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Abstract Objective The anti-COVID vaccination campaign has led to a significant increase in the demand for allergology consultations in patients considered at risk of reaction to anti-COVID-19 vaccines. This study aims to describe the experience of the vaccination campaign held in Piedmont (Italy) which developed a new service of Allergy Call Center (ACC) thus providing for the screening and management of allergy high-risk patients during pandemic. Study Design A retrospective analysis was performed on all patients considered at high risk for the development of allergic reactions who were referred by the Immunology and Allergy Unit of Azienda Ospedaliera Ordine Mauriziano in Turin, Italy, between December 2020 and December 2022 and also on ACC consultations. Methods During the COVID-19 pandemic, Piedmont Region instituted the ACC, active from May 10th, 2021 to December 31st 2022, to allow vaccinating doctors to require a telephonic consultation for patients who were considered at high risk for the development of allergic reactions. If further diagnostic evaluations were required, the ACC scheduled a visit with a Consultant of the Unit to better assess the clinical situation of the patient. Furthermore, patients referred by General Practitioners, Occupational Doctors and other consultants were also evaluated by the Unit when required. Results During the operational period the ACC received a total of 15,865 calls and referred only 336 patients to the unit (27.4% of the total referrals), while General Practitioners referred 499 patients (40.8%), Occupational Doctors referred 61 patients (4.9%), and other consultants referred 326 patients (26.6%). Conclusions Evaluation and management of a large volume of requests seemed to be facilitated by a proactive framework for screening patients at high risk for allergic reactions as the ones referred by our ACC. This approach led to a prominent decrease in allergological visits to our tertiary care Centre, reducing the waiting times and providing additional support for both patients and healthcare providers, thus allowing the vaccinations to be more easily handled.

Abstract Background Latency remains a major obstacle to finding a cure for HIV despite the availability of antiretroviral therapy. Due to virus dormancy, limited biomarkers are available to identify latent HIV-infected cells. Profiling of individual HIV-infected cells is needed to explore potential latency biomarkers and to study the mechanisms of persistence that maintain the HIV reservoir. Methods Single cell spatial transcriptomic characterization using the CosMx Spatial Molecular Imager platform was conducted to analyze HIV-infected cells in formalin-fixed paraffin-embedded sections of splenic tissue surgically obtained from an HIV-infected humanized mouse model. Regulation of over a thousand human genes was quantified in both viremic and aviremic specimens. In addition, in situ hybridization and immunohistochemistry were performed in parallel to identify HIV viral RNA- and p24-containing cells, respectively. Finally, initial findings from CosMx gene profiling were confirmed by isolating RNA from CD4 + T cells obtained from a person living with HIV on antiretroviral therapy following either PMA/Ionomycin or DMSO treatment. RNA was quantified using qPCR for a panel of targeted human host genes. Results Supervised cell typing revealed that most of the HIV-infected cells in the mouse spleen sections were differentiated CD4 + T cells. A significantly higher number of infected cells, 2781 (1.61%) in comparison to 112 (0.06%), and total HIV transcripts per infected cell were observed in viremic samples compared to aviremic samples, respectively, which was consistent with the data obtained from ISH and IHC. Notably, the expression of 55 genes was different in infected cells within tissue from aviremic animals compared to viremic. In particular, both spleen tyrosine kinase (SYK) and CXCL17, were expressed approximately 100-fold higher. This data was further evaluated against bulk RNA isolated from HIV-infected human primary CD4 + T cells. A nearly 6-fold higher expression of SYK mRNA was observed in DMSO-treated CD4 + T cells compared to those stimulated with PMA/Ionomycin. Conclusion This study found that the CosMx SMI platform is valuable for assessing HIV infection and providing insights into host biomarkers associated with HIV reservoirs. Higher relative expression of the SYK gene in aviremic-infected cells from the humanized mouse HIV model was consistent with levels found in CD4 + T cells of aviremic donors.

Abstract The tumor suppressor PTEN (phosphatase and tensin homolog deleted in chromosome 10) is genetically deleted or downregulated in many cancer types. Loss of PTEN protein expression is frequently found in lung cancer while genetic alterations are less abundant. PTEN expression is regulated at multiple genetic and epigenetic levels and even partial reduction of its expression increases cancer occurrence. We show that YAP and TAZ cooperate with EZH2, and MYC to transcriptionally repress onco-suppressor genes, including PTEN, in non-small cell lung cancer (NSCLC) cells. YAP/TAZ-EZH2-MYC transcriptional regulators form a nuclear complex that represses PTEN transcription, while their combinatorial targeting restores PTEN expression, attenuates NSCLC cell growth, and prevents compensatory responses induced by single treatments. Datasets analysis of NSCLC patients revealed that PTEN expression is negatively correlated to YAP/TAZ, EZH2 and MYC and that low expression of PTEN is predictive of poor prognosis, especially at earlier stages of the disease. These findings highlight the repressive role of the YAP/TAZ-EZH2-MYC axis on tumor-suppressor genes and offer a potential therapeutic strategy for lung cancer patients with low PTEN levels.

The commercial value of teak wood is associated with its heartwood, which has a naturally darker color than sapwood. To reduce this color disparity, thermal modification can be used to homogenize the color between sapwood and heartwood by minimizing color differences. This research aimed to assess the effectiveness of thermal modification in making the color of teak sapwood similar to that of heartwood. Thermal modification was carried out at 160, 180, 200, and 220 °C for 150 min. Thermal modification of teak sapwood at 180 °C ensured greater color similarity to the heartwood of a fast-growing 16-year-old plantation. The material darkened with increasing process temperature. There was a change in the content of soluble substances, and hot water extraction had greater correlations with hue angle, lightness, and yellowness. Thermal modification also reduced the number of hydroxyl groups and improved the wood’s thermal stability.

While research on videogames in education mostly focuses on demonstrating the effectiveness of Game Based Learning in a broad range of educational contexts, few studies have focused on examining in-depth stakeholders’ perceptions in the educational/teaching area concerning gaming experiences based on a first-person play session. To fill this gap, this study presents the results of a reflexive thematic analysis of the answers to a qualitative survey based on a gaming experience of 13 informants related to the educational field (teachers, researchers, and Master degree students). The game used in the experience was Assassin’s Creed Odyssey: Discovery Tour. The main aim was to understand their perceptions of possible uses of this digital game in formal educational contexts. Our analysis reveals the general perception of a significant overall advantage in the use of this game as an instructional tool compared to a traditional pedagogical approach. Pedagogical solutions for an instructional implementation and design, teaching interventions, critical perspectives are discussed.

Human induced pluripotent stem cells (hiPSCs) hold promises to model and understand human diseases, including those associated with ageing. Here, we describe ABCRIi001-A, a hiPSC line generated from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female enrolled in a study for development of an ageing score (ALFA Score). PBMCs were reprogrammed using three Sendai virus-based reprogramming vectors (hKOS, hc-Myc, and hKlf4). ABCRIi001-A showed normal morphology and karyotype, viral clearance, absence of genomic aberrations, and their pluripotency was confirmed by expression of pluripotency-related markers and their ability to differentiate into the three germ layers. ABCRIi001-A is valuable for ageing-related studies.

Solid Phase Peptide Synthesis (SPPS) is the preferred technique for synthesizing bioactive peptides. However, traditional SPPS generates significant waste and employs hazardous solvents like DMF and DCM. The aim of this research is to investigate solvents and agents of coupling that align with the green chemistry and are suitable for all stages of SPPS. Some solvents, such as p-cymene and anisole, taken into consideration in this work, can be derived from renewable sources like plants and biomass, rendering them environmentally sustainable choices. However, many of these alternative solvents possess different physicochemical properties compared to DMF. To overcome this challenge, solvent mixtures are employed. In this study, we identified a novel green solvent mixture by combining anisole with NOP; its ability to swell different resins and its capability to solubilize all Fmoc protected amino acids was investigated. The same mixture was also assessed with a green coupling agent, TBEC, in combination with ETT as additive. Model peptides Aib-enkephalin and Aib-ACP were synthesized resulting in favorable outcomes in terms of peptide synthesis efficiency, 97.81% and 98.86%, respectively.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has put enormous pressure on healthcare systems worldwide. While the majority of severe cases present with respiratory failure, thrombosis or bleeding have also been reported at unusual sites. Major bleeding, particularly in patients treated with therapeutic anticoagulation, has been observed between the second and third week after the onset of SARS-CoV-2 infection. This article describes three cases of patients admitted to the hospital with severe SARS-CoV-2 pneumonia who had spontaneous arterial bleeding from the thoracic and subscapular regions during treatment with helmet continuous positive airway pressure (H-CPAP) in the intensive care unit (ICU), requiring a percutaneous embolization procedure. A possible correlation with helmet-supported ventilation is hypothesized.

To report a rare case of a right interstitial pregnancy spontaneously occurring in a patient who had previously undergone homolateral salpingo-oophorectomy, and to propose possible explanations for the mechanisms involved in the genesis of this rare scenario. A 32-year-old G3P1 female presented to our emergency room with symptoms related to a suspected ectopic interstitial pregnancy managed in another hospital using a conservative pharmacological approach. After discussing the risks, firstly she underwent a transvaginal ultrasound examination, then a diagnostic hysteroscopy to clarify the unclear ultrasound finding, followed by a successful robot-assisted laparoscopic cornual resection. Hysteroscopy demonstrated an empty uterine cavity, confirming the suspect of pregnancy localization into the interstitial portion of the tubal stump. Through the robot-assisted laparoscopic approach, all the trophoblastic tissue was removed without causing significant damage to the surrounding myometrium and preserving the patient’s fertility. No post-operative complications were recorded. The robotic approach successfully allowed the cornual resection, with minimal blood loss and optimal suturing of the uterine defect. Although our knowledge is still limited, it is possible that the pregnancy nested in the tubal residue after being properly fertilized into the intact tube. However, it cannot be ruled out that there have been remodeling phenomena of the tubal residue so that it has acquired the ability to intercept the oocyte.

9p21.3 locus polymorphisms have the strongest correlation with coronary artery disease, but as a noncoding locus, disease connection is enigmatic. The lncRNA ANRIL found in 9p21.3 may regulate vascular smooth muscle cell (VSMC) phenotype to contribute to disease risk. We observed significant heterogeneity in induced pluripotent stem cell-derived VSMCs from patients homozygous for risk versus isogenic knockout or nonrisk haplotypes. Subpopulations of risk haplotype cells exhibited variable morphology, proliferation, contraction, and adhesion. When sorted by adhesion, risk VSMCs parsed into synthetic and contractile subpopulations, i.e., weakly adherent and strongly adherent, respectively. Of note, >90% of differentially expressed genes coregulated by haplotype and adhesion and were associated with Rho GTPases, i.e., contractility. Weakly adherent subpopulations expressed more short isoforms of ANRIL, and when overexpressed in knockout cells, ANRIL suppressed adhesion, contractility, and αSMA expression. These data suggest that variable lncRNA penetrance may drive mixed functional outcomes that confound pathology.

The clonal materials of Tectona grandis L. f. in fast-growing plantations exhibit faster growth than the seminal materials. Therefore, it is necessary to investigate the differences in wood drying to ensure the quality and yield of the final product. This study evaluated the outdoor drying behavior of three genotypes of teak lumber. Two clonal genotypes (G1 and G2) and one of seminal origin (G3) were assessed. Boards measuring 30 × 150 × 1000 mm (thickness × width × length) were produced from the basal logs. The average moisture content (79.3, 64.9, and 60,1%), final moisture content (10.8, 9.8, and 11.6%), and mean drying rate (1.2, 0.97, and 0.85%.day-1) were observed in the wood from genotypes G1, G2 and G3, respectively. The clonal material crooked and bowed below 5 mm.m-1, which is considered the tolerance limit for both warpings. The seminal material had a greater incidence of splitting. The clonal genotypes G1 and G2 had similar qualities and presented higher drying rates, final moisture contents below 11% and a lower incidence of defects, especially splitting, compared to the naturally seeded material.

This Article examines scenario analysis, a disruptive argumentation technique used by the German Federal Constitutional Court (GFCC) in recent high-profile cases, such as the so-called climate protection case (Klimaschutz) and other decisions on the fundamental right to intergenerational justice (Grundrecht auf Generationengerechitgkeit). After explaining the basic argumentative steps involved in scenario analysis, for example designing scenarios, identifying stakeholders, relating scenarios to strategies, determining the main driving forces, estimating scenario probabilities, the Article sketches a normative model for rational scenario design. The normative model is used as a lens for evaluating the arguments developed by the GFCC in the climate protection case. Such evaluation also builds on game-theoretic insights and points out some weaknesses in the Court’s argument. Finally, the Article observes that, as scenario analysis is used to assess the future impact of legislative decisions, it has the effect of imposing greater constraints on legislatures.

Abstract Nanoscale flows of liquids can be revealed in various biological processes and underlie a wide range of nanofluidic applications. Though the integral characteristics of these systems, such as permeability and effective diffusion coefficient, can be measured in experiments, the behaviour of the flows within nanochannels is still a matter of speculation. Herein, we used a combination of quadrupolar solid-state NMR spectroscopy, computer simulation, and dynamic vapour sorption measurements to analyse water diffusion inside peptide nanochannels. We detected a helical water flow coexisting with a conventional axial flow that are independent of each other, immiscible, and associated with diffusion coefficients that may differ up to 3 orders of magnitude. The trajectory of the helical flow is dictated by the screw-like distribution of ionic groups within the channel walls, while its flux is governed by external water vapour pressure. Similar flows may occur in other types of nanochannels containing helicoidally distributed ionic groups and be exploited in various nanofluidic lab-on-a-chip devices.

IntroductionIn patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients.MethodsA multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age ≥15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria.ResultsData are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies.ObjectivesTo evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data.MethodsA retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies – ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Smith) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher’s exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant.ResultsOne-hundred and twenty-seven patients (n=127, mean age 53.43 ± 14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune hemolytic anemia and thrombocytopenia.ConclusionsIn our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.