Flexible use of CCR5 in the absence of CXCR4 use explains the immune deficiency in HIV-1 infected children

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Outbreaks of Pneumocystis Pneumonia in 2 Renal Transplant Centers Linked to a Single Strain of Pneumocystis: Implications for Transmission and Virulence

By restriction fragment length polymorphism analysis, 2 outbreaks of Pneumocystis pneumonia in renal transplant patients in Europe were shown to be caused by the same strain of Pneumocystis; another outbreak in Japan was caused by a different strai

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

I meccanismi di coping in età evolutiva

La comprensione dei contributi teorici relativi all'eziologia e allo sviluppo dei meccanismi di coping in età evolutiva è possibile solo dopo avere analizzato i risultati a cui sono pervenute le ricerche che si sono occupate del fenomeno in età adulta. Per questo motivo, la parte iniziale della nostra rassegna affronta l'evoluzione del concetto di coping a partire da quello di meccanismo di difesa e presenta una sintesi dei diversi modelli teorici che sono stati sviluppati negli anni. Da questi hanno preso avvio gli studi sul coping nei bambini e negli adolescenti, giungendo alla conclusione che le strategie di coping sono dei meccanismi flessibili, che variano in funzione dell'età e su cui incidono fattori costituzionali e ambientali; l'incidenza di queste diverse variabili sarà analizzata nel corso della ricerca

Rappresentazione mentale del Sé e funzionamento psicologico in bambini vittime di violenza: Uno studio pilota

I vissuti traumatici conseguenti ad esperienze di violenza nell’infanzia rendono spesso difficile agli specialisti comprendere il mondo interno dei bambini, le loro competenze e le loro problematiche. Nel tentativo di indagare il funzionamento psicologico e la rappresentazione del Sé in minori maltrattati, è stato condotto uno studio pilota avvalendosi di una duplice metodologia: due questionari compilati da genitori o educatori (CBCL, Achenbach, 1991; PROPS, Greenwald, 1996) e un test grafico, il disegno del Bambino nella Pioggia (Crocetti, 1991). Lo studio, che ha coinvolto 54 bambini (18 del campione clinico e 36 del campione di controllo), di età compresa tra i 5 e i 13 anni, ha messo in luce l’effettiva utilità della scelta della doppia fonte di informazione per cogliere le differenze tra i bambini del gruppo normativo e i minori ospiti di comunità d’accoglienza.Past traumatic experiences connected to violence in childhood make it difficult for specialists to understand the inner world of child, their skills and problems. In pursuit of studying the psychological functioning and the representation of the Self of children victims of abuse, a pilot study has been conducted, making use of two methodologies; two questionnaires filled in by parents or educators (CBCL, Achenbach, 1991; PROPS, Greenwald, 1996) and Il Bambino nella Pioggia drawing test (Crocetti, 1991). The study, which involved 54 children (18 of the experimental sample and 36 of the control sample), from 5 to 13 years old, highlighted the actual utility of choosing a double information source in this area of study to understand the differences between the groups

Role of pamidronate disodium in the treatment of metastatic bone disease

Aims and Background: Bone metastases are a common feature of advanced neoplastic disease and are considered to be among the most frequent causes of pain and complications in oncologic patients. The main objective of the treatment of such patients is to control their symptoms and improve their quality of life. Pamidronate disodium is a second-generation bisphosphonate capable of inhibiting bone resorption (particularly osteoclast activity) without affecting bone remineralization. After a brief introduction concerning the pathophysiology of bone metastases and neoplastic bone pain, we herein present data on the clinical pharmacology and toxicity of bisphosphonates in general, and pamidronate in particular. We conclude by reviewing the literature on the use of pamidronate in phase II and III trials involving patients with metastatic bone disease. Methods: The paper is based on a review of articles published between 1984 and 1997 selected from the Cancerline and Medline databases. Results: In the considered phase II and III studies involving patients with bone metastases (breast cancer and multiple myeloma in particular), pamidronate proved to be efficacious in reducing the incidence of pain and skeletal complications, decreasing the excretion of metabolic markers of bone resorption and improving the quality of life. Intravenous infusions of 60-90 mg over a period of 2 hr every 3-4 weeks did not cause any significant toxic effects and was easily managed. Conclusions: Pamidronate is a bisphosphonate that is efficacious in the treatment of symptomatic bone metastases and can be considered an important therapeutic option in association with systemic treatments, radiotherapy and normal supportive care, especially in patients with breast cancer and multiple myeloma. Further randomized studies are necessary to confirm the positive preliminary results in other neoplasms, analyze the cost/benefit ratio of the treatment, and verify the possibility that, in addition to being used for palliative purposes, pamidronate may also prevent or delay the appearance of bone metastases