Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine surgery for degenerative spinal stenosis with instability: a retrospective case control study

<p>Abstract</p> <p>Background</p> <p>Degenerative spinal stenosis and instability requiring multilevel spine surgery has been associated with large blood losses. Factors that affect perioperative blood loss include time of surgery, surgical procedure, patient height, combined anterior/posterior approaches, number of levels fused, blood salvage techniques, and the use of anti-fibrinolytic medications. This study was done to evaluate the efficacy of tranexamic acid in reducing blood loss in spine surgery.</p> <p>Methods</p> <p>This retrospective case control study includes 97 patients who had to undergo surgery because of degenerative lumbar spinal stenosis and instability. All operations included spinal decompression, interbody fusion and posterior instrumentation (4-5 segments). Forty-six patients received 1 g tranexamic acid intravenous, preoperative and six hours and twelve hours postoperative; 51 patients without tranexamic acid administration were evaluated as a control group. Based on the records, the intra- and postoperative blood losses were measured by evaluating the drainage and cell saver systems 6, 12 and 24 hours post operation. Additionally, hemoglobin concentration and platelet concentration were reviewed. Furthermore, the number of red cell transfusions given and complications associated with tranexamic acid were assessed.</p> <p>Results</p> <p>The postoperative hemoglobin concentration demonstrated a statistically significant difference with a p value of 0.0130 showing superiority for tranexamic acid use (tranexamic acid group: 11.08 g/dl, SD: 1.68; control group: 10.29 g/dl, SD: 1.39). The intraoperative cell saver volume and drainage volume after 24 h demonstrated a significant difference as well, which indicates a less blood loss in the tranexamic acid group than the control group. The postoperative drainage volume at12 hours showed no significant differences; nor did the platelet concentration Allogenic blood transfusion (two red cell units) was needed for eight patients in the tranexamic acid group and nine in the control group because of postoperative anemia. Complications associated with the administration of tranexamic acid, e.g. renal failure, deep vein thrombosis or pulmonary embolism did not occur.</p> <p>Conclusions</p> <p>This study suggests a less blood loss when administering tranexamic acid in posterior lumbar spine surgery as demonstrated by the higher postoperative hemoglobin concentration and the less blood loss. But given the relatively small volume of blood loss in the patients of this study it is underpowered to show a difference in transfusion rates.</p

Frequency of single nucleotide polymorphisms in NOD1 gene of ulcerative colitis patients: a case-control study in the Indian population

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to IBD. The most significant finding in the IBD research has been identification of mutations in the gene that encodes Nod2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. However, a very similar gene encoding Nod1 protein still has not been well documented for its association with Ulcerative colitis patients. Detection of polymorphism in <it>NOD1 </it>gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain (NBD) of <it>NOD1 </it>gene in context to Indian population.</p> <p>Methods</p> <p>A total of 95 patients with ulcerative colitis and 102 controls enrolled in the Gastroenterology department of All India Institute of Medical Sciences, New Delhi were screened for SNPs by DHPLC and RFLP techniques. Exon 6 locus in the NBD domain of <it>NOD1 </it>gene was amplified and sequenced. Genotype and allele frequencies of the patients and controls were calculated by the Pearson's χ²test, Fisher's exact test and ANOVA with Bonferroni's correction using SPSS software version 12.</p> <p>Results</p> <p>We have demonstrated DHPLC screening technique to show the presence of SNPs in Exon 6 locus of NBD domain of <it>NOD1 </it>gene. The DHPLC analysis has proven suitable for rapid detection of base pair changes. The data was validated by sequencing of clones and subsequently by RFLP analysis. Analyses of SNP data revealed 3 significant mutations (W219R, <it>p </it>= 0.002; L349P, <it>p </it>= 0.002 and L370R, <it>p </it>= 0.039) out of 5 in the Exon 6 locus of NBD domain of the gene that encompasses ATP and Mg²⁺binding sites. No significant association was observed within different sub phenotypes.</p> <p>Conclusion</p> <p>We propose that the location of mutations in the Exon 6 spanning the ATP and Mg²⁺binding site of NBD in <it>NOD1 </it>gene may affect the process of oligomerization and subsequent function of the LRR domain. Further studies are been conducted at the protein level to prove this possibility.</p

Massive rotator cuff tears: functional outcome after debridement or arthroscopic partial repair

Background The surgical treatment of massive rotator cuff tears (RCT) is still controversial and can be based on a variety of different surgical repair methods. This study investigated the effectiveness of arthroscopic debridement or arthroscopic partial repair in patients with massive RCT. Materials and methods This prospective, randomized study involved forty-two patients with massive RCT (fatty infiltration stage 3 or 4) treated with either arthroscopic partial repair or arthroscopic debridement were selected to detect possible differences in functional outcome. Both groups were matched according to age and gender. Patients were examined before, and 16 ± 3 and 24 ± 2 months after surgery. The status of the rotator cuff repair was determined using ultrasonographic evaluation. Results Regardless of the treatment group, postoperative results demonstrated highly significant improvements compared with preoperative values in most parameters. The overall Constant score in the partial repair group was superior to the outcome in the debridement group (P \ 0.01, F = 8.561), according to better results in abductio

The use of microbubbles to target drug delivery

Ultrasound-mediated microbubbles destruction has been proposed as an innovative method for noninvasive delivering of drugs and genes to different tissues. Microbubbles are used to carry a drug or gene until a specific area of interest is reached, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. Furthermore, the ability of albumin-coated microbubbles to adhere to vascular regions with glycocalix damage or endothelial dysfunction is another possible mechanism to deliver drugs even in the absence of ultrasound. This review focuses on the characteristics of microbubbles that give them therapeutic properties and some important aspects of ultrasound parameters that are known to influence microbubble-mediated drug delivery. In addition, current studies involving this novel therapeutical application of microbubbles will be discussed

TRPM2 channel deficiency prevents delayed cytosolic Zn²⁺ accumulation and CA1 pyramidal neuronal death after transient global ischemia

Transient ischemia is a leading cause of cognitive dysfunction. Postischemic ROS generation and an increase in the cytosolic Zn²⁺ level ([Zn²⁺]c) are critical in delayed CA1 pyramidal neuronal death, but the underlying mechanisms are not fully understood. Here we investigated the role of ROS-sensitive TRPM2 (transient receptor potential melastatin-related 2) channel. Using in vivo and in vitro models of ischemia-reperfusion, we showed that genetic knockout of TRPM2 strongly prohibited the delayed increase in the [Zn²⁺]c, ROS generation, CA1 pyramidal neuronal death and postischemic memory impairment. Time-lapse imaging revealed that TRPM2 deficiency had no effect on the ischemia-induced increase in the [Zn²⁺]c but abolished the cytosolic Zn²⁺ accumulation during reperfusion as well as ROS-elicited increases in the [Zn²⁺]c. These results provide the first evidence to show a critical role for TRPM2 channel activation during reperfusion in the delayed increase in the [Zn²⁺]c and CA1 pyramidal neuronal death and identify TRPM2 as a key molecule signaling ROS generation to postischemic brain injury