A Critical Review on Go-Ghrita, Shata Dhouta Ghrita and Sahasra Dhouta Ghrita

Traditional medical system has always played an important role in the maintenance of health of mankind. Modern medicine has been drawing inputs from these traditional systems since their very beginning. Samskara in Ayurveda, is a process of transformation of inherent attributes of a substance. This is created by dilution, application of heat, cleansing, churning, storing in a specific place, maturing, flavoring, impregnation, preservation, container etc. Ancient scholars considered that Ghrita is able to perform multiple actions if processed accordingly. On the base of this, many Samskaras are employed for Ghrita and subsequently various pharmacological actions are observed. Shatadhouta Ghrita and Sahsradhouta Ghrita are also an outcome of that keen observation. Shatadhouta Ghrita and Sahasradhouta Ghrita are two Ayurvedic preparations, which are prepared by washing cow ghee for hundred and thousand times respectively. They are considered as best alleviators of Pitta Dosha and burning sensation, in the treatments of wound healing. On the basis of detailed literary review, it was understood that, Shatadhouta Ghrita and Sahasradhouta Ghrita should be prepared by pressure washing of Ghrita with water. These preparations are indicated for Dahashamana action. Both of them have the properties as that of oil in water kind of emulsion

Association of Rare Coding Mutations With Alzheimer Disease and Other Dementias Among Adults of European Ancestry

MPORTANCE Some of the unexplained heritability of Alzheimer disease (AD) may be due to rare variants whose effects are not captured in genome-wide association studies because very large samples are needed to observe statistically significant associations. OBJECTIVE To identify genetic variants associated with AD risk using a nonstatistical approach. DESIGN, SETTING, AND PARTICIPANTS Genetic association study in which rare variants were identified by whole-exome sequencing in unrelated individuals of European ancestry from the Alzheimer’s Disease Sequencing Project (ADSP). Data were analyzed between March 2017 and September 2018. MAIN OUTCOMES AND MEASURES Minor alleles genome-wide and in 95 genes previously associated with AD, AD-related traits, or other dementias were tabulated and filtered for predicted functional impact and occurrence in participants with AD but not controls. Support for several findings was sought in a whole-exome sequencing data set comprising 19 affected relative pairs from Utah high-risk pedigrees and whole-genome sequencing data sets from the ADSP and Alzheimer’s Disease Neuroimaging Initiative. RESULTS Among 5617 participants with AD (3202 [57.0%] women; mean [SD] age, 76.4 [9.3] years) and 4594 controls (2719 [59.0%] women; mean [SD] age, 86.5 [4.5] years), a total of 24 variants with moderate or high functional impact from 19 genes were observed in 10 or more participants with AD but not in controls. These variants included a missense mutation (rs149307620 [p.A284T], n = 10) in NOTCH3, a gene in which coding mutations are associated with cerebral autosomaldominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), that was also identified in 1 participant with AD and 1 participant with mild cognitive impairment in the whole genome sequencing data sets. Four participants with AD carried the TREM2 rs104894002 (p.Q33X) high-impact mutation that, in homozygous form, causes Nasu-Hakola disease, a rare disorder characterized by early-onset dementia and multifocal bone cysts, suggesting an intermediate inheritance model for the mutation. Compared with controls, participants with AD had a significantly higher burden of deleterious rare coding variants in dementia-associated genes (2314 vs 3354 cumulative variants, respectively; P = .006). CONCLUSIONS AND RELEVANCE Different mutations in the same gene or variable dose of a mutation may be associated with result in distinct dementias. These findings suggest that minor differences in the structure or amount of protein may be associated with in different clinical outcomes. Understanding these genotype-phenotype associations may provide further insight into the pathogenic nature of the mutations, as well as offer clues for developing new therapeutic targets

Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity

The Wnt family of proteins are secreted signaling proteins that play key roles in regulating cellular functions. Recently, carboxylesterase Notum was shown to act as a negative regulator of Wnt signaling by mediating the removal of an essential palmitoleate. Here we disclose two new chemical scaffolds that inhibit Notum enzymatic activity. Our approach was to create a fragment library of 250 acids for screening against Notum in a biochemical assay followed by structure determination by X-ray crystallography. Twenty fragments were identified as hits for Notum inhibition, and 14 of these fragments were shown to bind in the palmitoleate pocket of Notum. Optimization of 1-phenylpyrrole 20, guided by structure-based drug design, identified 20z as the most potent compound from this series. Similarly, the optimization of 1-phenylpyrrolidine 8 gave acid 26. This work demonstrates that inhibition of Notum activity can be achieved by small, drug-like molecules possessing favorable in vitro ADME profiles

Comparison of cardiovascular risk factors between sri lankans living in kandy and oslo

<p>Abstract</p> <p>Background</p> <p>South Asians living in western countries are known to have unfavourable cardiovascular risk profiles. Studies indicate migrants are worse off when compared to those living in country of origin. The purpose of this study was to compare selected cardiovascular risk factors between migrant Sri Lankans living in Oslo, Norway and Urban dwellers from Kandy, Sri Lanka.</p> <p>Methods</p> <p>Data on non fasting serum lipids, blood pressure, anthropometrics and socio demographics of Sri Lankan Tamils from two almost similar population based cross sectional studies in Oslo, Norway between 2000 and 2002 (1145 participants) and Kandy, Sri Lanka in 2005 (233 participants) were compared. Combined data were analyzed using linear regression analyses.</p> <p>Results</p> <p>Men and women in Oslo had higher HDL cholesterol. Men and women from Kandy had higher Total/HDL cholesterol ratios. Mean waist circumference and body mass index was higher in Oslo. Smoking among men was low (19.2% Oslo, 13.1% Kandy, P = 0.16). None of the women smoked. Mean systolic and diastolic blood pressure was significantly higher in Kandy than in Oslo.</p> <p>Conclusions</p> <p>Our comparison showed unexpected differences in risk factors between Sri Lankan migrants living in Oslo and those living in Kandy Sri Lanka. Sri Lankans in Oslo had favorable lipid profiles and blood pressure levels despite being more obese.</p

Genome Analysis of the Anaerobic Thermohalophilic Bacterium Halothermothrix orenii

Halothermothirx orenii is a strictly anaerobic thermohalophilic bacterium isolated from sediment of a Tunisian salt lake. It belongs to the order Halanaerobiales in the phylum Firmicutes. The complete sequence revealed that the genome consists of one circular chromosome of 2578146 bps encoding 2451 predicted genes. This is the first genome sequence of an organism belonging to the Haloanaerobiales. Features of both Gram positive and Gram negative bacteria were identified with the presence of both a sporulating mechanism typical of Firmicutes and a characteristic Gram negative lipopolysaccharide being the most prominent. Protein sequence analyses and metabolic reconstruction reveal a unique combination of strategies for thermophilic and halophilic adaptation. H. orenii can serve as a model organism for the study of the evolution of the Gram negative phenotype as well as the adaptation under thermohalophilic conditions and the development of biotechnological applications under conditions that require high temperatures and high salt concentrations

Design and management of an orthopaedic bone bank in the Netherlands

The design and management of an orthopaedic bone bank is a complex process in which medical organisation and legislation intertwine. Neither in the Netherlands, nor in any other European country, there are official guidelines for the organisation and management of an orthopaedic bone bank. In the Netherlands, the recently modified ‘law of security and quality for using human materials’ (WVKL) dictates requirements for technical and organisational aspects for the use of human tissue and cells. The bone bank procedures include a thorough questionnaire for donor selection, extensive serological, bacteriological and histopathological examination, as well as standard procedures for registration, processing, preservation, storage and distribution of bone allografts. This article describes the organisation of an accredited bone bank and can be used as a proposition for an official guideline or can be useful as an example for other orthopaedic bone banks in Europe