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ObjectivesTo investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).MethodsDemographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression.ResultsOf 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19.ConclusionOlder age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

Leishmaniasis represents a severe global health problem. In the last decades, there have been significant challenges in controlling this disease due to the unavailability of licensed vaccines, the high toxicity of the available drugs, and an unrestrained surge of drug-resistant parasites, and human immunodeficiency virus (HIV)–Leishmania co-infections. Leishmania spp. preferentially invade macrophage lineage cells of vertebrates for replication after subverting cellular functions of humans and other mammals. These early events in host–parasite interactions are likely to influence the future course of the disease. Thus, there is a continuing need to discover a simple cellular model that reproduces the in vivo pathogenesis. Acanthamoeba spp. are non-mammalian phagocytic amoeba with remarkable similarity to the cellular and functional aspects of macrophages. We aimed to assess whether the similarity reported between macrophages and Acanthamoeba spp. is sufficient to reproduce the infectivity of Leishmania spp. Herein, we analyzed co-cultures of Acanthamoeba castellanii or Acanthamoeba polyphaga with Leishmania infantum, Leishmania amazonensis, Leishmania major, and Leishmania braziliensis. Light and fluorescence microscopy revealed that the flagellated promastigotes attach to the A. castellanii and/or A. polyphaga in a bipolar and or random manner, which initiates their uptake via pseudopods. Once inside the cells, the promastigotes undergo significant changes, which result in the obligatory amastigote-like intracellular form. There was a productive infection with a continuous increase in intracellular parasites. However, we frequently observed intracellular amastigotes in vacuoles, phagolysosomes, and the cytosol of Acanthamoeba spp. Our findings corroborate that Leishmania spp. infects Acanthamoeba spp. and replicates in them but does not cause their rapid degeneration or lysis. Overall, the evidence presented here confirms that Acanthamoeba spp. have all prerequisites and can help elucidate how Leishmania spp. infect mammalian cells. Future work exposing the mechanisms of these interactions should yield novel insights into how these pathogens exploit amoebae. Author summary: Leishmaniasis represents a severe global health problem, and drug resistance is a growing concern. Leishmania spp. are obligate intracellular parasites that survive within cells of the vertebrate macrophage, modulating their activation. Understanding the multilayered relationship between metabolism and function of innate immune cells during infection has great therapeutic and preventive potential. Mammalian macrophages and Acanthamoeba spp. display similarities in the molecular mechanisms involved in directional motility, recognition, binding, engulfment, and the phagolysosomal processes, and they express similar receptors. Hence, we hypothesize that Acanthamoeba spp. represent a model that can be used to evaluate macrophage–pathogen interactions from the perspective of innate immunity. However, it has not yet been described whether Leishmania spp. can survive in Acanthamoeba spp. We found that Acanthamoeba spp. support Leishmania growth. Acanthamoeba spp. contain ancient pathogen recognition mechanisms, and Leishmania spp. could manipulate amoeboid functions to favor their survival and replication based on strategies of ancestral metabolic pathways. Our robust evidence highlights that amoebae could be used as a model to understand the biology and evolution of host–Leishmania interactions. [ABSTRACT FROM AUTHOR]

Purpose: Cross-language studies suggest more similarities than differences in how dysarthria affects the speech of people with Parkinson's disease (PwPD) who speak different languages. In this study, we aimed to identify the relative contribution of acoustic variables to distinguish PwPD from controls who spoke varieties of two Romance languages, French and Portuguese. Method: This bi-national, cross-sectional, and case-controlled study included 129 PwPD and 124 healthy controls who spoke French or Portuguese. All participants underwent the same clinical examinations, voice/speech recordings, and self-assessment questionnaires. PwPD were evaluated off and on optimal medication. Inferential analyses included Disease (controls vs. PwPD) and Language (French vs. Portuguese) as factors, and random decision forest algorithms identified relevant acoustic variables able to distinguish participants: (a) by language (French vs. Portuguese) and (b) by clinical status (PwPD on and off medication vs. controls). Results: French-speaking and Portuguese-speaking individuals were distinguished from each other with over 90% accuracy by five acoustic variables (the mean fundamental frequency and the shimmer of the sustained vowel /a/ production, the oral diadochokinesis performance index, the relative sound level pressure and the relative sound pressure level standard deviation of the text reading). A distinct set of parameters discriminated between controls and PwPD: for men, maximum phonation time and the oral diadochokinesis speech proportion were the most significant variables; for women, variables calculated from the oral diadochokinesis were the most discriminative. Conclusions: Acoustic variables related to phonation and voice quality distinguished between speakers of the two languages. Variables related to pneumophonic coordination and articulation rate were the more effective in distinguishing PwPD from controls. Thus, our research findings support that respiration and diadochokinesis tasks appear to be the most appropriate to pinpoint signs of dysarthria, which are largely homogeneous and language-universal. In contrast, identifying language-specific variables with the speech tasks and acoustic variables studied was less conclusive. [ABSTRACT FROM AUTHOR]

AbstractThe synthesis of composites comprising chitosan (CS) and magnetite using the co-precipitation method yielded a compound denoted as CS/Fe3O4, which demonstrated magnetic properties. FTIR analysis confirmed the presence of magnetite nanoparticles within the composite. This CS/Fe3O4 composite proved to be highly efficient in adsorbing tetracycline (TC) from solutions of tetracycline hydrochloride (HTCCl), achieving an adsorption efficiency exceeding 65%. Moreover, the composite maintained its adsorption capacity over five cycles of sorption-desorption, indicating its robustness and reusability. The Langmuir isotherm provided a suitable description of the liquid-solid equilibrium of TC at 25 °C and 35 °C. Thermodynamic analysis revealed interesting insights into the nature of TC adsorption on CS. At low concentrations, the adsorption process was found to be exothermic, while at very high concentrations, it became endothermic. This observation suggests that the adsorption of TC at low concentrations is governed by protonation of chitosan and, at high concentrations, by entropic factors, highlighting the importance of considering thermodynamic parameters in understanding the adsorption mechanism. Overall, these findings contribute to the development of efficient and cost-effective adsorbents for the removal of TC from aqueous solutions. [ABSTRACT FROM AUTHOR]

Objectives We aimed to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial SpA (axSpA), peripheral SpA (pSpA) and (PsA). Methods The ASAS-perSpA study data were analysed. Models for the three patient groups were run separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively. Results The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA. In axSpA, disease activity (β = –0.061), physical function (β = –0.041), female sex (β = –0.019) and fibromyalgia (FM) (β = –0.068) were associated with worse HRQoL; age (β = 0.001) and university education (β = 0.014) were associated with better HRQoL. In pSpA, disease activity (β = –0.04) and physical function (β = –0.054) were associated with worse HRQoL. In PsA, disease activity (β = –0.045), physical function (β = –0.053), axial disease (β = –0.041) and female sex (β = –0.028) were associated with worse HRQoL. In axSpA, disease activity (β = 0.889), physical function (β = 0.887), peripheral disease (β = 0.564), female sex (β = 0.812) and FM (β = 1.639) were associated with worse GH; age (β = –0.013) and university education (β = –0.274) were associated with better GH. In pSpA, physical function (β = 1.142) and female sex (β = 1.060) were associated with worse GH; university education (β = –0.611) was associated with better GH. In PsA, disease activity (β = 0.703), physical function (β = 1.025), axial involvement (β = 0.659), female sex (β = 0.924) and FM (β = 1.387) were associated with worse GH; age (β = –0.024) and university education (β = –0.856) were associated with better GH. Conclusion Disease activity and physical function are major HRQoL and GH determinants across SpA types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients. [ABSTRACT FROM AUTHOR]

Repressor element-1 silencing transcription factor (REST) is required for the formation of mature neurons. REST dysregulation underlies a key mechanism of neurodegeneration associated with neurological disorders. However, the mechanisms leading to alterations of REST-mediated silencing of key neurogenesis genes are not known. Here, we show that BRCA1 Associated ATM Activator 1 (BRAT1), a gene linked to neurodegenerative diseases, is required for the activation of REST-responsive genes during neuronal differentiation. We find that INTS11 and INTS9 subunits of Integrator complex interact with BRAT1 as a distinct trimeric complex to activate critical neuronal genes during differentiation. BRAT1 depletion results in persistence of REST residence on critical neuronal genes disrupting the differentiation of NT2 cells into astrocytes and neuronal cells. We identified BRAT1 and INTS11 co-occupying the promoter region of these genes and pinpoint a role for BRAT1 in recruiting INTS11 to their promoters. Disease-causing mutations in BRAT1 diminish its association with INTS11/INTS9, linking the manifestation of disease phenotypes with a defect in transcriptional activation of key neuronal genes by BRAT1/INTS11/INTS9 complex. Finally, loss of Brat1 in mouse embryonic stem cells leads to a defect in neuronal differentiation assay. Importantly, while reconstitution with wild-type BRAT1 restores neuronal differentiation, the addition of a BRAT1 mutant is unable to associate with INTS11/INTS9 and fails to rescue the neuronal phenotype. Taken together, our study highlights the importance of BRAT1 association with INTS11 and INTS9 in the development of the nervous system. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is caused by Toxoplasma gondii, an obligate intracellular apicomplexan parasite that infects up to one third of the human population (1-4). Humans are mainly infected by ingesting tissue cysts [...]

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered. [ABSTRACT FROM AUTHOR]