Antigen-Specific CD8+ T Cells Protect against Lethal Toxoplasmosis in Mice Infected with Neospora caninum

Neospora caninum is a coccidial protozoan parasite that appears morphologically indistinguishable from Toxoplasma gondii and that infects a large range of mammals. Both inbred and outbred strains of mice exhibit a high degree of resistance to infection with N. caninum. Three inbred strains of mice (A/J, BALB/c, and C57BL/6) that were infected intraperitoneally with N. caninum were protected against a lethal challenge from T. gondii. Vaccine-induced protection was Neospora dose dependent. A rise in the CD8+ T-cell population in mice that had been vaccinated with N. caninum and challenged with T. gondii was observed. Adoptive transfer of CD8+ T-cell splenocytes from N. caninum-infected mice was protective against challenge with Toxoplasma. The CD8+ T cells from Neospora-infected mice proliferate to both Neospora and Toxoplasma antigens in vitro and secrete substantial quantities of gamma interferon when pulsed with the parasite antigen. These observations demonstrate that N. caninum protects against lethal T. gondii infection by the induction of CD8+ T cells that are immunoreactive to both parasites

Co-existing spinal intradural ependymal cyst and sacral tarlov cyst in adult-onset tethered cord syndrome with syringomyelia: Case report and literature review

Background: Synchronous spinal intradural ependymal cysts and sacral Tarlov cysts in adult onset tethered cord syndrome are extremely rare.Case description: A 23-year-old male presented with back pain radiating into both lower extremities, accompanied by acute onset of gait difficulty and sphincter dysfunction. Magnetic resonance imaging identified a low lying conus medullaris, syringomyelia with septations extending from T12 to S1, a tethered cord, and a thickened filum terminale with a sacral Tarlov cyst. The patient underwent a L3-4 laminectomy for decompression of syringomyelia and excision/biopsy of a space occupying lesion along with S1-2 laminectomy for cord untethering and Tarlov cyst fenestration. Postoperative histopathology confirmed that the lesion was an ependymal cyst. Clinically, patient showed marked improvement in the neurological status.Conclusion: Simultaneous decompressive laminectomy of L3-4 and S1-2 effectively decompressed the syringomyelia while allowing for excision/biopsy of a space occupying lesion at the former and untethering and Tarlov cyst fenestration at the latter levels

A Dichotomous Role for Nitric Oxide During Acute Toxoplasma gondii Infection in Mice

Production of nitric oxide by macrophages is believed to be an important microbicidal mechanism for a variety of intracellular pathogens, including Toxoplasma gondii. Mice with a targeted disruption of the inducible nitric oxide synthase gene (iNOS) were infected orally with T. gondii tissue cysts. Time to death was prolonged compared with parental controls. Histologic analysis of tissue from infected mice showed scattered small foci of inflammation with parasites in various tissues of iNOS−/− mice, whereas tissue from the parental C57BL/6 mice had more extensive tissue inflammation with few visible parasites. In particular, extensive ulceration and necrosis of distal small intestine and fatty degeneration of the liver was seen in the parental mice at day 7 postinfection, as compared with the iNOS−/− mice where these tissues appeared normal. Serum interferon γ and tumor necrosis factor α levels postinfection were equally elevated in both mouse strains. Treatment of the parental mice with a NO synthase inhibitor, aminoguanidine, prevented early death in these mice as well as the hepatic degeneration and small bowel necrosis seen in acutely infected control parentals. These findings indicate that NO production during acute infection with T. gondii can kill intracellular parasites but can be detrimental, even lethal, to the host

Leveraging machine learning to analyze sentiment from COVID-19 tweets: A global perspective

Since the advent of the worldwide COVID-19 pandemic, analyzing public sentiment has become one of the major concerns for policy and decision-makers. While the priority is to curb the spread of the virus, mass population (user) sentiment analysis is equally important. Though sentiment analysis using different state-of-the-art technologies has been focused on during the COVID-19 pandemic, the reasons behind the variations in public sentiment are yet to be explored. Moreover, how user sentiment varies due to the COVID-19 pandemic from a cross-country perspective has been less focused on. Therefore, the objectives of this study are: to identify the most effective machine learning (ML) technique for classifying public sentiments, to analyze the variations of public sentiment across the globe, and to find the critical contributing factors to sentiment variations. To attain the objectives, 12,000 tweets, 3000 each from the USA, UK, and Bangladesh, were rigorously annotated by three independent reviewers. Based on the labeled tweets, four different boosting ML models, namely, CatBoost, gradient boost, AdaBoost, and XGBoost, are investigated. Next, the top performed ML model predicted sentiment of 300,000 data (100,000 from each country). The public perceptions have been analyzed based on the labeled data. As an outcome, the CatBoost model showed the highest (85.8 %) F1-score, followed by gradient boost (84.3%), AdaBoost (78.9 %), and XGBoost (83.1 %). Second, it was revealed that during the time of the COVID-19 pandemic, the sentiments of the people of the three countries mainly were negative, followed by positive and neutral. Finally, this study identified a few critical concerns that impact primarily varying public sentiment around the globe: lockdown, quarantine, hospital, mask, vaccine, and the like

A hearer-oriented evaluation of referring expression generation

This work is supported by a University of Aberdeen Sixth Century Studentship, and EPSRC grant EP/E011764/1.This paper discusses the evaluation of a Generation of Referring Expressions algorithm that takes structural ambiguity into account. We describe an ongoing study with human readers.peer-reviewe

