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To determine the causes of initiation and promotion of cannabis smoking among local transport drivers of Peshawar. Design, settings and duration: A descriptive observational study was conducted in main wagon and bus stoop in city, Haji camp bus stop and roadway house Hashtangri, from October 2009 to September 2010. Methods: A questionnaire was designed in accordance with the objectives of the study. Relevant information’s were recorded from the respondents on the pre-designed questionnaire. Results: A total of 400 smoker drivers were included. Of total 181(45.25%) were cannabis/marjuana smokers. The age range of the cannabis smokers was from 16 years to 65 years of age with mean age of 35.5 years. The distribution of smoking habits recorded was: cigarette smoking alone 19%, snuffing 23%, cannabis smoking 42.25%, heroin and cannabis smoking 3%, etc. Out of total cannabis smokers 43% were illiterate and 40% had primary education. Forty three percent had more than ten pack years of cannabis smoking. The exposure state of the respondents was: to compensate fatigue 39.21%, inspiration from friends 31.49%, parents were smokers 11.6%, pleasure to smoke 8.83% etc. Ninety percent were agree that cannabis is easily available to them. Fifty seven percent had poor social background. Thirty four percent had faced road accidents. The effect of cannabis on respondents was: lack of interest 36.46%, decreased memory 19%, depression 16%, sedation 5.52%, etc. Maximum number of the respondents (19.33%) wanted to quit cannabis smoking. Conclusion: Cannabis smoking is common in local transport drivers. The major causes that are involved in the initiation and progression of cannabis smoking are; driving in young age, poverty, lack of education, easy availability of cannabis, inspiration from colleagues and smoker parents.

A theoretical and experimental study was conducted on the mechanical behavior of nanocomposites based on PA6/NBR thermoplastic elastomer reinforced by single wall carbon nanotubes (SWNTs). The selected samples include 60 and 40% NBR with 0.5, 1.0 and 1.5% SWNT. The modeling methodology was based on the use of two-dimensional "representative volume elements" (RVE). The Abaqus/standard code was employed to carry out the non-linear finite element calculations. Plane stress elements were selected for discretization of the domain. Linear elastic and isotropic hardening elastic-plastic models were utilized to describe the mechanical behaviors of the carbon nanotubes and polymer matrix, respectively. The samples were simultaneously prepared using melt mixing method in a laboratory internal mixer. Different orientations including regular in both longitudinal and transverse directions and random were selected for the nanotubes in the matrix. Also, two structural forms including hollow and solid for the carbon nanotubes were chosen. The highest and lowest predicted moduli were obtained from models with regular orientation in longitudinal and transverse directions, respectively. On the other hand, comparison between the predicted elastic modulus and elastic-plastic behaviors of the samples with their corresponding experimental data revealed that the random orientation in conjunction with hollow structural form gives the best results. Moreover, the selected material model for the thermoplastic elastomer i.e., isotropic hardening can precisely describe the mechanical behavior in both tension and compression modes. It is also concluded that the main source of error in this modeling methodology can be attributed to the effects of interface between polymer and nanotubes and orientation in perpendicular directions.

Background: Youth smoking is a worldwide problem This study was conducted to determine the opinion of the physicians, community experts and school teachers regarding plan of action and strategies to combat smoking in children and youth of the nation. Material & Methods: It was a cross-sectional study conducted in two teaching hospitals of Peshawar, two schools of Nowshera and Department of Public Health, Ghandhara University, Peshawar, from 12th March to 15th May 2008. Seventy respondents were randomly selected, 28.56% school teachers, 50% physicians, 14.28% community experts from ICMS and 5(7.14%) from postgraduate technology college swat. Questionnaire was designed in accordance to the objectives of the study. Results: Analysis of questionnaires revealed: Restrict youth access to smoking (active as well as passive) (88.57%), mass media campaign (80%), tobacco control legislation and its empoverment (74.28%), national physical activity policy (48.57%), conducting workshops (30%), research promotion (25.71%). Community approaches should be more specific towards community education and awareness (68.57%), community meetings (51.42%), social environments are targeted for change (47.14%), walks (44.28%), understanding knowledge, attitude, and behaviors of youth towards smoking (41.42%) and community organizations involvement (22.85%). Individual approaches to combat tobacco smoking are to quit smoking (82.88%), appropriate medicine in time if is patient or at risk (32.85%) and leadership and advocacy (27.14%). SchoolBased Prevention of smoking in children and youth should target schools to develop and enforce tobacco free environment (88.57%), provision of information on consequences of smoking (72.85%), information on the social influences of smoking (65.71%) and educational programs and health promotion activities (48.57%). Conclusion: While establishing a strategy for prevention and control of tobacco smoking in youth there is need to offer multiple approaches on national, community, school and individual levels.

This research work is devoted to the simulation of a steel-belted radial tire under different static loads. The nonlinear finite element calculations were performed using the MSC.MARC code, installed on a computer system equipped with a parallel processing technology. Hybrid elements in conjunction with two hyperelastic models, namely Marlow and Yeoh, and rebar layer implemented in surface elements were used for the modeling of rubbery and reinforcing parts, respectively. Linear elastic material models were also used for the modeling of the reinforcing elements including steel cord in belts, polyester cord in carcass and nylon cord in cap ply section. Two-dimensional axisymmetric elements were used for the modeling of rim-mounting and inflation and three-dimensional models were developed for the application of the radial, tangential, lateral and torsional loads. Different finite element models were developed, in which both linear and quadratic elements were used in conjunction with different mesh densities in order to find the optimum finite element model. Based on the results of the load deflection (displacement) data, the tire stiffness under radial, tangential, lateral and torsional loads were calculated and compared with their corresponding experimentally measured values. The comparison was verified by the accuracy of the measured radial stiffness. However, due to the neglecting of the stiffness in shear and bending modes in cord-rubber composites, modeled with rebar layer methodology, the difference between computed values and real data are not small enough so that a more robust material models and element formulation are required to be developed.

A 185/65R15 steel belted radial tire was analyzed for the prediction of its rolling resistance using finite element method. The Abaqus code was used for this purpose. A two-dimensional axisymmetric model was first designed to form the tire layout in the mold. After analyzing for rim mounting, an internal pressure was applied to the tire. Having rotated the tire cross-section about rolling axis, a three-dimensional model was then created and used for the analyses under static vertical load and steady state rolling conditions. Owing to the use of arbitrary Lagrangian/Eulerian framework, a constant linear velocity was assumed and the analysis was performed for a range of angular velocity of the tire. An in-house developed user subroutine was employed and linked to the Abaqus for the accurate determination of the free rolling rotational speed (angular velocity) of the tire based on zero force/torque. Two sets of analyses were performed. In the first set, it was assumed that the mechanical behaviors of the rubbery parts could be described by the well-known Ogden hyperelastic model. In the second set, hyper-viscoelastic behaviors were assumed in which the Ogden model was combined with the Prony series to take the material history and time effect into consideration. The difference between the calculated longitudinal forces in rolling state using the mentioned models was attributed to the rolling resistance of the tire. In order to check the accuracy of the proposed method, the predicted rolling resistance force was compared with that of experimentally obtained data which confirmed the applicability and robustness of the model. The contact pressure distributions have been presented and discussed in relation to different types of material model.

Background: Orthodontic treatment requires good oral hygiene for successful completion of treatment. As protocol, patients are usually given instructions for oral hygiene and diet at the start of treatment, however, they are not fully followed. Different methods are employed in order to increase patient compliance including digital means, however, these are not possible in teaching hospitals with high burden of patient care and limited resources. The present study aims to correlate the patient reported behavior with their clinical findings and treatment need. This will enable us to identify potential sources of motivation which will be incorporated in daily practice and enable us to improve methods to enhance patient's behavior., Method: A cross-sectional study was conducted in the orthodontic department of a semi-government teaching hospital from August to October 2023 using a modified questionnaire. The clinical examination was done using a Community Periodontal Index for Treatment Need-C (CPITN-C) probe. The diagnosis of presenting clinical conditions and treatment need was done using Community Periodontal Index for Treatment Need (CPITN) and Gingival Bleeding Index (BI). Data collected was analyzed for frequencies and correlation was done using Spearman Correlation Coefficient. P- value ≤ 0.05 was taken as statistically significant., Result: The sample size consisted of 110 patients of which 60% were entitled to receive treatment. The predominant age group was 15-20 years (39.1%). Approximately 70% patients were in code 1 for CPITN and GI and in need of oral hygiene instructions. Overall patients' showed good level of awareness, however, they were not compliant in behavior., Conclusion: Although patients showed a good level of awareness towards oral hygiene practices, there was a lack of compliance in following them. Patients were more concerned for being affected by dental caries due to poor oral hygiene than its effect on overall treatment outcome., (© 2024. The Author(s).)

The New York State Office for People With Developmental Disabilities seeks to better understand the direct support professional (DSP) workforce and offer data-informed strategies for DSP retention. We used the 2018 NCI-IDD Staff Stability Survey (now called State of the Workforce Survey) to investigate agency-level factors influencing DSP tenure. A total 303 provider agencies completed the survey in New York State, representing 72,252 DSPs. Multiple linear regression analysis revealed that selected agency-level variables explained 12.6% of the variance in DSP tenure, R2 = .16, Radj2 = .126, F (11, 260) = 4.54, p < .05. This study yielded strong empirical evidence consistent with existing national reports and research on the role that wages, benefits, and supervisory support play on DSP tenure., (©AAIDD.)

P66Shc and Rac1 proteins are responsible for tumor-associated inflammation, particularly in brain tumors characterized by elevated oxidative stress and increased reactive oxygen species (ROS) production. Quercetin, a natural polyphenolic flavonoid, is a well-known redox modulator with anticancer properties. It has the capacity to cross the blood-brain barrier and, thus, could be a possible drug against brain tumors. In this study, we explored the effect of quercetin on Rac1/p66Shc-mediated tumor cell inflammation, which is the principal pathway for the generation of ROS in brain cells. Glioma cells transfected with Rac1, p66Shc, or both were treated with varying concentrations of quercetin for different time points. Quercetin significantly reduced the viability and migration of cells in an ROS-dependent manner with the concomitant inhibition of Rac1/p66Shc expression and ROS production in naïve and Rac1/p66Shc-transfected cell lines, suggestive of preventing Rac1 activation. Through molecular docking simulations, we observed that quercetin showed the best binding compared to other known Rac1 inhibitors and specifically blocked the GTP-binding site in the A-loop of Rac1 to prevent GTP binding and, thus, Rac1 activation. We conclude that quercetin exerts its anticancer effects via the modulation of Rac1-p66Shc signaling by specifically inhibiting Rac1 activation, thus restraining the production of ROS and tumor growth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baba, Mir, Mokhdomi, Bhat, Ahmad and Khanday.)

Two novel steroidal saponins, trilliumosides K ( 1 ) and L ( 2 ), were isolated from the rhizomes of Trillium govanianum led by bioactivity-guided phytochemical investigation along with seven known compounds: govanoside D ( 3 ), protodioscin ( 4 ), borassoside E ( 5 ), 20-hydroxyecdysone ( 6 ), 5,20-hydroxyecdysone ( 7 ), govanic acid ( 8 ), and diosgenin ( 9 ). The structure of novel compounds 1-2 was established using analysis of spectroscopic data including 1D and 2D nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-ESI-MS) data. All isolated compounds were evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. Compound 1 showed significant cytotoxic activity against the A-549 (Lung) and SW-620 (Colon) cancer cell lines with IC50 values of 1.83 and 1.85 µM, respectively whereas the IC50 value of Compound 2 against the A-549 cell line was found to be 1.79 µM. Among the previously known compounds 3 , 5 , and 9 , the cytotoxic IC50 values were found to be in the range of 5-10 µM. Comprehensive anti-cancer investigation revealed that Compound 2 inhibited in vitro migration and colony-forming capability in the A-549 cell line. Additionally, the mechanistic analysis of Compound 2 on the A-549 cell line indicated distinctive alterations in nuclear morphology, increased reactive oxygen species (ROS) production, and decreased levels of mitochondrial membrane potential (MMP). By upregulating the pro-apoptotic protein BAX and downregulating the anti-apoptotic protein BCL-2, the aforementioned actions eventually cause apoptosis, a crucial hallmark in cancer research, which activates Caspase-3. To the best of our knowledge, this study reports the first mechanistic anti-cancer evaluation of the compounds isolated from the rhizomes of T. govanianum with remarkable cytotoxic activity in the desired micromolar range., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lone, Tabassum, Bhushan, Rani, Dhiman, Ahmad, Mir, Gupta, Mondhe, Gairola and Gupta.)

P66Shc is the master regulator of oxidative stress whose pro-oxidant functioning is governed by ser36 phosphorylation. Phosphorylated p66Shc via Rac1 GTPase activation modulates ROS levels which in turn influence its pro-oxidative functions. Vitamin C at higher concentrations exhibits cytotoxic activity in various cancers, inducing ROS mediated cell death via pro-apoptotic mechanisms. Here we show a novel role of p66Shc in mediating pro-oxidant activity of vitamin C. Effect of vitamin C on the viability of breast cancer and normal cells was studied. High doses of vitamin C decreased viability of cancerous cells but not normal cells. Docking study displayed significant binding affinity of vitamin C with p66Shc PTB domain. Western blot results suggest that vitamin C not only enhances p66Shc expression but also induces its ser36 phosphorylation. Vitamin C at high doses was also found to activate Rac1, enhance ROS production and induce apoptosis. Interestingly, ser36 phosphorylation mutant transfection and pretreatment with antioxidant N-acetylcysteine results indicate that vitamin C induced Rac1 activation, ROS production and apoptosis is p66Shc ser36 phosphorylation dependent. Overall, results highlight that vitamin C mechanistically explores p66Shc/Rac1 pathway in inducing apoptosis and thus can pave a way to use this pathway as a potential therapeutic target in breast cancers., (Copyright © 2022 Elsevier B.V. All rights reserved.)

SNTA1 signaling axis plays an essential role in cytoskeletal organization and is also implicated in breast cancers. In this study, we aimed to investigate the involvement of actin cytoskeleton in the propagation of SNTA1/p66shc mediated pro-metastatic cascade in breast cancer cells.The effect of actin filament depolymerization on SNTA1-p66Shc interaction and the trimeric complex formation was analyzed using co-immunoprecipitation assays. Immunofluorescence and RhoA activation assays were used to show the involvement of SNTA1-p66Shc interaction in RhoA activation and F-actin organization. Cellular proliferation and ROS levels were assessed using MTT assay and Amplex red catalase assay. The migratory potential was evaluated using transwell migration assay and wound healing assay.We found that cytochalasin D mediated actin depolymerization significantly declines endogenous interaction between SNTA1 and p66Shc protein in MDA-MB-231 cells. Results indicate that SNTA1 and p66Shc interact with RhoA protein under physiological conditions. The ROS generation and RhoA activation were substantially enhanced in cells overexpressing SNTA1 and p66Shc, promoting proliferation and migration in these cells. In addition, we found that loss of SNTA1-p66Shc interaction impaired actin organization, proliferation, and migration in breast cancer cells. Our results demonstrate a novel reciprocal regulatory mechanism between actin modulation and SNTA1/p66Shc/RhoA signaling cascade in human metastatic breast cancer cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ali, Mir, Hamid, Bhat, Shah, Khanday and Bhat.)

Background: Alpha-1-syntrophin (SNTA1) is emerging as a novel modulator of the actin cytoskeleton. SNTA1 binds to F-actin and regulates intracellular localization and activity of various actin organizing signaling molecules. Aberration in syntrophin signaling has been closely linked with deregulated growth connected to tumor development/metastasis and its abnormal over expression has been observed in breast cancer. In the present work the effect of jasplakinolide, an actin-binding cyclodepsipeptide, on the SNTA1 protein activity and SNTA1 mediated downstream cellular events was studied in MDA-MB-231 breast cancer cell line., Methods: SNTA1 protein levels and phosphorylation status were determined in MDA-MB-231 cells post jasplakinolide exposure using western blotting and immunoprecipitation techniques respectively. MDA-MB-231 cells were transfected with WT SNTA1 and DM SNTA1 (Y 215/229 phospho mutant) and simultaneously treated with jasplakinolide. The effect of jasplakinolide and SNTA1 protein on cell migration was determined using the boyden chamber assay., Results: Jasplakinolide treatment decreases proliferation of MDA-MB-231 cells in both dose and time dependent manner. Results suggest that subtoxic doses of jasplakinolide induce morphological changes in MDA-MB-231 cells from flat spindle shape adherent cells to round weakly adherent forms. Mechanistically, jasplakinolide treatment was found to decrease SNTA1 protein levels and its tyrosine phosphorylation status. Moreover, migratory potential of jasplakinolide treated cells was significantly inhibited in comparison to control cells., Conclusion: Our results demonstrate that jasplakinolide inhibits cell migration by impairing SNTA1 functioning in breast cancer cells.

ShcA (Src homologous- collagen homologue), family of adapter proteins, consists of three isoforms which integrate and transduce external stimuli to different signaling networks. ShcA family consists of p46Shc, p52Shc and p66Shc isoforms, characterized by having multiple protein-lipid and protein-protein interaction domains implying their functional diversity. Among the three isoforms p66Shc is structurally different containing an additional CH2 domain which attributes to its dual functionality in cell growth, mediating both cell proliferation and apoptosis. Besides, p66Shc is also involved in different biological processes including reactive oxygen species (ROS) production, cell migration, ageing, cytoskeletal reorganization and cell adhesion. Moreover, the interplay between p66Shc and ROS is implicated in the pathology of various dreadful diseases. Accordingly, here we discuss the recent structural aspects of all ShcA adaptor proteins but are highlighting the case of p66Shc as model isoform. Furthermore, this review insights the role of p66Shc in progression of chronic age-related diseases like neuro diseases, metabolic disorders (non-alcoholic fatty liver, obesity, diabetes, cardiovascular diseases, vascular endothelial dysfunction) and cancer in relation to ROS. We finally conclude that p66Shc might act as a valuable biomarker for the prognosis of these diseases and could be used as a potential therapeutic target., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Apoptosis Inducing Factor (AIF), a phylogenetically conserved mitochondrial inter-membrane space flavoprotein has an important role in caspase independent cell death. Nevertheless, AIF is also essential for cell survival. It is required for mitochondrial organization and energy metabolism. Upon apoptotic stimulation, AIF induces DNA fragmentation after its mitochondrio-nuclear translocation. Although it executes critical cellular functions in a coordinated manner, the exact mechanism still remains obscure. The present study aims to understand AIF's role in cell survival, growth and development by its down-regulation in an interesting unicellular eukaryote, D. discoideum which exhibits multicellularity upon starvation. Constitutive AIF down-regulated (dR) cells exhibited slower growth and delayed developmental morphogenesis. Also, constitutive AIF dR cells manifested high intracellular ROS, oxidative DNA damage and calcium levels with lower ATP content. Interestingly, constitutive AIF dR cells showed amelioration in cell growth upon antioxidant treatment, strengthening its role as ROS regulator. Under oxidative stress, AIF dR cells showed early mitochondrial membrane depolarization followed by AIF translocation from mitochondria to nucleus and exhibited necrotic cell death as compared to paraptoptic cell death of control cells. Thus, the results of this study provide an exemplar where AIF is involved in growth and development by regulating ROS levels and maintaining mitochondrial function in D. discoideum, an evolutionarily significant model organism exhibiting caspase independent apoptosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Dictyostelium discoideum, a unicellular eukaryote, exhibits multicellularity upon nutrient starvation and is a good model system for developmental studies, and for the study of various signal transduction pathways. Reactive oxygen species at low doses act as signaling molecules; however, at high doses they are known to cause DNA damage that results in the activation of poly(ADP-ribose) polymerase (PARP). We have earlier reported the high resistance of the unicellular stage of D. discoideum to oxidative stress, and we now show the response of this organism to oxidative stress and the role of PARP during development. We used hydroxylamine (HA) to induce in situ generation of H(2)O(2) and monitored the effect of benzamide, a PARP inhibitor, on oxidative stress-induced changes in D. discoideum development. Interestingly, oxidative stress resulted in PARP activation within 5 min that was inhibited by benzamide. Oxidative stress-induced delay in developmental pattern was also partially restored by benzamide. We studied the long-term effects of PARP inhibition under oxidative stress, and our results demonstrated that spores formed under HA stress exhibited significant delay in germination in comparison to benzamide-pretreated HA-stressed cells. However, second-generation cells showed normal development, signifying that PARP inhibition has no deleterious effect on D. discoideum development under oxidative stress.

The social amoeba Dictyostelium discoideum, a powerful paradigm provides clear insights into the regulation of growth and development. In addition to possessing complex individual cellular functions like a unicellular eukaryote, D. discoideum cells face the challenge of multicellular development. D. discoideum undergoes a relatively simple differentiation process mainly by cAMP mediated pathway. Despite this relative simplicity, the regulatory signaling pathways are as complex as those seen in metazoan development. However, the introduction of restriction-enzyme-mediated integration (REMI) technique to produce developmental gene knockouts has provided novel insights into the discovery of signaling molecules and their role in D. discoideum development. Cell cycle phase is an important aspect for differentiation of D. discoideum, as cells must reach a specific stage to enter into developmental phase and specific cell cycle regulators are involved in arresting growth phase genes and inducing the developmental genes. In this review, we present an overview of the signaling molecules involved in the regulation of growth to differentiation transition (GDT), molecular mechanism of early developmental events leading to generation of cAMP signal and components of cAMP relay system that operate in this paradigm.