A study of the spectrum of Acanthamoeba keratitis: a three-year study at a tertiary eye care referral center in South India

PURPOSE: To determine the epidemiological and clinical characteristics of Acanthamoeba keratitis and also to determine the sensitivity and specificity of smears in the detection of Acanthamoeba. MATERIALS AND METHODS: A retrospective review of all culture-positive cases of Acanthamoeba keratitis seen between October 1999 and August 2002 was performed. Corneal scrapes were subjected to culture and microscopy using standard protocols. RESULTS: Out of 3183 consecutive patients with clinically diagnosed corneal ulcers evaluated, 33 (1.04%) were found to be due to Acanthamoeba. Twenty-four out of 33 (72.72%) were less than 51 years of age (P<0.001). All patients were from rural areas (P<0.001) and 26 (78.79%) of them were agricultural workers (P=0.031). All 33 had history of corneal injury (P<0.001) and 28 (84.85%) patients had injury with mud (P<0.001). All 33 (100%) patients had previous medical treatment (P=0.009) and 10 (30.3%) had used traditional eye medicines (P=0.183). A clinical pattern of ring infiltrate was characteristic in 15 (45.45%) patients. The diameter of the corneal ulcer was more than 6 mm in 27 (81.82%) eyes (P<0.001). Twenty-six (78.79%) patients had visual acuity of perception of light on initial presentation (P<0.001) and 24 (72.73%) had the same as their final visual outcome. The sensitivity of 10% potassium hydroxide (KOH) preparation was found to be higher (P<0.001) in the detection of Acanthamoeba cysts. CONCLUSION: The incidence of Acanthamoeba keratitis amongst the corneal ulcer patients was 1% in this setting and it was mainly due to corneal injury by mud. The KOH preparation is a sensitive diagnostic tool for the detection of Acanthamoeba. Delayed diagnosis or misdiagnosis and inappropriate antimicrobial therapy results in poor visual outcome.     

Neutrophil gelatinase-associated lipocalin: a novel suppressor of invasion and angiogenesis in pancreatic cancer

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa secreted acute phase protein, which is also up-regulated in multiple cancers, including breast, lung, and pancreas. Recently, NGAL has been proposed as an early biomarker in pancreatic cancer (PaCa). However, its biological role in PaCa is unknown. In this study, we examined in vitro and in vivo the functional role of NGAL in PaCa. Well- to moderately differentiated PaCa cells (AsPC-1, BxPC-3, and Capan-2) expressed high levels of NGAL but moderately to poorly differentiated PaCa cells (PANC-1 and MIAPaCa-2) expressed undetectable NGAL levels. Immunohistochemistry of untreated tissue microarray showed specific NGAL staining in resected PaCa specimens (P = 0.0167). Stable NGAL overexpression (MIAPaCa-2 and PANC-1) significantly blocked PaCa cell adhesion and invasion in vitro and vice versa with stable PaCa clones (BxPC-3 and AsPC-1). Moreover, NGAL overexpression reduced focal adhesion kinase (FAK) tyrosine-397 phosphorylation in PaCa cells. Furthermore, NGAL overexpression potently decreased angiogenesis in vitro partly through reduced vascular endothelial growth factor (VEGF) production and vice versa. Stable NGAL overexpression or underexpression had no effect on PaCa cell survival, viability, and response to chemotherapeutic drugs. Finally, MIAPaCa-2 cells overexpressing NGAL reduced tumor volume (P = 0.012), local and distant metastasis (P = 0.002), and angiogenesis (P = 0.05) with no effect on K-67 proliferation index (P > 0.1) in an orthotopic nude mouse PaCa model. Collectively, our results suggest that NGAL reduces adhesion/invasion partly by suppressing FAK activation and inhibits angiogenesis partly by blocking VEGF production in PaCa cells. Thus, NGAL is a potential suppressor of invasion and angiogenesis in advanced PaCa.     

First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and advances of new therapeutics

The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen‐activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio‐facio‐cutaneous syndrome, Legius syndrome, capillary malformation arterio‐venous malformation syndrome, and SYNGAP1 autism. Due to their common underlying pathogenetic etiology, all these syndromes have significant phenotypic overlap of which one common feature include a predisposition to tumors, which may be benign or malignant. Together as a group, they represent one of the most common multiple congenital anomaly syndromes estimating to affect approximately one in 1000 individuals worldwide. The subcontinent of India represents one of the largest populations in the world, yet remains underserved from an aspect of clinical genetics services. In an effort to bridge this gap, the First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and Advances of New Therapeutics was held in Kochi, Kerala, India. These proceedings chronicle this timely and topical international symposium directed at discussing the best practices and therapies for individuals with neurofibromatoses and RASopathies.     

