Although cytomegalovirus viral load is commonly used to guide pre-emptive therapy in the post-transplantation setting, few data are available correlating viraemia with clinical endpoints. We ...therefore investigated the association between cytomegalovirus viral load and mortality in the first year after haemopoietic stem cell transplantation.
In this retrospective cohort study, we included patients from the Fred Hutchinson Cancer Research Center, WA, USA, who received an allogeneic haemopoietic stem cell transplantation between Jan 1, 2007, and Feb 28, 2013, were cytomegalovirus seropositive or had a seropositive donor, and underwent weekly plasma cytomegalovirus monitoring by PCR through to day 100 post-transplantation. Cox proportional hazards models were used to estimate the association of cytomegalovirus viral load at different thresholds with overall mortality by 1 year post-transplantation, adjusting for the use of pre-emptive therapy and other factors such as neutropenia, and graft-versus-host disease.
Of the 1037 patients initially selected for inclusion in this cohort, 87 (8%) patients were excluded because of missing cytomegalovirus testing and 24 (2%) were excluded because of their participation in cytomegalovirus prophylaxis trials. In the remaining 926 patients included in this study, the cumulative overall mortality was 30·0% (95% CI 26·9-33·0) 1 year after haemopoietic stem cell transplantation. 95 patients developed cytomegalovirus disease; death was directly attributable to cytomegalovirus disease in three (1%) of 263 patients who died in the first year after transplantation. A cytomegalovirus viral load of 250 IU/mL or greater was associated with increased risk of early (day 0-60 post-transplantation) death (adjusted hazard ratio HR 19·8, 95% CI 9·6-41·1). The risk was attenuated after day 60 (adjusted HR 1·8, 95% CI 1·3-2·3). Similar associations were noted for higher cytomegalovirus viral load thresholds.
Cytomegalovirus viraemia is associated with an increased risk of overall mortality in the first year after haemopoietic stem cell transplantation, independent of the use of pre-emptive therapy, and with evidence of a positive dose-response relationship. These data indicate the suitability of viral load as a surrogate clinical endpoint for clinical trials for cytomegalovirus vaccines, biologics, and drugs.
Merck and Co, National Institutes of Health.
We present a case of a 13-year-old patient with a distinct tumor with both granular cell and perineurial elements, located on the lower lip. The patient presented with a long-standing lip mass that ...was clinically felt to most likely represent a mucocele. Following surgical excision, histopathological examination revealed a well-circumscribed tumor composed of granular cells with positive S100 protein staining and spindled cells positive for EMA and GLUT-1, confirming mixed neuroectodermal and perineurial origin. This is the first case documenting a perineurial-granular cell hybrid tumor in a patient under 18 years old, and the first to be reported in the head and neck. This case expands our understanding of hybrid PNSTs, emphasizing the importance of considering diverse clinical presentations, especially in the context of rare pediatric occurrences in atypical locations.
Cord blood transplant (CBT) recipients have a high incidence of herpes zoster (HZ) in the context of short-term peritransplant antiviral prophylaxis. In 2009, international guidelines recommended HZ ...prophylaxis for at least 1 year after hematopoietic cell transplant. The impact of longer-term antiviral prophylaxis on HZ incidence after CBT is unknown.
We retrospectively analyzed varicella zoster virus (VZV)-seropositive CBT recipients who were transplanted between 2006 and 2016. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ and used Cox proportional hazards regression to identify variables associated with HZ.
The study cohort consisted of 227 patients. Among 1-year survivors, 91% were still receiving prophylaxis, for a median duration of 20.6 months. HZ occurred in 44 patients (19%) at a median of 23.6 months. The cumulative incidence of HZ by 1 year after CBT was 1.8% (95% confidence interval CI, .1%-4%), but increased to 26% (95% CI, 19%-33%) by 5 years. In a multivariable analysis, acute graft-vs-host disease was associated with increased risk, whereas antiviral prophylaxis was associated with reduced risk for HZ (adjusted hazard ratio, 0.19 95% CI, .09-.4). There was no association between CD4+ T-cell counts at 1 year post-CBT and subsequent risk for HZ.
We found a high incidence of HZ after CBT despite antiviral prophylaxis for > 1 year. Based on these findings, we suggest longer duration of prophylaxis for HZ after CBT. Compliance with antiviral prophylaxis, VZV-specific immune monitoring, and vaccination to mitigate HZ after CBT also require further study.
P-glycoprotein (P-gp) mediates efflux of xenobiotics and bacterial toxins from the intestinal mucosa into the lumen. Dysregulation of P-gp has been implicated in inflammatory bowel disease. Certain ...probiotics have been shown to be effective in treating inflammatory bowel disease. However, direct effects of probiotics on P-gp are not known. Current studies examined the effects of Lactobacilli on P-gp function and expression in intestinal epithelial cells. Caco-2 monolayers and a mouse model of dextran sulfate sodium-induced colitis were utilized. P-gp activity was measured as verapamil-sensitive (3)Hdigoxin transepithelial flux. Multidrug resistant 1 (MDR1)/P-gp expression was measured by real-time quantitative PCR and immunoblotting. Culture supernatant (CS; 1:10 or 1:50, 24 h) of Lactobacillus acidophilus or Lactobacillus rhamnosus treatment of differentiated Caco-2 monolayers (21 days postplating) increased (∼3-fold) MDR1/P-gp mRNA and protein levels. L. acidophilus or L. rhamnosus CS stimulated P-gp activity (∼2-fold, P < 0.05) via phosphoinositide 3-kinase and ERK1/2 MAPK pathways. In mice, L. acidophilus or L. rhamnosus treatment (3 × 10(9) colony-forming units) increased mdr1a/P-gp mRNA and protein expression in the ileum and colon (2- to 3-fold). In the dextran sulfate sodium (DSS)-induced colitis model (3% DSS in drinking water for 7 days), the degree of colitis as judged by histological damage and myeloperoxidase activity was reduced by L. acidophilus. L. acidophilus treatment to DSS-treated mice blocked the reduced expression of mdr1a/P-gp mRNA and protein in the distal colon. These findings suggest that Lactobacilli or their soluble factors stimulate P-gp expression and function under normal and inflammatory conditions. These data provide insights into a novel mechanism involving P-gp upregulation in beneficial effects of probiotics in intestinal inflammatory disorders.
The problem of node localization in wireless sensor networks aims to assign th e geographical coordinates to each device with unknown position, in the deployment area. In this paper the meta ...heuristic optimization algorithm known as bat algorithm is described in order to evaluate the precision of node localization problem in wireless sensor networks. Meanwhile the existing bat algorithm has also been modified by using the bacterial foraging strategies of bacterial foraging optimization algorithm. Compared with the existing bat algorithm, the proposed modified bat algorithm is shown through simulations to perform constantly better not only in increasing localization success ratios and fast convergence speed but also enhance its robustness.
Wireless sensor networks (WSNs) contain sensor nodes in enormous amount to accumulate the information about the nearby surroundings, and this information is insignificant until the exact position ...from where data have been collected is revealed. Localization of sensor nodes in WSNs plays a significant role in several applications such as detecting the enemy movement in military applications. The major aim of localization problem is to find the coordinates of all target nodes with the help of anchor nodes. In this paper, two variants of bat optimization algorithm (BOA) are proposed to localize the sensor nodes in a more efficient way and to overcome the drawbacks of original BOA, i.e. being trapped in local optimum solution. The exploration and exploitation features of original BOA are modified in the proposed BOA variants 1 and 2 using improved global and local search strategies. To validate the efficiency of the proposed BOA variants 1 and 2, several simulations have been performed for various numbers of target nodes and anchor nodes, and the results are compared with original BOA and other existing optimization algorithms applied to node localization problem. The proposed BOA variants 1 and 2 outperform the other algorithms in terms of mean localization error, number of localized nodes and computing time. Further, the proposed BOA variants 1 and 2 and original BOA are also compared in terms of various errors and localization efficiency for several values of target and anchor nodes. The simulations results signify that the proposed BOA variant 2 is superior to the proposed BOA variant 1 and existing BOA in terms of several errors. The node localization based on the proposed BOA variant 2 is more effective as it takes less time to perform computations and has less mean localization error than the proposed BOA variant 1, BOA and other existing optimization algorithms.
Water and electrolytes are major constituents of the body in the preterm infant and undergo rapid changes in content and distribution within the body compartments during the first few days of ...postnatal adaptation. The changes can be amplified by the severity of the functional immaturity of organs and adverse environmental factors. A clear understanding of fetal physiology and postnatal adaptation, along with frequent and structured clinical assessment, is necessary to guide optimal fluid and electrolyte supplementation. An accurate fluid and electrolyte prescription is critical to delivery of optimum early nutrition. While survival of premature infants has leapt forward with widespread use of antenatal corticosteroids, postnatal surfactant and advances in respiratory support modalities, further improvement is dependent on multiple marginal gains. Meticulous attention to maintain a physiological milieu in the ex utero environment and providing high quality early nutrition to prevent catabolism and promote early growth have been shown to have a positive impact in reducing neonatal morbidities and improving long-term outcomes. This review offers a simple overview of the physiological changes during postnatal adaptation in the preterm infant. It provides practical guidance on fluid, electrolyte and nutritional management in the first few days following birth including advice about clinical assessment and preventative measures. A self-assessment exercise is also included.
Deployment of sensor nodes in three dimensional areas with sufficient coverage of sensor nodes is one of the major challenges in wireless sensor network. Coverage is main concern in node deployment ...because it influences the performance of wireless sensor network. For better performance of wireless sensor network it is essential to increase the coverage of nodes by locating the nodes at optimum positions with help of efficient optimization algorithm. In this paper the sensor nodes are located by using Hybrid fruit fly optimization algorithm and bat optimization algorithm in three dimensional environment. The exploration feature of fruit fly optimization algorithm is combined with exploitation characteristics of bat optimization algorithm in proposed algorithm. The grid points covered once by sensor node are removed from entire grid points for remaining nodes. With removal of grid points the overload on sensor nodes is reduced in proposed algorithm. The simulation results of Hybrid fruit fly optimization algorithm and bat optimization algorithm are compared in terms of variance, standard deviation, coverage rate and coefficient of dispersion with fruit fly optimization algorithm and bat optimization algorithm. Moreover, to verify the efficiency of proposed algorithm the results are also compared with other optimization algorithms such as artificial bee colony algorithm with dynamic search strategy, grey wolf optimization algorithm, enhanced grey wolf optimization algorithm, whale optimization algorithm, hybrid shuffled frog leaping algorithm and whale optimization algorithm, differential evolution algorithm, shuffled frog leaping algorithm, hybrid shuffled frog leaping algorithm and whale optimization algorithm based on differential evolution respectively. The simulation result signifies that proposed Hybrid fruit fly optimization algorithm and bat optimization algorithm is efficient than above stated existing optimization algorithm in terms of average coverage rate. The simulation results also demonstrate that proposed algorithm has attained maximum coverage about 99.25% which is higher as compared to existing algorithms. The standard deviation of proposed algorithm is least i.e. 0.0012 which means proposed algorithm is more reliable as compared to existing algorithms for deploying sensor nodes in three dimensional wireless sensor network.
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