Association of Common Single Nucleotide Polymorphisms of Candidate Genes with Gallstone Disease: A Meta-Analysis.

Numerous studies have investigated the relationship between various candidate gene polymorphisms and gallbladder stone disease (GSD) across ethnic populations; however, the results are often inconsistent. This meta-analysis aims to comprehensively evaluate the influence of common ABCG8 T400K, ABCG8 D19H, ABCG8 C54Y, ApoB100 EcoRI, ApoB100 XbaI, ApoE HhaI, CETP TaqI, CYP7A1 Bsa, LRPAP1 I/D and TNF-α A308G polymorphisms on the risk of gallbladder stone disease. 33 Full-text articles with 9250 cases and 12,029 healthy controls (total 21,279 subjects) were analyzed using the RevMan software (V5.1) and the Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) a Random-effects model was applied. Begg's funnel plots, Fail-safe number, Egger's regression intercept and Begg and Mazumdar rank correlation tests were performed for the potential publication bias and sensitivity analysis. The studies were also sub-grouped into European and non-European groups to find out role of ethnicity, if any, on GSD risk. Studies included in quantitative synthesis were ABCG8 T400K rs4148217 (cases/controls, n = 671/1416) (4 studies), ABCG8 D19H rs11887534 (n = 1633/2306) (8 studies), ABCG8 C54Y rs4148211 (n = 445/1194) (3 studies), ApoB100 EcoRI rs1042031 (n = 503/390) (4 studies), ApoB100 XbaI rs693 (n = 1214/1389) (9 studies), ApoE HhaI rs429358 (n = 1335/1482) (12 studies), CETP TaqI rs708272 (n = 1038/1025) (5 studies), CYP7A1 Bsa rs3808607 (n = 565/514) (3 studies), LRPAP1 I/D rs11267919 (n = 849/900) (3 studies), TNF-α A308G rs1800629 (n = 997/1413) (3 studies). The combined results displayed significant association of ABCG8 D19H (GC + CC) [OR with 95%CI = 2.2(1.7-2.8); p < 0.00001], ABCG8 Y54C (GA + GG) [OR with 95%CI = 0.65(0.5-0.9); p = 0.01]. APOB100 EcoRI (GG vs. AA) [OR with 95%CI = 0.51(0.3-0.9); p = 0.05], (GG vs. GA) [OR with 95%CI = 0.6(0.4-0.9); p = 0.04], (GA + AA) [OR with 95%CI = 0.6(0.4-0.9); p = 0.006]. APOB Xba I (X- vs. X+) [OR with 95%CI = 0.53(0.3-0.8); p = 0.006. APOE Hha I (E4/E4 vs. E3/E3) [OR with 95%CI = 3.5(1.1-14.9); p = 0.04] and LRPAP1 I/D (ID + II) [OR with 95%CI = 1.27(1.0-1.6); p = 0.03] with the GSD risk. It was found that ABCG D19H was significantly associated with GSD in both European and Non-European populations. While APOB XbaI and LRPAP1 I/D markers were associated with gallstone disease only in Non- European population. Additionally, APOE HhaI and APOB 100 ECoRI were found to be associated with GSD only in European population. The results of quantitative synthesis suggest that the ABCG8 D19H polymorphism was associated with the increased risk of GSD in both European and Non-European populations, APOE Hha I and LRPAP1 I/D polymorphisms were associated with the increased risk of GSD in European and Non-European population respectively. However, no association was found in ABCG8 T400K, CETP Taq1, CYP7A1 Bsa and TNF-A308G polymorphisms with Gallstone Disease.

Interplay of phosphorus doses, cyanobacterial inoculation, and elevated carbon dioxide on yield and phosphorus dynamics in cowpea.

Phosphorus (P) demand is likely to increase especially in legumes to harness greater benefits of nitrogen fixation under elevated CO2 condition. In the following study, seed yield and seed P uptake in cowpea increased by 26.8% and 20.9%, respectively, under elevated CO2 level. With an increase in phosphorus dose up to 12 mg kg-1, seed yield enhanced from 2.6 to 5.4 g plant-1. P application and cyanobacterial inoculation increased the microbial activity of soil, leading to increased availability of P. Under elevated CO2 condition, microbial activity, measured as dehydrogenase, acid phosphatase, and alkaline phosphatase activities showed stimulation. Soil available P also increased under elevated CO2 condition and was stimulated by both P application and cyanobacterial inoculation. Higher P uptake in elevated CO2 condition led to lower values of inorganic P in soil. Stepwise regression analysis showed that aboveground P uptake, soil available P, and alkaline phosphatase activity of soil influenced the yield while available P, and organic and inorganic P influenced the aboveground P uptake of the crop. This study revealed that under elevated CO2 condition, P application and cyanobacterial inoculation facilitated P uptake and yield, mediated through enhanced availability of nutrients, in cowpea crop.

