Chronotherapeutics in Ayurveda

In order to maximize health benefits and minimize adverse effects of a treatment, chronotherapeutics is administered to patients according to his/her daily, monthly, seasonal or yearly biological clock. According to Ayurveda observation of the specific features of disease corresponding to season, day and night, age and meal is known as Kaala Aveksha. The Dasha Bheshaja Kaala (ten different time period for the administration of medicine) is one among the Shadaveksha Kaala (Six observatory aspects of time). It is defined according to the biological clock. The medicines at proper Bheshaja Kaala help to attain the equilibrium of Doshas and Dhatus. Here chronotherapeutics can be correlated with Bheshaja Kaala. As it gives importance to the time of administration which can be responsible for variations of drug kinetics. Objective: To conduct an in-depth analysis of the literature in order to identify and evaluate the evidence base for chronotherapy. Data source: A literature search was conducted in classics of Ayurveda and electronic databases. Result: Review shows that the drug administered according to the Bheshaja kaala has more beneficial outcomes than the other methods. Conclusion: The review presents the scope of chronotherapy in drug administration

External validation of a COPD prediction model using population-based primary care data: a nested case-control study

Emerging models for predicting risk of chronic obstructive pulmonary disease (COPD) require external validation in order to assess their clinical value. We validated a previous model for predicting new onset COPD in a different database. We randomly drew 38,597 case-control pairs (total N = 77,194) of individuals aged ≥35 years and matched for sex, age, and general practice from the United Kingdom Clinical Practice Research Datalink database. We assessed accuracy of the model to discriminate between COPD cases and non-cases by calculating area under the receiver operator characteristic (ROC(AUC)) for the prediction scores. Analogous to the development model, ever smoking (OR 6.70; 95%CI 6.41–6.99), prior asthma (OR 6.43; 95%CI 5.85–7.07), and higher socioeconomic deprivation (OR 2.90; 95%CI 2.72–3.09 for highest vs. lowest quintile) increased the risk of COPD. The validated prediction scores ranged from 0–5.71 (ROC(AUC) 0.66; 95%CI 0.65–0.66) for males and 0–5.95 (ROC(AUC) 0.71; 95%CI 0.70–0.71) for females. We have confirmed that smoking, prior asthma, and socioeconomic deprivation are key risk factors for new onset COPD. Our model seems externally valid at identifying patients at risk of developing COPD. An impact assessment now needs to be undertaken to assess whether this prediction model can be applied in clinical care settings

Antibacterial Characterization of Novel Synthetic Thiazole Compounds against Methicillin-Resistant Staphylococcus pseudintermedius

Staphylococcus pseudintermedius is a commensal organism of companion animals that is a significant source of opportunistic infections in dogs. With the emergence of clinical isolates of S. pseudintermedius (chiefly methicillin-resistant S. pseudintermedius (MRSP)) exhibiting increased resistance to nearly all antibiotic classes, new antimicrobials and therapeutic strategies are urgently needed. Thiazole compounds have been previously shown to possess potent antibacterial activity against multidrug-resistant strains of Staphylococcus aureus of human and animal concern. Given the genetic similarity between S. aureus and S. pseudintermedius, this study explores the potential use of thiazole compounds as novel antibacterial agents against methicillin-sensitive S. pseudintermedius (MSSP) and MRSP. A broth microdilution assay confirmed these compounds exhibit potent bactericidal activity (at sub-microgram/mL concentrations) against both MSSA and MRSP clinical isolates while the MTS assay confirmed three compounds (at 10 μg/mL) were not toxic to mammalian cells. A time-kill assay revealed two derivatives rapidly kill MRSP within two hours. However, this rapid bactericidal activity was not due to disruption of the bacterial cell membrane indicating an alternative mechanism of action for these compounds against MRSP. A multistep resistance selection analysis revealed compounds 4 and 5 exhibited a modest (twofold) shift in activity over ten passages. Furthermore, all six compounds (at a subinihibitory concentration) demonstrated the ability to re-sensitize MRSP to oxacillin, indicating these compounds have potential use for extending the therapeutic utility of β-lactam antibiotics against MRSP. Metabolic stability analysis with dog liver microsomes revealed compound 3 exhibited an improved physicochemical profile compared to the lead compound. In addition to this, all six thiazole compounds possessed a long post-antibiotic effect (at least 8 hours) against MRSP. Collectively the present study demonstrates these synthetic thiazole compounds possess potent antibacterial activity against both MSSP and MRSP and warrant further investigation into their use as novel antimicrobial agents

The impact of rheumatoid foot on disability in Colombian patients with rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Alterations in the feet of patients with rheumatoid arthritis (RA) are a cause of disability in this population. The purpose of this research was to evaluate the impact that foot impairment has on the patients' global quality of life (QOL) based on validated scales and its relationship to disease activity.</p> <p>Methods</p> <p>This was a cross-sectional study in which 95 patients with RA were enrolled. A complete physical examination, including a full foot assessment, was done. The Spanish versions of the Health Assessment Questionnaire (HAQ) Disability Index and of the Disease Activity Score (DAS 28) were administered. A logistic regression model was used to analyze data and obtain adjusted odds ratios (AORs).</p> <p>Results</p> <p>Foot deformities were observed in 78 (82%) of the patients; hallux valgus (65%), medial longitudinal arch flattening (42%), claw toe (lesser toes) (39%), dorsiflexion restriction (tibiotalar) (34%), cock-up toe (lesser toes) (25%), and transverse arch flattening (25%) were the most frequent. In the logistic regression analysis (adjusted for age, gender and duration of disease), forefoot movement pain, subtalar movement pain, tibiotalar movement pain and plantarflexion restriction (tibiotalar) were strongly associated with disease activity and disability. The positive squeeze test was significantly associated with disability risk (AOR = 6,3; 95% CI, 1.28–30.96; P = 0,02); hallux valgus, and dorsiflexion restriction (tibiotalar) were associated with disease activity.</p> <p>Conclusion</p> <p>Foot abnormalities are associated with active joint disease and disability in RA. Foot examinations provide complementary information related to the disability as an indirect measurement of quality of life and activity of disease in daily practice.</p

Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge

<p>Abstract</p> <p>Background</p> <p>There is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown.</p> <p>Methods</p> <p>To address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation.</p> <p>Results</p> <p>Adolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors.</p> <p>Conclusion</p> <p>Our results demonstrate that predatory stress, an ethologically relevant stressor, can elicit changes in neuroinflammation and behavior. The predatory stress model may be useful in elucidating mechanisms by which psychological stress modulates diseases with an inflammatory component.</p

Reliability of the Preliminary OMERACT Juvenile Idiopathic Arthritis MRI Score (OMERACT JAMRIS-SIJ)

This study reports the reliability of the juvenile idiopathic arthritis magnetic resonance imaging scoring system (JAMRIS-SIJ). The study comprised of eight raters—two rheumatologists and six radiologists—and 30 coronal T1 and Short-Tau Inversion Recovery (STIR) MRI scans of patients with enthesitis-related juvenile spondylarthritis. The median age of patients was 15 years with a mean disease duration of 5 years and 22 (73.3%) of the sample were boys. The inter-rater agreement of scores for each of the JAMRIS-SIJ items was calculated using a two-way random effect, absolute agreement, and single rater intraclass correlation coefficient (ICC 2.1). The ICC was interpreted together with kurtosis, since the ICC is also affected by the distribution of scores in the sample. The eight-rater, single measure inter-rater ICC (and kurtosis) values for JAMRIS-SIJ inflammation and damage components were the following: bone marrow edema (BME), 0.76 (1.2); joint space inflammation, 0.60 (1.8); capsulitis, 0.58 (9.2); enthesitis, 0.20 (0.1); ankylosis, 0.89 (35); sclerosis, 0.53 (4.6); erosion, 0.50 (6.5); fat lesion, 0.40 (21); backfill, 0.38 (38). The inter-rater reliability for BME and ankylosis scores was good and met the a priori set ICC threshold, whereas for the other items it was variable and below the selected threshold. Future directives should focus on refinement of the scores, definitions, and methods of interpretation prior to validation of the JAMRIS-SIJ through the assessment of its measurement properties

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field