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.

Pediatric Cervical Spine Injuries.

Objective Pediatric cervical spine injuries are rare and account for 1 to 2% of all pediatric spine injuries. There is a paucity of data on pediatric cervical spine injuries in developing countries like India. The purpose of this study is to review and analyze our 5 years of experience with pediatric cervical spine injuries. Methods All the available medical records over the 5 years were reviewed retrospectively. The data was analyzed to know the epidemiology, mechanism of injury, injury patterns, management, and outcome. The patients were divided into two groups: 0 to 9 years and 10 to 18 years. Results Seventy-five eligible records were included in our study. The incidence of cervical spine injuries was significantly lower in younger children than the older ones ( p < 0.042). The most common mechanism of injury was fall from height: 33 (44%) patients followed by road traffic accidents: 27 (36%) patients. The involvement of the upper cervical spine was significantly higher in younger children ( p < 0.001). Fractures with subluxation were the most common pattern of injury, observed in 35 (47%) patients. However, fractures with subluxation were uncommon in younger children compared with older children ( p < 0.04). Spinal cord injury without radiographic abnormality (SCIWORA) was observed in 42% of younger children compared with 8% of older children ( p < 0.02). Thirty (40%) patients were managed surgically; anterior cervical corpectomy with fusion was the most commonly performed procedure in 19 (63%) patients. The overall mortality was 20%. Conclusion The results of our study revealed predominant involvement of the upper cervical spine in children younger than 10 years of age. SCIWORA was documented in both the age groups with a significantly higher incidence in younger children. The instrumentation and fusion techniques in children are safe; however, developing pediatric spine needs special considerations.

Magnetic field reveals vanishing Hall response in the normal state of stripe-ordered cuprates.

The origin of the weak insulating behavior of the resistivity, i.e. [Formula: see text], revealed when magnetic fields (H) suppress superconductivity in underdoped cuprates has been a longtime mystery. Surprisingly, the high-field behavior of the resistivity observed recently in charge- and spin-stripe-ordered La-214 cuprates suggests a metallic, as opposed to insulating, high-field normal state. Here we report the vanishing of the Hall coefficient in this field-revealed normal state for all [Formula: see text], where [Formula: see text] is the zero-field superconducting transition temperature. Our measurements demonstrate that this is a robust fundamental property of the normal state of cuprates with intertwined orders, exhibited in the previously unexplored regime of T and H. The behavior of the high-field Hall coefficient is fundamentally different from that in other cuprates such as YBa2Cu3O6+x and YBa2Cu4O8, and may imply an approximate particle-hole symmetry that is unique to stripe-ordered cuprates. Our results highlight the important role of the competing orders in determining the normal state of cuprates.

The association between cagL and cagA, vacAs-m, babA genes in patients with gastric cancer, duodenal ulcer, and non-ulcer dyspepsia related to Helicobacter pylori.

INTRODUCTION: As a component of the cag T4SS, the cagL gene is involved in the translocation of CagA into host cells and is essential for the formation of cag PAI-associated pili between H. pylori and gastric epithelial cells. AIM: We aimed to investigate the clinical association of the cagL gene with other virulence factors (VacA, CagA, EPIYA-C, and BabA protein) of H. pylori strains isolated from GC, duodenal ulcer (DU), and non-ulcer dyspepsia (NUD) cases. METHODS: The patient group (PG), including 47 patients (22 GC and 25 DU) and a 25 control group (CG= NUD) were included. Amplification of the H. pylori cagL, cagA, vacA, and babA2 genes and typing of EPIYA motifs were performed by PCR methods. RESULTS: Sixty-one (84.7%) H. pylori strains were detected with cagL (93.6% in SG, 68% in CG). We detected a significant difference between SG and CG for the presence of cagL (p=0.012) but no statistical comparison was done for (≥2) EPIYA-C repeats In the comparison of H. pylori strains with cagA/vacAs1m1 and cagA/ vacAs1m2 and babA2 for the presence of cagL, we could not detect a significant difference (p=1). CONCLUSION: We detected a significant difference between groups for the presence of cagL genotype (p=0.012). The vacAs1m1 (OR: 2.829), genotypes increased the GC and DU risk by 2.8 times, while multiple (≥2) EPIYA-C repeats incresed the GC and DU risk by 3.524 times. Gender (to be female) (OR: 0.454) decreased the GC and DU risk by inversly decreased in the multivariate analysis.

Radiation-induced Supratentorial Osteosarcoma Following Curative Treatment of Infratentorial Ependymoma in a Child.

