BackgroundNaswar is a type of finely ground, moistened smokeless dipping tobacco product being commonly used in Pakistan. Although, nicotine is the most important psychoactive agent present in Naswar, it also exerts immunosuppressive effects and could alter the levels of cytokines. Additionally, the effects of Naswar consumption on thyroid hormones are not known.MethodsEighty healthy males aged 16–43 years were selected for the study and were divided into a control group comprising 31 healthy subjects with no history of tobacco use in any form, with age matched test group comprising 49 exclusive Naswar users who were consuming Naswar for at least 1 year. Estimation of serum interleukin (IL)-1β, IL-6, free thyroxine (FT4), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) was carried out. The data was analyzed by statistical programme (SPSS) using student's independent samples t-test. One way Anova followed by post hoc Tukey test was applied to assess parameters in Naswar users grouped according to duration of Naswar usage. Pearson’s correlation coefficient was applied to assess correlations between parameters.ResultsIL-1β was found to be significantly lowered in Naswar users compared to the control group whereas serum FT3 and FT4 levels in Naswar users were significantly raised compared to the control group. However, no differences in the levels of serum IL-6 and TSH between Naswar users and the control group were found. Also, serum FT3 and FT4 were consistently raised whereas IL-1β was lowered in Naswar users irrespective of duration of Naswar consumption. IL-1β was negatively correlated with FT3 in Naswar users.ConclusionThe findings suggest that Naswar users might be in an immune suppressive state as evident by the lowered levels of interleukin 1β. Additionally, alterations in the levels of thyroid hormones signify the impact of Naswar consumption on thyroid function.

Regression techniques are generally used to predict a response variable using one or more predictor variables. In many fields of study, the regressors can be highly intercorrelated, which leads to the problem of multicollinearity. Consequently, the ordinary least squares estimates become inconsistent and lead to wrong inferences. To handle the problem, machine learning techniques particularly, the ridge regression approach, are commonly used. In this paper, we revisit the problem of estimating the ridge parameter "k" by proposing some new estimators using the Jackknife method and compare them with some existing estimators. The performance of the proposed estimators compared to the existing ones is evaluated using extensive Monte Carlo simulations as well as two real data sets. The results suggested that the proposed estimators outperform the existing estimators.

Nicotine is the principal addictive agent present in Naswar, a smokeless dipping tobacco product. 5-Hydroxytryptamine (5-HT) has been implicated in the reinforcement properties of nicotine. Also, the hypothalamic-pituitary-adrenal (HPA) axis is of vital importance in evaluating the response to stress and nicotine addiction. The study aimed to evaluate serum tryptophan and cortisol levels in Naswar users in relation to addiction. Additionally, serum cotinine levels were also determined to assess daily nicotine exposure. The study comprised 90 healthy Naswar users and 68 non-tobacco users. Estimation of serum cortisol, tryptophan and albumin was carried out. From the Naswar user group, 20 were selected for the estimation of serum cotinine for which blood was drawn twice first in the morning and then in the evening. Serum tryptophan and cortisol levels in Naswar users were significantly raised compared to the control group. However, no difference in the levels of albumin between Naswar users and the control group were found. The mean cotinine values rose from the morning value of 366.0 ± 40.69 ng/ml (mean ± SEM) to an evening value of 503.1 ± 42.96 ng/ml that in turn is equivalent to consumption of 40 cigarettes. Elevated cortisol levels might constitute an important aspect of Naswar addiction. Additionally, raised levels of serum tryptophan in Naswar users could lead to raised concentration of 5-HT which also might be a significant factor contributing to Naswar addiction. Also, serum cotinine concentrations equivalent to an intake of about 40 cigarettes per day is quite alarming.

Deletion of the tryptophan 2,3-dioxygenase (TDO2) gene induces an anxiolytic-like behaviour in mice and TDO inhibition by allopurinol elicits an antidepressant-like effect in rats exposed to restraint stress. Chronic nicotine administration inhibits TDO activity, enhances brain serotonin synthesis and exerts anxiolytic- and antidepressant-like effects in rodent models. There is a strong association between anxiety, depression and tobacco use, which is stronger in women than in men. The present study aimed to examine the relationship between behavioural measures of anxiety and depression with liver TDO activity, brain tryptophan concentration and serotonin synthesis in rats treated chronically with nicotine. Behavioural measures included the elevated plus maze (EPM), open field (OFT) and forced swim (FST) tests. Biochemical measures included TDO activity, serum corticosterone and brain Trp, 5-HT and 5-HIAA concentrations. Anxiolytic-like and antidepressant-like effects of chronic nicotine were confirmed in association with TDO inhibition and elevation of brain Trp and 5-HT. Sex differences in behaviour were independent of the biochemical changes. At baseline, female rats performed better than males in OFT and FST. Nicotine was less anxiolytic in females in the open arm test. Nicotine treatment did not elicit different responses between sexes in the FST. Our findings support the notion that liver TDO activity exhibits a strong association with behavioural measures of anxiety and depression in experimental models, but provide little evidence for sex differences in behavioural response to nicotine. The TDO-anxiety link may be underpinned by kynurenine metabolites as well as serotonin.

Objective: Excess body weight is the sixth most important risk factor contributing to the overall burden ofdisease worldwide. The circulating leptins have been found to play a vital role in the regulation of appetite,glucose homeostasis and body fat. Therefore, this study was designed to measure serum leptin and insulinresistance in non obese and obese young adults and to correlate them with obesity parameters: body massindex, waist circumference, waist-to-hip ratio and metabolic indices.Methods: A total of 43 non- obese subjects, 20 male and 23 female aged 20- 25 years and 46 obese subjects,25 male and 21 female with age 28- 37 years were studied. All subjects selected for study were normotensiveand non-diabetic. Variables measured were Body Mass Index (BMI), waist to hip ratio(WHR), bloodpressure, serum leptin, insulin, fasting blood glucose, oral glucose tolerance test (OGTT), and lipid profile.Results: Serum leptin was significantly higher in females than males 8.8 ± 2.10 SEM and 2.2 ± 0.26 ng/mlSEM respectively in non-obese.As well, Serum leptin was significantly higher in females than males 23.0 ±3.98 SEM and 12.5 ± 2.24 ng/ml SEM respectively in obese group. Serum leptin was significantly higher inobese males, and obese females compared to non- obese subjects. Serum leptin significantly, and positivelycorrelated with BMI (r = 0.440), hip circumference (r =0.425), insulin (r = 0.334), and homeostasis Model ofAssessment - Insulin Resistance (HOMA-IR)r= 0.334 whereas HOMA-IR positively correlated with BMI,waist Circumference, fasting insulin, fasting blood glucose, triglycerides (TG), TG/HDL-Cholesterol ratioand negatively correlated with HDL-Cholesterol.Conclusions: Serum leptin levels increase with obesity, and are higher in females in both non-obese andobese individuals. Serum leptin significantly correlated with hip circumference. Increased serum leptin,especially in obese subjects, should be taken as a warning sign of energy imbalance, poor diet,hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are stronglyassociated with cardiovascular diseases and type 2 diabetes. Key words: Anthropometry, body mass index, insulin resistance, leptin, obesity,