COMPARISON OF EFFICACY AND ADVERSE DRUG REACTIONS OF MONOTHERAPY VERSUS COMBINATION THERAPY OF ANTIHYPERTENSIVES AMONG DIABETIC HYPERTENSIVE PATIENTS IN A TERTIARY CARE HOSPITAL

Objective: To compare the efficacy and adverse drug reactions of monotherapy and combination therapy of antihypertensive drugs in diabetic hypertensive patients.Methods: A prospective observational study of 18 months duration was conducted in the Department of Medicine of a tertiary care hospital in South India. A total of 200 patients were included in the study. Using a standard proforma, the details of patients such as demographic data and antihypertensive medications were collected and analyzed for efficacy and safety.Results: Of 200 patients studied, 50% received monotherapy whereas the remaining 50% received combination therapy. There was male preponderance (54%) in the study population, with the mean age being 60.07±11.32 years. In monotherapy group, most commonly prescribed drug was amlodipine (38%), whereas in combination group, angiotensin receptor blocker (ARB) or calcium channel blocker (CCB) + beta blocker (18%) was commonly prescribed among 2-drug group and ARB+ thiazide+ CCB (25.6%) among 3-drug group. Monotherapy and combination therapy were analyzed to be equally efficacious in reducing systolic blood pressure and diastolic blood pressure. Based on the adverse effect profile, monotherapy comparatively produced more adverse effects than combination group. Amlodipine-induced pedal edema (56.7%) was the most common adverse effect observed, and it was predominantly managed by changing it to be a better tolerable CCB, namely cilnidipine.Conclusion: The combination therapy may be a better treatment option in selected patient population.Keywords: Systolic blood pressure, Diastolic blood pressure, Amlodipine, Cilnidipine, Pedal edema

How to realize a robust practical Majorana chain in a quantum dot-superconductor linear array

Semiconducting nanowires in proximity to superconductors are promising experimental systems for Majorana fermions, which may ultimately be used as building blocks for topological quantum computers. A serious challenge in the experimental realization of the Majorana fermions is the supression of topological superconductivity by disorder. We show that Majorana fermions protected by a robust topological gap can occur at the ends of a chain of quantum dots connected by s-wave superconductors. In the appropriate parameter regime, we establish that the quantum dot/superconductor system is equivalent to a 1D Kitaev chain, which can be tuned to be in a robust topological phase with Majorana end modes even in the case where the quantum dots and superconductors are both strongly disordered. Such a spin-orbit coupled quantum dot - s-wave superconductor array provides an ideal experimental platform for the observation of non-Abelian Majorana modes.Comment: 8 pages; 3 figures; version 2: Supplementary material updated to include more general proof for localized Majorana fermion

Phytochemical screening, antioxidant and antimicrobial activities of Prunella vulgaris for oral thrush

Plant imitative products have been used for medicinal purposes for centuries. In traditional Indian medicine or Ayurveda, Prunella Vulgaris and many other herbs have been used as medicine. Traditional uses of plants have led to investigating their bioactive compounds, which have resulted in the detection of a significant number of therapeutic properties. The aim of present investigation was carried out to evaluate the phytochemical, antioxidant and antimicrobial activity of chloroform and hydroalcoholic leaves extracts of Prunella Vulgaris against microbial strains causing oral infections. Both chloroform and hydroalcoholic extracts revealed the presence of carbohydrate, triterpenoids/ steroids, flavonoids, tannin, phenolic compound and saponins were absent in only the chloroform extract. The bioactivities of the leaf extracts were qualified to their phytochemical constituents. Quantitative analysis of phenolic and flavonoids was carried out by Folins Ciocalteau reagent method and aluminium chloride method respectively. The In vitro antioxidant activity of chloroform and hydroalcoholic leaves extracts of Prunella Vulgaris was assessed against 2,2-diphenyl-1-picryl- hydrazyl (DPPH) radical scavenging activity, reducing power assay using standard protocols. The antimicrobial activity of chloroform and hydroalcoholic extracts of medicinal plants was evaluated using well diffusion method against Escherichia coli and Candida albicans. The TPC in chloroform extract was higher than that of the hydroalcoholic extract with concentration being 0.443 mg/g equivalent to gallic acid. The TFC in hydroalcohoilc extract was higher than that of the chloroform extract with concentration being 0.358 mg/g equivalent to rutin.  The present study recognized leaves extract of Prunella vulgaris as a promising antioxidant and antimicrobial agent. However, further investigations are needed to understand the mechanistic basis of this effect of the extract and its chemical constituents thereof. Keywords: Prunella vulgaris, Phytochemical, Antioxidant, Antimicrobial activity, Folins Ciocalteau reagent, Quantitative analysi

Non-Abelian statistics and topological quantum information processing in 1D wire networks

Topological quantum computation provides an elegant way around decoherence, as one encodes quantum information in a non-local fashion that the environment finds difficult to corrupt. Here we establish that one of the key operations---braiding of non-Abelian anyons---can be implemented in one-dimensional semiconductor wire networks. Previous work [Lutchyn et al., arXiv:1002.4033 and Oreg et al., arXiv:1003.1145] provided a recipe for driving semiconducting wires into a topological phase supporting long-sought particles known as Majorana fermions that can store topologically protected quantum information. Majorana fermions in this setting can be transported, created, and fused by applying locally tunable gates to the wire. More importantly, we show that networks of such wires allow braiding of Majorana fermions and that they exhibit non-Abelian statistics like vortices in a p+ip superconductor. We propose experimental setups that enable the Majorana fusion rules to be probed, along with networks that allow for efficient exchange of arbitrary numbers of Majorana fermions. This work paves a new path forward in topological quantum computation that benefits from physical transparency and experimental realism.Comment: 6 pages + 17 pages of Supp. Mat.; 10 figures. Supp. Mat. has doubled in size to establish results more rigorously; many other improvements as wel

Dermatological remedies in the traditional pharmacopoeia of Vulture-Alto Bradano, inland southern Italy

Dermatological remedies make up at least one-third of the traditional pharmacopoeia in southern Italy. The identification of folk remedies for the skin is important both for the preservation of traditional medical knowledge and in the search for novel antimicrobial agents in the treatment of skin and soft tissue infection (SSTI). Our goal is to document traditional remedies from botanical, animal, mineral and industrial sources for the topical treatment of skin ailments. In addition to SSTI remedies for humans, we also discuss certain ethnoveterinary applications. Field research was conducted in ten communities in the Vulture-Alto Bradano area of the Basilicata province, southern Italy. We randomly sampled 112 interviewees, stratified by age and gender. After obtaining prior informed consent, we collected data through semi-structured interviews, participant-observation, and small focus groups techniques. Voucher specimens of all cited botanic species were deposited at FTG and HLUC herbaria located in the US and Italy. We report the preparation and topical application of 116 remedies derived from 38 plant species. Remedies are used to treat laceration, burn wound, wart, inflammation, rash, dental abscess, furuncle, dermatitis, and other conditions. The pharmacopoeia also includes 49 animal remedies derived from sources such as pigs, slugs, and humans. Ethnoveterinary medicine, which incorporates both animal and plant derived remedies, is addressed. We also examine the recent decline in knowledge regarding the dermatological pharmacopoeia. The traditional dermatological pharmacopoeia of Vulture-Alto Bradano is based on a dynamic folk medical construct of natural and spiritual illness and healing. Remedies are used to treat more than 45 skin and soft tissue conditions of both humans and animals. Of the total 165 remedies reported, 110 have never before been published in the mainland southern Italian ethnomedical literature

HER1-Targeted 86Y-Panitumumab Possesses Superior Targeting Characteristics than 86Y-Cetuximab for PET Imaging of Human Malignant Mesothelioma Tumors Xenografts

Malignant mesothelioma (MM), a rare form of cancer is often associated with previous exposure to fibrous minerals, such as asbestos. Asbestos exposure increases HER1-activity and expression in pre-clinical models. Additionally, HER1 over-expression is observed in the majority of MM cases. In this study, the utility of HER1-targeted chimeric IgG(1), cetuximab, and a human IgG(2), panitumumab, radiolabeled with (86)Y, were evaluated for PET imaging to detect MM non-invasively in vivo, and to select an antibody candidate for radioimmunotherapy (RIT).Radioimmunoconjugates (RICs) of cetuximab and panitumumab were prepared by conjugation with CHX-A''-DTPA followed by radiolabeling with (86)Y. The HER1 expression of NCI-H226, NCI-H2052, NCI-H2452 and MSTO-211H human mesothelioma cells was characterized by flow cytometry. In vivo biodistribution, pharmacokinetic analysis, and PET imaging were performed in tumor bearing athymic mice.In vivo studies demonstrated high HER1 tumor uptake of both RICs. Significant reduction in tumor uptake was observed in mice co-injected with excess mAb (0.1 mg), demonstrating that uptake in the tumor was receptor specific. Significant differences were observed in the in vivo characteristics of the RICs. The blood clearance T(½)α of (86)Y-cetuximab (0.9-1.1 h) was faster than (86)Y-panitumumab (2.6-3.1 h). Also, the tumor area under the curve (AUC) to liver AUC ratios of (86)Y-panitumumab were 1.5 to 2.5 times greater than (86)Y-cetuximab as observed by the differences in PET tumor to background ratios, which could be critical when imaging orthotopic tumors and concerns regarding radiation doses to normal organs such as the liver.This study demonstrates the more favorable HER1-targeting characteristics of (86)Y-panitumumab than (86)Y-cetuximab for non-invasive assessment of the HER1 status of MM by PET imaging. Due to lower liver uptake, panitumumab based immunoconjugates may fare better in therapy than corresponding cetuximab based immunoconjugates