The development of secondary neoplasms following therapeutic cranial irradiation is rare and quite often lethal. Meningiomas, sarcomas, and high-grade gliomas are the most common tumors that manifest as a result of radiation therapy. We report the case of an 11-year-old child who presented with symptoms of supratentorial space-occupying lesion 7 years after curative surgery and cranial irradiation for a posterior fossa ependymoma. Magnetic resonance imaging of the brain revealed a right-sided temporoparietal dural-based contrast-enhancing lesion with evidence of overlying bone and skin involvement. The histological report of ependymoma from the previous surgery led us to suspect that we were dealing with a recurrence until the histopathology of the second surgery revealed highly malignant osteosarcoma. The child recovered fully and underwent chemotherapy, but ultimately succumbed to the disease. We report this case to highlight the importance of recognizing these neoplasms and to review its management.

A Comparative Analysis Between Four-Quadrant Osteoplastic Decompressive Craniotomy versus Conventional Decompressive Craniectomy for Traumatic Brain Injury.

OBJECTIVE: Primary decompressive craniectomy (DC) is indicated to evacuate the hematoma and reduce intracranial pressure in traumatic brain injury (TBI). However, there are a myriad of complications because of absence of the bone flap. A novel technique, four-quadrant osteoplastic decompressive craniotomy (FoQOsD) retains the bone flap while achieving adequate cerebral decompression. METHODS: A single-center randomized controlled trial of 115 patients with TBI needing decompressive surgery was conducted. Of these patients, 59 underwent DC and 56 underwent FoQOsD. The primary outcome determined was functional status at 6 months using the Glasgow Outcome Scale-Extended. RESULTS: No significant differences were identified in baseline characteristics between both groups. Mean Glasgow Outcome Scale-Extended score was comparable at 6 months (4.28 in DC vs. 4.38 in FoQOsD; P = 0.856). Further, 22 of 58 patients in the DC group had died (38%) compared with 25 of 55 patients in the FoQOsD group (44.6%) (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.6-2.36; P = 0.6) (1 patient lost to follow-up in each group). A favorable outcome was seen in 56.8% of patients in the DC group versus 54.4% of patients in the FoQOsD group (P = 0.74). Presence of intraventricular hemorrhage and subarachnoid hemorrhage (OR, 7.17; 95% CI, 1.364-37.7; P = 0.020), opposite side contusions (OR, 3.838; 95% CI, 1.614-9.131; P = 0.002) and anisocoria (OR, 3.235; 95% CI, 1.490-7.026; P = 0.003) preoperatively were individual factors that played a significant role in final outcome. CONCLUSIONS: FoQOsD is as efficacious as conventional DC with the added benefit of avoiding a second surgery. The procedure is associated with better cosmesis and fewer complications.

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.

Disruption of Telomere Integrity and DNA Repair Machineries by KML001 Induces T Cell Senescence, Apoptosis, and Cellular Dysfunctions.

T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, and topoisomerase cleavage complex (TOPcc) accumulation, leading to telomere attrition. Mechanistically, KML001 compromised telomere integrity by inhibiting telomeric repeat binding factor 2 (TRF2), telomerase, topoisomerase I and II alpha (Top1/2a), and ataxia telangiectasia mutated (ATM) kinase activities. Importantly, these KML001-induced telomeric DNA damage and T cell senescent phenotype and machineries recapitulated our findings in patients with clinical HCV or HIV infection in that their T cells were also senescent with short telomeres and thus more vulnerable to KML001-induced apoptosis. These results shed new insights on the T cell aging network that is critical and essential in protecting chromosomal telomeres from unwanted DNA damage and securing T cell survival during cell crisis upon genomic insult.

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

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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.

Clinico-Radiological Outcome Analysis in Craniovertebral Junction Diseases: An Institutional Experience of 38 Patients in a Tertiary Care Centre.

BACKGROUND: Craniovertebral junction diseases, although considered rare, are common in northern parts of India. This study was conducted to evaluate the clinico-radiologic and surgical outcome of patients with a minimum follow-up of 1 year. Our study also compared bony fusion among various techniques of posterior fusion. METHODS: This retrospective study was performed with 38 patients who met the inclusion criteria for analysis. These patients were contacted by telephone and letters, and their clinical examination and radiologic investigations were performed at a follow-up visit. The preoperative, postoperative, and follow-up clinical evaluations of the patients were done using the Nurick grading system. RESULTS: The age range was 4-60 years with an average of 20.5 years. There were 31 male and 7 female patients, with a male:female ratio of 4.43:1. There were 13 cases of fixed atlantoaxial dislocation (AAD), 17 cases of mobile AAD, 6 cases of traumatic AAD, and 2 cases of postinfective AAD. The majority of these patients (n = 29; 76.31%) had neck pain and cerebellovestibular disturbances (n = 27; 71.1%). Sphincter disturbances were observed in 9 patients. An increase in craniovertebral angle was observed in postoperative period in all patients. Initially, 84% of the patients had a poor Nurick grade; this was reduced to 28% after the surgical intervention. One hundred percent bony fusion was attained in patients who underwent rigid fixation technique, and 80% was attained using a semirigid fixation technique. CONCLUSIONS: The key to successful management of craniovertebral junction disease is individualized selection of judicious surgical intervention from various available techniques.

