Design and development of a smart blind walking stick using machine learning.

Visually impaired people are often subjugated under extreme circumstances even in their day-to-day life. The daily requirements of a common man appear to be an impediment in their routine life. Simplest of tasks like walking, eating, bathing, conversing and even eating is of utmost difficulty to them.

Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males.

Lesinurad is a selective uric acid reabsorption inhibitor under investigation for the treatment of gout. Single and multiple ascending dose studies were conducted to evaluate pharmacokinetics, pharmacodynamics, and safety of lesinurad in healthy males. Lesinurad was administered as an oral solution between 5 mg and 600 mg (single ascending dose; N=34) and as an oral solution or immediate-release capsules once daily (qday) between 100 mg and 400 mg for 10 days under fasted or fed condition (multiple ascending dose; N=32).

Pharmacodynamic, pharmacokinetic and tolerability evaluation of concomitant administration of lesinurad and febuxostat in gout patients with hyperuricaemia.

Objective: The aim of this study was to evaluate the pharmacodynamics (PDs), pharmacokinetics (PKs) and safety of lesinurad (selective uric acid reabsorption inhibitor) in combination with febuxostat (xanthine oxidase inhibitor) in patients with gout.

Methods: This study was a phase IB, multicentre, open-label, multiple-dose study of gout patients with serum uric acid (sUA) >8 mg/dl following washout of urate-lowering therapy with colchicine flare prophylaxis. Febuxostat 40 or 80 mg/day was administered on days 1-21, lesinurad 400 mg/day was added on days 8-14 and then lesinurad was increased to 600 mg/day on days 15-21.

Phase 2a randomized controlled trial of short-term activity, safety, and pharmacokinetics of a novel nonnucleoside reverse transcriptase inhibitor, RDEA806, in HIV-1-positive, antiretroviral-naive subjects.

RDEA806 is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with potent in vitro activity against wild-type and NNRTI-resistant HIV-1. A phase 2a randomized, double-blind, placebo-controlled, dose-escalating study evaluated the short-term antiviral activity, safety, and pharmacokinetics (PKs) of RDEA806 monotherapy in antiretroviral-naïve, HIV-1-infected subjects. The subjects were randomized to four cohorts comprising four dosage regimens and two formulations of RDEA806 or placebo in a 3:1 ratio within each cohort.

Local convection enhanced delivery of IL4-Pseudomonas exotoxin (NBI-3001) for treatment of patients with recurrent malignant glioma.

Purpose: This was an open-label, dose-escalation trial of intratumoral administration of IL-4 Pseudomonas Exotoxin (NBI-3001) in patients with recurrent malignant glioma.

Patients And Methods: A total of 31 patients with histologically verified supratentorial grade 3 and 4 astrocytoma were studied. Of these, twenty-five patients were diagnosed with glioblastoma multiforme (GBM) while six were diagnosed with anaplastic astrocytoma (AA).

Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma.

Purpose: This was an open-label, dose-escalation trial of intratumoral administration of IL-4 Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma.

Patients And Methods: A total of 31 patients with histologically verified supratentorial grades 3 and 4 astrocytoma were studied. Of these, 25 patients were diagnosed with glioblastoma multiforme (GBM) while six were diagnosed with anaplastic astrocytoma.

Natural sex selection for safe motherhood and as a solution for population control.

For Safe Motherhood wanted children should be of desired sex. As Y sperm have a shorter life span and migrate faster, if coitus occurs before ovulation, sperm must wait in the tube for the ovum to arrive. By the time the ovum arrives, Y sperm have died and X sperm fertilize the ovum, resulting in a baby girl.

Idiopathic hemothorax.

Development of spontaneous hemothorax without predisposing conditions is extremely rare. We report a young man with a history of a seizure disorder who presented to the emergency department with spontaneous hemothorax. Exploratory thoracotomy evacuated 2,000 ml of old blood.

Aortic ornithine decarboxylase activity in deoxycorticosterone/salt hypertensive rats.

Previous studies from our own and other laboratories have shown that hypertension induces changes in the growth of arterial smooth muscle cells (SMC). The purpose of this study was to examine the role of ornithine decarboxylase (OrnDCase) in this process. OrnDCase, the rate limiting enzyme in polyamine biosynthesis, increases in activity early in the cell cycle, and has been used as a marker of cell growth or proliferation.

Identification of monoclonal antibody 4A-binding site on the transducin alpha subunit. Immunoblotting of submaxillary Arg-C protease fragments of transducin.

Monoclonal antibody 4A (mAb 4A) against the T alpha subunit of transducin has been widely used to study the structure and function of signal transducing GTP-binding proteins involved in the regulation of visual excitation, hormonal regulation of adenylyl cyclase and ionic channels. Results of mapping the epitope-binding site of mAb 4A on T alpha have been controversial. Hamm and co-workers (Deretic, D.

Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine.

Comparative phase I clinical trials were carried out in 5 centres with three formulations of beta-hCG-based vaccines inducing antibodies against human chorionic gonadotropin. The objectives of these trials were to determine their relative immunogenicity, duration, reversibility and safety. A total of 116 tubal ligated women volunteers were enrolled in the study and 101 subjects were followed-up for one year or more until the antibody titres declined to near zero levels.

Analysis of menstrual records of women immunized with anti-hCG vaccines inducing antibodies partially cross-reactive with hLH.

Menstrual data of 13 control subjects and 88 subjects immunized with three beta-hCG-based vaccine formulations were analysed. Immunization did not change the menstrual regularity; bleeding days were normal (3-7 days) and 89% of the menstrual cycles were within the normal range of 22-35 days. Irregular (short or long) cycles were observed in both immunized and control groups.

Chemical modification of bovine transducin: probing the GTP-binding site with affinity analogues.

The structure of the GTP-binding site of transducin, a signal-transducing G-protein involved in the visual excitation process, was studied by affinity labeling. Radioactive GTP analogues with reactive groups attached to different moieties of the GTP molecule were obtained and include 8-azido-GTP, P3-(4-azidoanilino)-P1-5'-GTP (AA-GTP), 5'-[p-(fluorosulfonyl)benzoyl]guanosine (FSBG), 3'-O-(3-[N-(4-azido-2-nitrophenyl)amino]propionyl)-GTP (ANPAP-GTP), the 2',3'-dialdehyde derivative of GTP (oGTP), and a bifunctional cross-linking analogue, 8-azido-P3-(4-azidoanilino)-P1-5'-GTP (8-azido-AA-GTP). With the exception of FSBG, all of the analogues were found to bind to transducin specifically and serve as a cofactor to activate the retinal cGMP cascade or act as a competitive inhibitor for the GTPase activity of transducin.

An antiprogestin steroid and PGE2 for an early pregnancy termination.

A non-surgical, preferably self-administered, procedure would be an attractive alternative to vacuum for the termination of early pregnancy. 20 patients with 49 days of amenorrhea and confirmation of pregnancy by ultrasound, urine testing and human chorionic gonadotrophin (beta-hCG) analysis, were administered RU 486, 25 mg twice daily for 4 days, (Group I). A further 20 patients received the same dose of RU 486 for 3 days (Group II).

Fluorescent labeling of signal-transducing G-proteins. Pertussis toxin-catalyzed etheno-ADP ribosylation of transducin.

Nicotinamide 1,N6-ethenoadenine dinucleotide (etheno-NAD, epsilon-NAD), a fluorescent analogue of NAD, was able to serve as a substrate for the bacterial toxin-catalyzed epsilon-ADP ribosylation of signal-transducing G-proteins. Pertussis toxin and transducin were used as a model system to characterize this reaction. Similar to ADP ribosylation using NAD as substrate, the epsilon-ADP ribosylation occurs at the carboxyl-terminal 5-kDa tryptic fragment of the T alpha subunit of transducin with the same labeling stoichiometry; however, the rate of labeling is slightly slower.

Phase III-clinical trial with Norplant-2 (covered rods). Report of a 24-month study. National Programme of Research in Human Reproduction. Division of Human Resource Development Research Indian Council of Medical Research Ansari Nagar, New Delhi, India.

In a phase III multicentre clinical trial, the subdermal implant NorplantR-2 was studied for its clinical use effectiveness, safety and bleeding pattern. A total of 1466 healthy volunteers, with no contraindication to steroid use, were observed for 29,669 woman-months of use. One method failure was reported at 18 months of NorplantR-2 use.

Chromium(III) beta, gamma-bidentate guanine nucleotide complexes as probes of the GTP-activated cGMP cascade of retinal rod outer segments.

The exchange-inert Cr(III) beta, gamma-bidentate guanine nucleotide complexes Cr(III)GTP and Cr(III)Gpp(NH)p were used to probe the role of transducin in activating the retinal cGMP cascade. The Cr(III) nucleotide complexes were found to have lower binding affinity for transducin as compared to the Mg2+ complexes. However, the rate of hydrolysis of the transducin-bound Cr(III)GTP was similar to that of Mg(II)GTP.

Chemical cross-linking of bovine retinal transducin and cGMP phosphodiesterase.

The bifunctional reagents para-phenyldimaleimide and maleimidobenzoyl-N-hydroxysuccinimide ester were used to chemically cross-link the subunits of the transducin and cGMP phosphodiesterase (PDE) complexes of bovine rod photoreceptor cells. The cross-linked products were identified by Western immunoblotting using antisera against purified subunits of transducin (T alpha and T beta gamma) and PDE. Oligomeric cross-linked products of transducin subunits as large as (T alpha beta gamma)3 were observed in the latent form of transducin with bound GDP.

A structural model for the alpha-subunit of transducin. Implications of its role as a molecular switch in the visual signal transduction mechanism.

Transducin is a GTP-binding protein which mediates the light activation signal from photolyzed rhodopsin to cGMP phosphodiesterase and is pivotal in the visual excitation process. Biochemical studies suggest that the T alpha subunit of transducin is composed of three functional domains, one for rhodopsin/T beta gamma interaction, another for guanine nucleotide binding, and a third for the activation of phosphodiesterase. The integration of the primary sequence of T alpha along with secondary structure, hydropathy and folding topology predictions, and a comparison with homologous proteins have led to the construction of a three-dimensional model of the T alpha subunit.

Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels.

Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either [6-14C]glucose or [1-14C]oleic acid and the incorporation of radioactivity into 14CO2, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.