An approach for automatic identification of fundamental and additional sounds from cardiac sounds recordings.

This paper presents an approach for automatic segmentation of cardiac events from non-invasive sounds recordings, without the need of having an auxiliary signal reference. In addition, methods are proposed to subsequently differentiate cardiac events which correspond to normal cardiac cycles, from those which are due to abnormal activity of the heart. The detection of abnormal sounds is based on a model built with parameters which are obtained following feature extraction from those segments that were previously identified as normal fundamental heart sounds. The proposed algorithm achieved a sensitivity of 91.79% and 89.23% for the identification of normal fundamental, S1 and S2 sounds, and a true positive (TP) rate of 81.48% for abnormal additional sounds. These results were obtained using the PASCAL Classifying Heart Sounds challenge (CHSC) database

Evaluation of Antitumor Activity of Cuscuta Reflexa Roxb (Cuscutaceae) Against Ehrlich Ascites Carcinoma in Swiss Albino Mice

Purpose: The aim of this study was to investigate the antitumor effect of the chloroform and ethanol extract of the whole plant of Cuscuta reflexa Roxb. (Cuscutaceae) in Swiss albino mice against Ehrlich Ascites Carcinoma (EAC) cell line.Methods: The antitumor activity of the chloroform and ethanol extracts of Cuscuta reflexa was evaluated against Ehrlich ascites carcinoma (EAC) tumor in mice at doses of 200 and 400 mg/kg body weight orally, respectively, while acute oral toxicity studies were performed to determine the safety of the extracts. Briefly, the EAC cells were injected (i.p.) into ninty six mice (divided into 6 numerically equal groups), and after a one-day incubation period, the extracts were administered to the mice daily for 16 days. On day 21, six animals in each group were sacrificed for observation of antitumor activity and the remaining animals were observed to determine host the life span. Antitumor effect was determined by evaluating tumor volume, viable and nonviable tumor cell count and hematological parameters of the host. The standard antitumor used was 5-fluorouracil.Results: Administration of the extracts resulted in a significant (p < 0.05) decrease in tumor volume and viable cell count, but increased non-viable cell count and mean survival time, thereby increasing the life span of the tumor-bearing mice. Restoration of hematological parameters - red blood cells (RBC), hemoglobin, white blood cells (WBC) and lymphocyte count - to normal levels in extract-treated mice was also observed.Conclusion: The results suggest that the chloroform and ethanol extracts of C. reflexa exhibit significant antitumor activity in EAC-bearing mice that is comparable to that of the reference standard, 5-fluorouracil.Keywords: Cuscuta reflexa, Ehrlich ascites carcinoma, 5-Fluorouracil, Tumor volume, Viable cell count

Possible mechanisms of hypotension produced 70% alcoholic extract of Terminalia arjuna (L.) in anaesthetized dogs

BACKGROUND: The bark of Terminalia arjuna L. (Combretaceae) is used in Ayurveda since ancient times for the treatment of cardiac disorders. Previous laboratory investigations have demonstrated the use of the bark in cardiovascular complications. The present study was aimed to find the effect of 70% alcoholic extract of Terminalia arjuna on anaesthetized dog blood pressure and probable site of action. METHODS: Six dogs were anaesthetized with intraperitoneal injection of thiopental sodium and the blood pressure of each dog (n = 6) was measured from the left common carotid artery connected to a mercury manometer on kymograph. The femoral vein was cannulated for administration of drug solutions. The extract of T. arjuna (dissolved in propylene glycol) in the dose range of 5 to 15 mg/kg were administered intravenously in a pilot study and the dose (6 mg/kg) which produced appreciable hypotension was selected for further studies. RESULTS: Intravenous administration of T. arjuna produced dose-dependent hypotension in anaesthetized dogs. The hypotension produced by 6 mg/kg dose of the extract was blocked by propranolol but not by atropine or mepyramine maleate. This indicates that muscarinic or histaminergic mechanisms are not likely to be involved in the hypotension produced by the extract. The blockade by propranolol of the hypotension produced by T. arjuna indicates that the extract might contain active compound(s) possessing adrenergic ß(2)-receptor agonist action and/or that act directly on the heart muscle. CONCLUSION: The results indicated the likely involvement of peripheral mechanism for hypotension produced by the 70% alcoholic extract of Terminalia arjuna and lends support for the claims of its traditional usage in cardiovascular disorders

A REVIEW ON AYURVEDA PERSPECTIVE AND THERAPEUTIC CONSIDERATION OF OLIGOZOOSPERMIA

Male infertility is one of the burning problems now a day’s and incidences of this problem increases day by day due to the disturbed pattern of living style. The Oligozoospermia is one of the conditions related to male infertility which associated with low sperm count. Ayurveda the science of Indian medical system described various terms related to male infertility such as; Kshina shukra, Kshina retasa, Alpa retasa and Shukra dosha which resembles conditions associated with oligozoospermia. Ayurveda also described various treatment modalities for the management of oligozoospermia such as use of herbs &amp; formulation, conduction of balanced life style and diet control, etc. This article presented a conclusive review on ayurveda perspective of oligozoospermia and its management.&nbsp; Keywords: Ayurveda, Male Infertility, Oligozoospermia, Sperm, Vajikarana. &nbsp

Publisher Correction: Graphene overcoats for ultra-high storage density magnetic media.

Publisher Correction: Graphene overcoats for ultra-high storage density magnetic media

Molecular Basis of ß-­arrestin Coupling to Formoterol-­Bound ß1-­adrenoceptor

The β1-adrenoceptor (β1AR) is a G-protein-coupled receptor (GPCR) that couples1 to the heterotrimeric G protein Gs. G-protein-mediated signalling is terminated by phosphorylation of the C terminus of the receptor by GPCR kinases (GRKs) and by coupling of β-arrestin 1 (βarr1, also known as arrestin 2), which displaces Gs and induces signalling through the MAP kinase pathway2. The ability of synthetic agonists to induce signalling preferentially through either G proteins or arrestins-known as biased agonism3-is important in drug development, because the therapeutic effect may arise from only one signalling cascade, whereas the other pathway may mediate undesirable side effects4. To understand the molecular basis for arrestin coupling, here we determined the cryo-electron microscopy structure of the β1AR-βarr1 complex in lipid nanodiscs bound to the biased agonist formoterol5, and the crystal structure of formoterol-bound β1AR coupled to the G-protein-mimetic nanobody6 Nb80. βarr1 couples to β1AR in a manner distinct to that7 of Gs coupling to β2AR-the finger loop of βarr1 occupies a narrower cleft on the intracellular surface, and is closer to transmembrane helix H7 of the receptor when compared with the C-terminal α5 helix of Gs. The conformation of the finger loop in βarr1 is different from that adopted by the finger loop of visual arrestin when it couples to rhodopsin8. β1AR coupled to βarr1 shows considerable differences in structure compared with β1AR coupled to Nb80, including an inward movement of extracellular loop 3 and the cytoplasmic ends of H5 and H6. We observe weakened interactions between formoterol and two serine residues in H5 at the orthosteric binding site of β1AR, and find that formoterol has a lower affinity for the β1AR-βarr1 complex than for the β1AR-Gs complex. The structural differences between these complexes of β1AR provide a foundation for the design of small molecules that could bias signalling in the β-adrenoceptors

Genetically encoded intrabody sensors report the interaction and trafficking of β-arrestin 1 upon activation of G protein-coupled receptors

Agonist stimulation of G protein-coupled receptors (GPCRs) typically leads to phosphorylation of GPCRs and binding to multifunctional proteins called β-arrestins (βarrs). The GPCR-βarr interaction critically contributes to GPCR desensitization, endocytosis, and downstream signaling, and GPCR-βarr complex formation can be used as a generic readout of GPCR and βarr activation. Although several methods are currently available to monitor GPCR-βarr interactions, additional sensors to visualize them may expand the toolbox and complement existing methods. We have previously described antibody fragments (FABs) that recognize activated βarr1 upon its interaction with the vasopressin V2 receptor C-terminal phosphopeptide (V2Rpp). Here, we demonstrate that these FABs efficiently report the formation of a GPCR-βarr1 complex for a broad set of chimeric GPCRs harboring the V2R C terminus. We adapted these FABs to an intrabody format by converting them to single-chain variable fragments (ScFvs) and used them to monitor the localization and trafficking of βarr1 in live cells. We observed that upon agonist simulation of cells expressing chimeric GPCRs, these intrabodies first translocate to the cell surface, followed by trafficking into intracellular vesicles. The translocation pattern of intrabodies mirrored that of βarr1, and the intrabodies co-localized with βarr1 at the cell surface and in intracellular vesicles. Interestingly, we discovered that intrabody sensors can also report βarr1 recruitment and trafficking for several unmodified GPCRs. Our characterization of intrabody sensors for βarr1 recruitment and trafficking expands currently available approaches to visualize GPCR-βarr1 binding, which may help decipher additional aspects of GPCR signaling and regulation

Social Media: The Good, the Bad, and the Ugly

Ye

Functional neurological disorders in Parkinson disease

OBJECTIVE: To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. METHODS: A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. RESULTS: Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036). CONCLUSIONS: A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients