Evaluation of Efficacy and Safety of Fixed Dose Lovastatin and NiacinER Combination in Asian Indian Dyslipidemic Patients: A Multicentric Study

Asian Indian dyslipidemia is characterized by: borderline high low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B; high triglycerides, low high-density lipoprotein (HDL) cholesterol and apoA1; and high lipoprotein(a) (lp[a]). We performed a controlled multicentric trial in India to evaluate the efficacy and safety of a fixed dose combination of lovastatin and niacin extended release (niacinER) formulation in patients with moderate to severe dyslipidemia. Consecutive subjects that satisfied the selection criteria, agreed to an informed consent, and with no baseline presence of liver/renal disease or heart failure were enrolled in the study. After a 4-week run-in period there were 142 patients with LDL levels ≥130 mg/dL. Eleven patients were excluded because of uncontrolled hyperglycemia and 131 patients were recruited. After baseline evaluation of clinical and biochemical parameters all subjects were administered lovastatin (20 mg) and niacinER (500 mg) combination once daily. Dose escalation was done on basis of lipid parameters at 8 weeks and in 11 patients increased to lovastatin (20 mg) and niacinER (1000 mg). An intention-to-treat analysis was performed and data was analyzed using nonparametric Wilcoxon signed rank test. Thirteen patients (10%) were lost to follow-up and 4 (3%) withdrew because of dermatological adverse effects: flushing, pruritus, and rash. The mean values of various lipid parameters (mg/dL) at baseline, and at weeks 4, 12, and 24 respectively were: total cholesterol 233.9 ± 27, 206.3 ± 27, 189.8 ± 31, and 174.9 ± 27 mg/dL; LDL cholesterol 153.4 ± 22, 127.3 ± 21, 109.2 ± 27, and 95.1 ± 23 mg/dL; triglycerides 171.1 ± 72, 159.5 ± 75, 149.2 ± 45, and 135.2 ± 40 mg/dL; HDL cholesterol 45.6 ± 7, 48.9 ± 7, 51.6 ± 9, and 53.9 ± 10 mg/dL; lp(a) 48.5 ± 26, 40.1 ± 21, 35.4 ± 21, and 26.9 ± 19 mg/dL; and apoA1/apoB ratio 0.96 ± 0.7, 1.04 ± 0.4, 1.17 ± 0.5, and 1.45 ± 0.5 (p < 0.01). The percentage of decline in various lipids at 4, 12, and 24 weeks was: total cholesterol 11.8%, 18.8%, and 25.2%; LDL cholesterol 17.0%, 28.8%, and 38.0%; triglyceride 6.8%, 12.8%, and 21.0%; lp(a) 17.5%, 26.9%, and 44.5% respectively (p < 0.01). HDL cholesterol and apoA1/apoB increased by 7.2%, 13.1%, and 18.2%; and 7.9%, 21.9%, and 51.6% respectively (p < 0.01). Target LDL levels (<100 mg/dL in subjects with manifest coronary heart disease or diabetes; <130 mg/dL in subjects with >2 risk factors) were achieved in 92 (80.7%) patients. No significant changes were observed in systolic or diastolic blood pressure, blood creatinine, transaminases, or creatine kinase. A fixed dose combination of lovastatin and niacinER significantly improved cholesterol lipoprotein lipids as well as lp(a) and apoA1/apoB levels in Asian Indian dyslipidemic patients. Satisfactory safety and tolerability profile in this population was also demonstrated

Pediatric carcinoma of rectum - Varanasi experience

Background : Primary gastrointestinal system malignancies constitute approximately 2% of pediatric neoplasm and of these; colorectal carcinoma is the second most common malignancy. This is one of the rarer diseases in children. Aim : We reviewed our records to study the clinical features, outcome and the follow-up of this condition with evaluation of the prognostic factors. Settings and Design: Tertiary care Pediatric Surgery centre. Retrospective study. Materials and Methods : The data of all patients with diagnosis of colorectal carcinoma from January 1986 to January 2006 were reviewed. The confirmation of the diagnosis was by biopsy from the lesion. The age, sex, family history, clinical features, response to the treatment and follow-up were studied. Results : There were four male patients. All had bleeding per rectum as the presenting complaint. Three patients had advanced disease at presentation. All the patients had signet cell adenocarcinoma. The two patients expired and one was lost to follow-up. One patient is alive after one year of follow up and is receiving treatment. Conclusion : Colorectal cancer in children though rare can be a reality, hence any children presenting with pain in abdomen along with doubtful history of constipation and rectal bleeding should be examined carefully with special emphasis on digital rectal examination

