Loss of RAB25 Cooperates with Oncogenes in the Transformation of Human Mammary Epithelial Cells (HMECs) to Give Rise to Claudin-Low Tumors.

The loss of RAB25 expression-RAS superfamily of GTPase characteristic of numerous breast cancers-corresponds with H-RAS point mutations, particularly in triple-negative breast cancers (TNBC), a subtype associated with a poor prognosis. To address the poorly understood factors dictating the progression of TNBC tumors, we examine the cooperative effects that loss of RAB25 expression in human mammary epithelial cell (HMEC) lines with H-RAS mutations confers in tumorigenesis. HMECs were immortalized by transduction with LXSN CDK4 R24C, a mutant form of cyclin-dependent kinase, followed by transduction with hTERT, a catalytic subunit of the telomerase enzyme. We found that with the loss of RAB25 and overexpression of mutant H-RAS61L, immortal HMECs transformed toward anchorage-independent growth and acquired an increased ability to migrate. Furthermore, cells express low CD24, high CD44, and low claudin levels, indicating stem-like properties upon transformation. Besides, loss of RAB25 and overexpression of H-RAS61L resulted in increased expression of transcription factors Snail and Slug that drive these cells to lose E-cadherin and undergo epithelial-mesenchymal transition (EMT). This study confirms that loss of RAB25 and overexpression of mutant H-RAS can drive HMECs toward a mesenchymal stem-like state. Our findings reveal that RAB25 functions as a tumor suppressor gene, and loss of RAB25 could serve as a novel biomarker of the claudin-low type of TNBC.

Low Cluster of Differentiation 4+ T Cell Count in People Living with HIV/AIDS Undergoing Antiretroviral Therapy Visiting a Reference Laboratory: A Descriptive Cross-sectional Study.

INTRODUCTION: Human Immunodeficiency Virus is a lentivirus that causes human immunodeficiency virus infection and over time, acquired immunodeficiency syndrome. Cluster of Differentiation 4+ T cell count of people living with this infection play a vital role to determine infection progression and necessary treatment changes. This study was conducted to find out the prevalence of low Cluster of Differentiation 4+ T Cell Count in the People Living with human immunodeficiency virus/ acquired immunodeficiency syndrome. METHODS: A descriptive cross-sectional study was conducted between June to August 2018 in the Human Immunodeficiency virus and Hepatitis Reference Unit of National Public Health Laboratory, Ministry of Health and Population Teku. Ethical approval was taken (Reference Number 2912) and a total of 550 seropositive cases of Human Immunodeficiency Virus-1 undergoing antiretroviral therapy were studied. Convenient sampling technique was used. Data was analysed by Statistical Package for the Social Sciences. RESULTS: Seventeen (3.1%) of patients had Cluster of Differentiation 4+ T cell counts below 100 cells/mm3 of blood. The mean Cluster of Differentiation 4+ T cell count was 509.3 cells/mm3 of blood. Of the total samples, 280 (50.9%) were males, 268 (48.7%) were females, and the rest 2 (0.4%) were of other gender. CONCLUSIONS: Majority of people living with human immunodeficiency virus/ acquired immunodeficiency syndrome were found immune-competent.

Lifestyle, behavior, perception and practices of Nepalese during lockdown due to COVID-19 pandemic.

INTRODUCTION: COVID-19 infection is caused by a new strain of SARS CoV-2 virus, which transmits directly from person-to-person and has become a pandemic. To counteract this, actions related to mass quarantines or stay-at-home orders have been used termed as lockdown. This study aims to study lifestyle, behaviour, perception and practice of people regarding during the lockdown. METHODS: An online survey was conducted with structured questionnaire in Google forms after ethical approval from Nepal Health Research Council (Ref-2631). The attributes of knowledge, attitude and practices were explored using multiple-choice questions and results were statistically analysed using Microsoft excel. RESULTS: Five hundred fifty-five respondents completed the survey with 280 (50.5%) males and 275 (49.5%) female. The knowledge regarding viral pandemic was increased in 496 (89.3%) respondents. 424 (76.4%) people developed stress due to pandemic. Three hundred fifty three (63.6%) were adversely affected by professional works or suffered economic loss in business. More than 42% participants are using their time for study in personal development, online classes etc. Conclusions: The knowledge of viral pandemic as well as personal hygiene habits have improved in majority of people but many also developed stress. They were convinced that lockdown lowered transmission of infection which in turn affected lifestyle behaviour and practices. Practicing social distancing becomes too difficult for the poor in the absence of proper social security system and government support. E-Learning has become more acceptable due to lockdown. Further studies with in-person interviews are warranted.