A conserved motif in the immune-subdominant RAP-1 related antigen of Babesia bovis contains a B-cell epitope recognized by antibodies from protected cattle.

Introduction: Babesia bovis, a tick-borne apicomplexan parasite causing bovine babesiosis, remains a significant threat worldwide, and improved and practical vaccines are needed. Previous studies defined the members of the rhoptry associated protein-1 (RAP-1), and the neutralization-sensitive rhoptry associated protein-1 related antigen (RRA) superfamily in B. bovis, as strong candidates for the development of subunit vaccines. Both RAP-1 and RRA share conservation of a group of 4 cysteines and amino acids motifs at the amino terminal end (NT) of these proteins. Methods and results: Sequence comparisons among the RRA sequences of several B. bovis strains and other Babesia spp parasites indicate a high level of conservation of a 15-amino acid (15-mer) motif located at the NT of the protein. BlastP searches indicate that the 15-mer motif is also present in adenylate cyclase, dynein, and other ATP binding proteins. AlphaFold2 structure predictions suggest partial exposure of the 15-mer on the surface of RRA of three distinct Babesia species. Antibodies in protected cattle recognize a synthetic peptide representing the 15-mer motif sequence in iELISA, and rabbit antibodies against the 15-mer react with the surface of free merozoites in immunofluorescence. Discussion and conclusion: The presence of the 15-mer-like regions in dynein and ATP-binding proteins provides a rationale for investigating possible functional roles for RRA. The demonstrated presence of a surface exposed B-cell epitope in the 15-mer motif of the B. bovis RRA, which is recognized by sera from protected bovines, supports its inclusion in future subunit epitope-based vaccines against B. bovis.

Predictors of mortality in hospitalised patients with COVID-19: a 1-year case-control study.

BACKGROUND: A paucity of predictive models assessing risk factors for COVID-19 mortality that extend beyond age and gender in Latino population is evident in the current academic literature. OBJECTIVES: To determine the associated factors with mortality, in addition to age and sex during the first year of the pandemic. DESIGN: A case-control study with retrospective revision of clinical and paraclinical variables by systematic revision of clinical records was conducted. Multiple imputations by chained equation were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalisation. No intervention was performed. SETTING: High-complexity centre above 2640 m above sea level (masl) in Colombia. PARTICIPANTS: A population sample of 564 patients admitted to the hospital with confirmed COVID-19 by PCR. Deceased patients (n=282) and a control group (n=282), matched by age, sex and month of admission, were included. MAIN OUTCOME MEASURE: Mortality during hospitalisation. MAIN RESULTS: After the imputation of datasets, CART analysis estimated 11 clinical profiles based on respiratory distress, haemoglobin, lactate dehydrogenase, partial pressure of oxygen to inspired partial pressure of oxygen ratio, chronic kidney disease, ferritin, creatinine and leucocytes on admission. The accuracy model for prediction was 80.4% (95% CI 71.8% to 87.3%), with an area under the curve of 78.8% (95% CI 69.63% to 87.93%). CONCLUSIONS: This study discloses new interactions between clinical and paraclinical features beyond age and sex influencing mortality in COVID-19 patients. Furthermore, the predictive model could offer new clues for the personalised management of this condition in clinical settings.

Bullying and cyberbullying, what do they have in common and what not? A latent class analysis / Acoso y ciberacoso, ¿qué es igual y qué es distinto? Un análisis de clases latentes

El acoso escolar y el ciberacoso se presentan como comporta-mientos de riesgo durante la adolescencia. Aunque se ha reconocido una importante relación entre ambos fenómenos, aspectos referidos a su preva-lencia, la semejanza y diferencia entre uno y otro, la transferencia de roles, así como los aspectos emocionales, sociales y morales asociados aún están sin resolver. El objetivo fue explorar los perfiles de implicación en acoso y ciberacoso a través de un análisis de clases latentes y examinar su asocia-ción con desconexión moral, ajuste social y normativo y rumiación de la ira. Se presenta un estudio longitudinal en dos tiempos con 3,006 escolares de secundaria (Medad= 13.53; 51.9% chicas). Se utilizaron autoinformes ampliamente validados en la población de referencia. Los resultados mos-traron cuatro clases latentes: no implicados, víctimas-cibervíctimas, agreso-res victimizados y totalmente implicados. Análisis de regresión logística identificaron un bajo ajuste social en los totalmente implicados, bajo ajuste normativo y alta desconexión moral en perfiles mixtos, y alta rumiación de la ira en todos los perfiles de implicación, principalmente en agresores vic-timizados. Se discuten estos resultados en términos de su valor para com-prender los matices que distinguen el acoso y ciberacoso, de la existencia de roles puros y mixtos y de las variables emocionales, sociales y morales asociadas.(AU)

Bullying and cyberbullying are risky behaviours which normally occur during adolescence. Although an important relationship has been recognized between the two phenomena, issues related to their prevalence, the similarity and difference between them, the transfer of roles, as well as the emotional, social, and moral aspects associated with them, remain un-resolved. The aim of this study was to explore the roles ofinvolvement in bullying and cyberbullying through an analysis of latent classes, and exam-ine their association with moral disengagement, social and normative ad-justment, and anger rumination. The study had a two-stage longitudinal de-sign, with 3,006 secondary school students (Mage= 13.53; 51.9% girls), us-ing extensively validated self-reports in the reference population. The re-sults showed four latent classes: uninvolved, victim-cybervictim, bully-victim and wholly involved. Logistic regression analyses identified a low social adjustment in those wholly involved, low normative adjustment and high moral disengagement in mixed profiles, and high anger rumination in all involvement profiles, mainly in bully-victim. These results are discussed in terms of their value in understanding the distinctions between bullying and cyberbullying, the existence of pure and mixed roles, and the associat-ed emotional, social, and moral variables.(AU)

Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia.

Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world's second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele's read peak and the slippage ratio of the allele's read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.

Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach-A Comprehensive Narrative Review.

The comprehensive narrative review conducted in this study delves into the mechanisms of communication and action at the molecular level in the human organism. The review addresses the complex mechanism involved in the microbiota-gut-brain axis as well as the implications of alterations in the microbial composition of patients with neurodegenerative diseases. The pathophysiology of neurodegenerative diseases with neuronal loss or death is analyzed, as well as the mechanisms of action of the main metabolites involved in the bidirectional communication through the microbiota-gut-brain axis. In addition, interventions targeting gut microbiota restructuring through fecal microbiota transplantation and the use of psychobiotics-pre- and pro-biotics-are evaluated as an opportunity to reduce the symptomatology associated with neurodegeneration in these pathologies. This review provides valuable information and facilitates a better understanding of the neurobiological mechanisms to be addressed in the treatment of neurodegenerative diseases.

Aggressive and Defensive Behaviour, Normative, and Social Adjustment in the Complex Dynamics of School Bullying.

Bullying is a group phenomenon in which schoolchildren take on different roles. Although certain contextual elements play a key role in its evolution, very few longitudinal studies have been carried out to date which investigate how these factors interact. This study aims to explore the different class groupings as regards bullying norms and to examine the effect of the type of norm, social, and normative adjustment and pro-sociality, also of the interaction of group norms with involvement in aggression and victim defence in bullying situations. A total of 3,358 secondary school students (50.71% girls, Mage = 13 years, SD = 1.34) participated in the study. Four groups of norms towards bullying were identified: anti-bullying, anti-bullying but not actively defending, indifference, and pro-bullying. Univariate linear regression models showed that normative adjustment and the type of norms had a direct inverse effect on both types of behaviour, while pro-sociality only had an effect on defence. In groups with pro-bullying norms, a greater effect of normative adjustment was observed for involvement in defence and aggression, and pro-social skills were associated with aggression. These results suggest the need to work on moral, social and emotional elements to improve school climate in schools.

El acoso escolar es un fenómeno grupal en el que los escolares asumen roles diferentes. Aunque determinadas características contextuales juegan un papel fundamental en su evolución, aún son escasos los estudios longitudinales que exploran cómo interactúan dichos factores. El presente estudio tiene como objetivos explorar los diferentes tipos de agrupamientos de clases según las normas de acoso escolar y examinar el efecto del tipo de norma, el ajuste social y normativo y la prosocialidad, así como la interacción de las normas del grupo con la implicación en la agresión y defensa de la víctima en situaciones de acoso. Un total de 3,358 escolares de secundaria (50.71 % chicas, Medad = 13 años, DT = 1.34) participaron en el estudio. Se identificaron cuatro grupos de normas hacia el acoso: antibullying, en contra del acoso, en contra pero sin defender activamente, neutral y a favor del acoso. Los modelos de regresión lineal univariados mostraron que el ajuste normativo y el tipo de normas tenían un efecto directo inverso en ambas conductas, mientras que la prosocialidad solo tuvo un efecto inverso sobre la conducta de defensa. En los grupos con normas antiacoso se observó un mayor efecto del ajuste normativo en la implicación en la defensa y agresión y que las habilidades prosociales se asociaban con la agresión. Los resultados sugieren que es necesario trabajar los aspectos morales, sociales y emocionales para mejorar el clima escolar.

Aggressive and Defensive Behaviour, Normative, and Social Adjustment in the Complex Dynamics of School Bullying / [La conducta agresiva y de defensa, y el ajuste normativo y social en las complejas dinámicas de acoso escolar]

Bullying is a group phenomenon in which schoolchildren take on different roles. Although certain contextual elements play a key role in its evolution, very few longitudinal studies have been carried out to date which investigate how these factors interact. This study aims to explore the different class groupings as regards bullying norms and to examine the effect of the type of norm, social, and normative adjustment and pro-sociality, also of the interaction of group norms with involvement in aggression and victim defence in bullying situations. A total of 3,358 secondary school students (50.71% girls, Mage = 13 years, SD = 1.34) participated in the study. Four groups of norms towards bullying were identified: anti-bullying, anti-bullying but not actively defending, indifference, and pro-bullying. Univariate linear regression models showed that normative adjustment and the type of norms had a direct inverse effect on both types of behaviour, while pro-sociality only had an effect on defence. In groups with pro-bullying norms, a greater effect of normative adjustment was observed for involvement in defence and aggression, and pro-social skills were associated with aggression. These results suggest the need to work on moral, social and emotional elements to improve school climate in schools.(AU)

El acoso escolar es un fenómeno grupal en el que los escolares asumen roles diferentes. Aunque determinadas características contextuales juegan un papel fundamental en su evolución, aún son escasos los estudios longitudinales que exploran cómo interactúan dichos factores. El presente estudio tiene como objetivos explorar los diferentes tipos de agrupamientos de clases según las normas de acoso escolar y examinar el efecto del tipo de norma, el ajuste social y normativo y la prosocialidad, así como la interacción de las normas del grupo con la implicación en la agresión y defensa de la víctima en situaciones de acoso. Un total de 3,358 escolares de secundaria (50.71 % chicas, Medad = 13 años, DT = 1.34) participaron en el estudio. Se identificaron cuatro grupos de normas hacia el acoso: antibullying, en contra del acoso, en contra pero sin defender activamente, neutral y a favor del acoso. Los modelos de regresión lineal univariados mostraron que el ajuste normativo y el tipo de normas tenían un efecto directo inverso en ambas conductas, mientras que la prosocialidad solo tuvo un efecto inverso sobre la conducta de defensa. En los grupos con normas antiacoso se observó un mayor efecto del ajuste normativo en la implicación en la defensa y agresión y que las habilidades prosociales se asociaban con la agresión. Los resultados sugieren que es necesario trabajar los aspectos morales, sociales y emocionales para mejorar el clima escolar.(AU)

Increased incidence of rheumatoid arthritis after COVID-19.

An increase in the incidence of inflammatory arthritis after COVID-19 has been reported. Since many diseases exhibit population-specific causal effect sizes, we aimed to evaluate the incidence trends of inflammatory arthritis, including rheumatoid arthritis (RA), after COVID-19 in a large admixed Colombian population. Data analysis for this retrospective, population-based cohort study was carried out using the COOSALUD EPS registry. The following codes were selected for analyses: M059, seropositive RA, M069, unspecified RA, M060 seronegative RA, and other RA-related diagnoses: M064, M139, M068, M058, M130 and M053. The study period was limited to January 01, 2018, through December 31, 2022. Incidence rates (IRs) and incidence rate ratios (IRRs) were assessed. A Cox survival model was built to evaluate the influence of age, gender, and COVID-19 vaccination status on the development of inflammatory arthritis. A bioinformatic analysis was performed to evaluate the homology between SARS-CoV-2 and autoantigen peptides related to RA. The entire population study comprised 3,335,084 individuals. During the pandemic period (2020-2022) the total IIR for seropositive and unspecified RA were 1.60 (95% CI, 1.16-2.22) and 2.93 (95% CI, 2.04-4.19), respectively, and the IIR for overall RA-related diagnosis was 2.01 (95% CI 1.59-2.53). The age groups hazard ratios (HRs) were increased until the age group of 51-60 years (HR: 9.16; 95% CI, 7.24-11.59) and then decreased slightly in the age group 61 years or older (HR: 5.364; 95% CI, 4.24-6.78) compared to those within 18-30 years. Men were less at risk than women to develop inflammatory arthritis (HR: 0.21; 95% CI, 0.18-0.24). The greater time since COVID-19 diagnosis was associated with a lower likelihood of developing inflammatory arthritis (HR: 0.99; 95% CI:0.998-0.999). Vaccination (all types of COVID-19 vaccines included) did not prevent the development of inflammatory arthritis after COVID-19. Low identity was found between the SARS-CoV-2 ORF1ab antigen and the human antigens Poly ADP-ribose polymerase 14 and Protein mono-ADP-ribosyltransferase PARP9 isoform D (39% and 29%, respectively). In conclusion, our study confirms increased incidence of inflammatory arthritis, including RA, after COVID-19, with the greatest increase occurring before the first year post-covid. Women in their fifties were more susceptible. Further research is required to examine the effectiveness of vaccination in preventing post-COVID inflammatory arthritis and the mechanisms implicated in the development of RA after COVID-19.

Molecular mimicry and autoimmunity in the time of COVID-19.

Infectious diseases are commonly implicated as potential initiators of autoimmune diseases (ADs) and represent the most commonly known factor in the development of autoimmunity in susceptible individuals. Epidemiological data and animal studies on multiple ADs suggest that molecular mimicry is one of the likely mechanisms for the loss of peripheral tolerance and the development of clinical disease. Besides molecular mimicry, other mechanisms such as defects in central tolerance, nonspecific bystander activation, epitope-determinant spreading, and/or constant antigenic stimuli, may also contribute for breach of tolerance and to the development of ADs. Linear peptide homology is not the only mechanism by which molecular mimicry is established. Peptide modeling (i.e., 3D structure), molecular docking analyses, and affinity estimation for HLAs are emerging as critical strategies when studying the links of molecular mimicry in the development of autoimmunity. In the current pandemic, several reports have confirmed an influence of SARS-CoV-2 on subsequent autoimmunity. Bioinformatic and experimental evidence support the potential role of molecular mimicry. Peptide dimensional analysis requires more research and will be increasingly important for designing and distributing vaccines and better understanding the role of environmental factors related to autoimmunity.

Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?

Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC is multifactorial and involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, ultimately leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are currently used as first- and second-line treatments, respectively. However, many patients do not respond adequately to UDCA, and the long-term effects of these drugs are limited. Recent research has advanced our understanding the mechanisms of pathogenesis in PBC and greatly facilitated development of novel drugs to target mechanistic checkpoints. Animal studies and clinical trials of pipeline drugs have yielded promising results in slowing disease progression. Targeting immune mediated pathogenesis and anti-inflammatory therapies are focused on the early stage, while anti-cholestatic and anti-fibrotic therapies are emphasized in the late stage of disease, which is characterized by fibrosis and cirrhosis development. Nonetheless, it is worth noting that currently, there exists a dearth of therapeutic options that can effectively impede the progression of the disease to its terminal stages. Hence, there is an urgent need for further research aimed at investigating the underlying pathophysiology mechanisms with potential therapeutic effects. This review highlights our current knowledge of the underlying immunological and cellular mechanisms of pathogenesis in PBC. Further, we also address current mechanism-based target therapies for PBC and potential therapeutic strategies to improve the efficacy of existing treatments.

Mutated Pkhd1 alone is sufficient to cause autoimmune biliary disease on the nonobese diabetic (NOD) genetic background.

We previously reported that nonobese diabetic (NOD) congenic mice (NOD.c3c4 mice) developed an autoimmune biliary disease (ABD) with similarities to human primary biliary cholangitis (PBC), including anti-mitochondrial antibodies and organ-specific biliary lymphocytic infiltrates. We narrowed the possible contributory regions in a novel NOD.Abd3 congenic mouse to a B10 congenic region on chromosome 1 ("Abd3") and a mutated Pkhd1 gene (Pkhd1del36-67) upstream from Abd3, and we showed via backcrossing studies that the NOD genetic background was necessary for disease. Here, we show that NOD.Abd3 mice develop anti-PDC-E2 autoantibodies at high levels, and that placing the chromosome 1 interval onto a scid background eliminates disease, demonstrating the critical role of the adaptive immune system in pathogenesis. While the NOD genetic background is essential for disease, it was still unclear which of the two regions in the Abd3 locus were necessary and sufficient for disease. Here, using a classic recombinant breeding approach, we prove that the mutated Pkhd1del36-67 alone, on the NOD background, causes ABD. Further characterization of the mutant sequence demonstrated that the Pkhd1 gene is disrupted by an ETnII-beta retrotransposon inserted in intron 35 in an anti-sense orientation. Homozygous Pkhd1 mutations significantly affect viability, with the offspring skewed away from a Mendelian distribution towards NOD Pkhd1 homozygous or heterozygous genotypes. Cell-specific abnormalities, on a susceptible genetic background, can therefore induce an organ-specific autoimmunity directed to the affected cells. Future work will aim to characterize how mutant Pkhd1 can cause such an autoimmune response.

The long and winding road: From mouse linkage studies to a novel human therapeutic pathway in type 1 diabetes.

Autoimmunity involves a loss of immune tolerance to self-proteins due to a combination of genetic susceptibility and environmental provocation, which generates autoreactive T and B cells. Genetic susceptibility affects lymphocyte autoreactivity at the level of central tolerance (e.g., defective, or incomplete MHC-mediated negative selection of self-reactive T cells) and peripheral tolerance (e.g., failure of mechanisms to control circulating self-reactive T cells). T regulatory cell (Treg) mediated suppression is essential for controlling peripheral autoreactive T cells. Understanding the genetic control of Treg development and function and Treg interaction with T effector and other immune cells is thus a key goal of autoimmunity research. Herein, we will review immunogenetic control of tolerance in one of the classic models of autoimmunity, the non-obese diabetic (NOD) mouse model of autoimmune Type 1 diabetes (T1D). We review the long (and still evolving) elucidation of how one susceptibility gene, Cd137, (identified originally via linkage studies) affects both the immune response and its regulation in a highly complex fashion. The CD137 (present in both membrane and soluble forms) and the CD137 ligand (CD137L) both signal into a variety of immune cells (bi-directional signaling). The overall outcome of these multitudinous effects (either tolerance or autoimmunity) depends upon the balance between the regulatory signals (predominantly mediated by soluble CD137 via the CD137L pathway) and the effector signals (mediated by both membrane-bound CD137 and CD137L). This immune balance/homeostasis can be decisively affected by genetic (susceptibility vs. resistant alleles) and environmental factors (stimulation of soluble CD137 production). The discovery of the homeostatic immune effect of soluble CD137 on the CD137-CD137L system makes it a promising candidate for immunotherapy to restore tolerance in autoimmune diseases.

Autoimmune and autoinflammatory conditions after COVID-19 vaccination. New case reports and updated literature review.

Autoimmunity linked to COVID-19 immunization has been recorded throughout the pandemic. Herein we present six new patients who experienced relapses of previous autoimmune disease (AD) or developed a new autoimmune or autoinflammatory condition following vaccination. In addition, we documented additional cases through a systematic review of the literature up to August 1st, 2022, in which 464 studies (928 cases) were included. The majority of patients (53.6%) were women, with a median age of 48 years (IQR: 34 to 66). The median period between immunization and the start of symptoms was eight days (IQR: 3 to 14). New-onset conditions were observed in 81.5% (n: 756) of the cases. The most common diseases associated with new-onset events following vaccination were immune thrombocytopenia, myocarditis, and Guillain-Barré syndrome. In contrast, immune thrombocytopenia, psoriasis, IgA nephropathy, and systemic lupus erythematosus were the most common illnesses associated with relapsing episodes (18.5%, n: 172). The first dosage was linked with new-onset events (69.8% vs. 59.3%, P = 0.0100), whereas the second dose was related to relapsing disease (29.5% vs. 59.3%, P = 0.0159). New-onset conditions and relapsing diseases were more common in women (51.5% and 62.9%, respectively; P = 0.0081). The groups were evenly balanced in age. No deaths were recorded after the disease relapsed, while 4.7% of patients with new-onset conditions died (P = 0.0013). In conclusion, there may be an association between COVID-19 vaccination and autoimmune and inflammatory diseases. Some ADs seem to be more common than others. Vaccines and SARS-CoV-2 may induce autoimmunity through similar mechanisms. Large, well-controlled studies are warranted to validate this relationship and assess additional variables such as genetic and other environmental factors.

Is post-COVID syndrome an autoimmune disease?

INTRODUCTION: Post-COVID syndrome (PCS) is recognized as a new entity in the context of SARS-CoV-2 infection. Though its pathogenesis is not completely understood, persistent inflammation from acute illness and the development of autoimmunity play a critical role in its development. AREAS COVERED: The mechanisms involved in the emergence of PCS, their similarities with post-viral and post-care syndromes, its inclusion in the spectrum of autoimmunity and possible targets for its treatment. EXPERT OPINION: An autoimmune phenomenon plays a major role in most causative theories explaining PCS. There is a need for both PCS definition and classification criteria (including severity scores). Longitudinal and controlled studies are necessary to better understand this new entity, and to find what additional factors participate into its development. With the high prevalence of COVID-19 cases worldwide, together with the current evidence on latent autoimmunity in PCS, we may observe an increase of autoimmune diseases (ADs) in the coming years. Vaccination's effect on the development of PCS and ADs will also receive attention in the future. Health and social care services need to develop a new framework to deal with PCS.

Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study.

BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

Autoimmunity is a hallmark of post-COVID syndrome.

Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies. Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days. Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively. Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5-10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms. In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.

Conocimientos y percepción de riesgo de estudiantes de Estomatología frente al VIH/sida / Risk perception and knowledge of dental students concerning HIV/AID

Introducción: El VIH se considera una de las pandemias que azota actualmente la humanidad. En este sentido, la educación de la sexualidad constituye una responsabilidad de toda la sociedad. En Cuba han sido pobremente estudiados la percepción de riesgo y los conocimientos de los estudiantes de ciencias médicas sobre esta afección. Objetivo: Determinar la percepción de riesgo y los conocimientos de estudiantes de la carrera de Estomatología sobre la infección por VIH. Métodos: Se realizó un estudio descriptivo y transversal desde septiembre hasta noviembre de 2019 en la Universidad de Ciencias Médicas de La Habana. Se trabajó con 157 estudiantes de la carrera de Estomatología, a los cuales se les aplicó la escala VIH/sida-65, que constó de 65 ítems y se dividió en siete subescalas. Los datos fueron procesados y se mostraron en tablas, mediante la estadística descriptiva. Resultados: El 46,50 por ciento de los estudiantes consideró falso que el VIH/sida fuera una enfermedad que amenazara la vida de las personas y el 19,75 por ciento creyó que se estaba invirtiendo en esta enfermedad demasiado tiempo, dinero y otros recursos en comparación con otras enfermedades. El 68,15 por ciento de los estudiantes refirió que el sexo no era tan placentero cuando se usaba condón y un 60,51 por ciento de los encuestados no se consideró el tipo de persona que pudiera contraer el virus del sida (susceptibilidad). Conclusiones: Los estudiantes tienen un nivel de conocimientos adecuado, a pesar de ideas erróneas, actitudes y prácticas negativas, que potencian el riesgo de infección(AU)

Introduction: HIV is considered one of the pandemics currently scourging humanity. In this respect, sexuality education is a responsibility of the whole society. In Cuba, risk perception and knowledge of medical science students about this condition have been poorly studied. Objective: To determine the risk perception and knowledge of dental students about HIV infection. Methods: A descriptive and cross-sectional study was conducted from September to November 2019 at the University of Medical Sciences of Havana. The work was carried out with 157 students of the dental medicine major, who were applied the HIV/AIDS-65 scale, which consisted of 65 items and was divided into seven subscales. The data were processed and shown in tables, using descriptive statistics. Results: 46.50 percent of the students considered it false that HIV/AIDS was a life-threatening disease and 19.75 percent believed that too much time, money and other resources were being invested in this disease in comparison with other diseases. 68.15 percent of the students referred that sex was not as pleasurable when a condom was used, while 60.51 percent of the respondents did not consider themselves the type of person who could contract the AIDS virus (susceptibility). Conclusions: Students have an adequate level of knowledge, despite misconceptions, negative attitudes and practices, which potentiate the risk of infection(AU)

Acciones docentes para atender la diversidad estudiantil en las clases de la disciplina Estomatología Integral

RESUMEN El adecuado desempeño docente para atender la diversidad estudiantil en la disciplina Estomatología Integral, puede garantizarla formación con calidad del egresado en la carrera de Estomatología. El objetivo de este trabajo es diseñar un sistema de acciones docentes para atender la diversidad estudiantil en las clases de la disciplina Estomatología Integral en la Universidad de Ciencias Médicas de Las Tunas. Se realizó una investigación de desarrollo, principalmente cualitativa, en la institución antes declarada, desde septiembre de 2020 a febrero 2021. La investigación define como objeto el proceso de enseñanza-aprendizaje de las clases de la disciplina Estomatología Integral y como campo las acciones docentes para atender diversidad estudiantil. La investigación se ejecutó en dos etapas, dedicadas a: revisar documentos rectores de la carrera, tesis, artículos, programas y elaborar las acciones. El sistema de acciones docentes para atender la diversidad estudiantil quedó estructurado por un objetivo general, acciones permanentes a realizar en el proceso de enseñanza-aprendizaje (relacionado con: superación docente, diagnóstico pedagógico integral y formación de valores); y acciones al planificar, ejecutar y controlar las clases. Las acciones propuestas promueven la unidad de la unidad de lo instructivo, educativo y desarrollador, de lo cognitivo y afectivo, de la formación del conocimiento y los valores, mediante un sistema didáctico integral y personalizado. Se proponen acciones docentes para atender la diversidad estudiantil, en el proceso enseñanza-aprendizaje de las clases de la disciplina Estomatología Integral, al planificar, ejecutar y controlar.

ABSTRACT The appropriate educational acting to assist the student diversity in the discipline of Family Dentistry, it can guarantee the formation with quality of the students in the Dentistry career. To design a system of educational actions to assist the student diversity in the classes of the of Family Dentistry in the University of Medical Sciences of Las Tunas. A development investigation, mainly qualitative, before in the institution declared, from September of 2020 to February 2021. The investigation defines like object the process of teaching-learning of the classes of the Family Dentistry and I eat field the educational actions to assist student diversity. The investigation was executed in two stages, dedicated to: to revise documents rectors of the career, thesis, articles, programs and to elaborate the actions. The system of educational actions to assist the student diversity was structured by a general objective, permanent actions to carry out in the teaching-learning process (related with: educational preparation, integral pedagogic diagnosis, and values formation); and work when planning, to execute and to control the classes. The proposed actions promote the unit of the unit of the instructive, educational and developer, of the cognitive, and affective, of the formation of the knowledge and the values, by means of an integral and personalized didactic system. They intended educational actions to assist the student diversity, in the process teaching-learning of the classes of the discipline Family Dentistry, when planning, to execute and to control.

RESUMO Desempenho adequado de ensino para abordar a diversidade dos alunos na disciplina abrangente de estomatologia pode garantir treinamento de qualidade para graduados nacarreira de estomatologia. O objetivo deste trabalho é projetar um sistema de ações de ensino para abordar a diversidade dos alunos nas classes da abrangente disciplina estomatológica nas ciências da Universidade de Tunas. Uma pesquisa de desenvolvimento, principalmente qualitativa, foi realizada na instituição acima mencionada, a partir de 2020 a fevereiro de 2021. A pesquisa define como objeto o processo de ensino-aprendizagem das classes da disciplina abrangente de estomatologia e como um campo as ações de ensino para a diversidade estudantil. A pesquisa foi realizada em dois estágios, dedicada a: Revisar os documentos orientadores da carreira, tese, artigos, programas e elaborar as ações. O sistema de ações de ensino para abordar a diversidade dos alunos foi estruturado por um objetivo geral, ações permanentes a serem realizadas no processo de ensino-aprendizagem (relacionado a: melhoria dos professores, diagnóstico pedagógico abrangente e formação de valores); e ações ao planejar, executar e controlar as aulas. As ações propostas promovem a unidade da unidade instrutiva, educacional e de desenvolvedora, do cognitivo e afetivo, da formação de conhecimento e valores, através de um sistema didático abrangente e personalizado. As ações de ensino são propostas para abordar a diversidade do aluno, no processo de ensino-aprendizagem das classes da disciplina abrangente de estomatologia, ao planejar, executar e controlar.