An epidemiological study on patients undergoing dacryocystorhinostomy

Dacryocystorhinostomy is performed in patients with naso-lacrimal duct obstruction to bypass the site of obstruction so as to relieve the patient of the irritating and socially embarrassing symptoms of epiphora. We discuss the various epidemiological aspects especially the vast difference by which the females out-number the males in patients undergoing DCR and the likely explanations for this difference in our study on 74 patients which underwent DCR in our institute.     

EXPLORING THE RELATIONSHIP BETWEEN WORD PROCESSING AND VERBAL SHORT-TERM MEMORY: EVIDENCE FROM ASSOCIATIONS AND DISSOCIATIONS

Abstract

A theory of the cognitive organisation of lexical processing, verbal short-term memory, and verbal learning is presented along with a summary of data that bear on this issue. We conceive of verbal STM as the outcome of processing that invokes both a specialised short-term memory and the lexical system. On this model, performance of verbal STM tasks depends on the integrity of lexical knowledge, access to that knowledge, and processes that encode serial order information.     

Left atrial ligation alters intracardiac flow patterns and the biomechanical landscape in the chick embryo

Background: Hypoplastic left heart syndrome (HLHS) is a major human congenital heart defect that results in single ventricle physiology and high mortality. Clinical data indicate that intracardiac blood flow patterns during cardiac morphogenesis are a significant etiology. We used the left atrial ligation (LAL) model in the chick embryo to test the hypothesis that LAL immediately alters intracardiac flow streams and the biomechanical environment, preceding morphologic and structural defects observed in HLHS. Results: Using fluorescent dye injections, we found that intracardiac flow patterns from the right common cardinal vein, right vitelline vein, and left vitelline vein were altered immediately following LAL. Furthermore, we quantified a significant ventral shift of the right common cardinal and right vitelline vein flow streams. We developed an in silico model of LAL, which revealed that wall shear stress was reduced at the left atrioventricular canal and left side of the common ventricle. Conclusions: Our results demonstrate that intracardiac flow patterns change immediately following LAL, supporting the role of hemodynamics in the progression of HLHS. Sites of reduced WSS revealed by computational modeling are commonly affected in HLHS, suggesting that changes in the biomechanical environment may lead to abnormal growth and remodeling of left heart structures. Developmental Dynamics 243:652–662, 2014. © 2013 Wiley Periodicals, Inc.     

Phase 2 of collaborative action around the implementation of virtual hearing aid care: Evaluation of a clinical practice guideline

Rationale

Following the onset of the COVID-19 pandemic, a clinical practice guideline (CPG) around virtual hearing aid practices was developed to fill a knowledge gap within the field of audiology. Details outlining the development and mobilization of this draft guideline were outlined as Phase 1 (described in a paired paper).

Aims and Objectives

This study describes Phase 2 of this project as part of the Knowledge-to-Action Framework, including an evaluation of the methodological quality of the guideline and the resulting tailored version of the document (v2.0).

Method

The Appraisal of Guidelines for Research and Evaluation II instrument was used to assess methodological quality and to guide revisions. Twenty-two clinicians, from a variety of clinical backgrounds, participated in the evaluation.

Results and Conclusion

Findings reported across six domains suggest high mean scores, ranging from 78% to 81%, in order of scope and purpose (highest rated), stakeholder involvement, rigour of development, applicability, clarity of presentation, and editorial independence. Specific recommendations made by in international co-creation team during the evaluation informed the final version of the CPG. Future development and evaluation efforts should aim to include greater representation from nontraditional practice contexts to strengthen global applicability.     

A clinical and computational study on anti-obesity effects of hydroxycitric acid

Hydroxycitric acid (HCA), a major active ingredient of Garcinia cambogia extracts, is known to suppress body weight gain and fat synthesis in animals and humans. But the underlying mechanism of HCA action is not fully understood. Clinical study on 100 obese individuals for a period of 3 months was performed followed by a computational study aimed to investigate the effects of HCA treatment on human subjects at anthropometric and plasma lipid profile levels. A detailed hepatic metabolic model was used to incorporate the effect of HCA at the metabolic pathway level. Perturbation analysis of ATP citrate lyase activity in the metabolic pathway was performed to simulate the net effect of HCA. Significant reductions in body weight, triceps, subscapular, and mid axillary measurements as well as in serum triglyceride, cholesterol, HDL and LDL levels were observed following HCA dosage. During the study, half of the subjects experienced a decline in body weight and the remainder experienced an increase in body weight. However, analysis of fat mass with the help of empirical correlations clearly showed significant reduction in the mean values due to HCA dosage in both cases. An extra increase in fat free mass was responsible for offsetting the decrease in fat mass for the subjects who experienced an increase in body weight during the trials. Perturbation analysis showed a net reduction in fatty acid, triglyceride and cholesterol synthesis along with urea cycle fluxes under lipogenetic conditions. Moreover, protein synthesis fluxes increased under these conditions. These results indicate that HCA treatment can reduce body weight gain and fat accumulation in obese subjects along with improving their anthropometric parameters and metabolic state.

Hydroxycitric acid (HCA), a major active ingredient of Garcinia cambogia extracts, is known to suppress body weight gain and fat synthesis in animals and humans.     

Effect of flaxseed supplementation on metabolic state,endocrine profiles,body composition and reproductive performance of sows

Objective: To assess the effect of flaxseed supplementation on metabolic profile, endocrine concentrations, non-esterified fatty acids (NEFA), body composition ...     

Therapeutic cooperation between auranofin,a thioredoxin reductase inhibitor and anti-PD-L1 antibody for treatment of triple-negative breast cancer

Triple-negative breast cancer (TNBCs) is a very aggressive and lethal form of breast cancer with no effective targeted therapy. Neoadjuvant chemotherapies and radiotherapy remains a mainstay of treatment with only 25–30% of TNBC patients responding. Thus, there is an unmet clinical need to develop novel therapeutic strategies for TNBCs. TNBC cells have increased intracellular oxidative stress and suppressed glutathione, a major antioxidant system, but still, are protected against higher oxidative stress. We screened a panel of antioxidant genes using the TCGA and METABRIC databases and found that expression of the thioredoxin pathway genes is significantly upregulated in TNBC patients compared to non-TNBC patients and is correlated with adverse survival outcomes. Treatment with auranofin (AF), an FDA-approved thioredoxin reductase inhibitor caused specific cell death and impaired the growth of TNBC cells grown as spheroids. Furthermore, AF treatment exerted a significant in vivo antitumor activity in multiple TNBC models including the syngeneic 4T1.2 model, MDA-MB-231 xenograft and patient-derived tumor xenograft by inhibiting thioredoxin redox activity. We, for the first time, showed that AF increased CD8^+Ve T-cell tumor infiltration in vivo and upregulated immune checkpoint PD-L1 expression in an ERK1/2-MYC-dependent manner. Moreover, combination of AF with anti-PD-L1 antibody synergistically impaired the growth of 4T1.2 primary tumors. Our data provide a novel therapeutic strategy using AF in combination with anti-PD-L1 antibody that warrants further clinical investigation for TNBC patients.