Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic Nephropathy in South Indian Population

This study reports on the association of genetic variants selected from previous genome‐wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30–2.30, P = 1.72 × 10^–4) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.     

Microsurgical clipping versus newer endovascular techniques in treatment of unruptured anterior communicating artery-complex aneurysms: a meta-analysis and systematic review

The aim of this study is to compare occlusion rate, complication rate, and clinical outcome of microsurgical clipping (MC) and advanced endovascular techniques (EVT) in unruptured anterior communicating artery-complex aneurysms (ACoCAs). We reviewed the scientific literature reporting occlusion rate, time of occlusion assessment, and clinical outcome of MC and EVT in patients with unruptured ACoCAs, from January 2009 to December 2019. We included in our analysis 25 studies and 872 patients with unruptured ACoCAs (434 treated with endovascular techniques and 438 with MC). Ninety-three (10.7%), 320 (36.7%), 21 (2.4%), and 438 (50.2%) were treated with flow diverter (FD), stent-assisted coiling (SAC), endosaccular devices (ES), and microsurgical clipping (MC) respectively. FD, SAC, ES, and MC subgroups presented minor complications in 11.8%, 3.8%, 14.3%, and 7.1% of cases (p=.016), and major complications in 3.2%, 4.4%, 0%, and 7.1% (p=.136) of patients. A total occlusion rate post-treatment has been achieved in 4.3%, 87.1%, 47.6%, and 98.2% of cases (p=.000), while at 12 months’ follow-up in 50%, 66%, 83.3%, and 80% of patients (p=.001). FD, SAC, ES, and MC subgroups had a good clinical outcome at 12 months in 93.5%, 90.5%, 100%, and 67.8% of cases. MC is associated with higher post-treatment total occlusion rate, but higher complication and lower good clinical outcome rates. EVT are promising in treating unruptured anterior cerebral artery aneurysms with high margin of safety and good clinical outcome, despite the lower total occlusion rate.

     

Sevoflurane for trans-sternal thymectomy in myasthenia gravis

Myasthenic gravis (MG) is an autoimmune disease associated with acetylcholine receptor deficiency. Patients with MG exhibit increased sensitivity to non-depolarising muscle relaxants. In an attempt to avoid neuromuscular blockers, we used sevoflurane in two myasthenic patients undergoing trans-sternal thymectomy. Inhalation of 8% sevoflurane in oxygen using vital capacity technique produced rapid, pleasant and smooth induction and provided good tracheal intubating conditions. In both patients anaesthesia was maintained with 1.5-2% end-tidal concentration of sevoflurane and nitrous oxide in oxygen without adjunctive neuromuscular blocking agents. There were minimal changes in cardiovascular variables and recovery was faster. It is suggested that sevoflurane may be the main anaesthetic for both induction and maintenance in myasthenic patients undergoing trans-sternal thymectomy.     

Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.     

Prosthetic Rehabilitation of Postsurgical Nasomaxillary Hypoplasia for a Patient Following Reconstructive Surgery: A Clinical Report

Repairs of the cleft nose, lip, and palatal deformity remain challenging endeavors for reconstructive surgeons. Postsurgical nasomaxillary hypoplasia is a common finding in patients with extensive clefts. This complex deformity has a pronounced impact on the social behavior and self image of the subject. Esthetic and functional rehabilitation of this postsurgical defect is scarcely reported in the literature. Support in the form of prostheses or stents to prevent tissue collapse is usually required in these patients following surgery. This clinical case presentation discusses the fabrication of an internal nasal stent for a cleft nose, lip, and palate patient following surgical reconstruction. Two prostheses using two prosthetic materials (Polymethyl methacrylate, flexible resin) were prepared to compare their efficacy. The final prostheses improved the patient's appearance, making the postsurgical defect less conspicuous.     

A novel rapid and effective donor arm disinfection method

BACKGROUND: The aim of the study was to derive a donor arm disinfection technique that was rapid, but with a disinfection efficacy equivalent to a previous "best-practice" technique. This method consisted of a two-stage procedure with an initial application of 70% isopropyl alcohol and then 2% tincture of iodine (IATI). The total time for the IATI method was 2 minutes in duration. A rapid technique (1 min in duration) was needed to obviate potential problems due to increased donor waiting time, had the IATI method been implemented at blood donation sessions.
STUDY DESIGN AND METHODS: A direct swabbing and plating technique was used to enumerate bacteria present before and after disinfection. In total, seven methods were evaluated.
RESULTS: The chlorhexidine/alcohol applicator (CAA) disinfection device containing 1.5 mL of 2% chlorhexidine gluconate and 70% isopropyl alcohol (99.91% reduction; confidence limits, 99.55%, 99.98%) was shown to have equivalent disinfection efficacy as the IATI method (99.89% reduction; confidence limits, 99.36%, 99.98%; p = 0.86). Procedural time for the 1.5-mL CAA method was 1 minute thereby avoiding potential problems of increased donor waiting time, inherent in the IATI 2-minute procedure at blood donation sessions.
CONCLUSIONS: The 1.5-mL CAA disinfection method offers blood services a rapid and effective donor arm disinfection procedure. In 2006, the 1.5-mL CAA procedure was implemented throughout the entire English blood service for all donations.     

Circulating Levels of High Molecular Weight (HMW) Adiponectin and Total Adiponectin in Relation to Fat Distribution,Oxidative Stress and Inflammation in Asian Indians

Aim: To look at the association of total and high molecular weight (HMW) adiponectin with markers of fat distribution, oxidative stress and inflammation in Asian Indians. Methods: A total of 120 subjects were chosen randomly from Chennai Urban Rural Epidemiological Study. Fasting HMW adiponectin levels, TNF-alpha and oxidized LDL were measured using ELISA. High sensitivity C reactive protein (hsCRP) was measured by a high sensitive nephelometric assay. Lipid peroxidation was measured by Tbars assay and protein carbonyl content was assessed by DNPH assay. Visceral and subcutaneous fat areas were assessed by computed tomography (CT) scan.When stratified based on the tertiles of visceral fat, the levels of total (p = 0.03) and HMW adiponectin (p = 0.007) were highest in the first tertile followed by tertiles 2 and 3 whereas in tertiles of subcutaneous fat, there was no such trend. With increasing tertiles of Tbars, the levels of total (p = 0.03) and HMW adiponectin decreased (p = 0.002). The levels of HMW (p < 0.001) but not total adiponectin was also found to decrease with increasing tertiles of Protein carbonyl content. The levels of Total (p = 0.02) and HMW adiponectin (p = 0.004) were highest in the first tertile of oxidized LDL followed by tertile 2 and tertile 3. With increasing tertiles of TNF-alpha total (p = 0.01) and HMW adiponectin (p = 0.004) was found to decrease. With increasing tertiles of hs-CRP, Total (p = 0.005) and HMWadiponectin (p = 0.007)was found to decrease. Conclusion: Oxidative stress markers, visceral but not subcutaneous fat and inflammation are associated with total and HMW adiponectin levles in Asian Indians.