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

Pediatric carcinoma of rectum - Varanasi experience

Background : Primary gastrointestinal system malignancies constitute approximately 2% of pediatric neoplasm and of these; colorectal carcinoma is the second most common malignancy. This is one of the rarer diseases in children. Aim : We reviewed our records to study the clinical features, outcome and the follow-up of this condition with evaluation of the prognostic factors. Settings and Design: Tertiary care Pediatric Surgery centre. Retrospective study. Materials and Methods : The data of all patients with diagnosis of colorectal carcinoma from January 1986 to January 2006 were reviewed. The confirmation of the diagnosis was by biopsy from the lesion. The age, sex, family history, clinical features, response to the treatment and follow-up were studied. Results : There were four male patients. All had bleeding per rectum as the presenting complaint. Three patients had advanced disease at presentation. All the patients had signet cell adenocarcinoma. The two patients expired and one was lost to follow-up. One patient is alive after one year of follow up and is receiving treatment. Conclusion : Colorectal cancer in children though rare can be a reality, hence any children presenting with pain in abdomen along with doubtful history of constipation and rectal bleeding should be examined carefully with special emphasis on digital rectal examination

The prognostic value of dobutamine stress echocardiography amongst British Indian Asian and Afro-Caribbean patients: a comparison with European white patients

Background The incidence of cardiovascular disease is considerably disparate among different racial and ethnic populations. While dobutamine stress echocardiography (DSE) has been shown to be useful in Caucasian patients, its role among ethnic minority groups remains unclear. This study aimed to investigate the prognostic importance of DSE in three ethnic groups in the UK. Methods DSE was performed on 6231 consecutive patients. After exclusions, 5329 patients formed the study (2676 [50.2 %] Indian Asian, 2219 [41.6 %] European white and 434 [8.1 %] Afro-Caribbean). Study outcome measures were non-fatal cardiac events (NFCE) and all-cause mortality. Results There were 849 (15.9 %) NFCE and 1365 (25.6 %) deaths over a median follow-up period of 4.6 years. In total 1174 (22 %) patients had inducible myocardial ischaemia during DSE, 859 (16.1 %) had fixed wall motion abnormalities and 3645 (68.4 %) patients had a normal study. Ethnicity did not predict events. Among the three ethnic groups, ischaemia on DSE was associated with 2 to 2.5 times the risk of non-fatal cardiac events and 1.2 to 1.4 times the risk of all-cause mortality. Peak wall motion score index was the strongest independent predictor of non-fatal cardiac events and all-cause mortality in all groups. The C statistic for the prediction of NFCE and all-cause mortality were significantly higher when DSE parameters were added to the standard risk factors for all ethnic groups. Conclusions DSE is a strong predictor of NFCE and all-cause mortality and provides predictive information beyond that provided by standard risk factors in three major racial and ethnic groups. No major differences among racial and ethnic groups in the predictive value of DSE was detected

Genetic enhancement of Trichoderma asperellum biocontrol potentials and carbendazim tolerance for chickpea dry root rot disease management.

Advances in biocontrol potentials and fungicide resistance are highly desirable for Trichoderma. Thus, it is profitable to use mutagenic agents to develop superior strains with enhanced biocontrol properties and fungicide tolerance in Trichoderma. This study investigates the N-methyl-n-nitro-N-nitrosoguanidine (NTG) (100 mg/L) induced mutants of Trichoderma asperellum. Six NTG (3 each from 1st & 2nd round) induced mutants were developed and evaluated their biocontrol activities and carbendazim tolerance. Among the mutant N2-3, N2-1, N1 and N2-2 gave the best antagonistic and volatile metabolite activities on inhibition of chickpea F. oxysporum f. sp. ciceri, B. cinerea and R. bataticola mycelium under in vitro condition. Mutant N2-2 (5626.40 μg/ml) showed the highest EC50 value against carbendazim followed by N2-3 (206.36 μg/ml) and N2-1 (16.41 μg/ml); and succeeded to sporulate even at 2000 μg/ml of carbendazim. The biocontrol activity of N2-2 and N2 with half-dose of carbendazim was evaluated on chickpea dry root rot under controlled environment. Disease reduction and progress of the dry root rot was extremely low in T7 (N2-2 + with half-dose of carbendazim) treatment. Further, carbendazim resistant mutants demonstrated mutation in tub2 gene of β-tubulin family which was suggested through the 37 and 183 residue changes in the superimposed protein structures encoded by tub2 gene in N2 and N2-2 with WT respectively. This study conclusively implies that the enhanced carbendazim tolerance in N2-2 mutant did not affect the mycoparasitism and plant growth activity of Trichoderma. These mutants were as good as the wild-type with respect to all inherent attributes

