Patients with STAT1 Gain-of-function Mutations Display Increased Apoptosis which is Reversed by the JAK Inhibitor Ruxolitinib.

INTRODUCTION: The signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is characterized by a broader clinical phenotype that may include bacterial, viral, or invasive fungal infections, autoimmunity, autoinflammatory manifestations, vascular complications, or malignancies. The severity of lymphopenia may vary and influence the infectious morbidity. METHODS: In our cohort of seven STAT1-GOF patients, we investigated the mechanisms that may determine T lymphopenia, we characterized the interferon gene signature (IGS) and analyzed the effect of ruxolitinib in reverting the immune dysregulation. RESULTS: STAT1-GOF patients exhibited increased T lymphocyte apoptosis that was significantly augmented in both resting conditions and following stimulation with mitogens and IFNα, as evaluated by flow cytometry by Annexin V/ Propidium iodide assay. The JAK inhibitor ruxolitinib significantly reduced the IFNα-induced hyperphosphorylation of STAT1 and reverted the stimulation-induced T-cell apoptosis, in vitro. In two adult STAT1-GOF patients, the JAKinib treatment ameliorated chronic mucocutaneous candidiasis and lymphopenia. Most STAT1-GOF patients, particularly those who had autoimmunity, presented increased IGS that significantly decreased in the two patients during ruxolitinib treatment. CONCLUSION: In STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations.

Do social media interventions increase vaccine uptake?

Introduction: The Italian mass COVID-19 vaccination campaign has included children aged 5-11 years as part of the target population since December 2021. One of the biggest challenges to vaccine uptake was vaccine hesitancy among parents and children's caregivers. Primary care pediatricians (PCPs), as the first point of contact between the National Health Service (NHS) and parents/caretakers, initiated various communication strategies to tackle this hesitancy. This study aims to evaluate the impact of a PCP-led social media intervention and a digital reminder service (DRS) on parental hesitancy regarding vaccinating their 5-11-year-old children against COVID-19. Methods: A prospective cohort study was designed, and the chosen target populations were parents and caretakers of children aged 5-11 years. Two PCP cohorts were recruited. The first group received a social media intervention and a DRS; while the second group did not. Both cohorts had access to traditional face-to-face and telephone-based counseling. The vaccination coverage rate in the two groups was evaluated. Results: A total of 600 children were enrolled. The exposed cohort (277 patients) received social media intervention, DRS, and counseling options (face-to-face and telephone-based), whereas the non-exposed cohort (323 patients) received only counseling options. In total, 89 patients from the exposed cohort did not receive any dose of the COVID-19 vaccine (32.5%), 165 were fully immunized (59.5%), and 23 received only one dose (8.5%). A total of 150 non-exposed patients did not receive any dose of the COVID-19 vaccine (47%), 147 were fully immunized (45.5%), and 24 only received one dose (7.4%). The difference between the two groups was statistically significant (chi square = 11.5016; p = 0.0006). Conclusion: Social media and DRS interventions had a positive impact on vaccine uptake and may be helpful in tackling vaccine hesitancy. Better-designed studies are needed to corroborate these findings.

First Results of an External Quality Assessment (EQA) Scheme for Molecular, Serological and Antigenic Diagnostic Test for SARS-CoV-2 Detection in Lombardy Region (Northern Italy), 2020-2022.

For diagnosing SARS-CoV-2 infection and for monitoring its spread, the implementation of external quality assessment (EQA) schemes is mandatory to assess and ensure a standard quality according to national and international guidelines. Here, we present the results of the 2020, 2021, 2022 EQA schemes in Lombardy region for assessing the quality of the diagnostic laboratories involved in SARS-CoV-2 diagnosis. In the framework of the Quality Assurance Programs (QAPs), the routinely EQA schemes are managed by the regional reference centre for diagnostic laboratories quality (RRC-EQA) of the Lombardy region and are carried out by all the diagnostic laboratories. Three EQA programs were organized: (1) EQA of SARS-CoV-2 nucleic acid detection; (2) EQA of anti-SARS-CoV-2-antibody testing; (3) EQA of SARS-CoV-2 direct antigens detection. The percentage of concordance of 1938 molecular tests carried out within the SARS-CoV-2 nucleic acid detection EQA was 97.7%. The overall concordance of 1875 tests carried out within the anti-SARS-CoV-2 antibody EQA was 93.9% (79.6% for IgM). The overall concordance of 1495 tests carried out within the SARS-CoV-2 direct antigens detection EQA was 85% and it was negatively impacted by the results obtained by the analysis of weak positive samples. In conclusion, the EQA schemes for assessing the accuracy of SARS-CoV-2 diagnosis in the Lombardy region highlighted a suitable reproducibility and reliability of diagnostic assays, despite the heterogeneous landscape of SARS-CoV-2 tests and methods. Laboratory testing based on the detection of viral RNA in respiratory samples can be considered the gold standard for SARS-CoV-2 diagnosis.

Role of LI-RADS Indeterminate Observations in the Risk of Hepatocellular Carcinoma after HCV Eradication with Direct-Acting Antivirals.

PURPOSE: To assess whether HCC (LR-5) occurrence may be associated with the presence of Liver Imaging Reporting and Data System (LI-RADS) indeterminate observations in patients with hepatitis C virus infection treated with direct acting antiviral (DAA) therapy. MATERIALS AND METHODS: This retrospective study included patients with HCV-related cirrhosis who achieved sustained virologic response (SVR) after DAA therapy between 2015 and 2019 and submitted to CT/MRI follow-ups with a minimum interval time of six months before and after DAA. Two blinded readers reviewed CT/MRI to categorize observations according to LI-RADS version 2018. Differences in rate of LI-RADS 5 observations (i.e., LR-5) before and after SVR were assessed. Time to LR-5 occurrence and risk factors for HCC after DAAs were evaluated by using Kaplan-Meier method and Cox proportional hazard model, respectively. RESULTS: Our final study population comprised 115 patients (median age 72 years) with a median CT/MRI follow-up of 47 months (IQR 26-77 months). Twenty-nine (25.2%) patients were diagnosed with LR-5 after DAA. The incidence of LR-5 after DAAs was 10.4% (12/115) at one year and 17.4% (20/115) at two years. LR-5 occurrence after DAA was significantly higher in patients with Child Pugh class B (log-rank p = 0.048) and with LR-3 or LR-4 observations (log-rank p = 0.024). At multivariate analysis, Child-Pugh class B (hazard ratio 2.62, p = 0.023) and presence of LR-3 or LR-4 observations (hazard ratio 2.40, p = 0.048) were independent risk factors for LR-5 occurrence after DAA therapy. CONCLUSIONS: The presence of LR-3 and LR-4 observations significantly increases HCC risk following the eradication of HCV infection.

Photodegradation of Bamboo: A Study on Changes in Mechanical Performances.

One of the main concerns in using natural materials in construction, such as bamboo, regards their durability. Ultra violet (UV)irradiation is claimed as a damaging agent; therefore, it is important to study its effect. Several studies have shown that bamboo components such as lignin are subjected to photochemical degradation, but it is not well understood how this affects the mechanical properties of bamboo. The aim of this paper is to explore the correlation between photodegradation and bamboo mechanical performance. Bamboo samples were exposed to accelerated UV ageing for different times (from 6 to 360 h) and then subjected to a four-point bending test. Since one of the ways to stabilize bamboo is to thermally treat it, the tests were conducted on natural untreated bamboo and treated bamboo with a traditional flame treatment. Modifications of the chemical features of the material were analyzed with Fourier Trasform Infra Red (FTIR) spectroscopy, while modifications of the morphological features were analyzed byEnvironmental Scanning Electron Microscopy ESEM and optical microscopy observations. The results show that the bending behavior of bamboo is not compromised by UV exposure up to 360 h. In fact, although a progressive degradation of lignin is reported and cracks in the fiber walls are highlighted from micrographs, no effects were found on the fiber length.

Long-term evolution of LI-RADS observations in HCV-related cirrhosis treated with direct-acting antivirals.

BACKGROUND & AIMS: The risk of progression of indeterminate observations to hepatocellular carcinoma (HCC) after direct-acting antivirals (DAA) is still undetermined. To assess whether DAA therapy changes the risk of progression of observations with low (LR-2), intermediate (LR-3) and high (LR-4) probability for HCC in cirrhotic patients and to identify predictors of progression. METHODS: This retrospective study included cirrhotic patients treated with DAA who achieved sustained virological response between 2015 and 2019. A total of 68 patients had pre-DAA indeterminate observations and at least six months CT/MRI follow-up before and after DAA. Two radiologists reviewed CT/MRI studies to categorize observations according to the LI-RADSv2018 and assess the evolution on subsequent follow-ups. Predictors of evolutions were evaluated by using the Cox proportional hazard model, Kaplan-Meier method and log-rank test. RESULTS: A total of 109 untreated observations were evaluated, including 31 (28.4%) LR-2, 67 (61.5%) LR-3 and 11 (10.1%) LR-4. During a median follow-up of 41 months, 17.4% and 13.3% of observations evolved to LR-5 or LR-M and LR-5, before and after DAA respectively (P = .428). There was no difference in rate of progression of neither LR-2 (P = 1.000), LR-3 (P = .833) or LR-4 (P = .505). At multivariate analysis, only initial LI-RADS category was an independent predictor of progression to LR-5 or LR-M for all observations (hazard ratio 6.75, P < .001), and of progression to LR-5 after DAA (hazard ratio 4.34, P = .047). CONCLUSIONS: DAA therapy does not increase progression of indeterminate observations to malignant categories. The initial LI-RADS category is an independent predictor of observations upgrade.

Neonatal diagnosis of Marcus Gunn jaw-winking syndrome.

This report highlights the importance for neonatologists/pediatricians of considering Marcus Gunn jaw-winking syndrome among differential diagnoses of ptosis. A detailed clinical assessment is crucial to promptly recognize and appropriately manage it.

Complications of hepatic echinococcosis: multimodality imaging approach.

Hydatid disease is a worldwide zoonosis endemic in many countries. Liver echinococcosis accounts for 60-75% of cases and may be responsible for a wide spectrum of complications in about one third of patients. Some of these complications are potentially life-threatening and require prompt diagnosis and urgent intervention. In this article, we present our experience with common and uncommon complications of hepatic hydatid cysts which include rupture, bacterial superinfection, and mass effect-related complications. Specifically, the aim of this review is to provide key imaging features and diagnostic clues to guide the imaging diagnosis using a multimodality imaging approach, including ultrasound (US), computed tomography (CT), magnetic resonance (MR), and endoscopic retrograde cholangiopancreatography (ERCP).

Preparation, characterization and in vitro test of composites poly-lactic acid/hydroxyapatite scaffolds for bone tissue engineering.

In this work, the possibility to produce composite Poly-L-lactic acid (PLLA)/Hydroxyapatite (HA) porous scaffolds via Thermally Induced Phase Separation (TIPS) for bone tissue engineering applications was investigated. Several PLLA/HA wt/wt ratios (95/5, 90/10, 70/30, 50/50, 34/66) were tested and the as-obtained scaffolds were characterized via Scanning Electron Microscopy, Wide Angle X-Ray Diffraction, Thermogravimetric analysis, Gas Pycnometry, Differential Scanning Calorimetry and mechanical compression test. Morphological analysis revealed an open structure with interconnected pores and HA particles embedded in the polymer matrix. Finally, cell cultures were carried out into the composite scaffolds in order to evaluate the effect of HA on the proliferation and differentiation of osteoblastic cells, showing a higher alkaline phosphatase activity on composite scaffolds compared to neat PLLA ones.

Double Flow Bioreactor for In Vitro Test of Drug Delivery.

In this work, double-structured polymeric scaffolds were produced, and a double flow bioreactor was designed and set up in order to create a novel system to carry out advanced in vitro drug delivery tests. The scaffolds, consisting of a cylindrical porous matrix, are able to host cells, thus mimicking a three-dimensional tumor mass: moreover, a "pseudo-vascular" structure was embedded into the matrix, with the aim of allowing a flow circulation. The structure that emulates a blood vessel is a porous tubular-shaped scaffold prepared by Diffusion Induced Phase Separation (DIPS), with an internal lumen of 2 mm and a wall thickness of 200 micrometers. The as-prepared vessel was incorporated into a three-dimensional matrix, prepared by Thermally Induced Phase Separation (TIPS), characterized by a high porosity (about 95%) and pore size adequate to accommodate tumor cells and/or mesenchymal cells. The morphology of the multifunctional scaffolds is easy-tunable in terms of pore size, porosity and thickness and therefore adaptable to various cell or tissue types. At the same time, a double flow bioreactor was designed and built up, in order to be able to carry out biological tests on the scaffold under dynamic conditions. The device allows a separate control of the two flows (one for the tubular scaffold, one for the porous matrix) through the scaffolds. Preliminary characterizations and tests carried out suggest the presented system as a candidate to suitably "in vitro" assess the effects of different drugs on various cell populations.

Galvanic deposition and characterization of brushite/hydroxyapatite coatings on 316L stainless steel.

In this work, brushite and brushite/hydroxyapatite (BS, CaHPO4·H2O; HA, Ca10(PO4)6(OH)2) coatings were deposited on 316L stainless steel (316LSS) from a solution containing Ca(NO3)2·4H2O and NH4H2PO4 by a displacement reaction based on a galvanic contact, where zinc acts as sacrificial anode. Driving force for the cementation reaction arises from the difference in the electrochemical standard potentials of two different metallic materials (316LSS and Zn) immersed in an electrolyte, so forming a galvanic contact leading to the deposition of BS/HA on nobler metal. We found that temperature and deposition time affect coating features (morphology, structure, and composition). Deposits were characterized by means of several techniques. The morphology was investigated by scanning electron microscopy, the elemental composition was obtained by X-ray energy dispersive spectroscopy, whilst the structure was identified by Raman spectroscopy and X-ray diffraction. BS was deposited at all investigated temperatures covering the 316LSS surface. At low and moderate temperature, BS coatings were compact, uniform and with good crystalline degree. On BS layers, HA crystals were obtained at 50°C for all deposition times, while at 25°C, its presence was revealed only after long deposition time. Electrochemical studies show remarkable improvement in corrosion resistance.

Synanthropy and temporal variability of Calliphoridae living in Cosenza (Calabria, southern Italy).

The aim of this study was to investigate the synanthropy of Diptera: Calliphoridae, insects of forensic importance, in Calabria (southern Italy). The study lasted 2 years, from February 2010 to January 2012, and was carried out in three areas of Cosenza province representing "urban", "rural", and "wild" environments. Bottle traps baited with pork were used to catch Calliphoridae. Six species were identified, Calliphora vicina Robineau-Desvoidy 1830, Calliphora vomitoria (L.), Chrysomya albiceps (Wiedemann 1819), Lucilia ampullacea Villeneuve 1922, Lucilia caesar (L.), and Lucilia sericata (Meigen 1826). Data on phenologies in the study areas are reported for these species and the Synanthropy Index was calculated to evaluate their relationship with the human environment.