Prevalence of Muscle Dysmorphia and Associated Health Activities in Male Medical Students in Karachi, Pakistan

Background: Muscle Dysmorphia (MD) is a subtype of body dysmorphic disorder (BDD) and is currently classified under anxiety disorders (subheading: Obsessive-compulsive disorder) in DSM 5. MD is hypothesized to affect the self-esteem and social outlook of the younger generation. MD shows a higher rate in males and may influence their self-confidence rendering them more prone towards using steroids, supplementary proteins and other drugs to alter their physical outlooks as shown in previous studies. This problem has been on the rise lately due to revolutionary advancement in the media and film industry and the abrupt changes about the standards of physical good looks and body shapes. With the lack of studies done in our population, our study will be helpful to consider the prevalence of the disease in our setting and increase awareness in the general public and clinicians. We hope to help clinicians/ therapists find better options in managing the disease. Materials: We performed a cross-sectional study with a sample size of 246 medical school students in Karachi to collect data through self-administered questionnaires. We used the DSM 5 criteria for the diagnosis of BDD and additional questions on the presence of MD. Nutritional habits, exercise routines, use of supplements and drugs were also obtained for exploratory analysis. Results: Our study predicted the prevalence of MD to be 25%. Other main findings included statistical significant associations between MD and the thoughts and practice of steroid use for muscularity. Conclusion: MD is an underdiagnosed and often unrecognized disease that we believe has significant consequences for the young male population. Further work is needed on this in our part of the world. Our research, we believe, can be a stepping stone for further studies that would incorporate wider populations

Budget impact and cost-effectiveness analyses of the COBRA-BPS multicomponent hypertension management programme in rural communities in Bangladesh, Pakistan, and Sri Lanka

Background: COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multi-component hypertension management programme that is led by community health workers, has been shown to be efficacious at reducing systolic blood pressure in rural communities in Bangladesh, Pakistan, and Sri Lanka. In this study, we aimed to assess the budget required to scale up the programme and the incremental cost-effectiveness ratios.Methods: In a cluster-randomised trial of COBRA-BPS, individuals aged 40 years or older with hypertension who lived in 30 rural communities in Bangladesh, Pakistan, and Sri Lanka were deemed eligible for inclusion. Costs were quantified prospectively at baseline and during 2 years of the trial. All costs, including labour, rental, materials and supplies, and contracted services were recorded, stratified by programme activity. Incremental costs of scaling up COBRA-BPS to all eligible adults in areas covered by community health workers were estimated from the health ministry (public payer) perspective.Findings: Between April 1, 2016, and Feb 28, 2017, 11 510 individuals were screened and 2645 were enrolled and included in the study. Participants were examined between May 8, 2016, and March 31, 2019. The first-year per-participant costs for COBRA-BPS were US$10·65 for Bangladesh,$10·25 for Pakistan, and $6·42 for Sri Lanka. Per-capita costs were$0·63 for Bangladesh, $0·29 for Pakistan, and$1·03 for Sri Lanka. Incremental cost-effectiveness ratios were $3430 for Bangladesh,$2270 for Pakistan, and $4080 for Sri Lanka, per cardiovascular disability-adjusted life year averted, which showed COBRA-BPS to be cost-effective in all three countries relative to the WHO-CHOICE threshold of three times gross domestic product per capita in each country. Using this threshold, the cost-effectiveness acceptability curves predicted that the probability of COBRA-BPS being cost-effective is 79·3% in Bangladesh, 85·2% in Pakistan, and 99·8% in Sri Lanka.Interpretation: The low cost of scale-up and the cost-effectiveness of COBRA-BPS suggest that this programme is a viable strategy for responding to the growing cardiovascular disease epidemic in rural communities in low-income and middle-income countries where community health workers are present, and that it should qualify as a priority intervention across rural settings in south Asia and in other countries with similar demographics and health systems to those examined in this study.Funding: The UK Department of Health and Social Care, the UK Department for International Development, the Global Challenges Research Fund, the UK Medical Research Council, Wellcome Trust

Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8+ T Cell Response against Toxoplasma gondii

CD8+ T cells play an essential role in the protection against both acute as well as chronic Toxoplasma gondii infection. Although the role of IL-15 has been reported to be important for the development of long-term CD8+ T cell immunity against the pathogen, the simultaneous roles played by both IL-15 and related γ-chain family cytokine IL-7 in the generation of this response during acute phase of infection has not been described. We demonstrate that while lack of IL-7 or IL-15 alone has minimal impact on splenic CD8+ T cell maturation or effector function development during acute Toxoplasmosis, absence of both IL-7 and IL-15 only in the context of infection severely down-regulates the development of a potent CD8+ T cell response. This impairment is characterized by reduction in CD44 expression, IFN-γ production, proliferation and cytotoxicity. However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8+ T cells. Interestingly, the absence of both cytokines did not impair initial CD8+ T cell generation but affected their survival and differentiation into memory phenotype IL-7Rαhi cells. Significantly lack of both cytokines severely affected expression of Bcl-2, an anti-apoptotic protein, but minimally affected proliferation. The overarching role played by these cytokines in eliciting a potent CD8+ T cell immunity against T. gondii infection is further evidenced by poor survival and high parasite burden in anti IL-7 treated IL-15−/− mice. These studies demonstrate that the two cytokines, IL-7 and IL-15, are exclusively important for the development of protective CD8+ T cell immune response against T. gondii. To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8+ T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported