An in-silico analysis of hydrodynamics and gas mass transfer characteristics in scale-down models for mammalian cell cultures.

Bioprocess scale-up and technology transfer can be challenging due to multiple variables that need to be optimized during process development from laboratory scale to commercial manufacturing. Cell cultures are highly sensitive to key factors during process transfer across scales, including geometric variability in bioreactors, shear stress from impeller and sparging activity, and nutrient gradients that occur due to increasing blend times. To improve the scale-up and scale-down of these processes, it is important to fully characterize bioreactors to better understand the differences that will occur within the culture environment, especially the hydrodynamic profiles that will vary in vessel designs across scales. In this study, a comprehensive hydrodynamic characterization of the Ambr® 250 mammalian single-use bioreactor was performed using time-accurate computational fluid dynamics simulations conducted with M-Star computational fluid dynamics software, which employs lattice-Boltzmann techniques to solve the Navier-Stokes transport equations at a mesoscopic scale. The single-phase and two-phase fluid properties within this small-scale vessel were analyzed in the context of agitation hydrodynamics and mass transfer (both within the bulk fluid and the free surface) to effectively characterize and understand the differences that scale-down models possess when compared to their large-scale counterparts. The model results validate the use of computational fluid dynamics as an in-silico tool to characterize bioreactor hydrodynamics and additionally identify important free-surface transfer mechanics that need to be considered during the qualification of a scale-down model in the development of mammalian bioprocesses.

Effect of educational intervention on risk factors of cardiovascular diseases among school teachers: a quasi-experimental study in a suburb of Kolkata, West Bengal, India.

OBJECTIVE: This prospective study aimed to evaluate the effects of a health education intervention on cardiovascular disease (CVD) risk factors among school teachers. METHODS: The study, conducted from August 2016 to May 2017, involved teachers from four schools in Baruipur, West Bengal, India. It was a multicentric, quasi-experimental study with an intervention group receiving tailored health education promoting lifestyle modifications, while the control group received no intervention. Baseline and endline assessments included behavioural and biological characteristics related to cardiovascular health and risk assessment. Data were analysed using JAMOVI. RESULTS: The intervention group showed significant improvements in physical activity levels [Cohen's d (Cd): 0.43, p = 0.006] and the consumption of fruits and vegetables (Cd: 1.00, p = < 0.001). Notably, there was a considerable reduction in the consumption of salt (Cd: -0.93, p = 0.039), oil (Cd: -0.98, p = < 0.001), fast food (Cd: -0.99, p = < 0.001), junk food (Cd: -0.99, p = < 0.001), and red meat (Cd: -1.00, p = < 0.001) among participants. However, there were no significant improvements in biological characteristics within the intervention group. In contrast, the control group exhibited no significant changes in behavioural and biological characteristics compared to baseline. The intervention group showed a minor non-significant reduction (3.0%) in their 10-year cardiovascular risk compared to baseline (Cd: -1.00, p = 0.50), while the control group had a negligible non-significant increase (0.7%) in their cardiovascular risk (Cd: 1.00, p = 1.00). CONCLUSION: Health education intervention positively influenced behavioural characteristics, such as physical activity and dietary habits, among school teachers. However, no significant improvements were observed in biological characteristics or cardiovascular risk factors.

Factors Associated with Intention and Attempt to Quit: A Study among Current Smokers in a Rural Community of West Bengal.

CONTEXT: Tobacco smoking is one of the preventable causes of death. Global Adult Tobacco Survey 2 report showed that 19% Indian males were current smokers. It is important to find out factors which help smokers on smoking cessation, ultimately to prevent of lung and other morbidities. There are few community-based studies on intention and attempt to quit smoking in rural area. AIMS: The present study aimed to determine the factors associated with intention and attempt to quit smoking among current smokers. SETTINGS AND DESIGN: A cross-sectional study was conducted from June to September 2019 among 198 male daily smokers residing in the rural field practice area of AllH and PH, Kolkata. SUBJECTS AND METHODS: After cluster sampling, data were collected by predesigned schedule by the face-to-face interview. RESULTS: 151 (76.3%) study subjects intended to quit smoking. 63 (31.8%) study subjects attempted to quit in last 1 year. Thirty-one (47.5%) showed high-to-medium nicotine dependence. There was a significant association of intention to quit with agriculture as occupation (acquisitive crime [AOR]-2.17, confidence interval [CI]-1.01-4.63), low nicotine dependence (AOR-2.98, CI-1.43-6.21), doctor's advice (AOR = 2.84, CI-1.27-6.33), and family pressure (AOR = 2.16, CI-1.07-4.38). Attempt to quit was significantly associated with low nicotine dependence (AOR = 5.85, CI-2.85-12.00), family pressure (AOR = 2.94, CI-1.47-5.91). CONCLUSION: Along with counseling to reduce nicotine dependence, comprehensive approach both from family members as well as health care providers, is vital to escalate the quitting behaviour in smoking habit.

Metabolic syndrome and its correlates: A cross-sectional study among adults aged 18-49 years in an Urban Area of West Bengal.

BACKGROUND: The prevalence of metabolic syndrome (MetS) is increasing dramatically of late, across all ages irrespective of gender, socioeconomic status, and ethnicity. People with MetS have twice the likelihood of developing and dying from cardiovascular disease and more than seven times the risk of developing diabetes. OBJECTIVES: This study was undertaken to determine the prevalence of MetS among adults who were in their first three decades of adulthood and to find out the risk factors of MetS among them. METHODS: This was a community based cross-sectional study among 388 subjects aged 18-49 years selected by multistage random sampling in an area of Kolkata, India, from November 2016 to October 2018 over 2 years. Data collection was done using a structured questionnaire along with anthropometry, blood pressure measurement, and relevant blood tests. Physical activity was classified by the International Physical Activity Questionnaire Short-Form questionnaire. Data were analyzed using the Statistical Package for the Social Sciences (version 16.0), and descriptive statistics were calculated as frequency and percentage. Logistic regression was done to determine the strength of association between MetS and different risk factors. RESULTS: The prevalence of MetS was 44.6% (35.4% in males and 55.6% in females), and female gender, poor economic status, sedentary lifestyle, poor diet, and addiction of tobacco were found to be the risk factors of MetS in the final model using multivariable logistic regression. CONCLUSION: This research revealed the high prevalence of MetS in the community. The effective primordial and primary level of prevention along with prevailing secondary or tertiary level of prevention should have been employed to curtail the epidemic of MetS.

Morbidities of rice mill workers and associated factors in a block of West Bengal: A matter of concern.

CONTEXT: Rice mill workers usually belong to unorganized sector and lack in training regarding hazard prevention. Unprotected exposure to suspended particles and fumes can lead to respiratory morbidities among them. Workers, especially loaders, were susceptible to work-related musculoskeletal diseases. AIM: To find out the morbidity profile and associated factors among rice mill workers. METHODOLOGY: A cross-sectional workplace-based study was conducted during July--September 2018 among 143 workers of two rice mills in Indas block, West Bengal. Workers, employed for at least 6 months in the rice mills and who gave informed written consent was interviewed using a predesigned pretested questionnaire and were clinically examined. Nonfasting capillary blood glucose estimation and spirometry were carried out. Workers contraindicated to spirometry were excluded. RESULT: Commonest morbidities were musculoskeletal discomfort (65%), hypertension (20.9%), and chronic respiratory morbidity (16.9%). No personal protective equipment (PPE) was used by these workers. Significant association of musculoskeletal discomfort was found with tobacco abuse (Adjusted Odds Ratio (AOR) =2.90), job of loader (AOR = 3.51), and central obesity (AOR = 3.39). Hypertension was significantly associated with increasing age (AOR = 1.06), and increasing body mass index (AOR = 1.17). Whereas increasing age (AOR = 1.08), working inside mill (AOR = 7.58), working more than 48 hours a week (AOR = 7.37) were significantly associated with chronic respiratory morbidity. CONCLUSION: Optimization of working hours, effective continuous use of PPE, and use of proper ventilation technology are recommended. Proper work placement, preplacement examination, and periodic health screening with spirometry are also needed.

Tobacco exposure is a menace among women: - A cross-sectional study in a rural area of West Bengal, India.

CONTEXT: In India, despite implementation of the strategies under National Tobacco Control Programme [NTCP], women are easily exposed to tobacco consumption that is smokeless (SLT) and smoking tobacco along with second-hand smoke [SHS], making them highly susceptible to tobacco hazards. AIMS: This study aimed to assess the exposure of women to tobacco use and SHS at home and to elicit predictors of tobacco exposure in a rural community of West Bengal. METHODOLOGY: A community based, cross-sectional study was conducted among 176 women aged 18 years and above. Data was collected by cluster sampling technique (16*11) using predesigned pretested structured schedule. Tobacco exposure was measured using a composite score including tobacco consumption and SHS at home. RESULTS: Tobacco use (SLT and smoking tobacco) was significantly associated with educational attainment [AOR = 2.12], occupation [AOR = 2.13] and knowledge [AOR = 1.22]. There was significant association between SHS at home with knowledge [AOR = 1.16] and attitude of the study subjects. [AOR = 1.93]. Overall tobacco exposure (SLT, smoking tobacco, and SHS), was found to be 79.5%. Significant association was found between high tobacco exposure with age group [AOR = 3.82], educational attainment [AOR = 1.74] and knowledge regarding hazards of tobacco [AOR = 1.31]. CONCLUSION: Prevalence of SLT use as well as exposure of women to SHS at home is unexpectedly high in the study population. Women specific information and education campaigns focusing on tobacco hazards (both tobacco use and SHS) through existing primary health care infrastructure should be strategized under NTCP.

A study on impact of oral health on general health among the elderly residing in a slum of Kolkata: A cross-sectional study.

CONTEXT: Oral health means more than only good teeth. It is a state-of-being-free from mouth and facial pain, oral and throat cancer, oral infections, periodontal diseases, tooth decay or loss, and other diseases/disorders. The age distribution of the world's population is changing. With advances in medicine, the proportion of older people continues to increase worldwide. AIMS, SETTING, MATERIALS AND METHODS: A cross-sectional study was carried out among 158 elderly (>60 years) residing in a slum of Kolkata during the period from April 2017 to June 2017 to assess the impact of oral health on general health. Data were collected using a pretested predesigned schedule containing Geriatric Oral Health Assessment Index. Data analysis was performed in R software. Poisson regression was used to find the associates of the impact of oral health. RESULTS: Mean (standard deviation) age was 68.54 (5.9) years. A total of 104 (65.8%) participants reported; foul breath as a problem and 88 (55.7%) reported gum bleeding as a problem. All participants used to clean their teeth daily but only 36.1% used to clean their teeth at least twice daily. More than half the participants reported that they have limited the kind of food they eat due to dental/gum condition and trouble chewing. CONCLUSION: There is a need to provide sensitive oral health services that are accessible, affordable, appropriate, and acceptable. Knowledge regarding oral health and hygiene should be provided to all elderly, especially diabetics. Further research with the broader conceptual framework, in different age groups and in different settings are warranted.

Effect of DOTS on quality of life among tuberculosis patients: A follow-up study in a health district of Kolkata.

CONTEXT AND AIMS: This study was carried out to assess quality of life (QoL) of tuberculosis patients receiving treatment from DOTS centres, to find out its change with treatment, and to ascertain its determinants. MATERIALS AND METHODS: An institution based follow-up study was conducted in Bagbazar Urban Health District (UHD), Kolkata where all the tuberculosis patients registered within 1st 4 months of data collection were followed up for their current course of treatment. Quality of Life (QoL) was assessed using SF36v2 questionnaire at the start of treatment and after continuation phase (CP) (within 14 days). STATISTICAL ANALYSIS USED: General Linear Model was used to assess the predictors of change of QoL with treatment. RESULTS: 61.4% and 16.4% patients were at the risk of depression at the start and end of their TB treatment respectively. Patient's per-capita monthly Income (PCI) and current smoking status interacted with time to predict trends in the Physical component scores. Similarly, PCI and educational status interacted with time to predict trends in the mental component scores. PCI and unemployment were found to be predictor of differences of Physical and mental component scores (between subject effects) respectively. CONCLUSIONS: QoL assessment in different stages of treatment should be incorporated in the ongoing RNTCP to make the programme more client-oriented and comprehensive, and to provide social support to those who need it most. Directly observed treatment should be supplemented with economic support, de-addiction campaign and Inter-personal counselling by the DOTS providers.

Vitamin D status among women aged 40 years and above in a rural area of West Bengal: A community-based study.

INTRODUCTION: Vitamin D deficiency is a recognized pandemic. Even in a tropical country like India, where there is plentiful sunshine, vitamin D deficiency is widely prevalent. Adult females, particularly those above the age of 40, are mostly affected because vitamin D determines the pattern of post-menopausal bone loss and age-related osteoporosis. METHODS: A community-based cross-sectional study was conducted from April-December 2017 among 194 women aged 40 years and above residing in the village of Singur, West Bengal. For this study, multistage random sampling method was used. Each respondent was interviewed using a structured schedule to collect data on sociodemographic characteristics, dietary pattern, their daily sun exposure, tobacco use, and morbidity profile. Individuals with 25OH vitamin D <30ng/ml were said to have vitamin D insufficiency (VDI). Data entry and analysis was done using SPSS version 16.0. RESULTS: Out of 194 participants, 70.6% had VDI (Vitamin D deficient-19.6%, Vitamin D insufficient-51.0%). Mean (SD) age of the participant was 56.9 (8.9) years. Mean (SD) duration of daily sun exposure was 138.5 (59.2) minutes. 74 (38.1%) had overweight/obesity. Only 73 (37.6%) had adequate diet. Test results revealed low SES, decreasing duration of daily sun exposure, diabetes, overweight/obesity, and inadequate diet as significant predictors of VDI, explaining 39.3% of the variance with model fit. CONCLUSION: The study has identified factors associated with VDI among the study participants. Emphasis on promoting consumption of vitamin D rich food and with vitamin D supplements, outdoor activities to increase sun exposure, maintaining optimum body weight, and strictly adhering to diabetes control will help alleviate the problem at large.

Determinants of menstrual hygiene among school going adolescent girls in a rural area of West Bengal.

BACKGROUND: Menstrual hygiene is a neglected issue in rural India. Lack of menstrual hygiene in adolescent girls can make them susceptible to various morbidities, for example, reproductive tract infection and urinary tract infection and their long-term consequences, for example, cervical cancer, infertility, and ectopic pregnancy. This study aims to find out the determinants of menstrual hygiene among the school going adolescent girls in a rural area of West Bengal. OBJECTIVES: To elicit the menstrual hygiene practices among the study population and to find out the association of poor menstrual hygiene practices with sociodemographic factors, such as age, occupation and education of the parents, housing, and presence of sanitary toilet. MATERIALS AND METHODS: A descriptive, cross-sectional study was conducted among 307 school going adolescent girls of 12-17 years age group in a rural area of West Bengal. RESULTS: Majority of the students in both schools (62.9%) were Hindu, general caste (54.1%) and belonged to nuclear family (69.7%). Most of the parents in both schools had completed their education up to primary level. Bivariate analyses were done, and the significant factors predicting good menstrual hygiene were entered into the multivariable logistic regression model. It revealed that good menstrual hygiene was more among those whose mothers were educated (adjusted odds ratios [AOR] 2.3 [1.06-5.01]), and who were homemakers (AOR 2.3 [1.06-5.01]). CONCLUSIONS: Menstrual hygiene among the study population was found to be poor. The improving education level of the mothers can go a long way in improving menstrual hygiene practice.

Prevalence and determinants of delay in diagnosis of pulmonary tuberculosis in Darjeeling district of West Bengal.

BACKGROUND: Delayed diagnosis of tuberculosis (TB) is a significant problem both in individual as well as community level. Different studies around globe revealed that these diagnostic delays are attributed to both patient delay and health system-related delay. AIMS: This study aims to assess the magnitude of delay in diagnosis and the association with sociodemographic profile among new sputum-positive pulmonary TB patients in Darjeeling district. MATERIALS AND METHODS: A cross-sectional study was conducted among 374 TB patients from October 2011 to March 2012 using a predesigned pretested schedule by face-to-face interview. STATISTICAL ANALYSIS: Logistic regression analysis, odds ratios (OR), adjusted ORs. RESULTS: Patient delay, health system delay and total diagnostic delay were 27 days, 20.1 days, and 20.6 days; mean delays were 23.64, 5.71, and 29.46 days, and median delays were 25, 5, and 32 days, respectively. Risk factors associated with patient delay were female gender, rural residence, illiteracy, smoking, alcohol consumption, taking two, or more alternate treatments; for health system delay were female sex, rural residence, time to reach health facility, time spent per visit; and for total diagnostic delay were female sex, alcoholism, and seeking more than two alternate treatment. CONCLUSIONS: The risk factors for delay identified may be the subject of future interventions.

AECHL-1 targets breast cancer progression via inhibition of metastasis, prevention of EMT and suppression of Cancer Stem Cell characteristics.

Triple negative breast cancer (TNBC) features among the most aggressive manifestations of cancer due to its enhanced metastatic potential and immunity to therapeutics which target hormone receptors. Under such scenarios, anti-cancer compounds with an ability to influence multiple targets, or an entire process, will have an advantage over specific signal transduction inhibitors. To counter the metastatic threat it is essential to target cellular components central to the processes of cancer cell migration and adaptation. Our previous work on a novel triterpenoid, AECHL-1, explored its anti-cancer potential, and linked it to elevated ER stress in cancer cells, while its anti-angiogenic potential was credited for its ability to manipulate the cytoskeleton. Here, we broaden its range of action by showing that it curbs the metastatic ability of TNBC cells, both in vitro in MDA-MB-231 cell line and in vivo, in mouse models of metastasis. AECHL-1 does so by disrupting the cytoskeletal network, and also suppressing NF-κB and ß-Catenin mediated key molecular pathways. These activities also contributed to AECHL-1 mediated suppression of TGF-ß/TNF-α induced Epithelial to Mesenchymal Transition (EMT) and cancer stem cell characteristic. Thus, we present AECHL-1 as a promising therapeutic inhibitor of metastatic disease.

Novel triterpenoid AECHL-1 induces apoptosis in breast cancer cells by perturbing the mitochondria-endoplasmic reticulum interactions and targeting diverse apoptotic pathways.

BACKGROUND: The modus operandi for an anti-cancer drug must allow for an efficient discrimination system between tumorigenic and non-tumorigenic cells. Targeting ER stress and mitochondrial function in cancer cells appears to be a suitable option, as these processes are dysregulated in tumor cells. AECHL-1, a novel triterpenoid, exhibits potent anticancer activity against an array of cancer cell lines however, its mechanism of action remains elusive. METHODS: Molecular targets of AECHL-1 were investigated using breast adenocarcinoma cells MCF-7, MDA-MB-231 and mammary epithelial cell line MCF 10A in vitro and xenograft tumors in SCID mice in vivo. Western blotting, flow cytometry, and immunohistochemical studies were employed to delineate the molecular pathways. RESULTS: AECHL-1 caused a transient elevation of ER stress proteins along with a prolonged phosphorylation of eIF2α in breast cancer cells. This was accompanied by a simultaneous release of calcium from ER stores and subsequent mitochondrial accumulation. These effects could be reversed by using ER stress inhibitors. AECHL-1 brings about mitochondria mediated, caspase independent cell death via AIF in MCF-7 cells; MDA-MB-231 succumbed to caspase dependent extrinsic pathway. Xenograft studies closely echoed our in vitro results. AECHL-1 did not alter cellular and molecular parameters in MCF 10A. CONCLUSION: These findings reveal that, AECHL-1 targets the Achilles Heel of cancer cell, namely dysfunctional ER and mitochondria while being non toxic to normal parenchyma and can thus be further explored as a potential chemotherapeutic intervention. GENERAL SIGNIFICANCE: Aggravation of ER stress by AECHL-1 uncovers a novel pathway for selective elimination of cancer cells.

AECHL-1, a novel triterpenoid, targets tumor neo-vasculature and impairs the endothelial cell cytoskeleton.

Tumor angiogenesis is characterized by abnormal vessel morphology leading to erratic and insufficient delivery of chemotherapeutics and oxygen, making the tumor core not only highly hypoxic but also unresponsive toward treatment. Such hypoxic conditions promote tumor aggressiveness, leading to the establishment of metastatic disease. Most anti-angiogenic treatments aim toward the destruction of tumor vasculature, which proves countereffective by further increasing its aggressive nature. Hence, developing drugs which target or regulate these processes might lead to a better delivery of chemotherapeutics resulting in tumor shrinkage. Plant-derived natural compounds having a bioactive ingredient, especially triterpenoids, have been known to possess anticancer properties. AECHL-1, a recently isolated novel triterpenoid with proven anticancer potential, is seemingly noncytotoxic toward HEK 293 and HUVECs. Also, cytotoxicity was absent during in vivo studies involving intraperitoneal injections with 5 µg/kg body weight AECHL-1 on SCID mice. When used at subtoxic doses, it was found to be effective in suppression of neo-vessel formation as demonstrated in the chick chorioallantoic membrane, rat aortic rings, Matrigel plugs and xenograft tumors implanted in SCID mice. Tumor vasculature from AECHL-1-treated mice showed greater mural cell coverage and relatively normalized architecture. Investigations into the molecular mechanisms responsible for these observations revealed an effect on the actin cytoskeleton of stimulated HUVECs as well as the VEGFR2-mediated MAPK pathway. AECHL-1 could effectively distinguish between stimulated and nonstimulated endothelial cells. AECHL-1 could also downregulate HIF-1α expression and VEGF secretion under hypoxic conditions, thus reducing the fears of unnecessarily aggravating tumor metastasis as a result of anti-angiogenic therapy. Results obtained from the aforementioned studies make it clear that though AECHL-1 shows promise in discouraging and pruning neo-vasculature, it may not affect existing vasculature as the doses used for the assays are significantly lower than the ones causing endothelial cell death and has potential to be considered as a candidate for therapeutic drug development.

Perceptions of people living with HIV/AIDS.

BACKGROUND: HIV/AIDS being a behavioral disease, appropriate knowledge is important for those who are infected. OBJECTIVES: To elicit and compare knowledge and attitude about HIV/AIDS among newly diagnosed and previously diagnosed HIV/AIDS patients attending or admitted in Calcutta School of Tropical Medicine, (CSTM), Kolkata. MATERIALS AND METHODS: A cross-sectional descriptive study was undertaken among previously diagnosed HIV/AIDS Patients admitted in indoor wards and newly diagnosed HIV/AIDS patients attending Integrated Counseling and Testing Centre (ICTC) of the School of Tropical Medicine, Kolkata. Data were gathered by interviewing patients using a predesigned, pretested, semi-structured questionnaire. RESULTS: More in-patients had heard about AIDS than ICTC patients. Television was the most popular source of information in both groups, followed by health personnel and friends. Correct knowledge about transmission, symptoms, prevention of AIDS, and lifestyles desirable for affected patients was significantly higher among in-patients who had already been counseled, than the newly diagnosed ICTC patients yet to receive. Within each group of patients, the knowledge score was significantly higher among females, Christians, urban residents, patients educated beyond middle school, and non- migrants. In-patients had a significantly higher attitudinal score toward HIV/AIDS. CONCLUSION: Repeated counseling is required to keep up high level of knowledge and positive attitude pertaining to HIV/AIDS to reduce risk behavior, prevent disease transmission, and improve quality of life.

Licit and illicit substance use by adolescent students in eastern India: Prevalence and associated risk factors.

BACKGROUND: Use of tobacco, alcohol, and other substances is a worldwide problem and affects many adolescents. OBJECTIVE: (1) To find out the magnitude of licit and illicit substance use among students; and (2) to find out the association between socioeconomic and demographic characteristics of the students and habits of use. MATERIALS AND METHODS: This was a population-based cross-sectional study conducted during June 2003 to May 2004. In a multistage random sampling among all the districts and schools in West Bengal, India, 416 high school students from two schools were selected. The main outcome measures were substance use, namely, tobacco, alcohol, and cannabinoids. From the schools, all the students in the classes VIII, IX, and X were taken as the study population and were administered a pretested close-ended anonymous self-administered questionnaire relating to pattern, frequency, and correlates of substance use. RESULTS: The ultimate response rate was 87.02% and 416 students could be covered in our study. The overall prevalence rates among rural and urban students were 6.14% and 0.6% for illicit drug use, 8.60% and 11.04% for tobacco, and 7.37% and 5.23% for alcohol consumption, respectively. Both licit and illicit substance use was associated more with male students. Current and regular use were mostly restricted to tobacco, and the use of a substance by family members had a significant impact on its use by their children. "Enjoyment" and "Curiosity" were found to have the major influence in their decision to use a substance. CONCLUSIONS: Early identification of the magnitude and the factors related to substance use can improve scopes for planning and preventive approaches for this vulnerable group before the problems get serious after which interventions become difficult.