Study of interaction of nifedipine with haloperidol on conditioned avoidance response and catalepsy in rats

Background: To study the interaction of calcium channel blocker (Nifedipine) with Antipsychotic drug (Haloperidol) on Conditioned avoidance Response and catalepsy in Rats.Methods: Every group consisted of 10 healthy albino rats of either sex. Different groups received Nifedipine (5, 10 & 20 mg/kg, i.p.), Haloperidol (ED50 -0.2mg/kg for CAR & 0.4mg/kg for catalepsy) alone and combined doses of both drugs. The Antipsychotic effect of drugs was measured by Conditioned avoidance response (CAR) using Cook’s Pole climbing apparatus and Adverse drug effect (Extra pyramidal syndrome) was measured by Catalepsy.Results: 5 mg/kg i.p. of Nifedipine inhibited CAR in 50 % of Rats (compared to control, p<0.001). 10mg/kg i.p. of Nifedipine inhibited CAR in 60% of Rats (p<0.001) & 20 mg/kg i.p. inhibited CAR in 70% of Rats (p<0.001). When Nifedipine (5 mg/kg i.p) was combined with Haloperidol ED50-0.2mg/kg  the CAR was inhibited in 70% of the rats (p<0.01) and after combining Nifedipine (10mg/kg) with Haloperidol ED50-0.2mg/kg the CAR was inhibited in 80% Rats (p<0.001). Nifedipine at the dose of 5 mg/kg and 10 mg/kg (i.p.) did not induce catalepsy in the rats at any testing time interval.  At 20 mg/kg i.p., it produced catalepsy in 2 rats at half hour and in 4 rats at 1 hour and 2 hour testing interval each (p<0.01). In the dose of 5, 10 and 20 mg/kg, pretreatment with Nifedipine significantly increased Haloperidol induced cataleptic scores at all testing intervals (p<0.05).Conclusions: Nifedipine blocked CAR. Its higher doses induced catalepsy and it is synergistic with haloperidol in blockade of CAR and catalepsy

Red cell glucose-6-phosphate dehydrogenase deficiency and haemoglobin variants among ten endogamous groups of Maharashtra and West Bengal

Over 900 individuals from ten endogamous groups in the Indian states of Maharashtra and West Bengal were studied for G-6-PD deficiency and haemoglobin variants. The incidence of G-6-PD varied from nil to 17.3%, while that of Hb-S varied from nil to 22.3%. In general, the tribal populations of Maharashtra are characterized by the presence of a high incidence of both Hb-S and G-6-PD deficiency. The caste Hindus showed an absence of Hb-S and rather low G-6-PD deficiency. Immigrant Parsis possessed the highest incidence of G-6-PD deficiency (17.3%)

Vulnerability analysis of satellite-based synchronized smart grids monitoring systems

The large-scale deployment of wide-area monitoring systems could play a strategic role in supporting the evolution of traditional power systems toward smarter and self-healing grids. The correct operation of these synchronized monitoring systems requires a common and accurate timing reference usually provided by a satellite-based global positioning system. Although these satellites signals provide timing accuracy that easily exceeds the needs of the power industry, they are extremely vulnerable to radio frequency interference. Consequently, a comprehensive analysis aimed at identifying their potential vulnerabilities is of paramount importance for correct and safe wide-area monitoring system operation. Armed with such a vision, this article presents and discusses the results of an experimental analysis aimed at characterizing the vulnerability of global positioning system based wide-area monitoring systems to external interferences. The article outlines the potential strategies that could be adopted to protect global positioning system receivers from external cyber-attacks and proposes decentralized defense strategies based on self-organizing sensor networks aimed at assuring correct time synchronization in the presence of external attacks

Percutaneous tricuspid valvotomy for pacemaker lead-induced tricuspid stenosis

AbstractPermanent pacemaker lead-induced tricuspid regurgitation is extremely uncommon. We report a patient with severe tricuspid stenosis detected 10 years after permanent single chamber pacemaker implantation in surgically corrected congenital heart disease. The loop at the level of the tricuspid valve may have caused endothelial injury and eventually led to stenosis. Percutaneous balloon valvotomy for such stenosis has not been reported from India

Sensitivity analysis methods for uncertainty budgeting in system design

Quantification and management of uncertainty are critical in the design of engineering systems, especially in the early stages of conceptual design. This paper presents an approach to defining budgets on the acceptable levels of uncertainty in design quantities of interest, such as the allowable risk in not meeting a critical design constraint and the allowable deviation in a system performance metric. A sensitivity-based method analyzes the effects of design decisions on satisfying those budgets, and a multi-objective optimization formulation permits the designer to explore the tradespace of uncertainty reduction activities while also accounting for a cost budget. For models that are computationally costly to evaluate, a surrogate modeling approach based on high dimensional model representation (HDMR) achieves efficient computation of the sensitivities. An example problem in aircraft conceptual design illustrates the approach.United States. National Aeronautics and Space Administration. Leading Edge Aeronautics Research Program (Grant NNX14AC73A)United States. Department of Energy. Applied Mathematics Program (Award DE-FG02-08ER2585)United States. Department of Energy. Applied Mathematics Program (Award DE-SC0009297

Case study in six sigma methadology : manufacturing quality improvement and guidence for managers

This article discusses the successful implementation of Six Sigma methodology in a high precision and critical process in the manufacture of automotive products. The Six Sigma define–measure–analyse–improve–control approach resulted in a reduction of tolerance-related problems and improved the first pass yield from 85% to 99.4%. Data were collected on all possible causes and regression analysis, hypothesis testing, Taguchi methods, classification and regression tree, etc. were used to analyse the data and draw conclusions. Implementation of Six Sigma methodology had a significant financial impact on the profitability of the company. An approximate saving of US$70,000 per annum was reported, which is in addition to the customer-facing benefits of improved quality on returns and sales. The project also had the benefit of allowing the company to learn useful messages that will guide future Six Sigma activities

The Temporal and Spatial Connectivity of the Gambles Mill Corridor, Richmond, VA

The City of Richmond and the Virginia Department of Transportation proposed to rehabilitate the Gambles Mill Trail connecting the University of Richmond (UR) to the intersection of Huguenot and River Road. Planners envision this trail as a sustainable model for the reduction of nutrient and sediment flow and as a vital path in a city-wide network of bike and pedestrian trails. Meanwhile, UR also proposes to rehabilitate the corridor in their new Master Plan. Nevertheless, until now, no substantive studies exist on the trail or the corridor linking the trail to the south side of the James River through the hazardous River-Huguenot Road intersection and the Huguenot Bridge currently under construction. The University of Richmond’s Geography 221 Course, Mapping Sustainability: Cartography and Geographic Information in an Environmental Context, is working with a variety of stakeholders (public, private, and community-based) to map the past, present, and future of the Gambles Mill Corridor and influence local and regional sustainability of transportation, hydrology, and recreation in a floodplain ecosystem. Students produce maps grouped around four scales: local corridor, UR to the River, a city scale sustainable transport network, and a temporal scale tracing previous transportation routes in the area such as the 1930s street car system and the colonial canal system.https://scholarship.richmond.edu/geography-posters/1001/thumbnail.jp

Bi-allelic mutations in MYL1 cause a severe congenital myopathy.

OBJECTIVE: Congenital myopathies are typically characterised by early onset hypotonia, weakness and hallmark features on biopsy. Despite the rapid pace of gene discovery, approximately 50% of patients with a congenital myopathy remain without a genetic diagnosis following screening of known disease genes. METHODS: We performed exome sequencing on two consanguineous probands diagnosed with a congenital myopathy and muscle biopsy showing selective atrophy/hypotrophy or absence of type II myofibres. RESULTS: We identified variants in the gene (MYL1) encoding the skeletal muscle fast-twitch specific myosin essential light chain in both probands. A homozygous essential splice acceptor variant (c.479-2A>G, predicted to result in skipping of exon 5 was identified in Proband 1, and a homozygous missense substitution (c.488T>G, p.(Met163Arg)) was identified in Proband 2. Protein modeling of the p.(Met163Arg) substitution predicted it might impede intermolecular interactions that facilitate binding to the IQ domain of myosin heavy chain, thus likely impacting on the structure and functioning of the myosin motor. MYL1 was markedly reduced in skeletal muscle from both probands, suggesting that the missense substitution likely results in an unstable protein. Knock down of myl1 in zebrafish resulted in abnormal morphology, disrupted muscle structure and impaired touch-evoked escape responses, thus confirming that skeletal muscle fast-twitch specific myosin essential light chain is critical for myofibre development and function. INTERPRETATION: Our data implicate MYL1 as a crucial protein for adequate skeletal muscle function and that MYL1 deficiency is associated with a severe congenital myopathy

Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial

Aim. To compare the efficacy and safety of armodafinil, the R-enantiomer of modafinil, with modafinil in patients of shift work sleep disorder (SWSD). Material and Methods. This was a 12-week, randomized, comparative, double-blind, multicentric, parallel-group study in 211 patients of SWSD, receiving armodafinil (150 mg) or modafinil (200 mg) one hour prior to the night shift. Outcome Measures. Efficacy was assessed by change in stanford sleepiness score (SSS) by at least 2 grades (responder) and global assessment for efficacy. Safety was assessed by incidence of adverse events, change in laboratory parameters, ECG, and global assessment of tolerability. Results. Both modafinil and armodafinil significantly improved sleepiness mean grades as compared to baseline (P < .0001). Responder rates with armodafinil (72.12%) and modafinil (74.29%) were comparable (P = .76). Adverse event incidences were comparable. Conclusion. Armodafinil was found to be safe and effective in the treatment of SWSD in Indian patients. The study did not demonstrate any difference in efficacy and safety of armodafinil 150 mg and modafinil 200 mg

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions