Effect of S-methylisothiourea,an inducible nitric oxide synthase inhibitor,in joint pain and pathology in surgically induced model of osteoarthritis

The aim of the present study was to evaluate in vivo modulatory effect of S-methylisothiourea (SMT), a preferential inhibitor of inducible nitric oxide synthase (iNOS) on pain and pathology in the surgical model of osteoarthritis (OA) in rats. The OA was produced by the anterior cruciate ligament transection (ACLT) and medial meniscectomy (MMx) of right knee. SMT was administered 1 day prior to the production of OA and continued up to day 42 postoperation. Mechanical hyperalgesia, thermal hyperalgesia, tail flick latency after repeated flexion and extension of OA knee and knee diameter of right knee were determined at weekly intervals. Serum levels of IL-1β, TNF-α and nitrite concentration were determined at the end of the experiment. Glycosaminoglycan (GAG) content, collagen content and histopathological evaluation of articular cartilage were also determined at the end of the experiment. SMT reduced mechanical hyperalgesia and the serum levels of IL-1β, TNF-α and nitrite. Further, SMT reduced the loss of GAG from articular cartilage. Microscopically, SMT reduced the severity of the cartilage lesion. The results indicate the effectiveness of SMT in attenuating the pain and pathology of experimental OA phase by reducing the production of nitric oxide and interleukin-1β and tumor necrosis factor-α, which are known to play a major role in the pathophysiology of OA.     

Evaluation of Efficacy of Microwave Irradiation in Disinfecting Dental Gypsum Casts: An Ex Vivo Study

The aim of this study is to assess the efficacy of microwave irradiation in disinfecting gypsum casts and also to compare its efficacy with validated method of chemical disinfection. The present study is an ex vivo study conducted on a sample of five irreversible hydrocolloid impressions in vitro and on ten patients gypsum casts in vivo following standard impression techniques to check the efficacy of microwave oven irradiation and compare its efficacy with standard chemical method of disinfection. Results were analysed using Mann–Whitney test and Wilcoxon signed rank test. Untreated gypsum casts showed cfu/ml counts with a median log value of 6, while microwave-irradiated ones had median cfu/ml counts of 0. Casts poured from chemically disinfected impressions demonstrated cfu/ml counts with a median log value of 5. Microwave irradiation was found to be effective in disinfecting gypsum casts when compared to chemical disinfectant in disinfecting dental impressions.     

Duplex PCR Assay for Identification of Tissue of Cattle and Buffalo Origin Targeting Mitochondrial Cytochrome b Gene

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The aim of this study was to develop PCR assay for simultaneous detection of tissues from cattle and buffalo...     

Selfie fundus imaging for diabetic retinopathy screening

BackgroundRegular screening for retinopathy and timely intervention reduces blindness from diabetes by 90%. Screening is currently dependent on the interpretation of images captured by trained technicians. Inherent barriers of accessibility and affordability with this approach impede widespread success of retinopathy screening programs. Herein, we report our observations on the potential of a novel approach, Selfie Fundus Imaging (SFI), to enhance diabetic retinopathy screening.MethodsThe study was undertaken over a two-month period during COVID 19 lockdown. 60 diabetic patients participated in the study. Retinal images were captured using three different approaches, handheld smartphone-based photographs captured by patients themselves after a short video-assisted training session (SFI group), and smartphone-based photographs captured by a trained technician and photographs taken on desktop conventional digital fundus camera (Gold standard). Sensitivity and kappa statistics was determined for retinopathy and macular oedema grading.FindingsMean age of the study participants was 52.4 years ± 9.8 years and 78% were men. Of 120 images captured using SFI, 90% were centred-gradable, 8% were decentred-gradable and 2% were ungradable. 82% patients captured the image within a minute (majority by 31–45 s). The sensitivity of SFI to detect diabetic retinopathy was 88.39%. Agreement between SFI grading and standard fundus photograph grading was 85.86% with substantial kappa (0.77). For the detection of diabetic macular oedema, the agreement between SFI images and standard images was 93.67, with almost perfect kappa (0.91).ConclusionFundus images were captured by patients using SFI without major difficulty and were comparable to images taken by trained specialist. With greater penetrance, advances, and availability of mobile photographic technology, we believe that SFI would positively impact the success of diabetic retinopathy screening programs by breaking the barriers of availability, accessibility, and affordability. SFI could ensure continuation of screening schedules for diabetic retinopathy, even in the face a highly contagious pandemic.Subject terms: Outcomes research, Retinal diseases, Physical examination     

The polyphenolic phytoalexin polydatin inhibits amyloid aggregation of recombinant human prion protein

Prion diseases involve misfolded and highly infectious aggregates of prion protein (PrP^Sc) which forms amyloid plaques leading to fatal neurodegeneration. The absence of clinically proven therapeutics makes the discovery of effective remedial interventions a prime concern. Herein, we report novel prion intervention by the polyphenolic phytoalexin, polydatin which binds with moderate affinity to the recombinant protease resistant core of human prion protein, encompassing the sequence 90–231 (rPrP^res) and inhibits its conversion into the highly neurotoxic forms. An extensive evaluation using biophysical techniques revealed that polydatin incubated rPrP^res samples generate off-pathway oligomers having reduced cross-β sheet signature, and relatively smaller in size than the native rPrP^res oligomers. The detailed structural analysis using molecular dynamics simulations elucidated the induction of antagonistic mobilities in the β2–α2 loop, α3 helix and the N-terminal amyloidogenic region of prions. This study puts forward novel prion fibrillogenesis inhibitory potential of polydatin, specifically by stabilizing the N-terminal amyloidogenic region. Collectively our results affirm the importance of polydatin in crippling the prion pathogenesis and may serve as a structural scaffold for designing novel therapeutic agents targeting amyloidogenic transition in prions.

Polydatin is found to be a pharmacologically-significant scaffold that can bind to the rPrP^res repertoire and inhibit its conversion to the highly infectious and neurotoxic PrP^Sc-like form, thus acting like a promising anti-prion drug lead.