Explore the vast range of titles available.

Although considered the ternary inflammasome structure, whether the singular, perinuclear NLRP3:ASC speck is synonymous with the NLRP3 inflammasome is unclear. Herein, we report that the NLRP3:ASC speck is not required for nigericin-induced inflammasome activation but facilitates and maximizes IL-1β processing. Furthermore, the NLRP3 agonists H 2 O 2 and MSU elicited IL-1β maturation without inducing specks. Notably, caspase-1 activity is spatially distinct from the speck, occurring at multiple cytoplasmic sites. Additionally, caspase-1 activity negatively regulates speck frequency and speck size, while speck numbers and IL-1β processing are negatively correlated, cyclical and can be uncoupled by NLRP3 mutations or inhibiting microtubule polymerization. Finally, when specks are present, caspase-1 is likely activated after leaving the speck structure. Thus, the speck is not the NLRP3 inflammasome itself, but is instead a dynamic structure which may amplify the NLRP3 response to weak stimuli by facilitating the formation and release of small NLRP3:ASC complexes which in turn activate caspase-1.

This study examines the association between food insecurity and mental health of women during the COVID-19 pandemic in a resource poor setting. Data were collected at two time-points (wave 1 and 2) from 2402 women, one per household, participating in a larger study during extended COVID-19 lockdown in the rural areas of the southwest region of Bangladesh. The primary outcome of the analyses is the association between food insecurity, measured using the Food Insecurity Experience Scale (FIES), and stress level, measured using the Perceived Stress Scale (PSS), for women during the lockdown. General awareness about COVID-19 and attitude towards prescribed preventive measures were also measured since COVID-19 health concerns could exacerbate food insecurity. An individual-level evaluation of the effect of wave 2 FIES score on PSS score showed that worsening of the food security status increasing the stress level of the participants (95% CI: 1.61; 2.13; p-value: <0.001). Additionally, a significant negative association was observed between the PSS score and change in food security status between the two waves (Coefficient: -1.15, 95% CI: -1.30; -0.99, p-value: <0.001), indicating that deterioration in food security status over the pandemic period increasing the stress level. At the village level, the results showed a similar pattern. General awareness around ways coronavirus spreads was high, yet there were misperceptions at a higher level. Maintaining hand hygiene, wearing face masks outside the home, and going outside only when necessary were widely practised. Fewer respondents could maintain a 1.5-metre distance from others in the outside and maintained cough and sneeze etiquette. The results indicate a higher stress level, a potential contributor to poor mental health, as food insecurity deteriorated. Policy initiatives in ameliorating immediate food insecurity during crises, improving long-term wellbeing, and expanding the reach of mental health support are warranted.

Functional recovery in psychosis remains a challenge despite current evidence-based treatment approaches. To address this problem, innovative interventions using virtual reality (VR) have recently been developed. VR technologies have enabled the development of realistic environments in which individuals with psychosis can receive psychosocial treatment interventions in more ecological settings than traditional clinics. These interventions may therefore increase the transfer of learned psychosocial skills to real-world environments, thereby promoting long-term functional recovery. However, the overall feasibility and efficacy of such interventions within the psychosis population remain unclear. This systematic review aims to investigate whether VR-based psychosocial interventions are feasible and enjoyable for individuals with psychosis, synthesize current evidence on the efficacy of VR-based psychosocial interventions for psychosis, and identify the limitations in the current literature to guide future research. This research followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Literature searches were conducted in PubMed and PsycINFO in May 2021. We searched for peer-reviewed English articles that used a psychosocial intervention with a VR component. Participants in the included studies were diagnosed with schizophrenia, schizoaffective disorder, or another psychotic disorder. The included studies were divided into four categories as follows: cognitive remediation interventions, social skills interventions, vocational skills interventions, and auditory verbal hallucinations and paranoia interventions. The risk of bias assessment was performed for each study. A total of 18 studies were included in this systematic review. Of these 18 studies, 4 (22%) studies used a cognitive remediation intervention, 4 (22%) studies used a social skills intervention, 3 (17%) studies used a vocational skills intervention, and 7 (39%) studies implemented an intervention aimed at improving auditory verbal hallucinations or paranoia. A total of 745 individuals with psychosis were included in the study. All the studies that evaluated feasibility showed that VR-based psychosocial interventions were feasible and enjoyable for individuals with psychosis. The preliminary evidence on efficacy included in this review suggests that VR-based psychosocial interventions can improve cognitive, social, and vocational skills in individuals with psychosis. VR-based interventions may also improve the symptoms of auditory verbal hallucinations and paranoia. The skills that participants learned through these interventions were durable, transferred into real-world environments, and led to improved functional outcomes, such as autonomy, managing housework, and work performance. VR-based interventions may represent a novel and efficacious approach for improving psychosocial functioning in psychosis. Therefore, VR-based psychosocial interventions represent a promising adjunctive therapy for the treatment of psychosis, which may be used to improve psychosocial skills, community functioning, and quality of life.

