Male Non-smokers Research Articles

Effect of Valproate Coprescription on Clozapine Pharmacokinetics in Clinical Practice

Abstract Background Sodium valproate has been coprescribed with clozapine for seizure prophylaxis and for augmentation in treatment-refractory schizophrenia. However, the effect of valproate on clozapine metabolism and on the incidence of clozapine-related side effects is unclear. Methods We compared clozapine dose and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in smokers and nonsmokers of both sexes in samples submitted for clozapine therapeutic drug monitoring, 1996–2017 in relation to valproate coprescription. Results There were 1217 (665 patients) and 3823 (1600 patients) samples from nonsmokers and from smokers, respectively, who were coprescribed valproate and clozapine. Data from 9774 (5065 patients) and 15,465 (7298 patients) samples from nonsmokers and from smokers, respectively, for whom drugs other than valproate were coprescribed were used as controls. Valproate coprescription in nonsmokers was associated with an increase in average plasma clozapine of 22.5%, suggesting moderate inhibition of clozapine metabolism, but there was no marked effect of valproate coprescription on plasma clozapine in smokers. In all the valproate-treated groups (male and female smokers and nonsmokers), the median plasma norclozapine concentration and the median plasma clozapine-to-norclozapine ratio were significantly lower and higher, respectively, as compared with the controls. Mixed-effects models showed a significant dose-response effect of valproate on lowering the plasma norclozapine concentration and on increasing the plasma clozapine-to-norclozapine ratio. Implications Given the complexity of the effect of valproate coadministration on clozapine pharmacokinetics and the possibility that the toxicity of clozapine may be enhanced in the presence of valproate, the use of these drugs in combination must now be questioned in all patients and not only in women of childbearing age.

Effect of Smoking on Red Blood Cell Parameters: A Cross-sectional Study in a Divisional City of Bangladesh

Background: Several metabolic and biochemical processes, hormone secretion, and the haematological system are all affected by smoking. Numerous studies have found that smoking is associated with higher levels of haemoglobin concentration (Hb%), total red blood cell count (RBC), and red cell distribution width (RDW). Objectives: To study the RBC parameters in healthy male smokers and non-smokers among adults. Methodology: This research was carried out in the Department of Physiology of Sylhet MAG Osmani Medical College, from July, 2021 to June, 2022. A total of 200 participants were included with healthy adult smokers and age-matched healthy adult non-smokers. History and physical examinations were used to evaluate each individual. We measured height and weight, and calculated body mass index of the subjects. Calculations were made on cigarette smoking intensity and duration. Blood was collected to determine RBC parameters, such as total RBC count, haemoglobin level, haematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red cell distribution width (RDW) by using Sysmex 500i automatic haematology analyzer (Japan). Results: Among the 200 participants, 100 were adult smokers and another 100 age-matched healthy adult non-smokers. The RBC indices were significantly elevated in smokers compared to non-smokers group: mean haemoglobin concentration (g/dl)+ standard deviation (SD) were 14.17 ± 2.13 versus 13.27 ± 1.39 respectively with p<0.001, mean haematocrit (HCT) (percent)+ SD were 41.60 ± 6.88 versus 39.13 ± 5.46 respectively with p=0.005, mean corpuscular volume (MCV) (fl) + SD 91.13 ± 8.86 versus 88.33 ± 5.58 respectively with p=0.033, mean corpuscular hemoglobin (MCH) (pg) + SD 31.16 ± 3.26 versus 30.05 ± 3.0 respectively with p=0.016 and mean red cell distribution width (RDW) (percent)+ SD 14.74 ± 1.63 versus 14.00 ± 1.57 respectively with p=0.001. However, RBC count (×106/μl) (4.60 ± 0.80 versus 4.46 ± 0.60; p=0.143) and mean corpuscular haemoglobin concentration (MCHC) (g/dl) (34.23 ± 2.11 versus 34.11 ± 2.32; p=0.707) did not differ significantly between smoker and non-smoker groups. There was no statistical difference between mild, moderate, and severe smokers, according to the study's variables. Conclusion: MCV, MCH, RDW, haematocrit, and haemoglobin concentration were all significantly higher in smokers. Journal of Monno Medical College December, 2023; 9 (2):41-46

Investigating the Effects of COVID-19 on Sperm in Male Smokers: A Prospective Integrated Proteomic and Metabolomic Study

Notable variations in semen parameters among non-smoking males have been documented post-COVID-19 pandemic. The role of smoking as a significant contributing factor to male infertility has been substantiated. Does the combined effect of smoking and SARS-CoV-2 infection impact male reproductive function? A prospective descriptive cohort study was performed using data from 90 smoking and 90 non-smoking males before and after coronavirus infection in a single center over a period of 3 months. Semen samples were collected before and within 15 days after COVID-19 infection, ensuring no more than three months elapsed between the two collections. The semen parameters evaluated included volume, concentration, progressive motility, normal morphology, and DNA fragmentation rate. Proteomic and metabolomic studies were further used to explore the differences between groups. Both non-smokers and smokers exhibited a marked reduction in sperm concentration, progressive motility, and normal morphology rate. Additionally, an increase in sperm DNA fragmentation index was noted for non-smokers and smokers. In the non-smoking group, dysregulation proteins including SEMG1, SEMG2 and DNAH5, and metabolites including L-glutamine, cis-9-Palmitoleic acid and Linoleamide were observed. In smokers, dysregulation proteins including SMCP, ROPN1B and IZUMO4, alongside metabolites including carnitine, gamma-Glutamylglutamic acid, and hypoxanthine were found. Comparative analysis between smoking and non-smoking patients post-COVID-19 also revealed significant differences in semen concentration, morphology and sperm DNA fragmentation rate. Dysregulated proteins including HSPA5, HSPA2 and PGK2, and metabolites such as acetylcarnitine, oxaloacetate and nicotinate were associated with impaired sperm function. Our study demonstrates that the virus also significantly compromises sperm quality in smoking males, who experience more pronounced declines post-infection compared to their non-smoking counterparts. This research underscores the necessity for comprehensive fertility assessments for smoking males after recovering from COVID-19.

The Factors Associated With Mutant Epidermal Growth Factor Receptor Positivity in Patients With Lung Cancer: A Study From a Tertiary Care Center in Pakistan.

Objective In this study, we sought to elucidate the relationship between demographic and clinical factors and epidermal growth factor receptor tyrosine kinase (EGFR-TK) positivity in patients with advanced-stage lung cancer at a tertiary care center in Pakistan. Methods This analytical cross-sectional study was conducted from February 2020 to July 2023 at Shaikh Zayed Hospital, Lahore, Pakistan, in collaboration with the Centre of Excellence in Molecular Biology (CEMB), University of the Punjab. The study included 70 consecutive patients with advanced-stage lung cancer, and aimed to identify common EGFR mutations (Exon 19 deletion and Exon 21 L858R mutation), determine their frequency, and correlate EGFR-TK mutation positivity with clinical and non-clinical factors. Tissue acquisition and processing involved bronchoscopy, pleuroscopy, or percutaneous ultrasound-guided lung mass biopsy, followed by molecular analysis using polymerase chain reaction (PCR) extraction, amplification, and sequencing. The study employed convenient sampling and included adults aged over 18 years with histologically confirmed lung cancer. Results We enrolled 70 lung cancer patients, with a mean age of 60.87 years, and a male-to-female ratio of 1.4:1. The majority (61.4%) had adenocarcinoma, and 34.3% harbored a mutant EGFR-TK. EGFR mutations were more common in adenocarcinoma (91.7%) and associated with female non-smokers. Binary logistic regression analysis revealed that age <50 years and adenocarcinoma type were significant predictors of EGFR mutations. We found no significant associations with gender, smoking status, or other variables. These findings have implications for personalized treatment approaches in lung cancerpatients. Conclusions Our study reveals a high frequency of occult EGFR mutations (Exon 19 deletion and Exon 21 L858R mutation) in non-small cell lung cancer (NSCLC) patients, particularly among male smokers and female non-smokers. These findings emphasize the importance of routine EGFR mutation testing to identify patients who may benefit from targeted therapies, ultimately improving treatment outcomes.

Gender-specific outcomes of low-dose computed tomography screening for lung cancer detection: A retrospective study in Chinese never-smoker population.

Low-dose computed tomography (LDCT) has emerged as a pivotal tool for detecting lung cancer among ever-smokers. This study aims to evaluate the gender-specific outcomes of LDCT screening within the Chinese never-smoking population. We conducted a single-center, retrospective cohort study, which analyzed LDCT screening outcomes for 42,018 asymptomatic participants. Specifically, we focused on assessing gender-specific differences in the prevalence of pulmonary nodules, and the incidence of lung cancer diagnosis among never-smokers. Among the 42,018 eligible participants, 41.50% were females and 58.50% were males. Most participants were non-smokers (77.57%), with a significantly higher proportion of non-smokers among females than males (99.33% vs. 62.14%). Pulmonary nodules were identified in 2.66% of participants, with a higher prevalence in females (2.99%) than males (2.43%) (p < 0.001). Non-smoking females had a higher incidence of positive nodules than non-smoking males (2.98% vs. 2.38%, p < 0.001). Invasive biopsies were performed in 334 individuals with nodules, confirming lung cancer in 258 cases. The majority of these cancer cases were non-smokers (212), with non-smoking females showing a higher incidence (0.85%) compared to males (0.43%) (p < 0.001). There was no significant difference in the false-positive rates between non-smoking females (0.14%) and males (0.13%). Multivariate analysis showed that never-smoking women were more likely to undergo biopsies (OR 1.65, p = 0.0016) and had a higher, though not statistically significant, probability of lung cancer diagnosis (OR 1.84, p = 0.06). This study elucidates sex-based differences within the Chinese population, revealing a higher prevalence of pulmonary nodules and lung cancers among non-smoking females. These findings offer valuable reference for both clinical practice and future research initiatives.

Janus kinase 2 mutation-negative polycythemia-associated retinal changes in otherwise asymptomatic patients

Purpose: The purpose of this study was to document secondary polycythemia (SP)-associated retinal changes and the favorable role of phlebotomy in the treatment of SP-induced retinal complications. Design: This was a retrospective, observational, noncomparative case series. Participants: A total of 8 eyes of 4 male patients with an age range of 28–78 years were studied. Materials and Methods: A total of 04 consecutive patients were received over a year on an outpatient basis at a single tertiary care center, with only vision-related complaints. After documentation of ocular findings, all the patients were subjected to meticulous clinical and laboratory evaluation to determine the cause of ocular conditions. Patients were subjected to the treatment for underlying pathological conditions based on the outcomes of their clinical and laboratory evaluation. Main Outcome Measures: Determination of Janus kinase 2 (JAK2) mutation-negative SP as a cause of associated retinal complications and favorable role of phlebotomy as a treatment measure. Results: All the patients were adult, nonsmoker, and nonalcoholic males. A total of 05 eyes were diagnosed with proliferative vitreoretinopathy while 2 eyes had retinal venous occlusion. One eye was normal. Except SP, no other cause for retinal lesions could be ascertained in all patients. Three patients underwent phlebotomy as decided by the hematologists. Each patient was followed monthly for 6 months. All the patients showed resolution of retinal lesions at the end of follow-up. Conclusion: Nonpolycythemia vera (PV) erythrocytosis or unmutated JAK2 SP is still a very poorly studied entity. Almost no information is available regarding ocular involvement and its treatment in SP. Our observations suggest that SP may run a chronic course causing serious retinal damage such as other myeloproliferative disorders or PV and that phlebotomy has an important role in the management of such cases.

Effect of the Heaviness of Smoking Index (HSI) and Duration of Smoking on Central Neural Processing Using Brainstem Auditory Evoked Responses (BAERs).

Purpose of study The goal of this research was to find the correlation of nicotine dependence and duration of smoking with the status of central neuronal processing in chronic smokers. Our primary objective was to record brainstem auditory evoked responses (BAERs) in chronic smokers and further find their correlation to the Heaviness of Smoking Index (HSI) scores and years of non-abstained smoking of the subjects. We postulated that smoking leads to myelination abnormalities which in turn causes decreased impulse conduction velocity. Methods After obtaining informed consent, we conducted BAER on 60 male smokers who were further classified into groups based on their HSI scores (low, moderate, and high nicotine dependency) and 20 age-matched, non-smoking males. The obtained data was examined using the two-way ANOVA test and the Kruskal-Wallis test. Pearson's coefficient of correlationand the median (as a measure of central tendency) were calculated. Results We observed a non-significant negative correlation between wave I BAER latency and the degree of nicotine dependence. Wave II showed minimal correlation, whereas a positive correlation was seen in waves III, IV, and V. Interpeak latencies (IPL) I-III and III-V showed a non-significant positive correlation with the HSI score, whereas IPL I-V showed a significant positive correlation with the same. When correlated with the duration of smoking (years), the latencies (msec) of BAER waves I-V showed a pattern of progressively decreasing negative correlation, out of which waves I, II, and III were significantly affected. The IPL (msec) of waves I-III was non-significantly, yet positively, correlated, while the IPL of waves I-V and III-V showed a significant positive correlation to the duration of smoking. Conclusions The degree of nicotine dependence and duration of tobacco smoking progressively affected the latencies of BAER waves at the pontomedullary level of the brainstem. This indicates slower central neuronal processing at this level and an increased central transmission time, the extent of which is directly dependent on the extent of tobacco smoking. This is attributed to the myelination defects caused by direct and indirect effects of the toxic metabolites of tobacco smoke, chronic hypoxia, hypercapnia, and respiratory acidosis.

Depressive symptoms among cigarette smokers and non-smokers during the first wave of COVID-19 pandemic: Preliminary findings from Bangladeshi male university students

University students may be particularly vulnerable to develop mental disorders, including depression, due to sudden and unexpected changes in their daily life during the COVID-19 pandemic. The present study aimed to assess depression among male smokers and non-smokers university students during the first wave of COVID-19 in Bangladesh. A web-based cross-sectional survey was conducted among 444 university male students using convenient and snowball sampling with a 1:1 ratio of male smokers and non-smokers from July to October, 2020. The prevalence estimates of moderate to severe depression were 53.6 % and 22.1 %, respectively among male smokers and non-smokers with an overall prevalence rate of 37.9 %. The participants who smoked cigarette were 4.05 times more likely to have depression compared to those who did not smoke (AOR = 4.05; 95 % CI = 2.60–6.30, p < 0.001). The following factors were found to be associated with depression: being smokers, having family members who lost jobs due to the impact of COVID-19, and having food scarcity due to COVID-19. The findings suggest mental health awareness and psychosocial support programs with a special focus on quitting smoking behavior among university students.

Fractal Dimension Analysis of Cervical Vertebra on Cone-Beam Computed Tomography Scans of Smoker Males

Objective: This study aimed to comparison of vertebral fractal dimension (FD) values among smoker and non-smoker males. Material and Methods: Cone-beam computed tomography (CBCT) images of 144 male patients were evaluated, 72 smokers constituted the study group, while 72 non-smokers formed the healthy control group in this study. In all CBCT images, the region of interest (ROI) assessing the second cervical vertebra (C2) was chosen as a 45x45 pixel size for ROI-v with reference to the coronal view of C2. Results: While the mean FD value of ROI-v in the smoker group was 1.118±0.85, the mean FD value of ROI-v in the non-smoker group was 1.221±1.12. This difference between ROI-v values is also statistically significant (p &amp;lt; 0.05). Conclusion: Fractal analysis of cervical vertebrae may help to evaluate osteoporotic changes in smoker males.

Comparative evaluation of ten blood biomarkers of inflammation in regular heated tobacco users and non-smoking healthy males–a pilot study

Heated tobacco products (HTPs) are novel tobacco products that are alternatives to cigarettes. The study aimed to investigate the effect of HTPs on blood biomarkers of inflammation as well as to provide a comparative evaluation between daily heated tobacco users and healthy men who do not use nicotine products. This case–control study was carried out among 92 healthy males in Poland (Lodz-Province) aged 20–56 years: 44 daily heated tobacco users (daily use in the past 90 days) and 48 controls who do not use nicotine products. The history of use of the nicotine-containing products was self-reported and verified using a saliva cotinine test. A 20 ml blood sample was collected and the levels of ten blood biomarkers were analyzed. Among all heated tobacco users (n = 44), only the levels of interleukin 8 (IL-8) were significantly higher when compared to controls: 6.86 vs. 3.95 (p = 0.01). Among exclusive heated tobacco users (n = 33), the levels of IL-8 were also significantly higher when compared to controls: 7.76 vs. 3.95 (p = 0.01). IL-8 level was positively correlated (r = 0.37; p = 0.01) with the daily number of heated tobacco sticks. Out of 10 different biomarkers of inflammation, only IL-8 levels were significantly elevated in heated tobacco use compared to controls.

The trial-by-trial fluctuations in primary motor cortex excitability during attentional bias among smokers: A transcranial magnetic stimulation study

BackgroundA relatively new computational approach called trial-level bias score (TL-BS) has shown that attentional bias to smoking-related stimuli in smokers fluctuates temporally, trial by trial, during attention tasks. Here, we investigated the reliability of using TL-BS values to assess attentional bias and the electrophysiology mechanisms undergirding fluctuations in attentional bias among smokers. MethodIn total, 26 male smokers and 26 male non-smokers performed a dot-probe task in Experiment 1. In Experiment 2, an additional 23 male smokers and 23 male non-smokers performed the same task while undergoing single-pulse transcranial magnetic stimulation, which was used to investigate corticospinal excitability. ResultsIt showed that assessing TL-BS parameters for reaction time (RT) was more reliable than calculating the traditional mean attentional bias score; however, this superior reliability was no longer apparent after controlling for general RT variability. There was a significant difference between smokers and non-smokers in TL-BS parameters calculated for both RT and motor-evoked potential (MEP) amplitude. However, TL-BS parameters for RT and MEP amplitude were strongly correlated with general RT variability and general MEP variability, respectively. ConclusionsOur findings indicated that TL-BS parameters may not be ideal for measuring attentional bias at either the behavioral or electrophysiology level; however, larger general RT and MEP amplitude variabilities in non-smokers may indicate dysregulation of cognitive processing in smokers.

Smoking affects symptom improvement in schizophrenia: a prospective longitudinal study of male patients with first-episode schizophrenia

Patients with schizophrenia (SCZ) smoke up to three times more than general people. However, there are conflicting results regarding the relationship between tobacco smoke and clinical symptom severity in SCZ. The aim of this study was to assess the impact of smoking on clinical symptoms after antipsychotic treatment in a 12-week cohort study after controlling for confounding factors. One hundred and forty-five male patients with drug-naïve first-episode (DNFE) SCZ received antipsychotic monotherapy for 12 weeks. Symptom severity was assessed at baseline and at week 12 by the Positive and Negative Syndrome Scale (PANSS). We found no differences in clinical symptoms among male smokers with SCZ compared with male nonsmokers. However, male smokers showed greater improvement in negative symptoms after 12 weeks of treatment, controlling for age, years of education, onset age, and baseline body mass index (BMI). Our study showed that after 12 weeks of treatment with antipsychotics, male smokers showed greater improvement in negative symptoms than male nonsmokers.

Effect of Coffee and Chocolate Ingestion on Clozapine Dose and on Plasma Clozapine and Norclozapine Concentrations in Clinical Practice.

Some reports point to dietary caffeine intake as a cause of increased plasma clozapine concentrations in certain patients. We compared clozapine dose and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in male and female smokers and nonsmokers in relation to reported (i) coffee (caffeine) and (ii) chocolate (caffeine and theobromine) intake in samples submitted for clozapine therapeutic drug monitoring, 1993-2017. There was information on coffee ingestion for 16,558 samples (8833 patients) from males and 5886 samples (3433 patients) from females and on chocolate ingestion for 12,616 samples (7568 patients) from males and 4677 samples (2939 patients) from females. When smoking was considered, there was no discernible effect of either coffee or chocolate ingestion either on the median dose of clozapine or on the median plasma clozapine and norclozapine concentrations in men and in women. However, cigarette smoking was associated with higher coffee and chocolate consumption. Although male nonsmokers who reported drinking 3 or more cups of coffee daily had significantly higher median plasma clozapine and norclozapine concentrations than those who drank less coffee, they were also prescribed a significantly higher clozapine dose. There was no clear effect of coffee ingestion on plasma clozapine and norclozapine in female nonsmokers. Inhibition of clozapine metabolism by caffeine at the doses of caffeine normally encountered in those treated with clozapine is unlikely even in male nonsmokers. Measurement of plasma caffeine in an appropriate sample should be considered in any future investigation into a presumed clozapine-caffeine interaction.

