Evidence of Antineutrinos from Distant Reactors Using Pure Water at SNO.

The SNO+ Collaboration reports the first evidence of reactor antineutrinos in a Cherenkov detector. The nearest nuclear reactors are located 240 km away in Ontario, Canada. This analysis uses events with energies lower than in any previous analysis with a large water Cherenkov detector. Two analytical methods are used to distinguish reactor antineutrinos from background events in 190 days of data and yield consistent evidence for antineutrinos with a combined significance of 3.5σ.

Using a Modeling-Based Approach to Assess and Optimize HIV Linkage to Care Services.

Evidence-based linkage to care interventions (LTCs) help recently diagnosed HIV+ individuals engage in care in a timely manner yet are heavily impacted by the systems in which they are embedded. We developed a prototype agent-based model informed by data from an established LTC program targeting youth and young adults aged 13-24 in Memphis, Tennessee. We then tested two interventions to improve LTC in a simulated environment: expanding testing sites versus using current testing sites but improving direct referral to LTC staff from organizations providing testing, to understand the impact on timely linkage to care. Improving direct referral to the LTC program decreased days to successful linkage from an average of 30 to 23 days but expanding testing sites increased average days to 31 days unless those sites also made direct referrals. We demonstrated how LTC is impacted by the system and interventions for shortening days to linkage to care.

Uptake and virological outcomes of single- versus multi-tablet antiretroviral regimens among treatment-naïve youth in the HIV Research Network.

OBJECTIVES: Several single-tablet regimens (STRs) are now available and are recommended for first-line antiretroviral therapy (ART); however, STR use for youth with HIV (YHIV) has not been systematically studied. We examined the characteristics associated with initiation of STRs versus multi-tablet regimens (MTRs) and the virological outcomes for youth with nonperinatally acquired HIV (nPHIV). METHODS: A retrospective cohort study of nPHIV youth aged 13-24 years initiating ART between 2006 and 2014 at 18 US HIV clinical sites in the HIV Research Network was performed. The outcomes measured were initiation of STRs versus MTRs, virological suppression (VS) at 12 months, and time to VS. Demographic and clinical factors associated with initiation of STR versus MTR ART and VS (< 400 HIV-1 RNA copies/mL) at 12 months after initiation were assessed using multivariable logistic regression. Cox proportional hazards regression was used to assess VS within the first year. RESULTS: Of 987 youth, 67% initiated STRs. Of the 589 who had viral load data at 1 year, 84% of those on STRs versus 67% of those on MTRs achieved VS (P < 0.01). VS was associated with STR use [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.01-2.58], white (AOR 2.41; 95% CI 1.13-5.13) or Hispanic (AOR 2.38; 95% CI 1.32-4.27) race/ethnicity, and baseline CD4 count 351-500 cells/µL (AOR 1.94; 95% CI 1.18-3.19) and > 500 cells/µL (AOR 1.76; 95% CI 1.0-3.10). STR use was not associated with a shorter time to VS compared with MTR use [hazard ratio (HR) 1.07; 95% CI 0.90-1.28]. CONCLUSIONS: Use of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV.

Whole-Genome Characterization of Bacillus cereus Associated with Specific Disease Manifestations.

Bacillus cereus remains an important cause of infections, particularly in immunocompromised hosts. While typically associated with enteric infections, disease manifestations can be quite diverse and include skin infections, bacteremia, pneumonia, and meningitis. Whether there are any genetic correlates of bacterial strains with particular clinical manifestations remains unknown. To address this gap in understanding, we undertook whole-genome analysis of B. cereus strains isolated from patients with a range of disease manifestations, including noninvasive colonizing disease, superficial skin infections, and invasive bacteremia. Interestingly, strains involved in skin infection tended to form a distinct genetic cluster compared to isolates associated with invasive disease. Other disease manifestations, despite not being exclusively clustered, nonetheless had unique genetic features. The unique features associated with the specific types of infections ranged from traditional virulence determinants to metabolic pathways and gene regulators. These data represent the largest genetic analysis to date of pathogenic B. cereus isolates with associated clinical parameters.

Dose-dependent response of Trichoderma harzianum in improving drought tolerance in rice genotypes.

