Evaluation of axial length and association with morphology of cataract

Background: Cataractogenesis is associated with alteration in the nature of lens epithelium. How a change in morphology of cataract relates to axial length and IOL power is an interesting area to explore. The aim of the study was to evaluate the association between axial length and age-related cataracts, and intra ocular lens (IOL) power in eyes undergoing cataract surgery.Methods: A cross sectional study was conducted from 2019 to 2020 on 550 eyes with age related cataract for morphology of cataract and axial length of eye. Data was analyzed using statistical software One-way ANOVA and Post HOC test.Results: Out of a total 550 eyes, 122 (22.2%) were Nuclear, 79 (14.4%) were PSC, and 349 (63.5%) were of Mixed morphology. Mean age of patients with PSC was 56.41±14.55 years, 58.52±14.16 years with Nuclear, and 62.88±9.86 years in Mixed morphology. This difference was found to be statistically significant with p value of 0.001. In this study, the mean axial length in eyes with only Nuclear, only PSC, and Mixed morphology, was measured to be 23.19±1.29, 23.26±0.91, 23.24±1.47 respectively. This was found to be statistically insignificant with p=0.92. The mean power intraocular lens 20.96±3.03 D in Nuclear Cataract, 21.25±2.39 D in PSC, and 21.25±2.60 D in Mixed cataract, and was statistically insignificant with p value of 1.Conclusions: This study suggests no impact of morphology of cataract on axial length or IOL power.

Diffusion MR microscopy of cortical development in the mouse embryo

Cortical development in the mouse embryo involves complex changes in the microstructure of the telencephalic wall, which are challenging to examine using three-dimensional (3D) imaging techniques. In this study, high-resolution 3D diffusion magnetic resonance (dMR) microscopy of the embryonic mouse cortex is presented. Using diffusion-weighted gradient- and spin-echo based acquisition, dMR microimaging data were acquired from fixed mouse embryos at 7 developmental stages from embryonic day (E)12.5 to E18.5. The dMR imaging (dMRI) contrasts revealed microscopic structural detail in the mouse telencephalic wall, allowing delineation of transient zones in the developing cortex based on their unique diffusion signatures. With the high-resolution 3D data of the mouse embryo, we were able to visualize the complex microstructure of embryonic cerebral tissue and to resolve its regional and temporal evolution during cortical formation. Furthermore, averaged dMRI contrasts generated via deformable registration revealed distinct spatial and temporal gradients of anisotropy variation across the developing embryonic cortical plate and the ventricular zone. The findings of this study demonstrate the potential of 3D dMRI to resolve the complex microstructure of the embryonic mouse cortex, and will be important for investigations of corticogenesis and its disruption in embryonic mouse models

SYNERGISTIC ACTION OF PENETRATION ENHANCERS IN TRANSDERMAL DRUG DELIVERY

Transdermal drug delivery system is a desirable form of drug delivery because of the obvious advantages over other routes of delivery. One promising challenge in designing transdermal drug delivery system is to overcome the natural transport barrier of the skin i.e. the stratum corneum which is the rate limiting step in percutaneous absorption of drugs. Various penetration enhancers are now being used alone or in combinations to enhance the penetration of the drug through the skin. The main objective of the present study is to review the synergistic action of various penetration enhancers on the efficacy and safety of the drug. It has been found from the literature study that systems employing synergistic mixtures of penetration enhancers offer superior skin permeation enhancement as compared to those employing single penetration enhancer. Various chemical, physical and carrier approaches have also been reviewed to increase skin permeation of the drug. Keywords: Transdermal, penetration enhancers, synergistic mixtures, permeation enhancement

Correlation of Self-Reported and Performance-Based Measures In Patients With Non-Traumatic Stiff Shoulder Pathologies: An Observational Study

Background: Self-reported measures represent patients' perspectives toward their disease, but their performance levels may vary. Performance-based measures mimic the patient's functional activity movement, which helps evaluate specific task components, including how the therapist approached the task. Both measures report the patient's functional level from the patient's or therapist's perspective. The study was done to determine the correlation between self-reported and performance-based measures outcomes in non-traumatic stiff shoulder pathologies. Method: Self-reported outcome measure scores were recorded using the Shoulder Pain And Disability Index (SPADI), Disabilities of Arm, Shoulder, and Hand (DASH), and Patient Specific Functional Scale (PSFS). Performance-based measures scores of the shoulder were given using function-related tests of the shoulder: 1) Hand to the neck, 2) Hand to scapula 3) Hand to the opposite scapula. Result: Inferential statistics were done using the Pearson correlation test, and the significance level was set at p<0.05. Pearson correlation test showed: 1) Weak statistically significant correlation between SPADI versus function-related test 1(r= 0.32), DASH versus Function-related test 1(r= 0.31), and function-related test 2(r= 0.31) and PSFS versus function-related test 1(r= 0.36). 2) Other correlations were Very Weak and non-significant. Conclusion: As the correlation between all three self-reported measures and each of the three function-related tests has become weak, there is a need to include both self-reported and performance-based measures in assessing patients with non-traumatic stiff shoulder pathologies

Discovery of Novel Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients: A Preliminary Study

Background: Liver biopsy is the reference standard for assessing liver fibrosis and no reliable non-invasive diagnostic approach is available to discriminate between the intermediate stages of fibrosis. Therefore suitable serological biomarkers of liver fibrosis are urgently needed. We used proteomics to identify novel fibrosis biomarkers in hepatitis C patients with different degrees of liver fibrosis.Methodology/Principal Findings: Proteins in plasma samples from healthy control individuals and patients with hepatitis C virus (HCV) induced cirrhosis were analysed using a proteomics technique: two dimensional gel electrophoresis (2-DE). This technique separated the proteins in plasma samples of control and cirrhotic patients and by visualizing the separated proteins we were able to identify proteins which were increasing or decreasing in hepatic cirrhosis. Identified markers were validated across all Ishak fibrosis stages and compared to the markers used in FibroTest, Enhanced Liver Fibrosis (ELF) test, Hepascore and FIBROSpect by Western blotting. Forty four candidate biomarkers for hepatic fibrosis were identified of which 20 were novel biomarkers of liver fibrosis. Western blot validation of all candidate markers using plasma samples from patients across all Ishak fibrosis scores showed that the markers which changed with increasing fibrosis most consistently included lipid transfer inhibitor protein, complement C3d, corticosteroid-binding globulin, apolipoprotein J and apolipoprotein L1. These five novel fibrosis markers which are secreted in blood showed a promising consistent change with increasing fibrosis stage when compared to the markers used for the FibroTest, ELF test, Hepascore and FIBROSpect. These markers will be further validated using a large clinical cohort.Conclusions/Significance: This study identifies 20 novel fibrosis biomarker candidates. The proteins identified may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.</br

Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India

Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL &lt;2,500) was noted in 63% of the patients. Based on immunophenotypic pattern, majority of the cases were T−B− SCID (39%) followed by T−B+ SCID (28%). MHC class II deficiency accounted for 10.5% of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (&lt;18 copies/μL)

Recommendations and guidelines from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 1 -- In vivo small-animal imaging

The value of in vivo preclinical diffusion MRI (dMRI) is substantial. Small-animal dMRI has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. Many of the influential works in this field were first performed in small animals or ex vivo samples. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the data. This work aims to serve as a reference, presenting selected recommendations and guidelines from the diffusion community, on best practices for preclinical dMRI of in vivo animals. In each section, we also highlight areas for which no guidelines exist (and why), and where future work should focus. We first describe the value that small animal imaging adds to the field of dMRI, followed by general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss how they are appropriate for different studies. We then give guidelines for in vivo acquisition protocols, including decisions on hardware, animal preparation, imaging sequences and data processing, including pre-processing, model-fitting, and tractography. Finally, we provide an online resource which lists publicly available preclinical dMRI datasets and software packages, to promote responsible and reproducible research. An overarching goal herein is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.Comment: 69 pages, 6 figures, 1 tabl

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease