A Macrophage Colony-Stimulating-Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence.

Despite evidence that γδ T cells play an important role during malaria, their precise role remains unclear. During murine malaria induced by Plasmodium chabaudi infection and in human P. falciparum infection, we found that γδ T cells expanded rapidly after resolution of acute parasitemia, in contrast to αß T cells that expanded at the acute stage and then declined. Single-cell sequencing showed that TRAV15N-1 (Vδ6.3) γδ T cells were clonally expanded in mice and had convergent complementarity-determining region 3 sequences. These γδ T cells expressed specific cytokines, M-CSF, CCL5, CCL3, which are known to act on myeloid cells, indicating that this γδ T cell subset might have distinct functions. Both γδ T cells and M-CSF were necessary for preventing parasitemic recurrence. These findings point to an M-CSF-producing γδ T cell subset that fulfills a specialized protective role in the later stage of malaria infection when αß T cells have declined.

The Aedes aegypti peritrophic matrix controls arbovirus vector competence through HPx1, a heme-induced peroxidase.

Aedes aegypti mosquitoes are the main vectors of arboviruses. The peritrophic matrix (PM) is an extracellular layer that surrounds the blood bolus. It acts as an immune barrier that prevents direct contact of bacteria with midgut epithelial cells during blood digestion. Here, we describe a heme-dependent peroxidase, hereafter referred to as heme peroxidase 1 (HPx1). HPx1 promotes PM assembly and antioxidant ability, modulating vector competence. Mechanistically, the heme presence in a blood meal induces HPx1 transcriptional activation mediated by the E75 transcription factor. HPx1 knockdown increases midgut reactive oxygen species (ROS) production by the DUOX NADPH oxidase. Elevated ROS levels reduce microbiota growth while enhancing epithelial mitosis, a response to tissue damage. However, simultaneous HPx1 and DUOX silencing was not able to rescue bacterial population growth, as explained by increased expression of antimicrobial peptides (AMPs), which occurred only after double knockdown. This result revealed hierarchical activation of ROS and AMPs to control microbiota. HPx1 knockdown produced a 100-fold decrease in Zika and dengue 2 midgut infection, demonstrating the essential role of the mosquito PM in the modulation of arbovirus vector competence. Our data show that the PM connects blood digestion to midgut immunological sensing of the microbiota and viral infections.

Rheumatoid arthritis molecular targets and their importance to flavonoid-based therapy.

Rheumatoid arthritis (RA) is a progressive, chronic, autoimmune, inflammatory, and systemic condition that primarily affects the synovial joints and adjacent tissues, including bone, muscle, and tendons. The World Health Organization recognizes RA as one of the most prevalent chronic inflammatory diseases. In the last decade, there was an expansion on the available RA therapeutic options which aimed to improve patient's quality of life. Despite the extensive research and the emergence of new therapeutic approaches and drugs, there are still significant unwanted side effects associated to these drugs and still a vast number of patients that do not respond positively to the existing therapeutic strategies. Over the years, several references to the use of flavonoids in the quest for new treatments for RA have emerged. This review aimed to summarize the existing literature about the flavonoids' effects on the major pathogenic/molecular targets of RA and their potential use as lead compounds for the development of new effective molecules for RA treatment. It is demonstrated that flavonoids can modulate various players in synovial inflammation, regulate immune cell function, decrease synoviocytes proliferation and balance the apoptotic process, decrease angiogenesis, and stop/prevent bone and cartilage degradation, which are all dominant features of RA. Although further investigation is necessary to determine the effectiveness of flavonoids in humans, the available data from in vitro and in vivo models suggest their potential as new disease-modifying anti-rheumatic drugs. This review highlights the use of flavonoids as a promising avenue for future research in the treatment of RA.

Identification of common MicroRNAs expression signatures in antiphospholipid syndrome and thromboembolic disease: A scoping review.

BACKGROUND: Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by distinct pathophysiological mechanisms leading to heterogeneous manifestations, including venous and arterial thrombosis. Despite the lack of specific markers of thrombosis risk in APS, some of the mechanisms responsible for thrombosis in APS may overlap with those of other thromboembolic diseases. Understanding these similarities is important for improving the assessment of thrombosis risk in APS. MicroRNAs (MiRNAs) are RNA molecules that regulate gene expression and may influence the autoimmune response and coagulation. PURPOSE: In this scoping review we aimed to investigate shared miRNAs profiles associated with APS and other thromboembolic diseases as a means of identifying markers indicative of a pro-thrombotic profile among patients with APS. DATA COLLECTION AND RESULTS: Through a comprehensive search of scientific databases, 45 relevant studies were identified out of 1020 references. miRs-124-3p, 125b-5p, 125a-5p, and 17-5p, were associated with APS and arterial thrombosis, while miRs-106a-5p, 146b-5p, 15a-5p, 222-3p, and 451a were associated with APS and venous thrombosis. Additionally, miR-126a-3p was associated with APS and both arterial and venous thrombosis. CONCLUSION: We observed that APS shares a common miRNAs signature with non-APS related thrombosis, suggesting that miRNA expression profiles may serve as markers of thrombotic risk in APS. Further validation of a pro-thrombotic miRNA signature in APS is warranted to improve risk assessment, diagnosis, and management of APS.

The plastomes of Lepismium cruciforme (Vell.) Miq and Schlumbergera truncata (Haw.) Moran reveal tribe-specific rearrangements and the first loss of the trnT-GGU gene in Cactaceae.

BACKGROUND: Recent studies have revealed atypical features in the plastomes of the family Cactaceae, the largest lineage of succulent species adapted to arid and semi-arid regions. Most plastomes sequenced to date are from short-globose and cylindrical cacti, while little is known about plastomes of epiphytic cacti. Published cactus plastomes reveal reduction and complete loss of IRs, loss of genes, pseudogenization, and even degeneration of tRNA structures. Aiming to contribute with new insights into the plastid evolution of Cactaceae, particularly within the tribe Rhipsalideae, we de novo assembled and analyzed the plastomes of Lepismium cruciforme and Schlumbergera truncata, two South American epiphytic cacti. METHODS AND RESULTS: Our data reveal many gene losses in both plastomes and the first loss of functionality of the trnT-GGU gene in Cactaceae. The trnT-GGU is a pseudogene in L. cruciforme plastome and appears to be degenerating in the tribe Rhipsalideae. Although the plastome structure is conserved among the species of the tribe Rhipsalideae, with tribe-specific rearrangements, we mapped around 200 simple sequence repeats and identified nine nucleotide polymorphism hotspots, useful to improve the phylogenetic resolutions of the Rhipsalideae. Furthermore, our analysis indicated high gene divergence and rapid evolution of RNA editing sites in plastid protein-coding genes in Cactaceae. CONCLUSIONS: Our findings show that some characteristics of the Rhipsalideae tribe are conserved, such as plastome structure with IRs containing only the ycf2 and two tRNA genes, structural degeneration of the trnT-GGU gene and ndh complex, and lastly, pseudogenization of rpl33 and rpl23 genes, both plastid translation-related genes.

Unravelling the Influence of Endocrine-Disrupting Chemicals on Obesity Pathophysiology Pathways.

Obesity represents a global health concern, affecting individuals of all age groups across the world. The prevalence of excess weight and obesity has escalated to pandemic proportions, leading to a substantial increase in the incidence of various comorbidities, such as cardiovascular diseases, type 2 diabetes, and cancer. This chapter seeks to provide a comprehensive exploration of the pathways through which endocrine-disrupting chemicals can influence the pathophysiology of obesity. These mechanisms encompass aspects such as the regulation of food intake and appetite, intestinal fat absorption, lipid metabolism, and the modulation of inflammation. This knowledge may help to elucidate the role of exogenous molecules in both the aetiology and progression of obesity.

MMIR: an open-source software for the registration of multimodal histological images.

BACKGROUND: Multimodal histology image registration is a process that transforms into a common coordinate system two or more images obtained from different microscopy modalities. The combination of information from various modalities can contribute to a comprehensive understanding of tissue specimens, aiding in more accurate diagnoses, and improved research insights. Multimodal image registration in histology samples presents a significant challenge due to the inherent differences in characteristics and the need for tailored optimization algorithms for each modality. RESULTS: We developed MMIR a cloud-based system for multimodal histological image registration, which consists of three main modules: a project manager, an algorithm manager, and an image visualization system. CONCLUSION: Our software solution aims to simplify image registration tasks with a user-friendly approach. It facilitates effective algorithm management, responsive web interfaces, supports multi-resolution images, and facilitates batch image registration. Moreover, its adaptable architecture allows for the integration of custom algorithms, ensuring that it aligns with the specific requirements of each modality combination. Beyond image registration, our software enables the conversion of segmented annotations from one modality to another.

Para Powerlifting Performance: A Systematic Review.

This research aimed to conduct a systematic review of para powerlifting strength performance. The searches were conducted in three electronic databases: PubMed, Scopus, and SPORTDiscus. Intervention studies related to para powerlifting performance were included. The main information was extracted systematically, based on criteria established by the authors. The data on study design, sample size, participant's characteristics (e. g. type of disability, sex, age, body weight, and height), training experience, assessment tools, physical performance criteria, and force-related outcomes were extracted and analyzed. The studies (n=9) describe factors related to biomechanics and performance. Outcomes revealed that the one-repetition maximum test is used as load prescription and that para powerlifting should work at high speeds and higher loads. Regarding technique, grip width with 1.5 biacromial distance provides a good lift and partial amplitude training as an alternative to training. There are no differences in total load and movement quality in the lumbar arched technique compared with the flat technique. As a monitoring method, repetitions in reserve scale was used for submaximal loads. Finally, our outcomes and discussion indicated strategies and techniques that can be used by para powerlifting coaches.

Age-Related Changes in Clinical and Analytical Variables in Chronic Hemodialyzed Patients.

Worldwide, the number of elderly individuals receiving chronic hemodialysis is rising. The aim of our study was to evaluate several clinical and analytical biomarkers in chronically dialyzed patients and analyze how they change with age. A cross-sectional study was performed by evaluating 289 end-stage renal disease patients undergoing dialysis. We evaluated the hemogram, adipokines, the lipid profile, and several markers related to inflammation, endothelial function/fibrinolysis, nutrition, iron metabolism, and cardiac and renal fibrosis. Clinical data and dialysis efficacy parameters were obtained from all patients. The relationships between studied biomarkers and age were assessed by a statistical comparison between younger (adults with age < 65 years) and older (age ≥ 65 years) patients and by performing regression analysis. Participants presented a mean age of 68.7 years (±13.6), with 66.8% (n = 193) being classified as older. Compared to younger patients, older patients presented the following: (a) significantly lower values of diastolic blood pressure (DBP) and ultrafiltration volume; (b) lower levels of phosphorus, uric acid, creatinine, and albumin; and (c) higher circulating concentrations of tissue-type plasminogen activator (tPA), D-dimer, interleukin-6, leptin, N-terminal pro B-type natriuretic peptide, and tissue inhibitor of metalloproteinase-1. In the multiple linear regression analysis, DBP values, tPA, phosphorus, and D-dimer levels were independently associated with the age of patients (standardized betas: -0.407, 0.272, -0.230, and 0.197, respectively; p < 0.001 for all), demonstrating relevant changes in biomarkers with increasing age at cardiovascular and nutritional levels. These findings seem to result from crosstalk mechanisms between aging and chronic kidney disease.

Resistance Exercise Sessions Comprising Multijoint vs. Single-Joint Exercises Result in Similar Metabolic and Hormonal Responses, But Distinct Levels of Muscle Damage in Trained Men.

ABSTRACT: Barbosa, PH, Bueno de Camargo, JB, Jonas de Oliveira, J, Reis Barbosa, CG, Santos da Silva, A, Dos-Santos, JW, Verlengia, R, Barreira, J, Braz, TV, and Lopes, CR. Resistance exercise sessions comprising multijoint vs. single-joint exercises result in similar metabolic and hormonal responses, but distinct levels of muscle damage in trained men. J Strength Cond Res 38(5): 842-847, 2024-Resistance-type exercise (RE) elicits distinct acute metabolic and hormonal responses, which can be modulated by the manipulation of training variables. The purpose of this study was to compare the metabolic (blood lactate and estimated lactic anaerobic system energy expenditure) and hormonal (growth hormone [GH]) responses to RE sessions composed exclusively of multijoint (MULTI) or single-joint (SINGLE) exercises. Assessments of creatine kinase (CK) levels were also performed. In a crossover design, 10 recreationally resistance-trained men (age: 26.9 ± 3.0 years, total body mass: 83.2 ± 13.8 kg; height: 176 ± 7.0 cm; training experience: 5.5 ± 2.4 years) were randomly submitted to both protocols. Blood collections were made pre, 3 minutes after, and 36 hours after each experimental session. No significant difference between MULTI vs. SINGLE was observed for the rises in blood lactate (p = 0.057) and GH (p = 0.285) levels. For CK, a significant difference between the protocols was noted, in which MULTI resulted in significant rises after 3 minutes (p = 0.017) and 36 hours (p = 0.043) compared with SINGLE. In conclusion, the findings of this study suggest that resistance-trained individuals display similar metabolic and hormonal responses when performing MULTI and SINGLE exercise protocols. Also, RE sessions comprising MULTI exercises induce a higher magnitude of muscle damage, which may require a longer recovery period compared with SINGLE.

The light intensity in the cultivation environment and the impact of glyphosate on plants of the Urochloa genus.

The variation in light within the environment triggers morphophysiological changes in plants and can lead to distinct responses in sun-exposed or shaded plants to glyphosate. The response of Urochloa genotypes subjected to desiccation with 2160, 1622.4, 1080, 524.4, 273.6, and 0.0 g ha-1 of glyphosate was evaluated in full sun and shade conditions. Cayana grass, mulato II grass, and sabiá grass - hybrids recently launched on the market, in addition to palisade grass and congo grass were evaluated. Under full sun, we achieved control of congo grass using 1080 g ha-1 of glyphosate, while the other grasses required 2160 g ha-1. In the low-light environment, sabiá grass was effectively controlled with 524.4 g ha-1 of glyphosate, but the other grasses needed 273.6 g ha-1. In shading, compared to full sun, the savings with glyphosate were 75 and 76% for the control of congo grass and sabiá grass, respectively, and 87% for palisade grass, mulato II grass and cayana grass. Increasing glyphosate doses leads to a decline in the quantum efficiency of photosystem II and in the electron transport rate, especially in the shade. Urochloa genotypes are more sensitive to glyphosate in the shade, which must be considered when determining the herbicide dose.

The role of flavonoids in the regulation of epithelial-mesenchymal transition in cancer: A review on targeting signaling pathways and metastasis.

One of the hallmarks of cancer is metastasis, a process that entails the spread of cancer cells to distant regions in the body, culminating in tumor formation in secondary organs. Importantly, the proinflammatory environment surrounding cancer cells further contributes to cancer cell transformation and extracellular matrix destruction. During metastasis, front-rear polarity and emergence of migratory and invasive features are manifestations of epithelial-mesenchymal transition (EMT). A variety of transcription factors (TFs) are implicated in the execution of EMT, the most prominent belonging to the Snail Family Transcriptional Repressor (SNAI) and Zinc Finger E-Box Binding Homeobox (ZEB) families of TFs. These TFs are regulated by interaction with specific microRNAs (miRNAs), as miR34 and miR200. Among the several secondary metabolites produced in plants, flavonoids constitute a major group of bioactive molecules, with several described effects including antioxidant, antiinflammatory, antidiabetic, antiobesogenic, and anticancer effects. This review scrutinizes the modulatory role of flavonoids on the activity of SNAI/ZEB TFs and on their regulatory miRNAs, miR-34, and miR-200. The modulatory role of flavonoids can attenuate mesenchymal features and stimulate epithelial features, thereby inhibiting and reversing EMT. Moreover, this modulation is concomitant with the attenuation of signaling pathways involved in diverse processes as cell proliferation, cell growth, cell cycle progression, apoptosis inhibition, morphogenesis, cell fate, cell migration, cell polarity, and wound healing. The antimetastatic potential of these versatile compounds is emerging and represents an opportunity for the synthesis of more specific and potent agents.

Maximal Exercise Improves the Levels of Endothelial Progenitor Cells in Heart Failure Patients.

The impact of exercise on the levels of endothelial progenitor cells (EPCs), a marker of endothelial repair and angiogenesis, and circulating endothelial cells (CECs), an indicator of endothelial damage, in heart failure patients is largely unknown. This study aims to evaluate the effects of a single exercise bout on the circulating levels of EPCs and CECs in heart failure patients. Thirteen patients with heart failure underwent a symptom-limited maximal cardiopulmonary exercise test to assess exercise capacity. Before and after exercise testing, blood samples were collected to quantify EPCs and CECs by flow cytometry. The circulating levels of both cells were also compared to the resting levels of 13 volunteers (age-matched group). The maximal exercise bout increased the levels of EPCs by 0.5% [95% Confidence Interval, 0.07 to 0.93%], from 4.2 × 10-3 ± 1.5 × 10-3% to 4.7 × 10-3 ± 1.8 × 10-3% (p = 0.02). No changes were observed in the levels of CECs. At baseline, HF patients presented reduced levels of EPCs compared to the age-matched group (p = 0.03), but the exercise bout enhanced circulating EPCs to a level comparable to the age-matched group (4.7 × 10-3 ± 1.8 × 10-3% vs. 5.4 × 10-3 ± 1.7 × 10-3%, respectively, p = 0.14). An acute bout of exercise improves the potential of endothelial repair and angiogenesis capacity by increasing the circulating levels of EPCs in patients with heart failure.

Simultaneous voltammetric determination of 7-methyl-guanine and 5-methyl-cytosine using a cathodically pre-treated boron-doped diamond electrode.

Given the importance of identifying the presence of biomarkers of human diseases in DNA samples, the main objective of this work was to investigate, for the first time, the electro-catalytic oxidation of 7-methyl-guanine (7-mGua) and 5-methyl-cytosine (5-mCyt) on a boron doped diamond electrode pre-treated cathodically (red-BDDE), using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). The anodic peak potentials of 7-mGua and 5-mCyt by DPV were at E = 1.04 V and E = 1.37 V at pH = 4.5, indicating excellent peak separation of approximately 330 mV between species. Using DPV, experimental conditions such as supporting electrolyte, pH and influence of interferents were also investigated to develop a sensitive and selective method for individual and simultaneous quantification of these biomarkers. The analytical curves for the simultaneous quantification of 7-mGua and 5-mCyt in the acid medium (pH = 4.5) were: concentration range of 0.50-5.00 µmol L-1 (r = 0.999), detection limit of 0.27 µmol L-1 for 7-mGua; from 3.00 to 25.00 µmol L-1 (r = 0.998), with a detection limit of 1.69 µmol L-1 for 5-mCyt. A new DP voltammetric method for the simultaneous detection and quantification of biomarkers 7-mGua and 5-mCyt using a red-BDDE is proposed.

Changes in Body Mass Index Are Associated with Squamous Cell Carcinomas of Oral Cavity, Oropharynx and Larynx: A Case-Control Study in Brazil.

Head and neck cancer (HNC) significantly impacts nutritional status because the tumor limits swallowing function. In this sense, it is important to monitor the nutritional status throughout the life of any individual. A multicenter case-control study was carried out to analyze the BMI at 30 years of age, two years before diagnosis and at the time of diagnosis of individuals with oral cavity, oropharynx, and larynx cancers. It was observed that a 5% reduction in BMI during the two years before enrollment was associated with an increased risk of the oral cavity (OR = 3.73), oropharyngeal OR = 5.25), and laryngeal (OR = 5.22). Reduced BMI of more than 5% over two years before diagnosis was associated with HNC. Weight loss remained significant at diagnosis, but it is not possible to exclude reverse causality since most cases are at an advanced stage. BMI monitoring of individuals at potential risk for HNC can promote early diagnosis and nutritional interventions for HNC.

Ontogenetic changes in bite force and gape in tufted capuchins.

Bite force and gape are two important performance metrics of the feeding system, and these metrics are inversely related for a given muscle size because of fundamental constraints in sarcomere length-tension relationships. How these competing performance metrics change in developing primates is largely unknown. Here, we quantified in vivo bite forces and gapes across ontogeny and examined these data in relation to body mass and cranial measurements in captive tufted capuchins, Sapajus spp. Bite force and gape were also compared across geometric and mechanical properties of mechanically challenging foods to investigate relationships between bite force, gape and food accessibility (defined here as the ability to breach shelled nuts). Bite forces at a range of gapes and feeding behavioral data were collected from a cross-sectional ontogenetic series of 20 captive and semi-wild tufted capuchins at the Núcleo de Procriação de Macacos-Prego Research Center in Araçatuba, Brazil. These data were paired with body mass, photogrammetric measures of jaw length and facial width, and food geometric and material properties. Tufted capuchins with larger body masses had absolutely higher in vivo bite forces and gapes, and animals with wider faces had absolutely higher bite forces. Bite forces and gapes were significantly smaller in juveniles compared with subadults and adults. These are the first primate data to empirically demonstrate the gapes at which maximum active bite force is generated and to demonstrate relationships to food accessibility. These data advance our understanding of how primates meet the changing performance demands of the feeding system during development.

Adipose Tissue-Derived Stromal/Stem Cells Transplantation with Cholecalciferol Supplementation in Recent-Onset Type 1 Diabetes Patients: Twelve Months Follow-Up.

To evaluate safety and therapeutic effect along 12 months of allogenic adipose tissue-derived stromal/stem cells (ASCs) transplantation with cholecalciferol (VITD) in patients with recent-onset type 1 diabetes (T1D). Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1xKgx106 cells) and VITD 2000UI/day for 12 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide area under the curve (CPAUC), insulin dose, HbA1c and frequency of FoxP3+ in CD4+ or CD8+ T-cells(flow cytometry) were evaluated at baseline(T0), after 3(T3), 6(T6) and 12 months(T12). Eleven patients completed follow up (7:group 1;4:group 2). Group 1 had lower insulin requirement at T3(0.24±0.18vs0.53±0.23UI/kg,p=0.04), T6(0.24±0.15vs0.66±0.33 UI/kg,p=0.04) and T12(0.39±0.15vs0.74±0.29 UI/Kg,p=0.04).HbA1c was lower at T6 (50.57±8.56vs72.25±10.34 mmol/mol,p=0.01), without differences at T12 (57.14±11.98 in group 1 vs. 73.5±14.57 mmol/min in group 2, p=0.16). CPAUC was not significantly different between groups at T0(p=0.07), higher in group 1 at T3(p=0.04) and T6(p=0.006), but similar at T12(p=0.23). IDAA1c was significantly lower in group 1 than group 2 at T3,T6 and T12 (p=0.006, 0.006 and 0.042, respectively). IDDA1c was inversely correlated to FoxP3 expression in CD4 and CD8+ T cells at T6 (p<0.001 and p=0.01, respectively). In group 1, one patient had recurrence of a benign teratoma that was surgically removed, not associated to the intervention. ASCs with VITD without immunosuppression were safe and associated lower insulin requirements, better glycemic control, and transient better pancreatic function in recent onset T1D, but the potential benefits were not sustained.

Well-being trajectories in breast cancer and their predictors: A machine-learning approach.

OBJECTIVE: This study aimed to describe distinct trajectories of anxiety/depression symptoms and overall health status/quality of life over a period of 18 months following a breast cancer diagnosis, and identify the medical, socio-demographic, lifestyle, and psychological factors that predict these trajectories. METHODS: 474 females (mean age = 55.79 years) were enrolled in the first weeks after surgery or biopsy. Data from seven assessment points over 18 months, at 3-month intervals, were used. The two outcomes were assessed at all points. Potential predictors were assessed at baseline and the first follow-up. Machine-Learning techniques were used to detect latent patterns of change and identify the most important predictors. RESULTS: Five trajectories were identified for each outcome: stably high, high with fluctuations, recovery, deteriorating/delayed response, and stably poor well-being (chronic distress). Psychological factors (i.e., negative affect, coping, sense of control, social support), age, and a few medical variables (e.g., symptoms, immune-related inflammation) predicted patients' participation in the delayed response and the chronic distress trajectories versus all other trajectories. CONCLUSIONS: There is a strong possibility that resilience does not always reflect a stable response pattern, as there might be some interim fluctuations. The use of machine-learning techniques provides a unique opportunity for the identification of illness trajectories and a shortlist of major bio/behavioral predictors. This will facilitate the development of early interventions to prevent a significant deterioration in patient well-being.

Impact of disease duration on proteomic bioprofile and prognosis in rheumatoid arthritis patients.

OBJECTIVES: Cardiovascular disease worsens the prognosis of rheumatoid arthritis (RA) and vice-versa. Inflammation may be a common pathway for both conditions. It is expected that a longer RA duration leads to a greater inflammatory cumulative exposure burden; however, studies on the association between RA disease duration and outcomes are scarce. Our aim is to compare the characteristics, biomarker expression and outcomes according to the duration of RA. METHODS: Prospective cohort study including 399 RA patients, with detailed clinical, echocardiographic, and proteomic phenotyping that were compared across tertiles of RA disease duration. Cox proportional models were used to study the association of disease duration with cardiovascular outcomes. RESULTS: RA duration tertiles were: tertile 1 with median of 3.2; tertile 2 with median of 8.8; and tertile 3 with median of 21.8 years. Compared to tertile 1, patients in tertile 3 were older, had more erosive disease, more frequent echocardiographic alterations, lower haemoglobin and walked a shorter distance on the 6MWT. Natriuretic peptides, cathepsin L1, galectin 9, matrix metalloproteinase-12, adrenomedullin and tumour necrosis factor receptor 11A were higher in patients with longer disease duration. Compared to patients in tertile 1, those in tertile 3 had higher risk of a subsequent cardiovascular hospitalisation or cardiovascular death (HR 2.71, 95%CI 1.06-6.92, p=0.04). CONCLUSIONS: RA patients with longer disease duration had more organ damage and worse outcomes than those with shorter disease duration. Biomarker expression suggested that patients with longer RA duration had activation of pathways related to inflammation, extracellular matrix organisation, fibrosis and congestion.

SARS-CoV-2 Infection Drives a Glycan Switch of Peripheral T Cells at Diagnosis.

COVID-19 is a highly selective disease in which SARS-CoV-2 infection can result in different clinical manifestations ranging from asymptomatic/mild to severe disease that requires hospitalization. In this study, we demonstrated that SARS-CoV-2 infection results in a glycosylation reprogramming of circulating lymphocytes at diagnosis. We identified a specific glycosignature of T cells, defined upon SARS-CoV-2 infection and apparently triggered by a serological factor. This specific glycan switch of T cells is detected at diagnosis being more pronounced in asymptomatic patients. We further demonstrated that asymptomatic patients display an increased expression of a viral-sensing receptor through the upregulation of DC-SIGN in monocytes. We showed that higher levels of DC-SIGN in monocytes at diagnosis correlates with better COVID-19 prognosis. This new evidence pave the way to the identification of a novel glycan-based response in T cells that may confer protection against SARS-CoV-2 infection in asymptomatic patients, highlighting a novel prognostic biomarker and potential therapeutic target.