Evolution of a Geriatric Syndrome: Pathophysiology and Treatment of Heart Failure with Preserved Ejection Fraction

The majority of older adults who develop heart failure (HF), particularly older women, have a preserved left ventricular ejection fraction (HFpEF). The prevalence of this syndrome is increasing, and the prognosis is not improving, unlike that of HF with reduced ejection fraction (HFrEF). Individuals with HFpEF have severe symptoms of effort intolerance, poor quality of life, frequent hospitalizations, and greater likelihood of death. Despite the importance of HFpEF, there are numerous major gaps in our understanding of its pathophysiology and management. Although it was originally viewed as a disorder due solely to abnormalities in left ventricular diastolic function, our understanding has evolved such that HFpEF is now understood as a systemic syndrome involving multiple organ systems, and it is likely that it is triggered by inflammation and other as‐yet‐unidentified circulating factors, with important contributions of aging and multiple comorbidities, features generally typical of other geriatric syndromes. We present an update on the pathophysiology, diagnosis, management, and future directions in this disorder in older persons.     

The Impact of Obesity on SARS-CoV-2 Pandemic Mortality Risk

The COVID-19 pandemic has uncovered the increased susceptibility of individuals with obesity to infection and severe disease leading to hospitalization and death. Studies in New York City demonstrated that after advanced age, obesity was the most common risk factor leading to severe disease and death from COVID-19. While the connection has been recognized, there has not been a general recognition of the potential mechanisms for this link between excess body fat and mortality from this viral pandemic including respiratory complications and sequelae of increased activation of the immune system. Despite plans for vaccination of the global population, the risk community spread of COVID-19 and future pandemics will be linked in part to obesity and immunity. This review will detail a number of potential mechanisms through which obesity may contribute to the lethality of this viral infection. These insights will hopefully lead to a greater emphasis on obesity prevention and treatment as part of the global response to this and future pandemic threats.     

The association between social support through contacts with Accredited Social Health Activists (ASHAs) and antenatal anxiety among women in Mysore,India: a cross-sectional study

Purpose

In India, antenatal anxiety prevalence estimates range from 6 to 48%. Social support is strongly associated with mental wellbeing, yet most studies have examined the impact of support from partners and family members rather than peers, community members, or health care providers. This study explores the supportive role of Accredited Social Health Activists (ASHA) contacts for antenatal anxiety.

Methods

Data were analyzed from the Saving Children, Improving Lives project, a quasi-experimental study conducted among rural, pregnant women in India. Regression models were used to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals for the relationship frequency of ASHA contacts and antenatal anxiety. Antenatal anxiety was measured using a subscale of the Edinburgh Postnatal Depression Scale.

Results

The sample consisted of 480 pregnant women. Reported antenatal anxiety prevalence was 27% (95% CI 23%, 31%). Participants who were more frequently visited by ASHAs at home (aPR: 0.90; 95% CI 0.76, 0.98) and more frequently accompanied by ASHAs to their antenatal care visits (aPR: 0.86, 95% CI 0.78, 0.95) were less likely to report antenatal anxiety. ASHA home visits were protective for the most vulnerable women (primigravida and those experiencing domestic violence) and ASHA accompaniment to antenatal care visits was equally protective for all women.

Conclusions

ASHAs are valued for their contribution towards maternal health education and linking women of reproductive age to healthcare services. Our findings additionally suggest the important role ASHAs play in providing social support to pregnant women, particularly those who are most vulnerable to experiencing antenatal anxiety.

     

Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design,synthesis, and in vitro and in silico evaluation of antimycobacterial activity against Mycobacterium tuberculosis

Mycobacterium tuberculosis resistance to commercially available drugs is increasing day by day. To address this issue, various strategies were planned and are being implemented. However, there is a need for new drugs and rapid diagnostic methods. For this endeavour, in this paper, we present the synthesis of acetylene containing 2-(2-hydrazinyl) thiazole derivatives and in vitro evaluation against the H37Rv strain of Mycobacterium tuberculosis. Among the developed 26 acetylene containing 2-(2-hydrazinyl) thiazole derivatives, eight compounds inhibited the growth of Mycobacterium tuberculosis with MIC values ranging from 100 μg ml⁻¹ to 50 μg ml⁻¹. The parent acetylene containing thiosemicarbazones showed promising antimycobacterial activity by inhibiting up to 75% of the Mycobacterium at 50 μg ml⁻¹. In addition, in silico studies were employed to understand the binding mode of all the novel acetylene-containing derivatives against the KasA protein of the Mycobacterium. Interestingly, the KasA protein interactions with the compounds were similar to the interactions of KasA protein with thiolactomycin and rifampicin. Cytotoxicity study results indicate that the compounds tested are non-toxic to human embryonic kidney cells.

In an attempt to find novel anti-mycobacterial agents, novel acetylene containing 2-(2-hydrazinyl)thiazole derivatives have been synthesized and evaluated against Mycobacterium tuberculosis.