One year in review 2021: pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by local and systemic inflammation where the close interaction between immune cells and soluble mediators leads to amplification and perpetuation of inflammatory and remodelling processes. The research carried out in the last year in the field of RA has made it possible to identify new mechanisms involved in the pathogenesis of the disease, enabling the discovery of new potential therapeutic targets. Thus, in this review we summarise new insights in RA pathogenesis, resulting from a literature research date published in the last year.

Neural Generative Models and the Parallel Architecture of Language: A Critical Review and Outlook.

According to the parallel architecture, syntactic and semantic information processing are two separate streams that interact selectively during language comprehension. While considerable effort is put into psycho- and neurolinguistics to understand the interchange of processing mechanisms in human comprehension, the nature of this interaction in recent neural Large Language Models remains elusive. In this article, we revisit influential linguistic and behavioral experiments and evaluate the ability of a large language model, GPT-3, to perform these tasks. The model can solve semantic tasks autonomously from syntactic realization in a manner that resembles human behavior. However, the outcomes present a complex and variegated picture, leaving open the question of how Language Models could learn structured conceptual representations.

Migrants from Low-Income Countries have Higher Heat-Health Risk Profiles Compared to Native Workers in Agriculture.

The present observational study was conducted to uncover potential differences in the risk of experiencing high occupational heat strain during agriculture work between migrants and their native coworkers, as well as to elucidate the factors that may contribute to such differences. The study took place over the period from 2016 through 2019 and involved monitoring 124 experienced and acclimatized individuals from high-income (HICs), upper-middle-income (UMICs), as well as lower-middle- and low-income (LMICs) countries. Baseline self-reported data for age, body stature, and body mass were collected at the start of the study. Second-by-second video recordings throughout the work shifts were captured using a video camera and were used to estimate workers' clothing insulation, covered body surface area, and body posture, as well as to calculate their walking speed, the amount of time they spent on different activities (and their intensity) and unplanned breaks throughout their work shifts. All information derived from the video data was used to calculate the physiological heat strain experienced by the workers. The core temperature of migrant workers from LMICs (37.81 ± 0.38 °C) and UMICs (37.71 ± 0.35 °C) was estimated to be significantly higher compared to the core temperature of native workers from HICs (37.60 ± 0.29 °C) (p < 0.001). Moreover, migrant workers from LMICs faced a 52% and 80% higher risk for experiencing core body temperature above the safety threshold of 38 °C compared to migrant workers from UMICs and native workers from HICs, respectively. Our findings show that migrant workers originating from LMICs experience higher levels of occupational heat strain, as compared to migrant workers from UMICs and native workers from HICs, because they take fewer unplanned breaks during work, they work at a higher intensity, they wear more clothing, and they have a smaller body size.

Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase.

Introduction: The impact of COVID-19 pandemic represents a serious challenge for 'frail' patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic. Patients and method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines. Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients (death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p < 0.0001). Conclusions: An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A careful monitoring of response to COVID-19 vaccines together with adequate preventive/therapeutical strategies are highly recommendable in the near course of pandemic in this frail patients' population.

BNT162b2 mRNA SARS-CoV-2 Vaccine Elicits High Avidity and Neutralizing Antibodies in Healthcare Workers.

The BNT162b2 vaccine, containing lipid nanoparticles-formulated mRNA encoding the full-length spike protein of SARS-CoV-2, has been employed to immunize health care workers in Italy, administered in two doses 21 days apart. In this study, we characterized the antibody response induced by the BNT162b2 vaccine in a group of health care workers, tested at baseline, after the first dose and after the booster. Thirty-nine subjects without previous exposure to SARS-CoV-2 were vaccinated with the BNT162b2 vaccine. IgM, IgG, and IgA anti-receptor binding domain (RBD) were tested by ELISA. Neutralizing antibodies were evaluated testing the inhibition of RBD binding to ACE2. Antibody avidity was measured by urea avidity ELISA. IgM anti-RBD are produced after the first dose of vaccine and persist after the booster. IgG and IgA anti-RBD antibodies are detected in high amounts in all the subjects after the first dose and further increase after the booster. A few subjects, already after the first dose, produce antibodies inhibiting RBD interaction with ACE2. After the booster, high levels of inhibitory antibodies are detected in all the subjects. Affinity maturation takes place with boosting and IgG anti-RBD avidity increases with the number of immunizations. A less pronounced increase is observed with IgA. These data indicate that the BNT162b2 vaccine can induce high levels of protective antibodies of high avidity in vaccinated subjects; both IgG and IgA anti-RBD antibodies are produced. Further studies are needed to evaluate antibody persistence over time.

Occupational Heat Stress: Multi-Country Observations and Interventions.

BACKGROUND: Occupational heat exposure can provoke health problems that increase the risk of certain diseases and affect workers' ability to maintain healthy and productive lives. This study investigates the effects of occupational heat stress on workers' physiological strain and labor productivity, as well as examining multiple interventions to mitigate the problem. METHODS: We monitored 518 full work-shifts obtained from 238 experienced and acclimatized individuals who work in key industrial sectors located in Cyprus, Greece, Qatar, and Spain. Continuous core body temperature, mean skin temperature, heart rate, and labor productivity were collected from the beginning to the end of all work-shifts. RESULTS: In workplaces where self-pacing is not feasible or very limited, we found that occupational heat stress is associated with the heat strain experienced by workers. Strategies focusing on hydration, work-rest cycles, and ventilated clothing were able to mitigate the physiological heat strain experienced by workers. Increasing mechanization enhanced labor productivity without increasing workers' physiological strain. CONCLUSIONS: Empowering laborers to self-pace is the basis of heat mitigation, while tailored strategies focusing on hydration, work-rest cycles, ventilated garments, and mechanization can further reduce the physiological heat strain experienced by workers under certain conditions.

Improvement of gross motor and cognitive abilities by an exercise training program: three case reports.

BACKGROUND: This work examined the efficacy of an integrated exercise training program (coach and family) in three children with Down syndrome to improve their motor and cognitive abilities, in particular reaction time and working memory. METHODS: The integrated exercise training program was used in three children with Down syndrome, comprising two boys (M1, with a chronological age of 10.3 years and a mental age of 4.7 years; M2, with a chronological age of 14.6 years and a mental age of less than 4 years) and one girl (F1, chronological age 14.0 years and a mental age of less than 4 years). RESULTS: Improvements in gross motor ability scores were seen after the training period. Greater improvements in task reaction time were noted for both evaluation parameters, ie, time and omissions. CONCLUSION: There is a close interrelationship between motor and cognitive domains in individuals with atypical development. There is a need to plan intervention programs based on the simultaneous involvement of child and parents and aimed at promoting an active lifestyle in individuals with Down syndrome.