Outpatient healthcare costs associated with overweight and obesity in Italy

To evaluate outpatient healthcare expenditure associated with different levels of BMI and glucose metabolism alterations

Psychotropic drug purchases during the COVID-19 pandemic in Italy and their relationship with mobility restrictions

Recent literature on the mental health consequences of social distancing measures has found a substantial increase in self-reported sleep disorders, anxiety and depressive symptoms during lockdown periods. We investigate this issue with data on monthly purchases of psychotropic drugs from the universe of Italian pharmacies during the first wave of the COVID-19 pandemic and find that purchases of mental health-related drugs have increased with respect to 2019. However, the excess volumes do not match the massive increase in anxiety and depressive disorders found in survey-based studies. We also study the interplay between mobility, measured with anonymized mobile phone data, and mental health and report no significant effect of mobility restrictions on antidepressants and anxiolytics purchases during 2020. We provide three potential mechanisms that could drive the discrepancy between self-reported mental health surveys and psychotropic drugs prescription registries: (1) stockpiling practices in the early phases of the pandemic; (2) the adoption of compensatory behavior and (3) unexpressed and unmet needs due to both demand- and supply-side shortages in healthcare services

Partial T cell defects and expanded CD56bright NK cells in an SCID patient carrying hypomorphic mutation in the IL2RG gene

X-linked severe combined immunodeficiency (X-SCID) caused by full mutation of the IL2RG gene leads to T- B+ NK- phenotype and is usually associated with severe opportunistic infections, diarrhea, and failure to thrive. When IL2RG hypomorphic mutation occurs, diagnosis could be delayed and challenging since only moderate reduction of T and NK cells may be present. Here, we explored phenotypic insights and the impact of the p.R222C hypomorphic mutation (IL2RGR222C ) in distinct cell subsets in an 8-month-old patient with atypical X-SCID. We found reduced CD4+ T cell counts, a decreased frequency of naïve CD4+ and CD8+ T cells, and an expansion of B cells. Ex vivo STAT5 phosphorylation was impaired in CD4+ CD45RO+ T cells, yet compensated by supraphysiological doses of IL-2. Sanger sequencing on purified cell subsets showed a partial reversion of the mutation in total CD3+ cells, specifically in recent thymic emigrants (RTE), effector memory (EM), and CD45RA+ terminally differentiated EM (EMRA) CD4+ T cells. Of note, patient's NK cells had a normal frequency compared to age-matched healthy subjects, but displayed an expansion of CD56bright cells with higher perforin content and cytotoxic potential, associated with accumulation of NK-cell stimulatory cytokines (IL-2, IL-7, IL-15). Overall, this report highlights an alteration in the NK-cell compartment that, together with the high disease-phenotype variability, should be considered in the suspicion of X-SCID with hypomorphic IL2RG mutation

Evaluation of humoral and cellular response to four vaccines against COVID-19 in different age groups: A longitudinal study

To date there has been limited head-to-head evaluation of immune responses to different types of COVID-19 vaccines. A real-world population-based longitudinal study was designed with the aim to define the magnitude and duration of immunity induced by each of four different COVID-19 vaccines available in Italy at the time of this study. Overall, 2497 individuals were enrolled at time of their first vaccination (T0). Vaccine-specific antibody responses induced over time by Comirnaty, Spikevax, Vaxzevria, Janssen Ad26.COV2.S and heterologous vaccination were compared up to six months after immunization. On a subset of Comirnaty vaccinees, serology data were correlated with the ability to neutralize a reference SARS-CoV-2 B strain, as well as Delta AY.4 and Omicron BA.1. The frequency of SARS-CoV-2-specific CD4+ T cells, CD8+ T cells, and memory B cells induced by the four different vaccines was assessed six months after the immunization. We found that mRNA vaccines are stronger inducer of anti-Spike IgG and B-memory cell responses. Humoral immune responses are lower in frail elderly subjects. Neutralization of the Delta AY.4 and Omicron BA.1 variants is severely impaired, especially in older individuals. Most vaccinees display a vaccine-specific T-cell memory six months after the vaccination. By describing the immunological response during the first phase of COVID-19 vaccination campaign in different cohorts and considering several aspects of the immunological response, this study allowed to collect key information that could facilitate the implementation of effective prevention and control measures against SARS-CoV-2

Induction of immune response after SARS-CoV-2 mRNA BNT162b2 vaccination in healthcare workers

[no abstract available

The Interplay between CD27dull and CD27bright B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory

Summary: Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27dull and CD27bright MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27dull into the CD27bright MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27dull MBCs transit to the more differentiated CD27bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27dull clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27dull MBCs that expand and differentiate in response to change. : Grimsholm et al. show that CD27dull and CD27bright represent sequential MBC developmental stages. T cell- and germinal center (GC)-independent CD27dull MBCs are the plastic source of strongly selected and GC-dependent CD27bright MBCs. CD27dull MBCs, able to expand and differentiate in response to change, ensure stability and flexibility of human B cell memory. Keywords: memory B cells, pregnancy, immunological memory, CD27, VH repertoire, immunodeficiency, aging, spleen, vaccine, germinal cente

LongITools:Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases

LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our “modern” postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.</p

L'emergenza Covid e il nuovo mondo che verrà. Una guida integrata tra le ragioni della salute e quelle dell'economia

La pandemia di COVID-19 rappresenta uno spartiacque importante per la società moderna, più di quanto non lo sia stato l’attacco alle torri gemelle del 2001. Il mondo come lo conosciamo attualmente non sarà più lo stesso. Quasi tutte le attività economiche e sociali andranno riviste, ripensate e adattate al nuovo contesto. Una pandemia arrivata in un momento in cui la possibilità di “divulgare” facendosi sentire da vaste platee è molto più ampia di quanto non lo fosse solo pochi anni fa. E, infatti, fino dai giorni di Wuhan, non c'è stato momento in cui i media non hanno raccontato l'epidemia, fino a parlare di “ìnfodemia” dopo sole poche settimane dalla dichiarazione dell'OMS della “pandemia”. Secondo Google Scholar, nei soli mesi di Marzo e Aprile 2020, la comunità scientifica aveva prodotto oltre 36.000 documenti, una cosa mai vista prima. A ciò vanno poi aggiunte le migliaia di contributi di chi fa comunicazione interpretando i risultati e le opinioni degli esperti. A fine dicembre 2020 il numero di documenti era salito a oltre 100.000. In questo contesto di “ìnfodemia" il libro prova a fare ordine e chiarezza, raccontando in modo semplice e rigoroso un fenomeno complesso da una prospettiva diversa che trova le sue radici in due mondi interconnessi: medicina ed economia. Non è possibile comprendere correttamente il fenomeno se non si conoscono i due mondi, le loro interconnessioni e le regole che li governano. La pandemia è stata tale non solo perché oltre 4 miliardi di persone sono state toccate da un punto di vista della salute personale. Lo è anche perché, per la prima volta, ci si è resi conto che “globale” non è solo il sistema finanziario, ma anche quello della produzione, come dimostrato dalle iniziali carenze sia di materiale sanitario a basso contenuto tecnologico (e.g., le mascherine), sia a più alto contenuto (e.g., i ventilatori polmonari). Inoltre, per la prima volta, abbiamo imparato a considerare che la struttura delle cosiddette supply chain può rappresentare un grosso vantaggio in periodi di “normalità”, ma essere un boomerang notevole in casi di emergenza come quello che sono stati vissuti in questi mesi. Rispecchiando la complessità del problema, l’ambito di analisi è multidisciplinare e coinvolge branche del sapere che spaziano dall’economia all’epidemiologia, dall’informatica alla statistica, dalla biologia alla medicina e alle scienze politiche. L’obiettivo del libro è, quindi, spiegare a un pubblico non (o poco) specializzato un fenomeno complesso che, anche a causa di una non sempre efficace comunicazione (istituzionale e scientifica), ha lasciato dubbi e incertezze tra chi voleva capire: anticamera questa di scelte spesso irrazionali (a tutti i livelli). Il libro cerca, quindi, di colmare alcune di queste lacune fornendo risposte a una serie di quesiti tra cui: perché l’epidemia ha avuto origine, come si è diffusa, come è stata gestita, per quanto dovremo conviverci, che effetti ha avuto sull’economia, chi sarà più colpito, come il nuovo mondo cambierà noi e come cambierà il nostro modo di vedere il mondo. Infine, vengono presentate e discusse una serie di “lezioni apprese” dall’attuale crisi pandemica che potranno tornare utili in futuro. Un futuro che secondo tanti esperti a breve potrebbe ripetersi come l’attuale presente se il genere umano non cambierà le sue abitudini abbracciando la logica del One-health approach, l’unica al momento in grado di garantire una transizione verso un futuro sostenibile. Un futuro che vede nella collaborazione tra Paesi l’unica soluzione possibile, contro ogni logica divisiva e isolazionista. I lettori saranno condotti per mano tra i vari argomenti seguendo un filo logico ben preciso, che aiuti a capire a) perché è importante un argomento e cosa permette di capire, b) quali evidenze sono disponibili e c) se è possibile dare risposte a quesiti rilevanti per decidere su interventi di politica sanitaria ed economica. I temi sono riportati in modo chiaro e semplice, con esempi concreti e semplici rappresentazioni grafiche. I lettori più esigenti troveranno riferimenti di approfondimento, appendici e box con materiale più tecnico