Experimental Infection of Mice with Avian Paramyxovirus Serotypes 1 to 9

The nine serotypes of avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds worldwide. APMV-1, also called Newcastle disease virus, was shown to be attenuated in non-avian species and is being developed as a potential vector for human vaccines. In the present study, we extended this evaluation to the other eight serotypes by evaluating infection in BALB/c mice. Mice were inoculated intranasally with a prototype strain of each of the nine serotypes and monitored for clinical disease, gross pathology, histopathology, virus replication and viral antigen distribution, and seroconversion. On the basis of multiple criteria, each of the APMV serotypes except serotype 5 was found to replicate in mice. Five of the serotypes produced clinical disease and significant weight loss in the following order of severity: 1, 2>6, 9>7. However, disease was short-lived. The other serotypes produced no evident clinical disease. Replication of all of the APMVs except APMV-5 in the nasal turbinates and lungs was confirmed by the recovery of infectious virus and by substantial expression of viral antigen in the epithelial lining detected by immunohistochemistry. Trace levels of infectious APMV-4 and -9 were detected in the brain of some animals; otherwise, no virus was detected in the brain, small intestine, kidney, or spleen. Histologically, infection with the APMVs resulted in lung lesions consistent with broncho-interstitial pneumonia of varying severity that were completely resolved at 14 days post infection. All of the mice infected with the APMVs except APMV-5 produced serotype-specific HI serum antibodies, confirming a lack of replication of APMV-5. Taken together, these results demonstrate that all APMV serotypes except APMV-5 are capable of replicating in mice with minimal disease and pathology

Three dimensional first-pass myocardial perfusion imaging at 3T: feasibility study

<p>Abstract</p> <p>Background</p> <p>In patients with ischemic heart disease, accurate assessment of the extent of myocardial perfusion deficit may be important in predicting prognosis of clinical cardiac outcomes. The aim of this study was to compare the ability of three dimensional (3D) and of two dimensional (2D) multi-slice myocardial perfusion imaging (MPI) using cardiovascular magnetic resonance (CMR) in determining the size of defects, and to demonstrate the feasibility of 3D MPI in healthy volunteers at 3 Tesla.</p> <p>Methods</p> <p>A heart phantom was used to compare the accuracy of 3D and 2D multi-slice MPI in estimating the volume fraction of seven rubber insets which simulated transmural myocardial perfusion defects. Three sets of cross-sectional planes were acquired for 2D multi-slice imaging, where each set was shifted along the partition encoding direction by ± 10 mm. 3D first-pass contrast-enhanced (0.1 mmol/kg Gd-DTPA) MPI was performed in three volunteers with sensitivity encoding for six-fold acceleration. The upslope of the myocardial time-intensity-curve and peak SNR/CNR values were calculated.</p> <p>Results</p> <p>Mean/standard deviation of errors in estimating the volume fraction across the seven defects were -0.44/1.49%, 2.23/2.97%, and 2.59/3.18% in 3D, 2D 4-slice, and 2D 3-slice imaging, respectively. 3D MPI performed in healthy volunteers produced excellent quality images with whole left ventricular (LV) coverage. Peak SNR/CNR was 57.6 ± 22.0/37.5 ± 19.7 over all segments in the first eight slices.</p> <p>Conclusion</p> <p>3D performed better than 2D multi-slice MPI in estimating the size of perfusion defects in phantoms. Highly accelerated 3D MPI at 3T was feasible in volunteers, allowing whole LV coverage with excellent image quality and high SNR/CNR.</p