Tightly Bound PMMA on Silica Has Reduced Heat Capacities.

The heat capacities of very small adsorbed amounts of poly(methyl methacrylate) on high-surface-area silica (Cab-O-Sil) were measured using temperature-modulated differential scanning calorimetry (TMDSC) using a quasi-isothermal method and interpreted via different models. The composition-dependent heat capacities of the adsorbed samples were measurably less than those predicted with a simple mixture model. A two-state model, composed of tightly and loosely bound polymer, fits the data better with heat capacities of the tightly bound polymer found to be 70-80% (glassy region) and 70-94% (rubbery region) of that of the bulk polymer at the same temperatures. The amount of tightly bound polymer was estimated to be about 1.2 mg/m2 (about 1 nm thickness) in both the glassy and rubbery regions, consistent with heat flow measurements. The data sets were also extensive enough to model them with a more detailed layered gradient model, including a nonzero heat capacity for the polymer at zero adsorbed amount, which increased based on an exponential growth function to bulk polymer value of the heat capacity away from the surface. More importantly, this gradient model mimicked the experimental dependence on adsorbed amounts in the tightly bound adsorbed amount region (approximately 1 mg/m2). This model provided, for the first time, an experimental estimate of the heat capacity of the polymer adsorbed closest to the surface. The fractional heat capacity of the adsorbed polymer closest to the silica surface, relative to bulk polymer, increased with temperature from 0.3 (well below) to 0.8 (well above the bulk Tg). It was also possible to estimate the exponential growth parameter of the development from the initial heat capacities to the bulk heat capacity as 0.4 to 0.6 mg/m2, identifying a distance scale (0.3 to 0.5 nm) consistent with the notion of a transition from tightly bound to loosely bound polymer.

Association between environmental exposure and CD4+CD25+ regulatory T cells.

BACKGROUND: It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. AIM: To compare CD4+/CD25+ T-regulatory cells and forkhead transcription factor Foxp3 expression in asthmatic children allergic to house dust mites (HDM) living in rural and farm areas. MATERIALS AND METHODS: This was a prospective analysis of 35 children living in farm areas (n=19) and rural areas (n=16), aged 8-16, with allergic rhinitis (allergic to dust mites) and newly diagnosed asthma. Surface molecule CD4+CD25+Foxp3+ expression on cultured PBMCs was estimated by flow cytometry using fluorophore-conjugated monoclonal antibodies in each patient. RESULTS: Thirty-five children were included into the analysis: 19 children living in farm areas and 16 in rural areas. Within and between-groups (farm area vs. rural area) differences in CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression did not reach the level of significance. CONCLUSION: The current analysis showed that CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression was not associated with place of living in asthmatic children sensitive to HDM.

What affects utilization of malaria control services? A qualitative approach to understanding community perception in highly malarious Gadchiroli district, Maharashtra, India.

National Vector Borne Disease Control Programme (NVBDCP) data have shown that nearly half of all malaria deaths in India occur in tribal-dominated areas. The present study took a qualitative approach to understanding community perceptions and practices related to malarial infection and anti-malarial programmes. Twelve focus group discussions and 26 in-depth interviews of Accredited Social Health Activists (ASHAs) were conducted in nine villages in the district of Gadchiroli, Maharashtra state in India in June 2016. A total of 161 village residents (94 males and 67 females) participated in the focus group discussions and 26 health workers participated in the in-depth interviews. Data were analysed using the content analysis approach. The findings revealed widespread misconceptions about malaria among village residents, and low use of preventive measures and anti-malarial services. Ignorance and treatment by unqualified traditional healers delay effective treatment seeking. Furthermore, failure to maintain drug compliance adds to the gravity of the problem. The study identified the social and behavioural factors affecting treatment uptake and use of treatment facilities in the study area. These should help the development of the behavioural change communication arm of any control strategy for malaria through improving community participation, so improving preventive practices and optimizing utilization of anti-malarial services.

Screening for subclinical subclavian artery stenosis before coronary artery bypass grafting: Should we do it?

Atherosclerotic subclavian artery disease is detected in about 5% of patients referred for coronary artery bypass (CABG) surgery. The internal mammary artery, a branch of the subclavian artery, is the most frequently utilized graft to restore coronary circulation because of its longevity. Stenosis or occlusion of the subclavian artery can cause retrograde blood flow in the ipsilateral internal mammary artery, known as "steal," compromising coronary circulation supplied by the graft. Steal may be asymptomatic or may result in symptoms of myocardial ischemia. Symptomatic subclavian artery stenosis post bypass is referred to as coronary subclavian steal syndrome post-CABG. The incidence is not well defined, and the benefits of screening patients referred for CABG are not known. Despite the various modalities available to detect subclavian artery stenosis, current guidelines fail to provide guidance about screening high-risk patients for this entity. Detection of subclavian artery disease prior to CABG can reduce complications posed by post-mammary artery graft cardiac ischemia. This review discusses the utility of preoperative subclavian artery screening prior to CABG.

Isolated Aneurysms of the Membranous Ventricular Septum Without Residual Shunts: Systematic Review and Description of 3 Cases in Adults.

A ventricular septal defect is the most common congenital cardiac abnormality encountered in infants and children. Many of them survive through adulthood before diagnosis. Two-thirds of the cases involve the membranous part of the septum. In the absence of an interventricular shunt or concomitant cardiac surgery, guidelines for surgical intervention or resection of isolated aneurysms of the membranous septum are not well established. In this report, we discuss a multi-imaging modality approach for the diagnosis and assessment of membranous ventricular septal aneurysms and review the experts' consensuses for follow-up and treatment strategies.

Health Insurance Paid Costs and Drivers of Costs for Patients With Crohn's Disease in the United States.

OBJECTIVES: The cost of medical care for Crohn's disease (CD) and comorbidities in the era of biologics is unclear. We examined insurance claims data from US health plans to understand this relationship. METHODS: Longitudinal CD patient data and reimbursement information from 11 health plans engaged with Accordant Health Services between 2011 and 2013 were analyzed. The analysis considered data for all CD patients and for the patient subgroup ≤20 years and >20 years of age. Descriptive statistics measured the mean health-plan paid costs per patient, the relative cost contribution of anti-tumor necrosis factor (TNF) agents, and health care costs for 31 specific comorbid conditions among CD patients. RESULTS: Overall, there were 5,090 CD patients (57% women) of which 587 CD patients were ≤20 years of age. The mean health-plan paid cost per member per year was $18,637 (s.d. $32,023) for all CD patients, $22,796 (s.d. $ 41,905) for CD patients ≤20 years, and $18,095 (s.d. $30,065) for patients >20 years of age. Twenty-eight percent of CD patients accounted for 80% of total costs. No differences were found in costs based on gender. Increased health-plan paid costs were significantly correlated with the number of comorbid conditions across all ages. Pharmacy utilization costs account for nearly one-half (45.5%) of the total CD-attributable costs, exceeding inpatient care costs. Anti-TNF agents alone comprised nearly one-third (29.5%) of total costs. Aside from anti-TNF costs, other major categories of expense were as follows: inpatient 23.1%, outpatient hospital setting 15.7%, and MD office 8.2%. CONCLUSIONS: Total health-care costs in CD exceed previous estimates, with the majority of costs being allocated to a relatively small subgroup of patients. Pharmacy utilization costs, owing to anti-TNF use, result in increasing total health-care costs and currently exceed costs for inpatient care. Pragmatic strategies to encourage gastroenterologists in the best clinical practice of optimizing anti-TNF use-in particular for younger age patients and those with multiple comorbidities-are necessary to reduce avoidable pharmacy utilization and inpatient care costs.

The anti-angiogenic and cytotoxic effects of the boswellic acid analog BA145 are potentiated by autophagy inhibitors.

BACKGROUND: While angiogenesis inhibitors represent a viable cancer therapy, there is preclinical and clinical data to suggest that many tumors develop resistance to such treatments. Moreover, previous studies have revealed a complex association between autophagy and angiogenesis, and their collective influence on tumorigenesis. Autophagy has been implicated in cytoprotection and tumor promotion, and as such may represent an alternative way of targeting apoptosis-resistant cancer cells. This study explored the anti-cancer agent and boswellic acid analog BA145 as an inducer of autophagy and angiogenesis-mediated cytoprotection of tumor cells. METHODS: Flow cytometry, western blotting, and confocal microscopy were used to investigate the role of BA145 mediated autophagy. ELISA, microvessel sprouting, capillary structure formation, aortic ring and wound healing assays were performed to determine the relationship between BA145 triggered autophagy and angiogenesis. Flow cytometery, western blotting, and microscopy were employed to examine the mechanism of BA145 induced cell death and apoptosis. Live imaging and tumor volume analysis were carried out to evaluate the effect of BA145 triggered autophagy on mouse tumor xenografts. RESULTS: BA145 induced autophagy in PC-3 cancer cells and HUVECs significantly impeded its negative regulation on cell proliferation, migration, invasion and tube formation. These effects of BA145 induced autophagy were observed under both normoxic and hypoxic conditions. However, inhibition of autophagy using either pharmacological inhibitors or RNA interference enhanced the BA145 mediated death of these cells. Similar observations were noticed with sunitinib, the anti-angiogenic properties of which were significantly enhanced during combination treatments with autophagy inhibitors. In mouse tumor xenografts, co-treatment with chloroquinone and BA145 led to a considerable reduction in tumor burden and angiogenesis compared to BA145 alone. CONCLUSION: These studies reveal the essential role of BA145 triggered autophagy in the regulation of angiogenesis and cytoprotection. It also suggests that the combination of the autophagy inhibitors with chemotherapy or anti-angiogenic agents may be an effective therapeutic approach against cancer.

Point of No Return From Water Loss in Coptotermes formosanus (Isoptera: Rhinotermitidae).

Describing desiccation stages based on the physical appearance of termites has not been evaluated previously. Formosan subterranean termites were studied to determine the rate of water loss, singly and in groups, in the laboratory. The stages of water loss are described based on changes in physical appearance and percent total body water loss evaluated at 2- to 8-h time intervals up to 32 h. Workers in groups lost water slower than individual worker trials. Weight loss was linear over time for worker groups and individuals, as was individual soldier only trials. Water loss in individual workers was significantly faster than in soldiers. Three physical stages of desiccation are described for living workers: (I) curling of antennae, (II) on back but with assistance able to right themselves and walk, and (III) unable to get off back; and two stages for living soldiers (II and III). Recovery was determined from termites in a second trial by transferring stage I, II, and III individuals from open, dry Petri dishes to those with moist filter paper at 4, 6, 10, 12, 14, 16, 24, 26 and 28 h. After 12 h on moist filter paper, stage I workers had a 83% recovery rate, stage II had a 33%, and stage III had a 7% recovery. Soldiers had a 56% recovery at stage II and was similar to the recovery of workers at stage III. Most termites that reached stage III were destined to die.

Patient demographics and health plan paid costs in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: We determined health plan paid costs and healthcare resource usage of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: CIDP patients from 9 U.S. commercial health plans with claims in 2011 were identified from the Accordant Health Services claims database. We examined demographics, prevalence of comorbidities, prescribed drugs, place of service, and mean annual health plan paid costs per patient. RESULTS: From 6.5 million covered lives, 73 (56% men; mean age 47) met study entry criteria. The most prescribed therapies were intravenous immunoglobulin (IVIg) (26% of patients), gabapentin (26%), and prednisone (16%). The annual health plan paid cost was $56,953. Pharmacy cost was the major cost driver (57% of the total), and IVIg totaled 90% of the pharmacy costs. CONCLUSIONS: Healthcare costs for CIDP patients are substantial, with a large burden in pharmacy usage. Studies are needed to determine optimal long-term treatment strategies for CIDP, particularly related to IVIg.

Lethal and sublethal effects of lufenuron on the Formosan subterranean termite (Isoptera: Rhinotermitidae).

A laboratory study was conducted to understand the effect of low concentrations of lufenuron on termite physiology and behavior. Survivorship, running speed, body water content, food consumption, tunneling, microbial infection, and two behavioral patterns (carcass-burying behavior and particle transport behavior) were compared among Formosan subterranean termites, Coptotermes formosanus Shiraki, fed lufenuron-treated (250, 500, or 1,000 ppm) or untreated (control) filter paper. In 30-32 d, all lufenuron treatments significantly reduced survivorship, running speed, consumption, and tunneling, but had no substantial effect on body water content. In addition, termites fed the three concentrations of lufenuron became infected by opportunistic pathogens. Carcass-burying and particle transport behaviors also were inhibited by lufenuron. Potential application of lufenuron at low concentrations for the control of C. formosanus is discussed.

Parkinsonism Associated with Snakebite.

Snakebites are a major cause of morbidity and mortality worldwide. Snake envenomation can cause acute local and systemic effects leading to severe complications, even death. Neurological complications such as intracranial hemorrhage, subarachnoid bleed, ischemic strokes, acute disseminated encephalomyelitis, and leukoencephalopathy have been reported. Anti-snake venom which forms the mainstay of therapy also has its own set of early and delayed complications. This report describes a rare case of snakebite resulting in leukoencephalopathy and parkinsonian features.

RésuméLes morsures de serpent sont une cause majeure de morbidité et de mortalité dans le monde. L'envenimation par les serpents peut provoquer des effets locaux et systémiques aigus, conduisant à de graves complications, voire à la mort. Complications neurologiques telles qu'hémorragie intracrânienne, hémorragie sous-arachnoïdienne, accidents vasculaires cérébraux ischémiques, une encéphalomyélite aiguë disséminée et une leucoencéphalopathie ont été rapportées. Le venin anti-serpent qui constitue le pilier de la thérapie a également son propre ensemble de complications précoces et retardées. Ce rapport décrit un cas rare de morsure de serpent ayant entraîné une leucoencéphalopathie et caractéristiques parkinsoniennes.

Successful Reversal of Refractory Posttransplant Thrombotic Microangiopathy with Eculizumab.

Posttransplant thrombotic microangiopathy (PT-TMA) can be caused by calcineurin inhibitors (CNIs), ischemic injury, infections, or antibody-mediated rejection (ABMR). Delayed recognition can result in allograft loss. We describe the first reported case of successful reversal of refractory PT-TMA with eculizumab in India. It highlights the importance of prompt diagnosis and benefit from an early initiation of eculizumab therapy in refractory cases.

Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice.

Blood vessels are continually exposed to circulating lipids, and elevation of ApoB-containing lipoproteins causes atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FAs) into triglyceride-rich (TG-rich) lipid droplets (LDs) is not known. In this study, we showed that deletion of the enzyme adipose TG lipase (ATGL) in the endothelium led to neutral lipid accumulation in vessels and impaired endothelial-dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL led to endoplasmic reticulum stress-induced inflammation in the endothelium. Consistent with this mechanism, deletion of endothelial ATGL markedly increased lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD affects endothelial cell homeostasis and consequently large vessel function during normal physiology and in a chronic disease state.

Comparative evaluation of 3-dimensional pseudocontinuous arterial spin labeling with dynamic contrast-enhanced perfusion magnetic resonance imaging in grading of human glioma.

INTRODUCTION: The study was performed to compare dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) with 3-dimensional (3D) pseudocontinuous arterial spin labeling (PCASL) MRI in gliomas with an aim to see whether arterial spin labeling (ASL)-derived cerebral blood flow (CBF) values can be used as an alternative to DCE-MRI for its grading. MATERIALS AND METHODS: Sixty-four patients with glioma (37 male; mean age, 43 years; 38 high grade and 26 low grade) underwent 3D-PCASL and DCE-MRI. The DCE indices (relative cerebral blood volume, rCBV; relative CBF, rCBF; permeability, k and kep; and leakage, ve) and ASL (absolute and rCBF) values were quantified from the tumors. Student independent t test was used to compare ASL and DCE-MRI indices. Pearson correlation was used to see correlation between DCE- and ASL-derived CBF values in tumor and normal parenchyma. RESULTS: On Student t test, neither ASL-derived absolute CBF (P = 0.78) nor rCBF (P = 0.12) values were found to be significantly different in 2 groups, whereas DCE indices except ve were significantly higher in high-grade gliomas. Arterial spin labeling-derived rCBF values weakly correlated with DCE-derived rCBF values, whereas these did not show correlation in normal grey (P = 0.12, r = 0.2) and white (P = 0.26, r = 0.14) matter regions. CONCLUSIONS: Three-dimensional pseudocontinuous arterial spin labeling does not appear to be a reliable technique in the current form and may not be a suitable replacement for DCE in grading of glioma.

Lufenuron suppresses the resistance of Formosan subterranean termites (Isoptera: Rhinotermitidae) to entomopathogenic bacteria.

Pesticides can negatively affect insect immunity. Although studies show that Formosan subterranean termites, Coptotermes formosanus Shiraki, are resistant to microbial infections, the effects of pesticides on disease resistance is not well studied. In this study, C. formosanus previously fed lufenuron was exposed to each of the three entomopathogenic bacteria, Pseudomonas aeruginosa (Schroeter) Migula, Serratia marcescens Bizio, and Bacillus thuringiensis Berliner subsp. israelensis. We found that termite mortality was significantly higher and synergistic in the combination of lufenuron and P. aeruginosa compared with treatment of lufenuron or P. aeruginosa alone. Other bacteria and lufenuron combinations were not quite as effective. Interestingly, only in treatments without lufenuron did termites show carcass-burying behavior. The results indicate that lufenuron, a chitin synthesis inhibitor, can suppress Formosan subterranean termite resistance to P. aeruginosa. Possible suppression mechanisms are discussed.

Horizontal transfer of fipronil is enhanced with increased group size in Coptotermes formosanus (Isoptera: Rhinotermitidae).

Fipronil is a widely used insecticide for termite control. Although transfer of fipronil among termite cohorts has been investigated in previous studies, no study has yet focused on the influence of termite group size (density) on horizontal transfer. In this study, the mortality of donor and recipient Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae) was compared among groups of 10, 25, and 50 workers. Most donor termites were dead within 20 h. There was a significantly higher mortality of recipient termites starting at 44 h when in bigger groups. LT50 and LT90 of recipient termites decreased with increase in group size, being significantly shorter in groups of 50 termites compared with groups of 10 termites. Moreover, the variance (within-group difference) of recipient mortality and lethal time estimations was lowest in the groups of 50 termites, indicating a more uniform horizontal transfer of fipronil by termites in bigger groups. Our findings suggest that group size has an influence on fipronil transfer among C. formosanus workers and should be considered as a variable of importance.

Estimated cost of treating myasthenia gravis in an insured U.S. population.

INTRODUCTION: In this study we estimated the costs paid by U.S. health plans for treating myasthenia gravis (MG) in 2009 and determined the major cost drivers. METHODS: One hundred thirteen MG patients were matched by propensity scores with 339 non-MG patients from a comprehensive health-care insurance database. The mean annual costs paid by the health plan for treating MG, costs by place of service, and costs for intravenous immunoglobulin (IVIg) and plasma exchange were determined. RESULTS: Mean annual costs paid by the health plan per MG patient were $20,190 (SEM $4,763) and costs attributable to treating MG were $15,675. Home health services accounted for 23% of MG patient costs and represented almost exclusively IVIg infusion costs. Six MG patients had a total of 136 outpatient IVIg infusions at an average annual cost of $109,463 ± $57,303. CONCLUSIONS: The estimated annual health plan paid costs for treating MG were $15,675. Home health services represented 23% of MG patient costs, largely driven by IVIg administration.

Health plan paid cost of epilepsy in 2009 in the U.S.

Our objectives were to estimate the health plan paid cost of epilepsy and to show major cost driver(s) of these costs. The health insurance claims and membership data from six U.S. health plans were analyzed. To prepare two comparison groups, individuals with epilepsy (n=5810) were match-paired with individuals without epilepsy (n=5810) using propensity scores derived from logistic regression using gender, age group, health plan product, and length of enrollment in the health plans. Total health plan paid cost per member per year (PMPY) was $11,232 for the epilepsy group and $3026 for the controls (p<0.001). The estimated cost PMPY for treatment of epilepsy was $8206. Relative distribution (%) of health plan paid costs ($) by cost driver category based on place of service (POS) indicated that the treatment of epilepsy places a larger cost burden in inpatient POS than in outpatient hospital or MD office POS compared to controls.

T2*-weighted MR angiography substantially increases the detection of hemorrhage in the wall of brain abscess: implications in clinical interpretation.

INTRODUCTION: The purpose of the present study was to identify the true prevalence of hemorrhage in the abscess using T2*-weighted angiography (SWAN) imaging and to study its influence on diffusion tensor imaging (DTI) metrics. METHODS: Fifteen patients of brain abscess underwent conventional, SWAN, and DT imaging on a 3-T MRI followed by its confirmation with histology. DTI metrics were quantified by region-of-interest analysis on hemorrhagic and non-hemorrhagic regions of the abscess wall. Prussian blue staining was performed on excised abscess walls to confirm hemorrhage on histology. RESULTS: Eleven of 15 patients showed evidence of hemorrhage on both Prussian blue staining as well as SWAN imaging. Fractional anisotropy (FA) and linear anisotropy (CL) values were significantly higher, while spherical anisotropy was significantly lower in hemorrhagic compared to non-hemorrhagic regions of the abscess wall. CONCLUSION: Hemorrhage in the abscess wall is a common feature and may not always indicate neoplasm. The presence of intracellular iron in addition to concentrically laid collagen fibers may have synergistic effect on FA and CL values in the abscess wall. Inclusion of SWAN to MRI protocol will define the true prevalence of hemorrhage in brain abscess.

Toxicity and horizontal transfer of 0.5% fipronil dust against Formosan subterranean termites.

The toxicity and horizontal transfer of a new formulation of fipronil, 0.5% fipronil dust, was tested against Coptotermes formosanus Shiraki in the laboratory. The formulation was applied in three different ways: 1) Directly applied to termites (donors) and mixed with untreated termites (recipients) at three ratios, viz., 50 donors: 50 recipients, 20 donors: 80 recipients and 10 donors: 90 recipients. 2) Applied onto the surface of 3 mm thick sand or soil substrate in a petri dish and then topped with another 3 mm thick sand or soil layer whereupon termites were released. 3) Applied to the inner surface of a tube (either 5 cm or 15 cm long) that connected two foraging dishes, one containing dry sand and the other moist sand plus a wood block and termites were released into the dry sand dish. All donors and >93% of the recipients were dead by 42 h after treatment in the direct treatment experiment. Significant mortalities of both donors and recipients were observed at 5 h after treatment at all donor: recipient ratios. During this period, the mortality of the recipients (but not donors) at 10:90 was significantly lower than those at the other two ratios. All termites were dead at 65 h after exposure (HAE) on the sand treatment and at 190 HAE on soil treatment. More than 96% mortality was observed at 40 HAE on the sand treatment as compared with only 6% mortality onsoil treatment during the same time period. In the tube treatment experiment, > 97% mortality was observed at 90 h after release for both tube lengths as compared with < 3% mortality in controls. About half of the termites were dead by 15 h after release regardless of the tube length. Our results showed that 0.5% fipronil dust is nonrepellent and readily transferred from treated to nontreated termites.