An effective theory for jet propagation in dense QCD matter: jet broadening and medium-induced bremsstrahlung

Two effects, jet broadening and gluon bremsstrahlung induced by the propagation of a highly energetic quark in dense QCD matter, are reconsidered from effective theory point of view. We modify the standard Soft Collinear Effective Theory (SCET) Lagrangian to include Glauber modes, which are needed to implement the interactions between the medium and the collinear fields. We derive the Feynman rules for this Lagrangian and show that it is invariant under soft and collinear gauge transformations. We find that the newly constructed theory SCET$_{\rm G}$ recovers exactly the general result for the transverse momentum broadening of jets. In the limit where the radiated gluons are significantly less energetic than the parent quark, we obtain a jet energy-loss kernel identical to the one discussed in the reaction operator approach to parton propagation in matter. In the framework of SCET$_{\rm G}$ we present results for the fully-differential bremsstrahlung spectrum for both the incoherent and the Landau-Pomeranchunk-Migdal suppressed regimes beyond the soft-gluon approximation. Gauge invariance of the physics results is demonstrated explicitly by performing the calculations in both the light-cone and covariant $R_{\xi}$ gauges. We also show how the process-dependent medium-induced radiative corrections factorize from the jet production cross section on the example of the quark jets considered here.Comment: 52 pages, 15 pdf figures, as published in JHE

The role of mothers-in-law in antenatal care decision-making in Nepal: a qualitative study

Background Antenatal care (ANC) has been recognised as a way to improve health outcomes for pregnant women and their babies. However, only 29% of pregnant women receive the recommended four antenatal visits in Nepal but reasons for such low utilisation are poorly understood. As in many countries of South Asia, mothers-in-law play a crucial role in the decisions around accessing health care facilities and providers. This paper aims to explore the mother-in-law’s role in (a) her daughter-in-law’s ANC uptake; and (b) the decision-making process about using ANC services in Nepal. Methods In-depth interviews were conducted with 30 purposively selected antenatal or postnatal mothers (half users, half non-users of ANC), 10 husbands and 10 mothers-in-law in two different (urban and rural) communities. Results Our findings suggest that mothers-in-law sometime have a positive influence, for example when encouraging women to seek ANC, but more often it is negative. Like many rural women of their generation, all mothers-in-law in this study were illiterate and most had not used ANC themselves. The main factors leading mothers-in-law not to support/ encourage ANC check ups were expectations regarding pregnant women fulfilling their household duties, perceptions that ANC was not beneficial based largely on their own past experiences, the scarcity of resources under their control and power relations between mothers-in-law and daughters-in-law. Individual knowledge and social class of the mothers-in-law of users and non-users differed significantly, which is likely to have had an effect on their perceptions of the benefits of ANC. Conclusion Mothers-in-law have a strong influence on the uptake of ANC in Nepal. Understanding their role is important if we are to design and target effective community-based health promotion interventions. Health promotion and educational interventions to improve the use of ANC should target women, husbands and family members, particularly mothers-in-law where they control access to family resources

Fabrication and Properties of Ag-nanoparticles Embedded Amorphous Carbon Nanowire/CNT Heterostructures

Carbon nanotubes were subjected to doping with an energetic Ag ion beam, and the carbon nanotubes on the top of the array were transformed into amorphous carbon nanowires with embedded Ag-nanoparticles. The field emission characteristics of these nanowires were investigated. The minimum turn-on and threshold fields were 0.68 and 1.09 V/μm, respectively, which were lower than those of the as-grown carbon nanotubes. This was probably because Ag-nanoparticles embedded in the carbon nanowires reduced the effective work function from 4.59 to 4.23 eV. Large doping amounts produced serious structural damage at the top of the nanowires and impaired the field emission characteristics