Atomistic simulations of graphite etching at realistic time scales.

Hydrogen-graphite interactions are relevant to a wide variety of applications, ranging from astrophysics to fusion devices and nano-electronics. In order to shed light on these interactions, atomistic simulation using Molecular Dynamics (MD) has been shown to be an invaluable tool. It suffers, however, from severe time-scale limitations. In this work we apply the recently developed Collective Variable-Driven Hyperdynamics (CVHD) method to hydrogen etching of graphite for varying inter-impact times up to a realistic value of 1 ms, which corresponds to a flux of ∼1020 m-2 s-1. The results show that the erosion yield, hydrogen surface coverage and species distribution are significantly affected by the time between impacts. This can be explained by the higher probability of C-C bond breaking due to the prolonged exposure to thermal stress and the subsequent transition from ion- to thermal-induced etching. This latter regime of thermal-induced etching - chemical erosion - is here accessed for the first time using atomistic simulations. In conclusion, this study demonstrates that accounting for long time-scales significantly affects ion bombardment simulations and should not be neglected in a wide range of conditions, in contrast to what is typically assumed.

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.

Single dose intratympanic mesna application inhibits propylene glycol induced cholesteatoma formation.

OBJECTIVE: Mesna (i.e. sodium 2-mercaptoethanesulfonate; C2H5NaO3S2) has been used in otological surgery such as cholesteatoma dissection and tympanic membrane lateralisation in atelectatic ears. However, this study aimed to investigate its effect on cholesteatoma formation. METHODS: A total of 20 Wistar rats were divided into two groups of 10 animals. The right and left ears of control animals were treated with saline (saline control group; n = 10 ears) and propylene glycol plus saline (propylene glycol control group; n = 10 ears), respectively. In the mesna group, both ears were treated with propylene glycol plus mesna (n = 20 ears). On days 1, 8 and 15, the saline control group had intratympanic injections of 0.2 ml saline and the propylene glycol control and mesna groups had intratympanic injections of 0.2 ml 100 per cent propylene glycol. On day 22, the propylene glycol control group had a single intratympanic injection of 0.2 ml saline and the mesna group had a single intratympanic injection of 10 per cent mesna. Animals were killed 12 weeks after the last injection and the temporal bones were sent for histopathological evaluation. RESULTS: The cholesteatoma formation rate was 88 per cent in the propylene glycol control group, but was significantly lower in the mesna group (p = 0.01). There were no significant differences in granulation tissue formation (p = 0.498), cyst formation in the bulla (p = 0.381), fibrosis (p = 0.072) and epithelial hyperplasia (p = 0.081) among experimental groups. CONCLUSION: Intratympanic propylene glycol administration is an effective method of promoting experimental cholesteatoma formation. Administration of a single dose of intratympanic mesna inhibited cholesteatoma formation in an animal model.

Impact of Ground-Applied Termiticides on the Above-Ground Foraging Behavior of the Formosan Subterranean Termite.

We conducted a laboratory study to determine the impact of ground-applied termiticides on the above-ground foraging behavior of Coptotermes formosanus. Two concentrations (1 and 10 ppm) each of three termiticides, viz. fipronil, imidacloprid and chlorantraniliprole, were tested. After one month post-treatment (fipronil 10 ppm was run for 12 days only and all other treatments were run for one month), fipronil had the lowest percentage of survival (3%-4%) at both concentrations. Termite survival ranged from 31% to 40% in the case of imidacloprid treatments and 10 ppm chlorantraniliprole. However, 1 ppm chlorantraniliprole did not cause significant mortality compared to the controls. Foraging on the bottom substrate was evident in all replicates for all chemicals initially. However, a portion of the foraging population avoided the ground treatment toxicants after several days of bottom foraging. Only the slower-acting non-repellents created this repellent barrier, causing avoidance behavior that was most likely due to dead termites and fungus buildup on the treated bottom substrate. Fipronil appeared more toxic and faster acting at the concentrations tested, thus limiting this repellent effect. Suggestions by the pest control industry in Louisiana that some non-repellents can create a repellent barrier stranding live termites above ground are supported by this laboratory study.

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.