MAIN CONCLUSION: This study demonstrates a dose-dependent response of Trichoderma harzianum Th-56 in improving drought tolerance in rice by modulating proline, SOD, lipid peroxidation product and DHN / AQU transcript level, and the growth attributes. In the present study, the effect of colonization of different doses of T. harzianum Th-56 strain in rice genotypes were evaluated under drought stress. The rice genotypes treated with increasing dose of T. harzianum strain Th-56 showed better drought tolerance as compared with untreated control plant. There was significant change in malondialdehyde, proline, higher superoxide dismutase level, plant height, total dry matter, relative chlorophyll content, leaf rolling, leaf tip burn, and the number of scorched/senesced leaves in T. harzianum Th-56 treated rice genotypes under drought stress. This was corroborated with altered expression of aquaporin and dehydrin genes in T. harzianum Th-56 treated rice genotypes. The present findings suggest that a dose of 30 g/L was the most effective in improving drought tolerance in rice, and its potential exploitation will contribute to the advancement of rice genotypes to sustain crop productivity under drought stress. Interaction studies of T. harzianum with three aromatic rice genotypes suggested that PSD-17 was highly benefitted from T. harzianum colonization under drought stress.

Chronic groin pain in Desarda versus Lichtenstein hernia repair - a randomised controlled study.

BACKGROUND: Chronic pain after inguinal hernia repair is a common complication. This study compared the difference between Desarda repair and Lichtenstein repair for inguinal hernia in chronic groin pain. METHODS: One hundred patients with unilateral uncomplicated inguinal hernia were randomised to either Desarda repair (n = 50) or Lichtenstein repair (n = 50) under local anaesthesia and were evaluated for pain postoperatively. Operative time, surgical complications, time to return to normal gait and work, and overall patient satisfaction were recorded. The patient was blinded to the procedure. Any pain at three months (numerical rating scale 1 or more) was considered chronic pain. RESULTS: Mean operation time was approximately 5 minutes less for Desarda (p = 0.33). There was no significant difference in terms of pain level postoperatively between Lichtenstein and Desarda groups. Twenty-two (44%) patients in the Lichtenstein group had chronic pain, and twenty-one (45.7%) patients had chronic pain in the Desarda group (p = 0.871). No significant difference was observed in haematoma formation, wound infection, recurrence rate, seroma, or foreign body sensation. The mean time for patients to return to normal gait was approximately 0.5 day earlier for the Desarda group (p = 0.29). The mean time for patients to return to normal work was comparable (p = 0.99). Desarda group had a slightly higher satisfaction rate than the Lichtenstein group (9.1%). CONCLUSION: Desarda repair is not inferior to Lichtenstein repair in the short-term concerning complications or pain.

Patterns of left ventricular hypertrophy in chronic kidney disease: an echocardiographic evaluation.

BACKGROUND: We evaluated the chronic kidney disease (CKD) patients having different degree of uremia for the prevalence of Left Ventricular Hypertrophy (LVH), different patterns of left Ventricular Hypertrophy by echocardiographic variables to define the most sensitive and powerful predictor of cardiovascular disease (CVD) and premature morbidity and mortality. METHODS: We used clinical and biochemical data from the prospective study done by us to evaluate "The Echocardiographic assessment of cardiac functions in patients with chronic kidney disease". The diagnosis of CKD was made on the basis of serum creatinine (sCr) concentration of more than 1.5 mg/dl, persistent and with no evidence of recovery over a period of 3 months. Glomerular filtration rate (GFR) was calculated by the Modification of Diet in Renal Disease (MDRD) equation and cut-off for CKD was taken to be < 60 ml/min/1.73 m2 as per existing guidelines. The study population consisted of a total of 75 subjects divided into three groups of 25 subjects each, all between the age of 20-65 yrs: GROUP A: Healthy normal controls (sCr < 1.5 mg/dl); GROUP B: Patients with mild to moderate CKD (sCr 1.5 - 6.0 mg/dl); GROUP C: Patients with severe CKD (sCr > 6.0 mg/dl). RESULTS: A progressive rise in prevalence of LVH was observed with the severity of kidney disease from 64% (mild/ moderate CKD group) to 96% (severe CKD group) and higher prevalence of LVH in females than males in the severe CKD group. The mean LVMI in both the groups of CKD was significantly higher than the healthy controls (76.62 +/- 10.97). Also, mean LVMI in severe CKD (139.23 +/- 17.47) patients was significantly higher than in mild/moderate CKD (114.91 +/- 15.20) patients. The prevalence of concentric remodeling in both the CKD groups was alike (20%). While that of concentric hypertrophy in severe CKD patients (68%) was significantly higher than in mild/moderate CKD group (40%) (p < 0.05), but no significant difference was observed for eccentric pattern of hypertrophy between the two CKD groups. This suggests that concentric hypertrophy is more prevalent in CKD patients. CONCLUSIONS: The mean left ventricular mass index (LVMI) showed a proportionate increase with the severity of renal failure and a progressive rise with increase in severity of disease. Patients of CKD groups revealed occurrence of concentric remodeling which is a predictor of high vulnerability for progressing into concentric and eccentric hypertrophy. Hence early medical intervention may reverse the concentric remodeling, thereby preventing the advancement to concentric or eccentric LVH.