The Coronavirus Disease 2019 (COVID-19) pandemic and associated mitigation policies created a global economic and health crisis of unprecedented depth and scale, raising the estimated prevalence of depression by more than a quarter in high-income countries. Low- and middle-income countries (LMICs) suffered the negative effects on living standards the most severely. However, the consequences of the pandemic for mental health in LMICs have received less attention. Therefore, this study assesses the association between the COVID-19 crisis and mental health in 8 LMICs. We conducted a prospective cohort study to examine the correlation between the COVID-19 pandemic and mental health in 10 populations from 8 LMICs in Asia, Africa, and South America. The analysis included 21,162 individuals (mean age 38.01 years, 64% female) who were interviewed at least once pre- as well as post-pandemic. The total number of survey waves ranged from 2 to 17 (mean 7.1). Our individual-level primary outcome measure was based on validated screening tools for depression and a weighted index of depression questions, dependent on the sample. Sample-specific estimates and 95% confidence intervals (CIs) for the association between COVID-19 periods and mental health were estimated using linear regressions with individual fixed effects, controlling for independent time trends and seasonal variation in mental health where possible. In addition, a regression discontinuity design was used for the samples with multiple surveys conducted just before and after the onset of the pandemic. We aggregated sample-specific coefficients using a random-effects model, distinguishing between estimates for the short (0 to 4 months) and longer term (4+ months). The random-effects aggregation showed that depression symptoms are associated with a increase by 0.29 standard deviations (SDs) (95% CI [−.47, −.11], p -value = 0.002) in the 4 months following the onset of the pandemic. This change was equivalent to moving from the 50th to the 63rd percentile in our median sample. Although aggregate depression is correlated with a decline to 0.21 SD (95% CI [−0.07, −.34], p -value = 0.003) in the period thereafter, the average recovery of 0.07 SD (95% CI [−0.09, .22], p -value = 0.41) was not statistically significant. The observed trends were consistent across countries and robust to alternative specifications. Two limitations of our study are that not all samples are representative of the national population, and the mental health measures differ across samples. Controlling for seasonality, we documented a large, significant, negative association of the pandemic on mental health, especially during the early months of lockdown. The magnitude is comparable (but opposite) to the effects of cash transfers and multifaceted antipoverty programs on mental health in LMICs. Absent policy interventions, the pandemic could be associated with a lasting legacy of depression, particularly in settings with limited mental health support services, such as in many LMICs. We also demonstrated that mental health fluctuates with agricultural crop cycles, deteriorating during “lean”, pre-harvest periods and recovering thereafter. Ignoring such seasonal variations in mental health may lead to unreliable inferences about the association between the pandemic and mental health.

The NLRP3 inflammasome is central to host defense and implicated in various inflammatory diseases and conditions. While the favored paradigm of NLRP3 inflammasome activation stipulates a unifying signal intermediate that de-represses NLRP3, this view has not been tested. Further, structures within NLRP3 required for inflammasome activation are poorly defined. Here we demonstrate that while the NLRP3 LRRs are not auto-repressive and are not required for inflammasome activation by all agonists, distinct sequences within the NLRP3 LRRs positively and negatively modulate inflammasome activation by specific ligands. In addition, elements within the HD1/HD2 \"hinge\" of NLRP3 and the nucleotide-binding domain have contrasting functions depending upon the specific agonists. Further, while NLRP3 1-432 is minimally sufficient for inflammasome activation by all agonists tested, the pyrin, and linker domains (1-134) function cooperatively and are sufficient for inflammasome activation by certain agonists. Conserved cysteines 8 and 108 appear important for inflammasome activation by sterile, but not infectious insults. Our results define common and agonist-specific regions of NLRP3 that likely mediate ligand-specific responses, discount the hypothesis that NLRP3 inflammasome activation has a unified mechanism, and implicate NLRP3 as an integrator of agonist-specific, inflammasome activating signals.