Effect of cigarette smoking on lipid profile, high sensitivity c-reactive protein, and malondialdehyde

Background: One of the most common reasons for preventable mortality is the smoking habit. Cigarette smoke promotes the process of atherogenesis by producing oxygen-derived free radicals which cause damage to the lipids. Cigarette smoking is associated with impaired endothelium-dependent vasodilatation and cardiovascular disease (CVD). Aims and Objectives: The objectives of the study were the following: (i) to compare the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very LDL (VLDL) in asymptomatic male smokers and non-smokers of the age group 25–50 years; (ii) to determine and compare the levels of high sensitivity C-reactive protein (hs-CRP) in the above two groups, and (iii) to study and compare the levels of malondialdehyde (MDA) in the above groups. Materials and Methods: The study was conducted on 60 males in which 30 smokers and 30 non-smokers of the age group 25–50 years were incorporated. It was a cross-sectional comparative study, which included the participants who met all the inclusion and exclusion criteria. Before the conduct of the study, informed consent was obtained from all the participants. Moreover, the selection of participants was done in a consecutive manner until the sample size was achieved. TC and TGs were estimated by the enzymatic colorimetric method, HDL cholesterol by the phosphotungstic acid method, and LDL and VLDL by Friedwald’s formula. MDA was determined by spectrophotometry and hs-CRP by the immunoturbidometric method. The data acquired were analyzed by utilizing the Statistical Package for the Social Sciences version 18. Results: Dyslipidemia was seen in smokers as evidenced by significantly elevated levels of TC, TG, LDL, and VLDL; and significantly reduced levels of HDL. The mean values of hs-CRP were significantly elevated in smokers when compared to that of non-smokers. Oxidative stress was increased in subjects who were smokers. The mean values of MDA were significantly elevated in the smokers. Conclusion: The smoking habit is associated with dyslipidemia, oxidative stress, and inflammation which predisposes to the development of endothelial dysfunction and atherosclerosis. The significance of early screening measures to be undertaken in asymptomatic smokers for dyslipidemia, oxidative stress, and hs-CRP is unveiled by the present study. Therefore, early screening can be used to advise smokers to refrain from smoking to avoid complications of CVDs, so that they can upgrade the quality of their life.

Liver function parameters in asymptomatic smokers – A cross-sectional study

Background: Smoking remains the single most common cause of preventable deaths. The liver is affected by the process of smoking through various inflammatory pathways. This will lead to aggravation of pathogenic impact on the liver tissue. The present study was undertaken to determine the liver function parameters in cigarette smokers. Aims and Objectives: The objective was to estimate and compare the parameters of liver function – alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin, total protein, albumin, and globulin in asymptomatic male smokers and non-smokers of the age group 25–50 years in the above two groups. Materials and Methods: A cross-sectional comparative study was conducted on 60 males with 30 smokers and 30 non-smokers of the age group 25–50 years. All the subjects who have satisfied the inclusion and exclusion criteria were incorporated in the study. Informed consent was taken before the conduct of the study. The participants were selected in a consecutive manner till the sample size was achieved. AST, ALT, ALP, total bilirubin, total protein, and albumin were estimated using ERBA EM 360 fully automatic analyzer. The difference between the total protein and albumin was used to calculate the level of globulin. The Statistical Package for the Social Sciences version 18 was used for data analysis. Results: The mean values of AST, ALT, and ALP were significantly elevated in smokers when compared to non-smokers. The mean values of total bilirubin, total protein, albumin, and globulin were significantly decreased in smokers. Conclusion: Smoking leads to the development of hepatic damage which increases the intensity of complications. The study reveals the importance of screening asymptomatic smokers for liver function parameters to avoid complications of hepatic diseases hence improving the quality of life.

Evaluation of Periodontal Status and Serum C-Reactive Protein Levels in Adult Cigarette Smokers

Background: This study aimed to evaluate the periodontal status of adult smokers and assess their serum C-reactive protein (CRP) levels, hypothesizing an association between periodontal inflammation, smoking, and elevated serum CRP, a marker for cardiovascular diseases. The primary objective is to contribute to the assessment and prevention of potential cardiovascular diseases in adult smokers. Methods: This cross-sectional study was conducted at HIT Hospital and Dental Hospital HITEC-IMS Taxila Cantt over five months from October 20, 2021, to March 31, 2022, the study included 60 healthy male adult smokers and 20 healthy male non-smokers as a control. Basic periodontal examination involved the use of a periodontal probe, assessing parameters such as gingival index, bleeding on probing, oral pigmentation, presence of periodontal pockets, and gingival recession. Blood samples were collected to evaluate serum CRP levels. Results: Smokers exhibited higher rates of gingival recession (38.3%), gingival pigmentation (43.3%), and periodontal pocket formation (33.3%) compared to the nonsmokers control group, with significant p-values of 0.040 in gingival recession and 0.035 in the presence of periodontal pockets. Serum CRP levels were significantly elevated in adult smokers, with a significant p-value of 0.024. Conclusion: The study concluded that adult smokers show signs of periodontitis, and their serum CRP levels are elevated. Assessing periodontal status and serum CRP in adult smokers may aid in risk assessment and reducing the likelihood of developing future cardiovascular diseases.

Effect of wearing surgical mask during controlled aerobic training on functional capacity and perceived stress in inactive men: a randomized trial

The study aims to assess the impact of wearing a surgical mask during training on inactive men’s functional capacity and perceived stress. Seventy non-smoker males with body mass index of 25–30 kg/m2 and moderate-intensity activity of fewer than 150 min/week were allocated randomly into two equal groups. The surgical mask group performed a controlled endurance exercise while wearing a surgical mask of three protection layers. The mask-less group performed a controlled endurance exercise without wearing any mask. Functional capacity and Perceived Stress were evaluated before and after the intervention. A significant improvement was observed within groups post-intervention in favor of the mask group regarding the Time Up and Go test (P < 0.05), with a 15.1% percentage improvement. Post-intervention, there was a significant change in the perceived stress score for the mask and mask-less groups (P < 0.05). The improvement in PSS was in favor of mask-less group participants as they changed from being categorized as moderate to mild stress on the PSS, with a 27.1% percentage improvement. Exercising while wearing a surgical mask Positive impacts functional capacity and negatively impacts Perceived Stress in inactive adults. An additional study evaluating the physiological effects of masks on continuous exercise is necessary.

Comprehensive molecular analysis of driver mutations in non-small cell lung carcinomas and its correlation with PD-L1 expression, An Indian perspective

BackgroundThe understanding of molecular mechanisms involved in non-small cell lung carcinoma (NSCLC) has revolutionized significantly in the recent years. These have helped to develop personalized management strategies by identifying specific molecular alterations such as mutations in EGFR, ROS1, BRAF, ERBB2, MET, ALK, and KRAS genes. These mutations are targetable ensuring a better clinical outcome. Next-generation sequencing (NGS) methodology is the recommended technique for the identification of driver mutations in the five hot-spot genes (EGFR, ALK, ROS1, MET, and BRAF) involved in the NSCLC. NGS has numerous advantages including multiplexing, tissue conservation, identification of rare and novel variants, and reduced cost over the sequential single gene testing. Herein, we sought to demonstrate the mutational profile in NSCLC and their clinicopathologic correlation in a contemporary cohort of Indian NSCLC patients. Additionally, we studied the correlation of oncogenic driver mutations with PD-L1 status in these patients. Materials and MethodsFive fifty-two stage IV NSCLC patients (adenocarcinoma=490; squamous cell carcinoma=51; adenosquamous carcinoma=5; large cell carcinoma=2; sarcomatoid carcinoma=3; spindle cell carcinoma=1) underwent broad molecular profiling by a custom-made, targeted DNA- and RNA-based five hot-spot genes lung cancer panel (EGFR, ALK, ROS1, BRAF, and MET), compatible with the NGS Ion S5 system. The mutations were correlated with the clinicopathologic characteristics. Additionally, PD-L1 expression status, available on 252 tumors, was correlated with the oncogenic drivers. ResultsValidation of the 5 gene panel yielded the following results: a) specificity of 99.74%; b) sensitivity of 100% for single nucleotide variants (SNVs) (>5% variant allele frequency, VAF), indels (>10% VAF) and fusions; c) 100% intra- and inter-run reproducibility; d) 88% inter-laboratory agreement. Validated panel was then used to analyze clinical samples. Sixty percentage tumors harbored either one (54.71%) or multiple (3.26%) mutations. EGFR and BRAF V600E mutations, ALK and ROS1 rearrangements, and MET exon 14 skipping mutation were observed in 38.41% (n = 212) and 2.72% (n = 15) patients, 12.14% (n = 67) and 3.62% (n = 20) patients, and 1.09% (n = 6) patients, respectively. EGFR exon 19 deletion accounted for 52.83% of all mutations, followed by L858R (35.85%), T790M (5.19%), exon 20 insertions (6.6%), and other rare mutations (G719X, L861Q, S768I) (9.91%). Concurrent EGFR with ALK, EGFR with ROS1, EGFR with MET, and EGFR with BRAF were observed in 10, 4, 1, and 3 patients, respectively. PD-L1 was expressed in 134 patients (53.2%). Exon 19 deletion was more prevalent in PD-L1 negative tumors whereas exon 21 substitution (L858R) was seen more in PD-L1 positive tumors. ConclusionsThis is one of the largest cohorts of NSCLC for comprehensive targeted mutational profiling and correlation with the PD-L1 expression. The mutations are more prevalent in non-smoker females for all genes, except ALK (non-smoker males). MET and BRAF mutations are more common in elderly population whereas EGFR mutations, and ALK and ROS1 genes rearrangements are more prevalent in younger population. The most common histopathologic subtype/feature associated with various mutations was as follows: acinar with EGFR, solid with ALK, macronucleoli with ROS1, signet ring with MET, and micropapillary with BRAF.

Effect of Cigarette Smoking on Clozapine Dose and on Plasma Clozapine and N-Desmethylclozapine (Norclozapine) Concentrations in Clinical Practice

Abstract Background Cigarette smoking enhances plasma clozapine clearance and thus affects the clozapine dose requirement. Methods We compared clozapine daily dose and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in male and female smokers and nonsmokers in samples submitted for clozapine therapeutic drug monitoring (1996–2017). Results There were 105,316/60,792 and 34,290/31,309 samples with dose information from male and female smokers/nonsmokers, respectively. There was information on the number of cigarettes smoked daily for 12,842 samples (8409 patients) and 3948 samples (2753 patients) from men and women, respectively. Of these, 574 and 253 samples were from men and women, respectively, who reported smoking 1–9 cigarettes daily. In both sexes, the median clozapine doses in the nonsmokers were 75%–80% of those in the smokers, but the median plasma clozapine and norclozapine concentrations were 136% higher. The effect of smoking on the dose and on median plasma clozapine and norclozapine concentrations seemed maximal after 2–3, perhaps fewer, cigarettes daily in males. In females, the effect of smoking seemed to be near maximal after some 4–5 cigarettes per day. Implications The optimum target range for predose plasma clozapine may be different in smokers (0.35–0.45 mg L−1) as opposed to nonsmokers (0.50–0.60 mg L−1). That changes in clozapine clearance are likely near maximal with cigarette smoking as low as 2–3 d−1 in males, perhaps slightly more in females, emphasizes that covert or passive smoking may be an important factor in seemingly random changes in plasma clozapine concentration at constant dose.

Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study

IntroductionPost-tuberculosis lung damage (PTLD) refers to the residual pulmonary impairment following the completion of antituberculosis (TB) therapy, characterised by persistent respiratory symptoms and abnormal pulmonary function. The risk factors and...