Antagonistic effects of the cytotoxic molecules granzyme B and TRAIL in the immunopathogenesis of sclerosing cholangitis.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and fibrosis. We showed an elevated interferon γ response in patients with primary sclerosing cholangitis and in multidrug resistance protein 2-deficient ( Mdr2-/- ) mice developing sclerosing cholangitis. Interferon γ induced expression of the cytotoxic molecules granzyme B (GzmB) and TRAIL in hepatic lymphocytes and mediated liver fibrosis in sclerosing cholangitis. APPROACH AND RESULTS: In patient samples and Mdr2-/- mice, we identified lymphocyte clusters with a cytotoxic gene expression profile using single-cell RNA-seq and cellular indexing of transcriptomes and epitopes by sequencing analyses combined with multi-parameter flow cytometry. CD8 + T cells and NK cells showed increased expression of GzmB and TRAIL in sclerosing cholangitis. Depletion of CD8 + T cells ameliorated disease severity in Mdr2-/- mice. By using Mdr2-/- × Gzmb-/- and Mdr2-/- × Tnfsf10-/- mice, we investigated the significance of GzmB and TRAIL for disease progression in sclerosing cholangitis. Interestingly, the lack of GzmB resulted in reduced cholangiocyte apoptosis, liver injury, and fibrosis. In contrast, sclerosing cholangitis was aggravated in the absence of TRAIL. This correlated with elevated GzmB and interferon γ expression by CD8 + T cells and NK cells enhanced T-cell survival, and increased apoptosis and expansion of cholangiocytes. CONCLUSIONS: GzmB induces apoptosis and fibrosis in sclerosing cholangitis, whereas TRAIL regulates inflammatory and cytotoxic immune responses, subsequently leading to reduced liver injury and fibrosis.

Smart License Plate in Combination with Fluorescent Concentrator for Vehicular Visible Light Communication System.

Vehicle-to-vehicle communication based on visible light communication has gained much attention. This work proposes a smart license plate receiver incorporated with a fluorescent concentrator, enabling a fast vehicle-to-vehicle communication with a large field of view and high optical gain. Communication performance is experimentally analyzed using off-the-shelf light-emitting diode-based headlamps for low-latency direct line of sight channel. Additionally, a blue laser diode-based beam-steering and tracking system, through image processing of taillights with a steerable mirror, is investigated. Data rates of 54 Mbps from the headlamps and 532 Mbps from the beam-steering channel with ±25° are demonstrated. In addition, real-time video streaming through the beam-steering channel is presented.

Development of Optimized Sumatriptan-Prochlorperazine Combined Orodispersible Films Without Disintegrant: in vitro, ex vivo and in vivo Characterization.

Sumatriptan succinate and prochlorperazine maleate are a clinically proven combination for treating migraine and associated nausea and vomiting. Classical oral dosage forms are not frequently workable in migraine because of the associated nausea/vomiting, and no effective fixed dose combination is available. Thus, the aim of the study was to optimize a combined sumatriptan-prochlorperazine orodispersible film for rapid release of drugs. Orodispersible films were prepared by solvent casting method using varied amounts of polyvinyl alcohol and glycerol as film former and plasticizer, respectively, along with fixed levels of other ingredients employing central composite design. The optimum film (VF) demonstrated disintegration and total dispersion times as 21 s and 2.3 min, respectively. Tensile strength and Young's modulus were 8.86 ± 0.37 MPa and 24.15 ± 0.07 MPa, respectively. The in vitro T80% of both drugs from the ODF was achieved within 4 min. The film was palatable and disintegrated in 2 min in buccal cavity of human volunteers. Permeation study through goat mucosa demonstrated 100% permeation of both drugs within 15 min. X-Ray diffraction and differential scanning calorimetry supported drugs being amorphous and Fourier transform infrared demonstrated drug-excipient compatibility in optimized film. A judicious combination of sumatriptan succinate and prochlorperazine maleate could be prepared in orodispersible films for the possible relief of migraine.

Simultaneous quantification of sumatriptan succinate and prochlorperazine maleate in orodispersible films using two validated UV-spectroscopic methods.

The study aimed at simultaneous quantification of sumatriptan succinate (SUM) and prochlorperazine maleate (PCP) in an orodispersible film using two validated spectroscopic methods viz. simultaneous equation (Method I) and the Q-absorption ratio (Method II). The Method I involved measurement of absorbances at λmax of both drugs while in Method II, absorbances were measured at isosbestic wavelength and λmax of one of the two components. Method validation were accomplished as per the ICH guidelines. A 1:1 mixture of the drugs and an orodispersible film (ODF) containing these drugs were assayed by both methods. The absorbance data of SUM and PCP in both methods were linear at respective wavelengths with correlation coefficient values >0.995. Both methods were precise as % RSD in repeatability, interday and intraday precision was less than 2. The estimation of SUM and PCP from the film dosage form by method I was104.74% and 98.34% and by method II was 103.45% and 98.85%, respectively, with a standard deviation <2. The study concluded that both the methods were simple, reliable and robust and can be applied successfully for the simultaneous quantification of SUM and PCP in mixture and orodispersible film dosage form.

Utilization of LED Grow Lights for Optical Wireless Communication-Based RF-Free Smart-Farming System.

Indoor smart-farming based on artificial grow lights has gained attention in the past few years. In modern agricultural technology, the growth status is generally monitored and controlled by radio-frequency communication networks. However, it is reported that the radio frequency (RF) could negatively impact the growth rate and the health condition of the vegetables. This work proposes an energy-efficient solution replacing or augmenting the current RF system by utilizing light-emitting diodes (LEDs) as the grow lights and adopting visible light communications and optical camera communication for the smart-farming systems. In particular, in the proposed system, communication data is modulated via a 24% additional green grow LED light that is also known to be beneficial for the growth of the vegetables. Optical cameras capture the modulated green light reflected from the vegetables for the uplink connection. A combination of white ceiling LEDs and photodetectors provides the downlink, enabling an RF-free communication network as a whole. In the proposed architecture, the smart-farming units are modularized, leading to flexible mobility. Following theoretical analysis and simulations, a proof-of-concept demonstration presents the feasibility of the proposed architecture by successfully demonstrating the maximum data rates of 840 b/s (uplink) and 20 Mb/s (downlink).

Increased frequency of fibromyalgia among patients with chronic pain presenting to internal medicine clinics of a tertiary care hospital: A cross sectional study.

OBJECTIVE: To estimate fibromyalgia frequency among patients presenting with complaints of chronic fatigue and or generalised body pain for at least six weeks. METHODS: The cross-sectional study was conducted at the Department of Internal Medicine, Indus Hospital, Karachi, between December 2016 and March 2018, and comprised patients of either gender presenting with complaints of chronic fatigue and or generalised body pain for at least six weeks. They were assessed for fibromyalgia according to the 2010 Fibromyalgia Diagnostic criteria questionnaire. The Data was analysed using SPSS 21. RESULTS: Of the 267 patients, 197(73.8%) were females and 70(26.2%) were males. Fibromyalgia was detected in 149(55.80%) patients. The mean age of patients with fibromyalgia was 42.3±14.6 years and it was 38.9±13.7 years in patients without fibromyalgia (p<0.05). No significant association was found between gender and fibromyalgia (p>0.05). CONCLUSIONS: All patients with generalised pain should be evaluated for fibromyalgia and a diagnosis made to reduce the cost of further referrals and investigations, and delay in the management of this debilitating disorder.

Killer cell immunoglobulin receptor profile on CD4(+) CD28(-) T cells and their pathogenic role in non-dialysis-dependent and dialysis-dependent chronic kidney disease patients.

There is a progressive increase in cardiovascular disease with declining renal function, unexplained by traditional risk factors. A CD4(+) T-cell subpopulation (CD4(+)  CD28(-) ), activated by human heat-shock protein 60 (hHSP 60), expands in patients with acute coronary syndrome and is associated with vascular damage. These cells exhibit cytotoxicity via expression of activating killer cell-immunoglobulin-like receptor KIR2DS2, mainly in the absence of inhibitory KIR2DL3. We investigated expansion of these cells and the pathogenic role of the KIR in non-dialysis-dependent chronic kidney disease (NDD-CKD) and end-stage haemodialysis-dependent renal disease (HD-ESRD) patients. CD4(+)  CD28(-) cells were present in 27% of the NDD-CKD and HD-ESRD patients (8-11% and 10-11% of CD4(+) compartment, respectively). CD4(+)  CD28(-) cells were phenotyped for KIR and DAP12 expression. Cytotoxicity was assessed by perforin and pro-inflammatory function by interferon-γ expression on CD4(+)  CD28(-) clones (NDD-CKD n = 97, HD-ESRD n = 262). Thirty-four per cent of the CD4(+)  CD28(-) cells from NDD-CKD expressed KIR2DS2 compared with 56% in HD-ESRD patients (P = 0·03). However, 20% of clones expressed KIR2DL3 in NDD-CKD compared with 7% in HD-ESRD patients (P = 0·004). DAP12 expression in CD28(-)  2DS2(+) clones was more prevalent in HD-ESRD than NDD-CKD (92% versus 60%; P < 0·001). Only 2DS2(+)  2DL3(-)  DAP12(+) clones were cytotoxic in response to hHSP 60. CD4(+)  CD28(-) cells exhibited increased KIR2DS2, reduced KIR2DL3 and increased DAP12 expression in HD-ESRD compared with NDD-CKD patients. These findings suggest a gradual loss of expression, functionality and protective role of inhibitory KIR2DL3 as well as increased cytotoxic potential of CD4(+)  C28(-) cells with progressive renal impairment. Clonal expansion of these T cells may contribute to heightened cardiovascular events in HD-ESRD.

Validation of ethnopharmacological uses of Heliotropium strigosum Willd. as spasmolytic, bronchodilator and vasorelaxant remedy.

BACKGROUND: Heliotropium strigosum is used in traditional medicine to manage gastrointestinal pain, respiratory distress and vascular disorders. The present study was undertaken to provide scientific evidences for these folkloric uses by in vitro experimental settings. METHODS: A crude methanol extract of the Heliotropium strigosum (Hs.Cr) was tested in vitro on isolated rabbit jejunum preparations to detect the possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. RESULTS: The Hs.Cr exhibited relaxant effects in rabbit jejunum in a concentration dependent manner (0.01-3.0 mg/ml). The Hs.Cr also relaxed K(+) (80 mM)-induced spastic contractions in rabbit jejunum and shifted the Ca(2+) concentration response curves towards right. The extract relaxed carbachol (1 µM)- as well as K(+) (80 mM)-induced contractions in rabbit trachea at concentrations ranging from 0.01 to 10 mg/ml. Moreover, Hs.Cr. also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 µM)- and K(+) (80 mM)-induced contractions in isolated rabbit aorta. CONCLUSIONS: The Hs.Cr was found to exhibit spasmolytic, bronchodilator and vasorelaxant activities on isolated rabbit jejunum, trachea and aorta preparations, likely mediated through Ca(2+) channel blockade. This finding may provide a scientific basis for the folkloric uses of the plant.

On characterization of entropy measure using logarithmic regression model for Copper(II) Fluoride.

The versatile uses of Copper(II) Fluoride (CuF2) are well known; these include its usage as a precursor in chemical synthesis as well as its contribution to the creation of sophisticated materials and electronics. There are interesting opportunities to study the interactions between these elements because of their unique crystal structure, which contains copper ions and fluoride anions. Its potential in optoelectronic devices and conductive qualities also make it a viable material for next-generation technologies. To better understand the structural properties of CuF2 and how they affect its entropy, we present new Zagreb indices in this study and use them to calculate entropy measures. We also build a regression model to clarify the relationship between the calculated indices and entropy levels. The findings of our investigation offer significant understanding regarding the ability of the suggested Zagreb indices to extract meaningful content and their correlation with entropy in the context of CuF2. This information is important for understanding CuF2 alloys and for exploring related complex materials.

Assessing the Safety and Efficacy of Rivaroxaban for Stroke Prevention in Patients With Atrial Fibrillation: A Systemic Review and Meta-Analysis.

An effective anticoagulation therapy is required for patients with atrial fibrillation because it presents a significant risk of stroke. The current study evaluates the relative safety as well as efficacy of rivaroxaban in patients who are diagnosed with atrial fibrillation. A thorough literature review of relevant databases was conducted, focusing on academic and clinical studies that were published from 2017 onward. Inclusion criteria comprised randomized controlled trials and other observational studies comparing the incidence of stroke and the safety index of rivaroxaban in atrial fibrillation. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) for data overview reporting and overview. A total of 21 studies were selected based on the inclusion criteria. A total of 19/21 studies advocated the adoption of rivaroxaban for minimizing stroke incidence. Rivaroxaban also showed superiority in achieving the therapeutic objectives, i.e., reduction in the incidence of stroke. The results for rivaroxaban against warfarin showed an improved safety index and effectiveness of rivaroxaban. The total effect size for the analysis was calculated to be Z=2.62 (p-value=0.009). The individual effect of all studies favored the "rivaroxaban" group. The heterogeneity in the study was as follows: tau2=0.10; chi2=110.10, df=6; I2=95%. The second analysis for risk reduction and incidence of stroke after rivaroxaban therapy also showed a bias towards rivaroxaban therapy. The combined effect for the analysis was found to be as follows: HR=0.73 ((95% CI: 0.50, 1.07). The total effect was calculated to be Z=1.61 (p-value= 0.10). The heterogeneity was found to be as follows: tau2= 0.20, chi2=89.97, df=6, I2=93%. Standard dosing of rivaroxaban emerges as a preferred strategy for stroke prevention, balancing efficacy and safety. Clinical decision-making should consider individual patient characteristics and future research should delve into specific subpopulations and long-term outcomes to further refine treatment guidelines.

On network construction and module detection for molecular graph of titanium dioxide.

Titanium dioxide is the most common and valuable oxide among four types of oxides of titanium. Its physicochemical properties make it a very valuable compound. The main objective of this article is to initially detect the modules based on highly connected links of the network of the degree-based topological indices. This information is lately integrated with different physical properties of the chemical compound of titanium dioxide to develop different mathematical frameworks based on master regulatory indices of the modules. This connection can be helpful in studying the physical measures at a deeper level in the form of different degree based topological indices.Communicated by Ramaswamy H. Sarma.

Visualizing P2X7-Dependent Inflammasome Formation in Human Monocytes by Fluorescence Microscopy and Flow Cytometry.

One of the most prominent effects of P2X7 activation in myeloid cells is the induction of the assembly of the NLRP3 inflammasome, a central process controlling the secretion of pro-inflammatory cytokines of the IL-1 family such as IL-1ß and IL-18. The ability to visualize inflammasome formation greatly facilitates research into the role of P2X7 in inflammation. In this chapter, a method to monitor the formation of the NLPR3 inflammasome in monocytes and other myeloid cells could be demonstrated. Following priming by lipopolysaccharide (LPS), P2X7 was stimulated by ATP to mediate inflammasome assembly. This causes cytosolically disperse ASC, a central component of the inflammasome, to aggregate into microscopically visible specks due to its recruitment to the inflammasome. Methods to monitor this change in the spatial distribution of ASC in human peripheral blood monocytes by flow cytometry and fluorescence microscopy are presented.

Modeling the impact of the vaccine on the COVID-19 epidemic transmission via fractional derivative.

To achieve the goal of ceasing the spread of COVID-19 entirely it is essential to understand the dynamical behavior of the proliferation of the virus at an intense level. Studying this disease simply based on experimental analysis is very time consuming and expensive. Mathematical modeling might play a worthy role in this regard. By incorporating the mathematical frameworks with the available disease data it will be beneficial and economical to understand the key factors involved in the spread of COVID-19. As there are many vaccines available globally at present, henceforth, by including the effect of vaccination into the model will also support to understand the visible influence of the vaccine on the spread of COVID-19 virus. There are several ways to mathematically formulate the effect of disease on the population like deterministic modeling, stochastic modeling or fractional order modeling etc. Fractional order derivative modeling is one of the fundamental methods to understand real-world problems and evaluate accurate situations. In this article, a fractional order epidemic model S p E p I p E r p R p D p Q p V p on the spread of COVID-19 is presented. S p E p I p E r p R p D p Q p V p consists of eight compartments of population namely susceptible, exposed, infective, recovered, the quarantine population, recovered-exposed, and dead population. The fractional order derivative is considered in the Caputo sense. For the prophecy and tenacity of the epidemic, we compute the reproduction number R 0 . Using fixed point theory, the existence and uniqueness of the solutions of fractional order derivative have been studied. Furthermore, we are using the generalized Adams-Bashforth-Moulton method, to obtain the approximate solution of the fractional-order COVID-19 model. Finally, numerical results and illustrative graphic simulation are given. Our results suggest that to reduce the number of cases of COVID-19 we should reduce the contact rate of the people if the population is not fully vaccinated. However, to tackle the issue of reducing the social distancing and lock down, which have very negative impact on the economy as well as on the mental health of the people, it is much better to increase the vaccine rate and get the whole nation to be fully vaccinated.

Physical Analysis of Heat for Formation and Entropy of Ceria Oxide Using Topological Indices.

BACKGROUND: Cerium oxide nanoparticles (CeO2 NPs) have gained their importance as engineered nanomaterials (ENMs) that have wide applications as catalysts in industry, which direct to their prominent occurrence in natural and engineered water systems. Cerium oxide nanoparticles (CeO2 NPs) have gained their importance as engineered nanomaterials (ENMs) that have wide applications as catalysts in industry, which direct to their prominent occurrence in natural and engineered water systems. In wastewater treatment plants, CeO2 NPs can stay colloidally stable and be unconstrained in the secondary effluents. As they entered into tertiary treatment, such as advanced oxidation processes (AOPs), it is noteworthy that how the generated reactive oxygen species will change the colloidal stability, aggregation, and the surface chemistry of CeO2 NPs. AIM AND OBJECTIVE: The study was aimed to analyze the chemical graph of the crystal structure of Ceria Oxide(cuprite) CeO2. Also, our main objective is to compute the Heat of Formation and Entropy using degree based topological indices. MATERIALS AND METHODS: Chemical graph theory plays an important role in modeling and designing any chemical structure. The topological indices are the numerical invariants of a molecular graph and are very useful for predicting their physical properties. For calculation, we have utilized the combinatorial processing strategy, edge partition technique, vertex partition strategy, analytic procedures, graph hypothetical tools, degree counting technique and entirety of degrees of neighbor technique. Moreover, Matlab programming has been utilized for numerical computations and checks. We likewise utilized the maple for plotting these numerical outcomes. RESULTS: We have computed Heat of Formation and Entropy using degree based topological indices. Our main results are based on some degree based topological indices, namely, the atom bond connectivity index ABC, geometric arithmetic index GA, general Randi index, Forgotten index, Augmented zagreb index and Balban index for the chemical graph of the crystal structure of cuprite CeO2[p, q, t] We also provide a detailed application of the computed results. CONCLUSION: We discuss these indices exhibited difference with the reported heat of formation and entropy of cuprite CeO2[p, q, t] In almost all the cases, an exponential increase of aforementioned indices is observed with the increase in the number of cells or other words size of cuprite CeO2[p, q, t] nanocrystal. On the other hand, a linear relationship of indices with respect to the number of formula units suggests a slight modification of these indices for an appropriate explanation of the physical properties of cuprite CeO2[p, q, t] nanocrystal of varying size and hence its prospective application in nanoceria engineering.

Lithium toxicity following Roux-en-Y gastric bypass: Mini review and illustrative case.

Lithium is among the mainstays of treatment for bipolar disorder. Bariatric surgery can considerably change the oral bioavailability of drugs, particularly lithium. In this review, a 36-year-old male patient is described, who presented with lithium toxicity, including neurologic and gastric symptoms after undergoing Roux-en-Y gastric bypass. The mechanism of lithium toxicity is discussed; recommendations for clinicians regarding lithium use in postsurgical patients are provided; and previous case reports of lithium toxicity post-gastric bypass surgery are analyzed. Awareness and education of lithium absorption changes postbariatric surgery is essential for optimal patient care. Close clinical and drug concentration level monitoring is warranted.

Psychosis during the COVID-19 pandemic: A systematic review of case reports and case series.

BACKGROUND: Preliminary data suggest that patients with COVID-19 may experience psychiatric symptoms, including psychosis. We systematically reviewed the literature to evaluate the concurrence of new-onset psychosis or exacerbation of clinically stable psychosis through case reports and case series. METHODS: Six databases were searched, followed by an electronic and manual search of the relevant articles. Studies were identified using predetermined eligibility criteria. We evaluated the demographic characteristics, clinical history, course of illness, management, and prognosis of the patients in these studies. RESULTS: Case reports and case series, altogether consisting of 57 unique cases were included. The mean patient age for onset of psychotic symptoms was 43.4 years for men and 40.3 years for women. About 69% of patients had no prior history of psychiatric disorders. Most patients had mild COVID-19-related symptoms, with only 15 (26.3%) presenting with moderate to severe COVID-19-related disease and complications. The most commonly reported psychotic symptoms were delusions and hallucinations. Patients with psychotic symptoms were treated with antipsychotics, benzodiazepines, valproic acid, and electroconvulsive treatment. In 36 cases, psychotic symptoms resolved completely or improved significantly. Ten cases had partial improvement with residual psychotic symptoms, and one patient died due to cardiac arrest. CONCLUSION: Most patients responded to a low-to-moderate dose of antipsychotics with a quick recovery. However, the residual psychiatric symptoms highlight the need for careful monitoring and longer follow-up. Clinicians should be mindful of the occurrence of psychosis due to COVID-19 infection in a subset of COVID-19 patients that can be misdiagnosed as a psychotic disorder alone.

Esketamine-A quick-acting novel antidepressant without the disadvantages of ketamine.

Esketamine, which is an S-enantiomer of ketamine, is better than conventional antidepressants and even better than R-ketamine. This article discusses the mechanism of action of Esketamine, how different it is from other antidepressants, its side effect profile, indications for use, various routes of administration and the review of existing literature on Esketamine.

Social Media Reinvented: Can Social Media Help Tackle the Post-Pandemic Mental Health Onslaught?

Social media plays an omnipresent role in our modern lives, influencing every aspect of it, mental health being one of them. There has been increased focus on social media in recent times, especially its role in the ongoing coronavirus disease 2019 (COVID-19) pandemic. With various forms of social media, we hope to review the impact of various online platforms and emphasize their usage during the novel COVID-19 pandemic, which has led to a universal feeling of consternation throughout the world, mainly as a consequence of social distancing norms and cancellations of schools and places of work, which has affected not only the livelihood but also the way of life of scores of people. Despite the negative press social media often receives in the field of mental health, there are opportunities to utilize its impact positively. This is not limited to connecting persons to mental health resources, spreading information about available COVID-19 treatment, and allowing social connection across the world. In this article, we review the renewed role that social media has had and future possibilities for its usage in the fight against the current pandemic.

Neurocysticercosis presenting as psychosis: A case report and a brief literature review.

Patients with neurocysticercosis, a common infection of the central nervous system caused by Taenia solium, have been reported to develop neuropsychiatric complications. We report a unique case of recurrent psychosis caused by neurocysticercosis in a 37-year-old El Salvador immigrant woman and discuss the underlying pathophysiological mechanisms of the complications. We reviewed published case reports of neurocysticercosis that presented with psychotic features and compared their diagnostic evaluation, the underlying pathophysiology of complications and treatment regimen with our case. This review concludes that neurocysticercosis should be considered in the differential diagnosis of patients presenting with psychosis with a history of residence in an endemic area.

A Scoping Review of Vaping, E-Cigarettes and Mental Health Impact: Depression and Suicidality.

Electronic cigarettes have grown in popularity due to natural curiosity, novel flavors, and advertising as both a means to aid smoking cessation and a "safe" smoking option. There is a substantial body of research on the harmful physical health effects of vaping, but there are relatively few studies on its mental health effects, particularly in adolescents 10-21 years of age. The purpose of this review is to examine the negative effects of vaping on mental health, in particular depression and suicidality. Using the databases PubMed, Scopus, Cochrane Library, and the search engine Google Scholar, we focused on observational studies looking into association between vaping, depression and suicidality. We found 7255 studies; after removing duplicates and other irrelevant articles, 106 articles were left. After reviewing the abstracts and titles, 99 citations were manually removed, 7 studies were included in the final review. Suicide attempts were significantly higher among e-cigarette users compared to non-users. E-cigarette use was associated with depression, suicidal ideation and suicide attempt. Suicide attempts were significantly higher among e-cigarette users compared to non-users. It is critical to raise awareness about the association between electronic cigarettes and adolescent mental health.