Background Despite being one of the few evidence-based treatments for acute ischemic stroke, intravenous thrombolysis has low implementation rates—mainly due to a narrow therapeutic window and the health system changes required to deliver it within the recommended time. This systematic review and meta-analyses explores the differential effectiveness of intervention strategies aimed at improving the rates of intravenous thrombolysis based on the number and type of behaviour change wheel functions employed. Method The following databases were searched: MEDLINE, EMBASE, PsycINFO, CINAHL and SCOPUS. Multiple authors independently completed study selection and extraction of data. The review included studies that investigated the effects of intervention strategies aimed at improving the rates of intravenous thrombolysis and/or onset-to-needle, onset-to-door and door-to-needle time for thrombolysis in patients with acute ischemic stroke. Interventions were coded according to the behaviour change wheel nomenclature. Study quality was assessed using the QualSyst scoring system for quantitative research methodologies. Random effects meta-analyses were used to examine effectiveness of interventions based on the behaviour change wheel model in improving rates of thrombolysis, while meta-regression was used to examine the association between the number of behaviour change wheel intervention strategies and intervention effectiveness. Results Results from 77 studies were included. Five behaviour change wheel interventions, ‘Education’, ‘Persuasion’, ‘Training’, ‘Environmental restructuring’ and ‘Enablement’, were found to be employed among the included studies. Effects were similar across all intervention approaches regardless of type or number of behaviour change wheel-based strategies employed. High heterogeneity ( I 2 > 75%) was observed for all the pooled analyses. Publication bias was also identified. Conclusion There was no evidence for preferring one type of behaviour change intervention strategy, nor for including multiple strategies in improving thrombolysis rates. However, the study results should be interpreted with caution, as they display high heterogeneity and publication bias.

Introduction : Dual-task studies have demonstrated that walking is attention-demanding for younger adults. However, numerous studies have attributed this to task type rather than the amount of required to accomplish the task. This study examined four tasks: two discrete (i.e., short intervals of attention) and two continuous (i.e., sustained attention) to determine whether greater attentional demands result in greater dual-task costs due to an overloaded processing capacity. Methods : Nineteen young adults (21.5 ± 3.6 years, 13 females) completed simple reaction time (SRT) and go/no-go (GNG) discrete cognitive tasks and n-back (NBK) and double number sequence (DNS) continuous cognitive tasks with or without self-paced walking. Prefrontal cerebral hemodynamics were measured using functional near-infrared spectroscopy (fNIRS) and performance was measured using response time, accuracy, and gait speed. Results : Repeated measures ANOVAs revealed decreased accuracy with increasing cognitive demands ( p = 0.001) and increased dual-task accuracy costs ( p < 0.001). Response times were faster during the single compared to dual-tasks during the SRT ( p = 0.005) and NBK ( p = 0.004). DNS gait speed was also slower in the dual compared to single task ( p < 0.001). Neural findings revealed marginally significant interactions between dual-task walking and walking alone in the DNS ( p = 0.06) and dual -task walking compared to the NBK cognitive task alone ( p = 0.05). Conclusion : Neural findings suggest a trend towards increased PFC activation during continuous tasks. Cognitive and motor measures revealed worse performance during the discrete compared to continuous tasks. Future studies should consider examining different attentional demands of motor tasks.

The gram-negative bacterium Francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. The presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. Previously we reported in vitro culture conditions for this bacterium which, in contrast to typical methods, yielded a bacterial phenotype that mimics that of the bacterium's mammalian, extracellular phase. SDS-PAGE and carbohydrate analysis of differentially-cultivated F. tularensis LVS revealed that bacteria displaying the host-adapted phenotype produce both longer polymers of LPS O-antigen (OAg) and additional HMW carbohydrates/glycoproteins that are reduced/absent in non-host-adapted bacteria. Analysis of wildtype and OAg-mutant bacteria indicated that the induced changes in surface carbohydrates involved both OAg and non-OAg species. To assess the impact of these HMW carbohydrates on the access of outer membrane constituents to antibody we used differentially-cultivated bacteria in vitro to immunoprecipitate antibodies directed against outer membrane moieties. We observed that the surface-carbohydrates induced during host-adaptation shield many outer membrane antigens from binding by antibody. Similar assays with normal mouse serum indicate that the induced HMW carbohydrates also impede complement deposition. Using an in vitro macrophage infection assay, we find that the bacterial HMW carbohydrate impedes TLR2-dependent, pro-inflammatory cytokine production by macrophages. Lastly we show that upon host-adaptation, the human-virulent strain, F. tularensis SchuS4 also induces capsule production with the effect of reducing macrophage-activation and accelerating tularemia pathogenesis in mice. F. tularensis undergoes host-adaptation which includes production of multiple capsular materials. These capsules impede recognition of bacterial outer membrane constituents by antibody, complement, and Toll-Like Receptor 2. These changes in the host-pathogen interface have profound implications for pathogenesis and vaccine development.

Francisella tularensis (Ft) is a highly infectious intracellular pathogen and the causative agent of tularemia. Because Ft can be dispersed via small droplet-aerosols and has a very low infectious dose it is characterized as a category A Select Agent of biological warfare. Respiratory infection with the attenuated Live Vaccine Strain (LVS) and the highly virulent SchuS4 strain of Ft engenders intense peribronchiolar and perivascular inflammation, but fails to elicit select pro-inflammatory mediators (e.g., TNF, IL-1β, IL-6, IL-12, and IFN-γ) within the first ~72 h. This in vivo finding is discordant with the principally TH1-oriented response to Ft frequently observed in cell-based studies wherein the aforementioned cytokines are produced. An often overlooked confounding factor in the interpretation of experimental results is the influence of environmental cues on the bacterium's capacity to elicit certain host responses. Herein, we reveal that adaptation of Ft to its mammalian host imparts an inability to elicit select pro-inflammatory mediators throughout the course of infection. Furthermore, in vitro findings that non-host adapted Ft elicits such a response from host cells reflect aberrant recognition of the DNA of structurally-compromised bacteria by AIM2-dependent and -independent host cell cytosolic DNA sensors. Growth of Ft in Muller-Hinton Broth or on Muller-Hinton-based chocolate agar plates or genetic mutation of Ft was found to compromise the structural integrity of the bacterium thus rendering it capable of aberrantly eliciting pro-inflammatory mediators (e.g., TNF, IL-1β, IL-6, IL-12, and IFN-γ). Our studies highlight the profound impact of different growth conditions on host cell response to infection and demonstrate that not all in vitro-derived findings may be relevant to tularemia pathogenesis in the mammalian host. Rational development of a vaccine and immunotherapeutics can only proceed from a foundation of knowledge based upon in vitro findings that recapitulate those observed during natural infection.

Background Oral squamous cell carcinoma (OSCC) is the most prevalent form of oral cancer. Very few researches have been carried out for the automatic diagnosis of OSCC using artificial intelligence techniques. Though biopsy is the ultimate test for cancer diagnosis, analyzing a biopsy report is a very much challenging task. To develop computer‐assisted software that will diagnose cancerous cells automatically is very important and also a major need of the hour. Aim To identify OSCC based on morphological and textural features of hand‐cropped cell nuclei by traditional machine learning methods. Methods In this study, a structure for semi‐automated detection and classification of oral cancer from microscopic biopsy images of OSCC, using clinically significant and biologically interpretable morphological and textural features, are examined and proposed. Forty biopsy slides were used for the study from which a total of 452 hand‐cropped cell nuclei has been considered for morphological and textural feature extraction and further analysis. After making a comparative analysis of commonly used methods in the segmentation technique, a combined technique is proposed. Our proposed methodology achieves the best segmentation of the nuclei. Henceforth the features extracted were fed into five classifiers, support vector machine, logistic regression, linear discriminant, k‐nearest neighbors and decision tree classifier. Classifiers were also analyzed by training time. Another contribution of the study is a large indigenous cell level dataset of OSCC biopsy images. Results We achieved 99.78% accuracy applying decision tree classifier in classifying OSCC using morphological and textural features. Conclusion It is found that both morphological and textural features play a very important role in OSCC diagnosis. It is hoped that this type of framework will help the clinicians/pathologists in OSCC diagnosis.