Phonons, phase transitions and thermal expansion in LiAlO2: an ab initio density functional study.

We have used the ab initio density functional theory technique to understand the phase transitions and structural changes in various high temperature/pressure phases of LiAlO2. The electronic band structure as well as phonon spectra is calculated for various phases as a function of pressure. The phonon entropy used for the calculations of Gibbs free energy is found to play an important role in the phase stability and phase transitions among various phases. A sudden increase in the polyhedral bond lengths (Li/Al-O) signifies the change from the tetrahedral to octahedral geometry at high-pressure phase transitions. The activation energy barrier for the high-pressure phase transitions is calculated. The phonon modes responsible for the phase transition (upon heating) from high pressure phases to ambient pressure phases are identified. Moreover, ab initio lattice dynamics calculations in the framework of quasi-harmonic approximations are used to study the anisotropic thermal expansion behavior of γ-LiAlO2.

Investigating anomalous thermal expansion of copper halides by inelastic neutron scattering and ab initio phonon calculations.

We investigate the detailed lattice dynamics of copper halides, CuX (X = Cl, Br, and I), using neutron inelastic scattering measurements and ab initio calculations aimed at a comparative study of their thermal expansion behavior. We identify the low energy phonons which soften with pressure and are responsible for negative thermal expansion. The eigenvector analysis of these modes suggests that softening of the transverse-acoustic modes would lead to NTE in these compounds. The calculations are in very good agreement with our measurements of phonon spectra and thermal expansion behavior as reported in the literature. Our calculations at high pressure further reveal that a large difference in negative thermal expansion behavior in these compounds is associated with the difference in the unit cell volume.

A prospective randomized controlled trial comparing early postoperative complications in patients undergoing loop colostomy with and without a stoma rod.

AIM: A stoma rod or bridge has been traditionally placed under the bowel loop while constructing a loop colostomy. This is believed to prevent stomal retraction and provide better faecal diversion. However, the rod can cause complications such as mucosal congestion, oedema and necrosis. This single-centre prospective randomized controlled trial compared outcomes after creation of loop colostomy with and without a supporting stoma rod. The primary outcome studied was stoma retraction rate; other stoma-related complications were studied as secondary outcomes. METHOD: One hundred and fifty-one patients were randomly allotted to one of two arms, colostomy with or without a supporting rod. Postoperative complications such as retraction, mucocutaneous separation, congestion and re-exploration for stoma-related complications were recorded. RESULTS: There was no difference in the stoma retraction rate between the two arms (8.1% in the rod arm and 6.6% in the no-rod arm; P = 0.719). Stomal necrosis (10.7% vs 1.3%; P = 0.018), oedema (23% vs 3.9%; P = 0.001), congestion (20.3% vs 2.6%; P = 0.001) and re-admission rates (8.5% vs 0%; P = 0.027) were significantly increased in the arm randomized to the rod. CONCLUSION: The stoma rod does not prevent stomal retraction. However, complication rates are significantly higher when a stoma rod is used. Routine use of a stoma rod for construction of loop colostomy can be avoided.

Evaluation of Effect of Vitamin D Deficiency on Anemia and Erythropoietin Hyporesponsiveness in Patients of Chronic Kidney Disease.

