Effect of topical brinzolamide on visual function and waveform in patients of infantile nystagmus syndrome: A randomized control trial.

PURPOSE: To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS). DESIGN: Prospective, placebo-controlled, double-blind, cross-over study. METHODS: Setting- A tertiary eye care center. Patients- Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention- Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure- Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position. RESULTS: A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture).A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy. CONCLUSIONS: While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence.

Molecular docking analysis of PARγ with compounds from Ocimum tenuiflorum.

The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) has become a major target for type 2 diabetes. It belongs to the nuclear receptor superfamily, which controls the expression of proteins involved in glucose metabolism, lipid metabolism, adipocyte proliferation and differentiation, and insulin sensitivity. Ocimum tenuiflorum, often known as Krishna tulsi, is the most sacred herb in India. It was utilized for a variety of medicinal purposes. Therefore, it is of interest to document the molecular docking analysis data of PARγ modulators from Ocimum tenuiflorum. Four of the twenty substances (rosmarinic acid, permethrin, luteolin, and isosakuranetin) have a considerable binding affinity for the PPARγ. These phytochemicals are a source of potential anti-diabetic medicines.

Molecular docking analysis of glycogen phosphorylase with inhibitors from Cissampelos pareira Linn.

Cissampelos pareira Linn. is a climbing herb known in Indian traditional medicine as laghupatha. It belongs to the Menispermaceae family. The enzyme glycogen phosphorylase (GP) is a promising target for the treatment of type-2 diabetes (T2DM). A variety of natural product inhibitors with both pharmaceutical and nutraceutical potential have been reported in the search for powerful, selective and drug-like GP inhibitors that could lead to hypoglycemic medicines. Therefore, it is of interest to document the molecular docking analysis data of glycogen phosphorylase with compounds from Cissampelos pareira Linn. We report the optimal binding features of 4 compounds namely Trans-N-feruloyltyramine, Coclaurine, Magnoflorine, and Curine with the target protein for further consideration in the context of T2DM.

Renal Carcinoma Is Associated With Increased Risk of Coronavirus Infections.

Background: The current COVID-19 pandemic has affected most severely people with old age, or with comorbidities like hypertension, diabetes mellitus, and cancer. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential. Method: We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors (DPP4, ANPEP, ENPEP, TMPRSS2) in human normal and cancer tissues of multiple organs including the brain, liver, kidney, heart, lung, skin, GI tract, pancreas, endocrine tissues, and the reproductive organs. RNA-Seq data from The Cancer Genome Atlas (TCGA) and GTeX databases were used for extensive profiling analysis of these receptors across 9,736 tumors and 8,587 normal tissues comparing coronavirus receptors. Protein expression from immunohistochemistry data was assessed from The Human Protein Atlas database including 144 samples, corresponding to 48 different normal human tissue types, and 432 tumor samples from 216 different cancer patients. The correlations between immune cell infiltration, chemokine, and cytokines were investigated via Tumor Immune Estimation Resource (TIMER) and TCGA. Result: We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus infection in renal carcinoma patients. The other receptors DPP4, ANPEP, and ENPEP may act as the compensatory receptor proteins to help ACE2. The receptors' expression levels were variable in different tumor stage, molecular, and immune subtypes of renal carcinoma. Intriguingly, in clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion. Conclusion: Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches.

Sex hormones and COVID-19: tussle between the two.

Novel coronavirus disease (COVID-19) has affected nearly 7 million individuals and claimed more than 0.4 million lives to date. There are several reports of gender differences related to infection and death due to COVID-19. This raises important questions such as "Whether there are differences based on gender in risk and severity of infection or mortality rate?" and "What are the biological explanation and mechanisms underlying these differences?" Emerging evidences have proposed sex-based immunological, genetic, and hormonal differences to explain this ambiguity. Besides biological differences, women have also faced social inequities and economic hardships due to this pandemic. Several recent studies have shown that independent of age males are at higher risk for severity and mortality in COVID-19 patients. Although susceptibility to SARS-CoV-2 was found to be similar across both genders in several disease cohorts, a disproportionate death ratio in men can be partly explained by the higher burden of pre-existing diseases and occupational exposures among men. At immunological point of view, females can engage a more active immune response, which may protect them and counter infectious diseases as compared to men. This attribute of better immune responses towards pathogens is thought to be due to high estrogen levels in females. Here we review the current knowledge about sex differences in susceptibility, the severity of infection and mortality, host immune responses, and the role of sex hormones in COVID-19 disease.

COVID 19 diagnostic multiplicity and its role in community surveillance and control.

Diagnosis of persons exposed to/infected with severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is central to controlling the global pandemic of COVID-19. Currently, several diagnostic modalities are available for COVID-19, each with its own pros and cons. Although there is a global consensus to increase the testing capacity, it is also essential to prudently utilize these tests to control the pandemic. In this paper, we have reviewed the current array of diagnostics for SARS-CoV-2, highlighted the gaps in current diagnostic modalities, and their role in community surveillance and control of the pandemic. The different modalities of COVID-19 diagnosis discussed are: clinical and radiological, molecular based (laboratory based and point-of-care), Immunoassay based (ELISA, rapid antigen and antibody detection tests) and digital diagnostics (artificial intelligence based algorithms). The role of rapid antigen/antibody detection tests in community surveillance has also been described here. These tests can be used to identify asymptomatic persons exposed to the virus and in community based seroprevalence surveys to assess the epidemiology of spread of the virus. However, there are few concerns about the accuracy of these tests which needs to evaluated beforehand.

Cortical Potentials Prior to Movement in Parkinson's Disease.

INTRODUCTION: Recording cortical potentials prior to movement (bereitschaftspotentials, BP) offer a good non invasive method for studying activity of motor related cortices in Parkinson's Disease (PD). Dopaminergic medications provide some symptomatic relief in advanced stages but they do not stop the progression of the disease. Assessing BP may be a good idea to see the response of anti PD drugs. It remains unclear whether the anti PD medications also improve cortical activity prior to movement even in advanced stages of the disease. AIM: In this study we recorded scalp BP in patients with varying grades of severity to study the relationship between disease severity and various components of BP. MATERIALS AND METHODS: We successfully recorded BP at Cz, C3 and C4 sites during self-initiated 100 right wrist movements in 12 male patients with PD having severity Hoehn and Yahn (H&Y) scale 4 (PD3 group). These potentials were compared with age matched patients with H&Y scale 2 (PD1) and scale 3 (PD2) and also with age matched healthy controls. RESULTS: We found flatter waveforms with increasing severity of disease. Amplitude is first to be affected in mild severity as compared to controls (p=0.011); while with increasing severity early as well as late part of potentials is affected. Such changes are prominently seen at Cz site across the groups. CONCLUSION: These findings imply that there is increasing defect in cortical activity during movement especially in supplementary motor area with increasing severity in PD in spite of dopaminergic medications. This dynamic nature of dysfunction in supplementary motor cortices must be taken in account while treating advanced cases using newer stimulation techniques.