Genome-Wide Association Study and Post-genome-Wide Association Study Analysis for Spike Fertility and Yield Related Traits in Bread Wheat.

Spike fertility and associated traits are key factors in deciding the grain yield potential of wheat. Genome-wide association study (GWAS) interwoven with advanced post-GWAS analysis such as a genotype-phenotype network (geno-pheno network) for spike fertility, grain yield, and associated traits allow to identify of novel genomic regions and represents attractive targets for future marker-assisted wheat improvement programs. In this study, GWAS was performed on 200 diverse wheat genotypes using Breeders' 35K Axiom array that led to the identification of 255 significant marker-trait associations (MTAs) (-log10P ≥ 3) for 15 metric traits phenotyped over three consecutive years. MTAs detected on chromosomes 3A, 3D, 5B, and 6A were most promising for spike fertility, grain yield, and associated traits. Furthermore, the geno-pheno network prioritised 11 significant MTAs that can be utilised as a minimal marker system for improving spike fertility and yield traits. In total, 119 MTAs were linked to 81 candidate genes encoding different types of functional proteins involved in various key pathways that affect the studied traits either way. Twenty-two novel loci were identified in present GWAS, twelve of which overlapped by candidate genes. These results were further validated by the gene expression analysis, Knetminer, and protein modelling. MTAs identified from this study hold promise for improving yield and related traits in wheat for continued genetic gain and in rapidly evolving artificial intelligence (AI) tools to apply in the breeding program.

The T cell receptor repertoire influences V beta element usage in response to myoglobin.

T cell clones recognizing the sperm whale myoglobin (SpWMb) epitope 110-121 in association with H-2d major histocompatibility complex class II molecules display a very limited heterogeneity of T cell receptor (TCR) V beta usage in DBA/2 mice. All clones previously tested used the same V beta 8.2 gene segment and very restricted junctional regions. To investigate the significance of this observation in vivo, we immunized DBA/2 mice with the intact SpW Mb protein or peptide 110-121. Only the V beta 8+ T cells showed any significant response to the 110-121 epitope. The response to peptide 110-121 was then analyzed in mice which, either as a consequence of antibody depletion or through genetic deletion of TCR V beta genes, lacked V beta 8+ peripheral T cells. DBA/2 mice depleted of V beta 8+ T cells by antibody treatment responded poorly to the 110-121 peptide, and only at high antigen concentrations. In contrast, DBA/2V beta a mice (homozygous for a deletion of multiple V beta gene segments including the V beta 8 family) made a response at least as great as that made by DBA/2 mice, even though the DBA/2V beta a mice had a very restricted TCR V beta repertoire compared with DBA/2 mice. Mechanisms which might determine differences in the 110-121 specific response of DBA/2, DBA/2V beta a and F23.1-treated DBA/2 mice are discussed.

Role of Prophylactic Antibiotics in Laparoscopic Cholecystectomy.

BACKGROUND: Antibiotic prophylaxis is routinely administered in laparoscopic cholecystetomy but its role is debatable. METHODS: From January 2004 to August 2008, 417 patients were randomized into 208 in antibiotic group (AG) and 209 in non antibiotic group (NAG). AG received one dose each of injection ciprofloxacin (200 mg) and metronidazole (500mg) preoperatively. NAG was given only intravenous fluids. Besides routine care, all underwent abdominal sonography and liver function tests at least once during the 30 postoperative days. RESULT: Age, sex and co-morbidity distribution were similar in both the groups. One patient who was on weekly 5mg methotraxate (NAG) had erythema around umbilical port. Other three having umbilical discharge recovered without antibiotics. Nine patients had subhepatic collection (5 AG and 4 NAG). One from NAG underwent re-laparoscopy and drainage. Ten patients had fever. Two from AG had basal lung collapse and were given antibiotics. CONCLUSION: Antibiotic prophylaxis is not needed for laparoscopic cholecystectomy.

Impact of incarceration on nutritional status and oral health among male inmates of central jail of Jaipur city, India.

AIM: Prison is an especially difficult environment for promoting oral health and leads to the exacerbation of unhealthy behaviors. This study set out to assess the impact of incarceration on nutritional status and oral health among the male prison inmates of Central Jail of Jaipur city, Rajasthan, India. MATERIAL AND METHOD: A cross sectional study was conducted among 181 male inmates. Dental caries and periodontal status were assessed by using modified the Decayed Missing Filled Teeth (DMFT) index and Community Periodontal Index (CPI) and Loss of Attachment (LOA) index as per the WHO methodology 1997. Nutritional status was assessed by Body Mass Index (BMI) and weight (kg)/height (m2). RESULTS: Out of 181 inmates, 141 (77.90%) had normal BMI. The majority (n=128, 70.70%) of inmates were incarcerated for less than 6 years. A significant difference (P<0.05) was found between age and periodontal status. A significant difference was observed (P<0.05) in the CPI score 3 and LOA 0 and 1 score. However, no significant difference (P>0.05) was observed in DMFT and period of incarceration. Age was the significant (P<0.001) risk factor for CPI and LOA. DISCUSSION: Dental caries and periodontal health deteriorates with age and period of incarceration. Oral hygiene maintenance along with comprehensive oral care can be accomplished by establishing dental care facilities in prisons.

Requirement for CD8+ cells in T cell receptor peptide-induced clonal unresponsiveness.

T cell receptor (TCR) vaccination in rats prevents the development of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. The mechanism of this potential immunotherapy was examined by vaccinating mice with an immunogenic peptide fragment of the variable region of the TCR V beta 8.2 gene. Another immunogen that usually induces an immune response mediated by V beta 8.2+ T cells was subsequently inhibited because specific clonal unresponsiveness (anergy) had been induced. Depletion of CD8+ cells before TCR peptide vaccination blocked such inhibition. Thus, the clonal anergy was dependent on CD8+ T cells, and such immunoregulatory T cells may participate in the normal course of EAE.

Amelioration of autoimmune encephalomyelitis by myelin basic protein synthetic peptide-induced anergy.

Experimental autoimmune encephalomyelitis (EAE), a demyelinating disease of the central nervous system that can be induced in susceptible strains of mice by immunization with myelin basic protein (MBP) or its immunodominant T cell determinants, serves as a model of human multiple sclerosis. Tolerance to MBP in adult mice was induced by intraperitoneal injection of synthetic peptides of immunodominant determinants of MBP and prevented MBP-induced EAE. Furthermore, tolerance-inducing regimens of peptides administered to mice after the disease had begun (10 days after induction with MBP) blocked the progression and decreased the severity of EAE. Peptide-induced tolerance resulted from the induction of anergy in proliferative, antigen-specific T cells.

3D echocardiography: "The most powerful predictor of masked CVD in metabolic syndrome".