BACKGROUND: The role of vitamin D deficiency and inflammation levels in renal anemia has been documented. However, no study is available in India where the role of vitamin D supplementation in patients with hyporesponsiveness to increased doses of erythropoietin is available. Hence this study. MATERIAL AND METHODS: This study was conducted on 50 adult patients of CKD, on regular, twice weekly hemodialysis. It included 38 cases in group A with deficient serum vitamin D levels (<30 ng/ml) and 12 cases in group B with sufficient vitamin D levels (>30 ng/ml). Both groups of cases were receiving erythropoietin in a dose of 4000 I.U. subcutaneously twice weekly following dialysis and had failed to show rise in hemoglobin (Hb) >1gm/dl after one month, hence erythropoietin was increased to 6000 I.U. Group A was given additional vitamin D in a dose of 60000 I.U. orally, once a week for next three months along with erythropoietin 6000 I.U. where as Group B served as control. Hematological and renal parameters, ESR, high sensitivity C reactive protein (HsCRP) and serum ferritin were estimated at baseline and then at one monthly intervals for next four months. Parathyroid hormone (iPTH), serum B12, folic acid and vitamin D (25OHD3) were measured at the start and end of the study only. Erythropoietin resistance index (ERI) was calculated to evaluate dose response. RESULTS: Basal ERI, HsCRP and ESR and serum ferritin were raised in both the groups. At the end of four months, there was a significant increase in the Hb and hematocrit (Hct) (p<.001) and a significant fall in ERI, ESR, HsCRP, serum ferritin and iPTH (p<.001) in group A. Group B, also had a significant increase in the hemoglobin and hematocrit (p<.001) and decrease in ERI, ESR, HsCRP, serum ferritin and iPTH which was not significant. Basal vitamin D and ERI had a positive and insignificant correlation (r=0.05; p=0.756) in group A where as a negative and insignificant correlation was observed between them at the end of four months (r= -0.195; p >0.05). CONCLUSIONS: vitamin D play an important role in reducing inflammation and thereby in the cure of anemia in EPO hyporesponsive CKD patients and needs to be supplemented, if deficiency is found.

Evaluation of Effect of Ascorbic Acid on Ferritin and Erythropoietin Resistance in Patients of Chronic Kidney Disease.

OBJECTIVE: This study was planned to evaluate the effect of short term intravenous ascorbic acid on reducing ferritin and erythropoietin resistance in patients of chronic kidney disease (CKD) on maintenance haemodialysis (MHD). METHODS: Forty adult patients [20 patients in group A with increased serum ferritin level (>500 ng/ml), transferrin saturation (TSAT) ≤20% and 20 patients in group B with normal serum ferritin level (<200 ng/ml), TSAT ≤20%] of end stage renal disease (ESRD) with erythropoietin hyporesponsiveness undergoing maintenance hemodialysis were included in the study. Group A was given intravenous (i.v.) ascorbic acid in a dose of 500 mg once a week after each 4 hours session of dialysis for 3 weeks in a month (total 1500 mg/month), for a period of 3 months along with erythropoietin 6000 IU subcutaneous (S/C) twice weekly without iron therapy. Group B was given erythropoietin (6000 IU S/C twice weekly after each hemodialysis) and intravenous (IV) iron 100 mg/week for 3 months. Hematological and renal investigations, erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (HsCRP), serum ferritin and TSAT were done at baseline and then one monthly intervals for three months whereas intact parathyroid hormone (iPTH) was measured at the start and end of the study. RESULTS: At the end of 3 months of study, in group A, Hemoglobin (Hb) and TSAT significantly increased while ferritin, HsCRP and erythropoietin resistance index (ERI) decreased significantly. In group B, the increase in Hb and TSAT were not significant statistically while ferritin increased significantly and fall in HsCRP and ERI were not significant statistically. The mean rise in Hb between subsequent months was higher in group A as compared to group B. CONCLUSIONS: Short term i.v ascorbic acid could be a new successful adjuvant in reducing ferritin and erythropoietin resistance and enhancing Hb and TSAT in CKD patients on MHD.

Kallman Syndrome.

Kallman syndrome (KS) is a rare genetic disorder characterized clinically by failure to attain puberty or failure to fully complete it along with an absent or impaired sense of smell with absence of bilateral olfactory bulbi and sulci alongwith absent olfactory tracts. Only very few cases of Kallman syndrome have been reported in females in Indian population.

Survivin: A molecular biomarker in cancer.

Survivin, a member of the inhibitor of apoptosis (IAP) protein family that inhibits caspases and blocks cell death, is highly expressed in most cancers and is associated with a poor clinical outcome. Survivin has consistently been identified by molecular profiling analysis to be associated with high tumour grade cancers, different disease survival and recurrence. Polymorphisms in the survivin gene are emerging as powerful tools to study the biology of the disease and have the potential to be used in disease prognosis and diagnosis. The survivin gene polymorphisms have also been reported to influence tumour aggressiveness as well as survival of cancer patients. The differential expression of survivin in cancer cells compared to normal tissues and its role as a nodal protein in a number of cellular pathways make it a high target for different therapeutics. This review discusses the complex circuitry of survivin in human cancers and gene variants of survivin, and highlights novel therapy that targets this important protein.

Neuroendocrine dysfunction in acute phase of moderate-to-severe traumatic brain injury: a prospective study.

OBJECTIVES: Most of the retrospective studies have demonstrated that traumatic brain injury mediated hypopituitarism could be more frequent than previously known. Therefore, this study has prospectively investigated pituitary function and their correlation with severity, pressure effect and Glasgow Outcome Scale in the acute phase of moderate-to-severe traumatic brain injury. PATIENTS AND METHODS: One hundred consecutive moderate-to-severe traumatic brain injury patients from August 2012 to November 2013 formed the study group. Apart from clinical assessment, non-contrast computed tomography of the head was performed on all patients on admission. The hormonal analysis (fT3, fT4, TSH, GH, Cortisol, Prolactin) was performed within 24 hours of traumatic brain injury and was repeated on the 7th day amongst the patients who survived. RESULTS: Growth hormone was the most common hormone to decrease. Cortisol was the most common hormone to increase. Risk of pituitary insufficiency was increased in patients with severe traumatic brain injury, patients with increased intracranial pressure and who had low Glasgow Outcome Scale. CONCLUSION: Neuroendocrine dysfunction occurs often in the acute phase of moderate-to-severe traumatic brain injury, more commonly in patients with severe traumatic brain injury, patients with pressure effects and low Glasgow Outcome Scale. Hormonal analysis should be considered in patients with moderate-to-severe traumatic brain injury, so that appropriate hormonal replacement can be done to optimize the clinical outcome.

Occipital post-traumatic intradiploic arachnoid cyst converted to pseudomeningocele after re-trauma: a rare complication of rare pathology.

BACKGROUND: Growing skull fracture (GSF)/pseudomeningocele is a rare complication of head injury in children. Post-traumatic intradiploic arachnoid cyst (PTIAC) is a variant but it is extremely rare. PTIACs are usually asymptomatic or with mild symptoms like headache. The rupture of PTIAC due to re-trauma leading to pseudomeningocele formation has not been seen or reported before. PATIENT AND METHOD: We present a case of occipital PTIAC where pseudomeningocele developed after re-trauma, and discuss the pathogenesis and management. RESULT: En masse removal of the ruptured PTIAC was performed along with dural-defect repair. The post-operative recovery was good. CONCLUSION: PTIAC is an extremely rare occurrence as a variant of GSF. It is usually asymptomatic, but it may rupture with trivial trauma due to a thinned-out outer table and then converts into pseudomengocele. En masse excision with dural-defect repair gives good results in cases of ruptured PTIAC due to re-trauma.

A hash based mutual RFID tag authentication protocol in telecare medicine information system.

Radio Frequency Identification (RFID) is a technology which has multidimensional applications to reduce the complexity of today life. Everywhere, like access control, transportation, real-time inventory, asset management and automated payment systems etc., RFID has its enormous use. Recently, this technology is opening its wings in healthcare environments, where potential applications include patient monitoring, object traceability and drug administration systems etc. In this paper, we propose a secure RFID-based protocol for the medical sector. This protocol is based on hash operation with synchronized secret. The protocol is safe against active and passive attacks such as forgery, traceability, replay and de-synchronization attack.

Raising cut-off value of prostate specific antigen (PSA) for biopsy in symptomatic men in India to reduce unnecessary biopsy.

BACKGROUND & OBJECTIVES: The characteristics of prostate specific antigen (PSA) for trans-rectal ultrasonography guided prostate biopsy in men with lower urinary tract symptoms (LUTS) are not well defined. This study was carried out to analyse the threshold of PSA for biopsy in symptomatic men in India. METHODS: From January 2000 to June 2011, consecutive patients who had digital rectal examination (DRE) and PSA testing done for LUTS were included in this study. PSA was done with ELISA technique. Patients with acute or chronic prostatitis, prostatic abscess, history of surgery on prostate within the previous three months and patients on 5α-reductase inhibitors or on urethral catheter were excluded. RESULTS: Of the 4702 patients evaluated, 70.9 per cent had PSA of less than 4 ng/ml and 29.1 per cent had PSA of more than 4 ng/ml. Of these, 875 men with a mean age of 65.72±7.4 (range 50-75 yr) had trans rectal ultrasonography (TRUS) guided biopsy. Twenty five men had biopsy at PSA level of <4 ng/ml due to positive DRE, 263 at 4.1-10ng/ml, 156 at 10.1-20 ng/ml and 431 at >20 ng/ml. Positive predictive value of PSA in ranges of 4.1-10, 10.1-20, >20 ng/ml was 15.2, 24 and 62.6 per cent, respectively with negative DRE. PSA cut-off to do biopsy was derived by ROC curve as 5.82 ng/ml for all the men. When the subjects were further stratified on the basis of DRE findings, a cut-off of 5.4 ng/ml was derived in men with normal DRE. INTERPRETATION & CONCLUSIONS: A cut-off for biopsy in symptomatic men with negative DRE could safely be raised to 5.4 ng/ml, which could avoid subjecting 10 per cent of men to undergo unnecessary biopsy.

