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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.