The prognostic significance of lysosomal protective protein (Cathepsin A) in breast ductal carcinoma in situ

Background: Cathepsin A (CTSA) is a key regulatory enzyme for galactoside metabolism. Additionally, it has a distinct proteolytic activity and plays a role in tumour progression. CTSA is differentially expressed at the mRNA level between breast ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). In this study, we aimed to characterise CTSA protein expression in DCIS and evaluate its prognostic significance. Methods: A large cohort of DCIS (n=776 for pure DCIS and n=239 for DCIS associated with IBC (DCIS/IBC)) prepared as tissue microarray was immunohistochemically stained for CTSA. Results: High CTSA expression was observed in 48% of pure DCIS. High expression was associated with features of poor DCIS prognosis including younger age at diagnosis (less than 50 years), higher nuclear grade, hormone receptor negativity, HER2 positivity, high proliferative index and high hypoxia inducible factor 1 alpha expression. High CTSA expression was associated with shorter recurrence free interval (RFI) (p=0.0001). In multivariate survival analysis for patients treated with breast conserving surgery, CTSA was an independent predictor of shorter RFI (p=0.015). DCIS associated with IBC showed higher CTSA expression than pure DCIS (p=0.04). In the DCIS/IBC cohort, CTSA expression was higher in the invasive component than DCIS component (p less than 0.0001). Conclusion: CTSA is not only associated with aggressive behaviour and poor outcome in DCIS but also a potential marker to predict co-existing invasion in DCIS

The impact of COVID-19 on mental health outcomes among hospital fever clinic attendants across Nepal: A cross-sectional study.

BackgroundThe COVID-19 pandemic has been creating a panic and distressing situations among the entire population globally including Nepal. No study has been conducted assessing the psychological impact of this pandemic on the general public in Nepal. The objective of this study is to assess the mental health status during COVID-19 outbreak and explore the potential influencing factors among the population attending the hospital fever clinics with COVID-19 symptoms.MethodsA cross-sectional survey was conducted between May-June, 2020 with a sample of 645 participants aged 18 and above in 26 hospitals across Nepal. Telephone interviews were conducted using a semi-structured questionnaire along with a validated psychometric tool, the Depression, Anxiety and Stress (DASS-21) scale. The metrics and scores of symptoms and their severity were created and analyzed. Multivariate logistic regression was used to determine the association of potential covariates with outcome variables.ResultsThe prevalence of anxiety, depression and stress were 14%, 7% and 5% respectively. In reference to Karnali, participants from Bagmati province reported higher level of anxiety (OR 3.44, 95% CI 1.31-9.06), while stress (OR 4.27, 95% CI 1.09-18.32) and depressive symptoms (OR 3.11, 95% CI 1.05-9.23) observed higher among the participants in Province 1. Women were more at risk of anxiety (OR 3.41, 95% CI 1.83-6.36) than men. Similarly, people currently living in rented houses reported more stress (OR 2.97, 95% CI 1.05-8.43) and those living far from family reported higher rates of depressive symptoms (OR 3.44, 95% CI 1.03-11.46).ConclusionThe study identified increased prevalence of stress, anxiety and depressive symptoms during the initial stage of COVID-19 pandemic in Nepal. Considering the findings, there is urgent need to develop and implement appropriate community-based mental health programs targeting individuals who have had COVID-19 symptoms and who are prone to develop adverse mental health outcomes

Morphogenetic and chemical stability of long-term maintained <i>Agrobacterium</i>-mediated transgenic <i>Catharanthus roseus</i> plants

<div><p>Transgenic <i>Catharanthus roseus</i> plants (transgenic Dhawal [DT] and transgenic Nirmal [NT]) obtained from the <i>Agrobacterium tumefaciens</i> and <i>Agrobacterium</i><i>rhizognenes</i>-mediated transformations, respectively, have been maintained <i>in vitro</i> for 5 years. Plants were studied at regular intervals for various parameters such as plant height, leaf size, multiplication rate, alkaloid profile and presence of marker genes. DT plant gradually lost the <i>GUS</i> gene expression and it was not detected in the fifth year while NT plant demonstrated the presence of genes <i>rol</i><i>A</i>, <i>rol</i><i>B</i> and <i>rol</i><i>C</i> even in the fifth year, indicating the more stable nature of <i>Ri</i> transgene. Vindoline content in the DT was two times more than in non-transformed control plants. Alkaloid and tryptophan profiles were almost constant during the 5 years. The cluster analysis revealed that the DT plant is more close to the control Nirmal plant followed by NT plant.</p></div

Analytical methods for determination of terbinafine hydrochloride in pharmaceuticals and biological materials

Terbinafine is a new powerful antifungal agent indicated for both oral and topical treatment of mycosessince. It is highly effective in the treatment of determatomycoses. The chemical and pharmaceutical analysis of the drug requires effective analytical methods for quality control and pharmacodynamic and pharmacokinetic studies. Ever since it was introduced as an effective antifungal agent, many methods have been developed and validated for its assay in pharmaceuticals and biological materials. This article reviews the various methods reported during the last 25 years