UNLABELLED: AIMS & OBJECTIVE: To evaluate the impact of the Metabolic Syndrome (MetS) on various echo variables by 3D Echocardiography. MATERIALS AND METHODS: 100 patients of MetS from indoor and outdoor patient departments were subjected to Echocardiographic and Carotid Doppler evaluation. They were divided into three groups: Group A, Group B and Group C on the basis of age <40 yrs, 40-60 yrs and >60 yrs respectively. The echo variables included left ventricular myocardial performance index (LVMPI), left ventricular mass index (LVMi), left ventricular diastolic dysfunction (LVDD), systolic function (LVEF), left atrial volume index (LAVi) and composite common carotid intima media thickness (CCIMT). RESULTS: The mean LVMPI was abnormal in all the groups and showed an increasing trend with prolonged LVMPI (> 0.4) in 74% of the total population. Prolonged LVMPI in Group A, Group B and Group C were 12.1%, 52.7% and 35.1% respectively. There was also a strong correlation between LVMPI & LVDD (p-value < 0.0001). Only 9% had systolic dysfunction (LVEF < 50%), but 68% of patients had abnormal diastolic function, of which 53% had grade I LVDD, 12% had grade II LVDD and 3% had grade III diastolic dysfunction. None of our patients had grade IV diastolic dysfunction. The mean LA Vi was normal in all the groups, but LAVi increased with worsening LVDD. The mean LVMi indexed to Body Surface Area (BSA) was normal in all the groups, but showed a statistically significant increasing trend from Group A to Group C (p-value < 0.05). Statistically significant higher LVMi values were observed for males as compared to females (p-value < 0.0001). On analysis of patients having left ventricular hypertrophy (LVH), 76% had concentric remodeling; only 11 % had concentric hypertrophy, but none had eccentric hypertrophy. Most of our patients in Group B & Group C had higher mean Composite CCIMT (0.73 +/- 0.33 & 0.84 +/- 0.42 respectively) which was statistically very significant (p-value < 0.001) CONCLUSION: Metabolic Syndrome is associated with masked cardiovascular disease (CVD) as evident by 3D Echo in this series of patients. LVMPI was an early indicator and the most robust marker of early LVDD. Impaired relaxation was highly prevalent; while LAVi was less robust predictor of LVDD in this series of patients. Concentric left ventricular remodeling was the most common pattern of LVH. Most of our series of patients had increased Composite CCIMT. Thus 3D Echocardiography has great potential and is very useful for early detection and timely therapeutic interventions in patients with subclinical CVD in MetS.

A cross-sectional study to assess the prevalence of early childhood caries and associated risk factors in preschool children in district Mandi, Himachal Pradesh.

AIM: The aim of this cross-sectional study is to investigate the prevalence and related risk factors of early childhood caries (ECC) in preschool children of district Mandi, Himachal Pradesh, India. MATERIALS AND METHODS: A total sample of 2859 children aged between 2 and 6 years were selected from various parts of district Mandi. The status of dental caries and decayed missing and filled teeth (DMFT) score was recorded. RESULTS: ECC increased significantly with age. Boys had significantly higher caries prevalence and mean DMFT score as compared to girls. Children who belonged to low socioeconomic group showed higher caries prevalence and mean DMFT score. Children aged 3-6 years who brushed their teeth twice daily had the least prevalence of dental caries as well as DMFT score when compared to children with one time and no brushing. CONCLUSION: The early identification of poor oral hygiene and improper feeding habits should be considered in preventive health promotion in low socioeconomic communities of district Mandi, Himachal Pradesh.

Observations on carbapenem resistance by minimum inhibitory concentration in nosocomial isolates of Acinetobacter species: an experience at a tertiary care hospital in North India.

Acinetobacter species are emerging as an important nosocomial pathogen. Multidrug-resistant Acinetobacter spp. has limited the option for effective treatment. Although carbapenems are effective for the treatment of such infections, resistance to this drug has recently been reported. This study was undertaken to assess resistance to carbapenem in clinical isolates of Acinetobacter spp. from hospitalized patients by both disc-diffusion and minimum inhibitory concentration (MIC) methods. All clinical samples from suspected cases of nosocomial infections were processed, and 265 isolates were identified as Acinetobacter species. These isolates were tested for antibiotic resistance by the disc-diffusion method with 14 antimicrobials, including meropenem and imipenem. Thereafter, all Acinetobacter species were subjected to MIC for meropenem. More than 80% resistance to second- and third-generation cephalosporins, aminoglycosides, and quinolones was recorded. Thirty percent of the strains were resistant to cefoperazone/sulbactam. Resistance to meropenem was observed in 6.4% of Acinetobacter spp. while 8.3% of the isolates showed intermediate resistance detected by MIC. All carbapenem-resistant/intermediate strains were also resistant to other (>10) antibiotics tested by the disc-diffusion method. The rising trend of resistance to carbapenem poses an alarming threat to the treatment for such infections. Regular monitoring, judicious prescription, and early detection of resistance to carbapenem are necessary to check further dissemination of drug resistance in Acinetobacter spp.

Effect of aluminium on lipid profile and atherogenic index in prepubertal and young adult female rats: A pilot study

Objectives: Exposure of aluminium (Al) to mankind is inescapable, and its dyslipidaemic impact is a possible contributing factor to health hazards like cardiovascular diseases. The health effects due to the metalloestrogenic property of the metal need imperative consideration. The current experimental work was undertaken to explore Al-induced dyslipidaemia due to its metalloestrogenic property. Materials and Methods: To fulfil this objective, prepubertal (PP) and young adult (YA) female Wistar rats were intraperitoneally administered to two doses of Al [5 and 10 mg/Kg body weight (BW)] once daily for 2 weeks. After the completion of the acute exposure protocol, plasma and hepatic tissue lipid profiles were estimated. Analysis of variance was carried out by the Kruskal–Wallis test and the differences between the groups were analysed by Mann–Whitney U post hoc test Results: Increased triglyceride, total cholesterol, low-density lipoprotein (LDL) cholesterol and very-LDL cholesterol in plasma were found in YAs treated with both doses of Al in a dose-dependent manner. Similar changes were not present in PP female rats. Decreased levels of lipid levels were observed in the case of hepatic lipid profile. Conclusion: The study ushers light towards the dyslipidaemic alterations in experimental female rats after acute Al exposure. Impacts of Al on the growth and organosomatic index during the vital developmental days were significantly decided by the pubertal status of the female rats. The results of this study indicate the impact of puberty on the Al-induced modifications in lipid profile parameters and cardiovascular risk factors.

A disease-associated cellular immune response in type 1 diabetics to an immunodominant epitope of insulin.

The 9-23 amino acid region of the insulin B chain (B9-23) is a dominant epitope recognized by pathogenic T lymphocytes in nonobese diabetic mice, the animal model for type 1 diabetes. We describe herein similar (B9-23)-specific T-cell responses in peripheral lymphocytes obtained from patients with recent-onset type 1 diabetes and from prediabetic subjects at high risk for disease. Short-term T-cell lines generated from patient peripheral lymphocytes showed significant proliferative responses to (B9-23), whereas lymphocytes isolated from HLA and/or age-matched nondiabetic normal controls were unresponsive. Antibody-mediated blockade demonstrated that the response was HLA class II restricted. Use of the highly sensitive cytokine-detection ELISPOT assay revealed that these (B9-23)-specific cells were present in freshly isolated lymphocytes from only the type 1 diabetics and prediabetics and produced the proinflammatory cytokine IFN-gamma. This study is, to our knowledge, the first demonstration of a cellular response to the (B9-23) insulin epitope in human type 1 diabetes and suggests that the mouse and human diseases have strikingly similar autoantigenic targets, a feature that should facilitate development of antigen-based therapeutics.

Altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway.

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. N-terminal asparagine and glutamine are tertiary destabilizing residues, in that they are enzymatically deamidated to yield secondary destabilizing residues aspartate and glutamate, which are conjugated to arginine, a primary destabilizing residue. N-terminal arginine of a substrate protein is bound by the Ubr1-encoded E3alpha, the E3 component of the ubiquitin-proteasome-dependent N-end rule pathway. We describe the construction and analysis of mouse strains lacking the asparagine-specific N-terminal amidase (Nt(N)-amidase), encoded by the Ntan1 gene. In wild-type embryos, Ntan1 was strongly expressed in the branchial arches and in the tail and limb buds. The Ntan1(-/-) mouse strains lacked the Nt(N)-amidase activity but retained glutamine-specific Nt(Q)-amidase, indicating that the two enzymes are encoded by different genes. Among the normally short-lived N-end rule substrates, only those bearing N-terminal asparagine became long-lived in Ntan1(-/-) fibroblasts. The Ntan1(-/-) mice were fertile and outwardly normal but differed from their congenic wild-type counterparts in spontaneous activity, spatial memory, and a socially conditioned exploratory phenotype that has not been previously described with other mouse strains.