randomised clinical trials. Included patients had blinded clinical disease activity measures and MRI at baseline, 24 and 52 weeks. Synovitis, osteitis and total inflammation scores were determined using the RA MRI scoring system. Multivariable logistic regression analyses compared odds of achieving Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) remission, low component measures, or low MRI inflammation measures at 24 weeks in patients with obesity versus no obesity. Results: At 24 weeks, patients with obesity were significantly less likely to achieve DAS28(CRP) remission (OR 0.47; 95% CI 0.24 to 0.92, p=0.03). In contrast, patients with obesity had similar odds of achieving low synovitis (OR 0.94; 95% CI 0.51 to 1.72, p=0.84) and inflammation scores (OR 1.16; 95% CI 0.61 to 2.22, p=0.64) and greater odds of achieving low osteitis scores (OR 2.06; 95% CI 1.10 to 3.84, p=0.02) versus normal weight patients. Conclusions: Patients with RA and obesity have lower rates of DAS28 remission but similar rates of low MRI activity compared with patients without obesity, suggesting that obesity and its associated comorbidities can bias clinical disease activity measures. Trial registration number: NCT00361335 and NCT00264550; Post-results

Type 2 diabetes and its correlates among adults in Bangladesh: a population based stud

Type 2 diabetes is one of the most prevalent non-communicable diseases in Bangladesh. However, the correlates of type 2 diabetes among adults in Bangladesh remain unknown. We aimed to investigate the correlates of type 2 diabetes among the adults in Bangladesh. Methods : We conducted a cross-sectional study using data from the nationally representative 2011 Bangladesh Demographic and Health Survey. A random sample of 7,543 (3,823 women and 3,720 men) adults of age 35 years and older from both urban and rural areas, who participated in the survey was included. Diabetes was defined as having a fasting plasma blood glucose level of ≥ 7 mm/L or taking diabetes medication during the survey. Hypothesized factors, e.g., age, sex, education, place of residence, social status, body mass index, and hypertension were considered in the analyses. Multivariable logistic regression models were used to identify the important correlates of type 2 diabetes. Results : Among the respondents, the overall prevalence of diabetes was 11 %, and the prevalence was slightly higher in women (11.2 %) than men (10.6 %). Respondents with the age group of 55–59 years had higher odds of having diabetes (odds ratios (OR) = 2.37, 95 % confidence interval (CI): 1.76–3.21) than the age group of 35–39 years. Moreover, respondents who had higher educational attainment (OR = 1.67, 95 % CI: 1.18–2.36) and higher social status (OR = 2.01, 95 % CI: 1.50–2.70) had higher odds of having diabetes than the respondents with no education and lower social status, respectively. We also found socioeconomic status, place of residence (rural or urban), regions of residence (different divisions), overweight and obesity, and hypertension as significant correlates of type 2 diabetes in Bangladesh. Conclusions: Our study shows that older age, higher socioeconomic status, higher educational attainment, hypertension, and obesity were found to be significant correlates of type 2 diabetes. Need-based policy program strategies including early diagnosis, awareness via mass media, and health education programs for changing lifestyles should be initiated for older age, wealthy, and/or higher educated individuals in Bangladesh. Moreover, area-specific longitudinal research is necessary to find out the underlying causes of regional variations

Ion Channel Formation by Amyloid-β42 Oligomers but not Amyloid-β40 in Cellular Membranes

A central hallmark of Alzheimer's disease (AD) is the presence of extracellular amyloid plaques chiefly consisting of amyloid-β (Aβ) peptides in the brain interstitium. Aβ largely exists in two isoforms, 40 or 42 amino acids long, while a large body of evidence points to Aβ(1-42) rather than Aβ(1-40) as the cytotoxic form. One proposed mechanism by which Aβ exerts toxicity is the formation of ion channel pores that disrupt intracellular Ca2+ homeostasis. However, previous studies using membrane mimetics have not identified any notable difference in the channel-forming properties between Aβ(1-40) and Aβ(1-42). Here, we tested whether a more physiological environment-membranes excised from HEK293 cells of neuronal origin-would reveal differences in the relative channel-forming ability of monomeric, oligomeric, and fibrillar forms of both Aβ(1-40) and Aβ(1-42). Aβ preparations were characterized with transmission electron microscopy and Thioflavin-T fluorescence. Aβ was then exposed to the extracellular face of excised membranes and transmembrane currents were monitored using patch-clamp. Our data indicated that Aβ(1-42) assemblies in oligomeric preparations form voltage-independent, non-selective ion channels. In contrast, Aβ(1-40) oligomers, fibres and monomers did not form channels. Ion channel conductance results suggested that Aβ(1-42) oligomers—but not monomers and fibres—formed 3 distinct pore structures with 1.7, 2.1, and 2.4 nm pore diameters. Our findings demonstrate that only Aβ(1-42) contains unique structural features that facilitate membrane insertion and channel formation, now aligning ion channel formation with the differential neurotoxic effect of Aβ(1-40) and Aβ(1-42) in AD.Life Science initiative, Queen Mary, University of London and Biotechnology and Biological Sciences Research Council Grant BB/M023877/1

Incorporation of tic particulates on AISI 4340 low alloy steel surfaces via tungsten inert gas arc melting

Surface cladding utilizes a high energy input to deposit a layer on substrate surfaces providing protection against wear and corrosion. In this work, TiC particulates were incorporated by melting single tracks in powder preplaced onto AISI 4340 low alloy steel surfaces using a Tungsten Inert Gas (TIG) torch with a range of processing conditions. The effects of energy input and powder content on the melt geometry, microstructure and hardness were investigated. The highest energy input (1680 J/mm) under the TIG torch produced deeper (1.0 mm) and wider melt pools, associated with increased dilution, compared to that processed at the lowest energy (1008 J/mm). The melt microstructure contained partially melted TiC particulates associated with dendritic, cubic and globular type carbides precipitated upon solidification of TiC dissolved in the melt; TiC accumulated more near to the melt-matrix interface and at the track edges. Addition of 0.4, 0.5 and 1.0 mg/mm2 TiC gave hardness values in the resolidified melt pools between 750 to over 1100Hv, against a base hardness of 300 Hv; hardness values are higher in tracks processed with a greater TiC addition and reduced energy input