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Chloroquine (CQ) and hydroxychloroquine (HCQ) have recently become the focus of global attention as possible treatments for Coronavirus Disease 2019 (COVID-19). The current systematic review aims to assess their safety in short treatments (≤14 days), whether used alone or in combination with other drugs. Following the PRISMA and SWiM recommendations, a search was conducted using four health databases for all relevant English-, Chinese-, and Spanish-language studies from inception through 30 July 2021. Patients treated for any condition and with any comparator were included. The outcomes of interest were early drug adverse effects and their frequency. A total of 254 articles met the inclusion criteria, including case and case-control reports as well as cross-sectional, cohort, and randomised studies. The results were summarised either qualitatively in table or narrative form or, when possible (99 studies), quantitatively in terms of adverse event frequencies. Quality evaluation was conducted using the CARE, STROBE, and JADAD tools. This systematic review showed that safety depended on drug indication. In COVID-19 patients, cardiac adverse effects, such as corrected QT interval prolongation, were relatively frequent (0–27.3% and up to 33% if combined with azithromycin), though the risk of torsade de pointes was low. Compared to non-COVID-19 patients, COVID-19 patients experienced a higher frequency of cardiac adverse effects regardless of the regimen used. Dermatological adverse effects affected 0–10% of patients with autoimmune diseases and COVID-19. A broad spectrum of neuropsychiatric adverse effects affected patients treated with CQ for malaria with variable frequencies and some cases were reported in COVID-19 patients. Gastrointestinal adverse effects occurred regardless of drug indication affecting 0–50% of patients. In conclusion, CQ and HCQ are two safe drugs widely used in the treatment of malaria and autoimmune diseases. However, recent findings on their cardiac and neuropsychiatric adverse effects should be considered if these drugs were to be proposed as antivirals again.

(1) Background: The volume-viscosity swallow test (V-VST) is a clinical tool for screening and diagnosis of oropharyngeal dysphagia (OD). Our aims were to examine the clinical utility of the V-VST against videofluoroscopy (VFS) or fiberoptic endoscopic evaluation of swallow (FEES) and to map the V-VST usage with patients at risk of OD across the years since it was described for the first time, carrying a systematic and a scoping review. (2) Methods: We performed both a systematic review (SR) including studies that look at the diagnostic test accuracy, and a scoping review (ScR) with articles published from September 2008 to May 2020. Searches were done in different databases, including PubMed and EMBASE from September 2008 until May 2020, and no language restrictions were applied. A meta-analysis was done in the SR to assess the psychometric properties of the V-VST. Quality of studies was assessed by Dutch Cochrane, QUADAS, GRADE (SR), and STROBE (ScR) criteria. The SR protocol was registered on PROSPERO (registration: CRD42020136252). (3) Results: For the diagnostic accuracy SR: four studies were included. V-VST had a diagnostic sensitivity for OD of 93.17%, 81.39% specificity, and an inter-rater reliability Kappa = 0.77. Likelihood ratios (LHR) for OD were 0.08 (LHR–) and 5.01 (LHR+), and the diagnostic odds ratio for OD was 51.18. Quality of studies in SR was graded as high with low risk of bias. In the ScR: 34 studies were retrieved. They indicated that V-VST has been used internationally to assess OD’s prevalence and complications. (4) Conclusions: The V-VST has strong psychometric properties and valid endpoints for OD in different phenotypes of patients. Our results support its utility in the screening and clinical diagnosis and management of OD.

Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases.

The performance of an industrial air amplifier is assessed through experimental and numerical characterization, with a focus on examining the influence of various operating conditions (isolated, “blowing,” and “suction” modes) and direct geometric scaling of the device within the specified range of the injection gap (δ) and the inlet pressure characteristic values. The findings underscore the presence of a linear trend of the entrained mass flow and a nonlinear decay of the amplification factor, both with notable sensitivity to the gap width. Numerical RANS simulations validate the experimental data, characterize the asymmetric flow downstream from the device, and facilitate the exploration of more complex scenarios. In this regard, scaling the device’s dimensions reveals an optimal aspect ratio between the minimum diameter (Dm) and δ to maximize the entrained mass flow. This research provides valuable insights into the behavior of air amplifiers, offering guidance for their design and application across various industrial contexts.

This paper presents a reversible heat pump based on CO2 as the refrigerant, able to provide heating, cooling, and domestic hot water to high energy demand buildings. The unit was developed and tested under the EU H2020 project MultiPACK, which has the main goal of assuring the market about the feasibility, reliability, and energy efficiency of CO2 integrated systems for heating and cooling and promoting a fast transition to low environmental impact solutions. Within the project, the confidence raising was performed by installation and monitoring of fully integrated state-of-the art CO2 systems in the Southern European Climate. With the aim of predicting the unit behaviour under variable load and boundary conditions, a dynamic model of the entire unit was developed with commercial software, considering actual components and the implemented control system and it was validated with experimental data, collected at the factory’s lab before commissioning. The validation against experimental data collected during operation as a heat pump demonstrated a maximum percentage difference between the experimental and predicted value of gas–cooler heat flow rate equal to +5.0%. A preliminary comparison with the experimental data in chiller configuration is reported, however further development was required to achieve a satisfactory validation. Lastly, the numerical model was utilized to simulate a typical operation in heat pump configuration with the system coupled with a hot water tank storage for the production of domestic hot water and space heating; the model predicts higher COP when operating in domestic hot water operation due to the lower water inlet temperature.