Evaluation of candidate genes related to litter traits in Indian pig breeds.

Improvement in litter traits is the key to profitable pig farming that directly enhances the economic standing of the farmers in developing countries. The present study aimed to explore oestrogen receptor (ESR), epidermal growth factor (EGF), follicle-stimulating hormone beta subunit (FSHß), prolactin receptor (PRLR) and retinol-binding protein 4 (RBP4) genes as possible candidate genetic markers for litter traits in indigenous pigs of India. The breeds included in the study were Ghungroo, Mali, Niang Megha and Tenyi Vo, and the reproductive traits considered were litter size at birth (LSB), number born alive (NBA), litter weight at birth (LWB), litter size at weaning (LSW) and litter weight at weaning (LWW) at their first parity. PCR-RFLP and primer-based mutation detection methods were used to identify polymorphism, and associations between the genotypes and the traits were analysed using a general linear model. The Ghungroo pigs recorded the best litter performances among the breeds (p < .05, LWB p < .01). Different alleles and genotypes of the genes under study were detected. Short interspersed nuclear element (SINE) -/- genotype of FSHß revealed significantly higher litter traits (p < .05, LSB p < .01). The LWW was also found to be significantly influenced by ESR BB and AB, EGF AB and BB, and PRLR CC genotypes (p < .05). Although we did not find statistically significant and consistently superior litter traits with respect to different genotypes of other studied genes than genotype SINE -/- of the FSHß, PRLR CC genotype demonstrated superior performances for all the litter traits. Our study revealed the FSHß as a potential candidate genetic marker for litter traits in indigenous pig breeds of India.

Influence of fish protein hydrolysate produced from industrial residues on antioxidant activity, cytokine expression and gut microbial communities in juvenile barramundi Lates calcarifer.

The present study investigated the supplemental effects of tuna hydrolysate (TH) in poultry by-product meal (PBM) and dietary fishmeal (FM) diets on antioxidant enzymatic activities, gut microbial communities and expression of cytokine genes in the distal intestine of juvenile barramundi, Lates calcarifer. Fish were fed with fermented (FPBM + TH) as well as non-fermented PBM (PBM + TH) and FM (FMBD + TH) diets with 10% TH supplementation for 10 weeks. A basal diet prepared without TH supplementation served as control. The results showed that the activity of glutathione peroxidase was significantly higher in FPBM + TH than the control, while the malondialdehyde and catalase activities were unchanged. FPBM + TH diet significantly (P < 0.05) upregulated the pro-inflammatory cytokines including IL-1ß and TNF-α while considerable downregulation (P < 0.05) was observed in the mRNA expression levels of anti-inflammatory cytokine, IL-10 in the distal intestine of fish. The 16SrRNA analysis using V3-V4 region evidenced the ability of FPBM + TH to modulate the distal intestinal gut microbiome, augmenting the richness of Firmicutes and Fusobacteriaat at phylum level and Bacillus, Lactococcus and Cetobacterium at genus level. All these results have shown that fermented PBM with TH supplementation could improve the antioxidant capacity and inflammatory responses of juvenile barramundi while influencing the microbial communities at both phylum and genera levels.

Chemical characterization and quantitativ e assessment of source-specific health risk of trace metals in PM1.0 at a road site of Delhi, India.

This study presents the concentration of submicron aerosol (PM1.0) collected during November, 2009 to March, 2010 at two road sites near the Indian Institute of Technology Delhi campus. In winter, PM1.0 composed 83% of PM2.5 indicating the dominance of combustion activity-generated particles. Principal component analysis (PCA) proved secondary aerosol formation as a dominant process in enhancing aerosol concentration at a receptor site along with biomass burning, vehicle exhaust, road dust, engine and tire tear wear, and secondary ammonia. The non-carcinogenic and excess cancer risk for adults and children were estimated for trace element data set available for road site and at elevated site from another parallel work. The decrease in average hazard quotient (HQ) for children and adults was estimated in following order: Mn > Cr > Ni > Pb > Zn > Cu both at road and elevated site. For children, the mean HQs were observed in safe level for Cu, Ni, Zn, and Pb; however, values exceeded safe limit for Cr and Mn at road site. The average highest hazard index values for children and adults were estimated as 22 and 10, respectively, for road site and 7 and 3 for elevated site. The road site average excess cancer risk (ECR) risk of Cr and Ni was close to tolerable limit (10-4) for adults and it was 13-16 times higher than the safe limit (10-6) for children. The ECR of Ni for adults and children was 102 and 14 times higher at road site compared to elevated site. Overall, the observed ECR values far exceed the acceptable level.

Lifestyle as Medicine: The Case for a True Health Initiative.

The power of lifestyle as medicine was perceived thousands of years ago. There is now consistent and compelling science to support the important influence of lifestyle on health. Approximately 80% of chronic disease and premature death could be prevented by not smoking, being physically active, and adhering to a healthful dietary pattern. Cardiovascular disease, diabetes, stroke, dementia, and cancer are all influenced by lifestyle choices. Despite the ample evidence about what behaviors promote health, confusion still prevails among the general population. This is particularly true with regard to diet. Confusing nutrition messages from scientists, the media, the food industry, and other sources have made it all but impossible for any single authority to convey persuasively the fundamentals of healthful eating. The case is made here that a global coalition of diverse experts has the power to do what no individual can: clarify and popularize an understanding of the fundamentals of a health-promoting, sustainable pattern of diet and lifestyle, and rally the general public to their consistent support.

Deceased donor renal transplantation at army hospital research and referral: Our experience.

CONTEXT: In India, there are a large number of end-stage renal disease (ESRD) patients waiting for renal transplant. Deceased donor organ transplantation (DDOT) is the possible solution to bridge the disparity between organ supply and demand. The concept of expanded criteria donors (ECDs) was developed to combat the huge discrepancy between demand and organ availability. However, ECD kidneys have a higher propensity for delayed graft function (DGF), and therefore worse long-term survival. We present our experience of deceased donor renal transplantation. AIMS: We report single centre experience on DDOT including ECDs vis-à-vis patient/graft survival, graft function in terms of serum creatinine (SCr), rejection episodes, and delayed graft function in 44 DDOT. MATERIALS AND METHODS: Between August 1998 and April 2011, 44 renal transplants from 35 deceased donors were performed, of which 37.2% were expanded criteria donors. Results were analyzed in terms of age of donor, terminal SCr, graft ischemia time, graft function, post-transplant complications, and graft and patient survival. All recipients received sequential triple drug immunosuppression and induction with rabbit antithymocyte globulin (rATG). The induction is commenced by giving first dose of rATG intraoperatively (dose 1.5 mg/kg) and subsequent rATG infusions were administered daily for a minimum of 5 and maximum of 7 doses depending on initial graft function. RESULTS: We have been able to achieve a mean cold ischemia time of 6.25 ± 2.55 h due to the coordinated team efforts. Delayed graft function occurred in 34% patients and 31.8% had prolonged drainage. There were no urinary leaks. Seven (16%) patients had biopsy-proven rejection episodes, all of which were reversed with treatment. Two patients underwent graft nephrectomy. One of these was due to hyperacute rejection and another due to anastomotic hemorrhage. One-year graft survival was 92.4% and the patient survival was 83.8%. CONCLUSION: Deceased donor renal transplants have satisfactory graft function and patient survival despite the high incidence of delayed graft function. Retrieving kidneys from marginal donors can add to the donor pool.

TWEAK causes myotube atrophy through coordinated activation of ubiquitin-proteasome system, autophagy, and caspases.

Proinflammatory cytokine TWEAK has now emerged as a key mediator of skeletal muscle-wasting in many catabolic conditions. However, the mechanisms by which TWEAK induces muscle proteolysis remain poorly understood. Here, we have investigated the role of ubiquitin-proteasome system, autophagy, and caspases in TWEAK-induced muscle wasting. Addition of TWEAK to C2C12 myotubes stimulated the ubiquitination of myosin heavy chain (MyHC) and augmented the expression of E3 ubiquitin ligase MuRF1. Pretreatment of myotubes with proteasome inhibitors MG132 or lactacystin or knockdown of MuRF1 by RNAi blocked the TWEAK-induced degradation of MyHC and myotube atrophy. TWEAK increased the expression of several autophagy-related molecules. Moreover, the inhibitors of autophagy improved the levels of MyHC in TWEAK-treated myotubes. TWEAK also increased activity of caspases in C2C12 myotubes. Pan-caspase or caspase 3 inhibitory peptide inhibited the TWEAK-induced loss of MyHC and myotube diameter. Our study demonstrates that nuclear factor-kappa B (NF-κB) transcription factor is essential for TWEAK-induced expression of MuRF1 and Beclin1. Furthermore, our results suggest that caspases contribute, at least in part, to the activation of NF-κB in response to TWEAK treatment. Collectively, the present study provides novel insight into the mechanisms of action of TWEAK in skeletal muscle.

Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice.

Skeletal muscle wasting is a major human morbidity, and contributes to mortality in a variety of clinical settings, including denervation and cancer cachexia. In this study, we demonstrate that the expression level and autoubiquitination of tumor necrosis factor (α) receptor adaptor protein 6 (TRAF6), a protein involved in receptor-mediated activation of several signaling pathways, is enhanced in skeletal muscle during atrophy. Skeletal muscle-restricted depletion of TRAF6 rescues myofibril degradation and preserves muscle fiber size and strength upon denervation. TRAF6 mediates the activation of JNK1/2, p38 mitogen-activated protein kinase, adenosine monophosphate-activated protein kinase, and nuclear factor κB, and induces the expression of muscle-specific E3 ubiquitin ligases and autophagy-related molecules in skeletal muscle upon denervation. Inhibition of TRAF6 also preserves the orderly pattern of intermyofibrillar and subsarcolemmal mitochondria in denervated muscle. Moreover, depletion of TRAF6 prevents cancer cachexia in an experimental mouse model. This study unveils a novel mechanism of skeletal muscle atrophy and suggests that TRAF6 is an important therapeutic target to prevent skeletal muscle wasting.

Tumor necrosis factor-α regulates distinct molecular pathways and gene networks in cultured skeletal muscle cells.

BACKGROUND: Skeletal muscle wasting is a debilitating consequence of large number of disease states and conditions. Tumor necrosis factor-α (TNF-α) is one of the most important muscle-wasting cytokine, elevated levels of which cause significant muscular abnormalities. However, the underpinning molecular mechanisms by which TNF-α causes skeletal muscle wasting are less well-understood. METHODOLOGY/PRINCIPAL FINDINGS: We have used microarray, quantitative real-time PCR (QRT-PCR), Western blot, and bioinformatics tools to study the effects of TNF-α on various molecular pathways and gene networks in C2C12 cells (a mouse myoblastic cell line). Microarray analyses of C2C12 myotubes treated with TNF-α (10 ng/ml) for 18h showed differential expression of a number of genes involved in distinct molecular pathways. The genes involved in nuclear factor-kappa B (NF-kappaB) signaling, 26s proteasome pathway, Notch1 signaling, and chemokine networks are the most important ones affected by TNF-α. The expression of some of the genes in microarray dataset showed good correlation in independent QRT-PCR and Western blot assays. Analysis of TNF-treated myotubes showed that TNF-α augments the activity of both canonical and alternative NF-κB signaling pathways in myotubes. Bioinformatics analyses of microarray dataset revealed that TNF-α affects the activity of several important pathways including those involved in oxidative stress, hepatic fibrosis, mitochondrial dysfunction, cholesterol biosynthesis, and TGF-ß signaling. Furthermore, TNF-α was found to affect the gene networks related to drug metabolism, cell cycle, cancer, neurological disease, organismal injury, and abnormalities in myotubes. CONCLUSIONS: TNF-α regulates the expression of multiple genes involved in various toxic pathways which may be responsible for TNF-induced muscle loss in catabolic conditions. Our study suggests that TNF-α activates both canonical and alternative NF-κB signaling pathways in a time-dependent manner in skeletal muscle cells. The study provides novel insight into the mechanisms of action of TNF-α in skeletal muscle cells.

Rare etiology of obstructive uropathy: pelvic lipomatosis.

We present a case of a 32-year-old hypertensive and obese male who had bilateral obstructive uropathy, and who was diagnosed as having pelvic lipomatosis on the basis of clinicoradiological findings. Cystoscopy and biopsy revealed cystitis cystica. He was successfully managed with bilateral extravesical modified Lich-Gregoir ureteric reimplantation by intraperitoneal approach. At 5 months follow-up, the patient had normal serum creatinine and was clinically asymptomatic.

Minimally invasive retrieval of a bullet from the L5-S1 neural foramina after transperitoneal gunshot wound.

BACKGROUND CONTEXT: In victims of gunshot wounds with retained bullet fragments in the central nervous system, delayed neurological deficit may result from copper-induced neurotoxicity. The mainstay of therapy involves surgical exploration and retrieval of fragments. PURPOSE: A patient who presented with delayed neurological deficit after a transperitoneal gunshot wound is presented. STUDY DESIGN: Technical report. METHODS: A 25-year-old male, who was the victim of a transperitoneal gunshot wound with a copper-jacketed bullet, presented several weeks after recovering from his abdominal injury. The patient presented with a worsening radiculopathy in the L5 distribution and progressive dorsiflexion weakness. Subsequent imaging demonstrated a bullet lodged lateral to the L5-S1 neural foramina. RESULTS: A minimally invasive approach with the use of a tubular retractor was used to retrieve the retained bullet. The lateral location of the bullet, the proximity of the nerve root to the bullet, and the limited visualization of the operative field from a minimally invasive approach, placed the nerve root at increased risk. Intraoperative myelography and electrophysiological monitoring were used to locate the nerve root in relation to the bullet and guide the extraction of the bullet. Postoperatively, the patient had complete resolution of his preoperative symptoms. CONCLUSIONS: In cases where proximity to neural structures and limited visualization of bony landmarks may increase the risk of injury when extracting a foreign body, intraoperative myelography and electrophysiological monitoring are valuable adjuncts to further elucidate the surgical anatomy for a minimally invasive approach.

Regulation of UDP-glucose pyrophosphorylase isozyme UGP5 associated with cold-sweetening resistance in potatoes.

The regulation of UDP-Glc pyrophosphorylase (UGPase) isozyme, UGP5, was investigated in potato tuber. The cDNA for UGP5 was cloned into the bacterial expression vector pET21d and recombinant (RC) enzyme was expressed in E. coli (BL21 star cells). The RC-UGP5 isozyme was purified to near homogeneity using salt precipitation, hydrophobic interaction, and anion-exchange column chromatography. Kinetic analysis revealed that in the synthesis direction, K(m) values for Glc-1-P (0.83 mM) and UTP (0.22 mM) were similar to those observed previously with the mother tuber (MT)-UGP5. In the pyrophosphorolysis direction, the K(m) values for UDP-Glc (0.68 mM) and PPi (0.56 mM) were slightly higher than those observed previously. Maximum reaction velocities (V(max)) for RC-UGP5 were also elevated. Since the molecular mass, charge, and amino acid sequence of the MT- and RC-UGP5 isozymes were identical, it was assumed that altered kinetic constants may be due to an improper folding of RC-UGP5 polypeptide. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and proteomic analysis demonstrated that the UGP5 isozyme was a single polypeptide with a calculated molecular mass of 51.8kDa consisting of 477 amino acids. Native PAGE and kinetic analysis revealed that this polypeptide was monomeric in nature. Immunoblotting with specific antibodies and LC-MS/MS data indicated that UGP5 did not require any post-translational modification (e.g., phosphorylation, O-glycosylation, oligomerization/de-oligomerization, or the presence of the regulatory 14-3-3 proteins) for its regulation. Additionally, the two closely associated isozymes UGP5 and UGP6 in the cv. Snowden are likely the result of allelic differences of UGPase at a single locus.

Osteolysis after total knee arthroplasty.

Osteolysis ranks as the most significant cause of revision surgery in both total hip arthroplasty and total knee arthroplasty (TKA). The factors leading to osteolysis in TKA are unique and sometimes preventable. Changes in polyethylene manufacturing and implant design are striving to improve overall wear. In this review, we discuss osteolysis as it relates to TKAs. The etiology, diagnosis, contributing factors, and management are presented. The final section focuses on future improvements in TKA design, which may ultimately decrease the rate of osteolysis.

Spontaneous bacterial peritonitis causing Serratia marcescens and Proteus mirabilis ventriculoperitoneal shunt infection. Case report.

The authors report their experience treating a polymicrobial ventriculoperitoneal (VP) shunt infection in a developmentally delayed 21-year-old woman. Cerebrospinal fluid (CSF) cultures grew Serratia marcescens and Proteus mirabilis. On admission and throughout her hospitalization, results of physical examination of her abdomen were normal, and radiographic studies showed no evidence of bowel perforation or pseudocyst formation. Contrast-enhanced computed tomography of the abdomen revealed a small fluid collection. After a course of intravenous gentamicin and imipenem with cilastatin in conjunction with intrathecal gentamicin, the infection was resolved and the VP shunt was reimplanted. Although VP shunt infections are not uncommon, S. marcescens as a causative agent is exceedingly rare and potentially devastating. Only two previous cases of S. marcescens shunt infection have been reported in the literature. Authors reporting on S. marcescens infections in the central nervous system (CNS) have observed significant morbidity and death. Although more common, the presence of P. mirabilis in the CSF is still rare and highly suggestive of bowel perforation, which was absent in this patient. Spontaneous bacterial peritonitis was the likely source from which these bacteria gained entrance into the VP shunt system, eventually causing ventriculitis in this patient. The authors conclude that in light of the high morbidity associated with S. marcescens infection of the CNS, intrathecal administration of gentamicin should be strongly considered as part of first-line therapy for S. marcescens infections in VP shunts.