Mail versus telephone administration of the Oxford Knee and Hip Scores.

Telephone and postal methods of administration of the Oxford Knee Score (OKS) and the Oxford Hip Score (OHS) were compared on 85 and 61 patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA), respectively. The test for equivalence was significant for both the knee (P<0.001) and hip participants (P<0.001) indicating that the modes of administration yielded similar results. The ICCs of the OKS and OHS were 0.79 (95% Confidence Interval (CI) 0.70, 0.86) and 0.87 (0.79, 0.92) respectively. The 95% limits of agreement were wide for both scores (OKS LOA, -8.6, 8.2; OHS LOA, -7.7, 5.3). The two modes of administration of the OKS and OHS produce equivalent survey responses at a group level but the same method of administration should be constant for individual monitoring in a clinical setting.

Liver dysfunction in alcoholics in Western Nepal.

To estimate liver function tests in patients with alcoholic fatty liver disease, alcoholic hepatitis and alcoholic cirrhosis and to compare the levels of enzymes between the groups. A hospital based case control study was carried out at Nepalgunj Medical College, Nepal from January 2013 to June 2013. A total of 150 alcoholic associated liver disorders patients aged between 20-70 years and 50 sex age matched normal healthy controls were taken to assess liver function tests (LFTs) by measuring Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma glutamyltranspeptidase (GGT) & Albumin. The mean±SD of liver function tests (LFTs) of patients of alcoholic fatty liver disease is highest followed by alcoholic hepatitis patients. All the 3 groups of alcoholic associated liver disorders patients when compared to normal healthy control subjects showed statistically significant increase in the levels of AST (p<0.000), ALT (p<0.000), ALP (p<0.006), GGT (p<0.000), & Albumin (p<0.000). Liver function tests values for alcoholic associated liver disorders patients when compared to the healthy control subjects was significantly altered.

Computational modeling of phonatory dynamics in a tubular three-dimensional model of the human larynx.

Simulation of the phonatory flow-structure interaction has been conducted in a three-dimensional, tubular shaped laryngeal model that has been designed with a high level of realism with respect to the human laryngeal anatomy. A non-linear spring-based contact force model is also implemented for the purpose of representing contact in more general conditions, especially those associated with three-dimensional modeling of phonation in the presence of vocal fold pathologies. The model is used to study the effects of a moderate (20%) vocal-fold tension imbalance on the phonatory dynamics. The characteristic features of phonation for normal as well as tension-imbalanced vocal folds, such as glottal waveform, glottal jet evolution, mucosal wave-type vocal-fold motion, modal entrainment, and asymmetric glottal jet deflection have been discussed in detail and compared to established data. It is found that while a moderate level of tension asymmetry does not change the vibratory dynamics significantly, it can potentially lead to measurable deterioration in voice quality.

Comparison of lipid profile in type-2 obese diabetics and obese non-diabetic individuals. a hospital based study from Western Nepal.

BACKGROUND: Type-2 diabetes mellitus is an independent risk factor for coronary artery disease and risk of coronary disease is three to four fold increased in patients with diabetes compared with non-diabetic population and 60-80% 0f type-2 diabetics are obese. METHODS: This study was conducted in Nepalgunj Teaching Hospital, Kohalpur, Banke, Nepal, between 1st March, 2011 and 28th February, 2012. A total of 150 samples were taken to assess the lipid profile in type-2 diabetic patients associated with obesity and 25 obese controls for their lipid profile. Venous blood samples were taken from all the subjects in the morning after fasting overnight. Exclusion criteria included pregnancy, chronic infectious disease, heart failure; renal failure and drug allergy were confirmed from the subject's personal physician report and a detailed history. The data was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. RESULTS: The mean ± SD age of diabetic patients with obesity was 53.76± 6.23 while the mean ± SD age of control was 49.61 ± 4.8. Out of 150 patients 105 (70%) were males and 45 (30%) were females. Among control subjects 16 (64%) were males and 9 (36%) were females. Obese type-2 diabetic patients when compared to obese control subjects showed statistically significant increase in the levels of serum total cholesterol (p < 0.001), serum triglycerides (p < 0.001), serum LDL-cholesterol (p < 0.001) while serum HDL-cholesterol levels did not show statistically significant difference in the two group (p > 0.05). CONCLUSION: This study showed obese diabetic individuals have dyslipidemia and more prone to develop cardiovascular diseases.