Identification of new benzofuran derivatives as STING agonists with broad-spectrum antiviral activity

The Stimulator of Interferon Genes (STING) is involved in cytosolic DNA sensing and type I Interferons (IFN-I) induction. Aiming to identify new STING agonists with antiviral activity and given the known biological activity of benzothiazole and benzimidazole derivatives, a series of benzofuran derivatives were tested for their ability to act as STING agonists, induce IFN-I and inhibit viral replication. Compounds were firstly evaluated in a gene reporter assay measuring luciferase activity driven by the human IFN-β promoter in cells expressing exogenous STING (HEK293T). Seven of them were able to induce IFN-β transcription while no induction of the IFN promoter was observed in the presence of a mutated and inactive STING, showing specific protein-ligand interaction. Docking studies were performed to predict their putative binding mode. The best hit compounds were then tested on human coronavirus 229E replication in BEAS-2B and MRC-5 cells and three derivatives showed EC50 values in the μM range. Such compounds were also tested on SARS-CoV-2 replication in BEAS-2B cells and in Calu-3 showing they can inhibit SARS-CoV-2 replication at nanomolar concentrations. To further confirm their IFN- dependent antiviral activity, compounds were tested to verify their effect on phospho-IRF3 nuclear localization, that was found to be induced by benzofuran derivatives, and SARS-CoV-2 replication in Vero E6 cells, lacking IFN production, founding them to be inactive. In conclusion, we identified benzofurans as STING- dependent immunostimulatory compounds and host-targeting inhibitors of coronaviruses representing a novel chemical scaffold for the development of broad-spectrum antivirals

System Level PDN Impedance Optimization Utilizing the Zeros of the Decoupling Capacitors

System-Level Power Distribution Network (PDN) Impedance Optimization Utilizing the Zeros of the Decoupling Capacitors (Decaps) is Discussed in This Paper. an Example of a Practical PDN Application is Proposed to Validate the Poles and Zeros Algorithm (P&Z) Presented. the System-Level PDN is with the Printed Circuit Board (PCB), Package (PKG), and Chip, as Well as the Low-Frequency Decaps on the PCB and the On-PKG Decoupling Capacitors. the PDN Optimization Results Are Compared with Those from the Genetic Algorithm (GA) to Show the Reasonableness and Validity of the P&Z Algorithm

A Methodical Approach for Pcb Pdn Decoupling Minimizing overdesign with Genetic Algorithm Optimization

An optimization routine is applied for the decoupling capacitor placement on Power Distribution Networks to identify the limit beyond which the placement of additional decaps is no longer effective, thus leading to wasting layout area and components, and to a cost increase. A specific test example from a real design is used together with the required target impedance and frequency band of interest for the PDN design. The effectiveness of the decap placement while selecting different layers of the stack-up, and while moving the upper limit of the PDN design band is analyzed. Such analysis leads to helpful insights based on the progression of the input impedance during the optimization process, and to develop useful guidelines for avoiding over-design of the PDN

Postoperative Intensive Care Management of Aortic Repair

Vascular surgery patients have multiple comorbidities and are at high risk for perioperative complications. Aortic repair surgery has greatly evolved in recent years, with an increasing predominance of endovascular techniques (EVAR). The incidence of cardiac complications is significantly reduced with endovascular repair, but high-risk patients require postoperative ST-segment monitoring. Open aortic repair may portend a prohibitive risk of respiratory complications that could be a contraindication for surgery. This risk is greatly reduced in the case of an endovascular approach, and general anesthesia should be avoided whenever possible in the case of endovascular repair. Preoperative renal function and postoperative kidney injury are powerful determinants of short- and long-term outcome, so that preoperative risk stratification and secondary prevention are critical tasks. Intraoperative renal protection with selective renal and distal aortic perfusion is essential during open repair. EVAR has lower rates of postoperative renal failure compared to open repair, with approximately half the risk for acute kidney injury (AKI) and one-third of the risk of hemodialysis requirement. Spinal cord ischemia used to be the most distinctive and feared complication of aortic repair. The risk has significantly decreased since the beginning of aortic surgery, with advances in surgical technique and spinal protection protocols, and is lower with endovascular repair. Endovascular repair avoids extensive aortic dissection and aortic cross-clamping and is generally associated with reduced blood loss and less coagulopathy. The intensive care physician must be aware that aortic repair surgery has an impact on every organ system, and the importance of early recognition of organ failure cannot be overemphasized

Nutritional knowledge, parenting styles and feeding practices of a South African sample of parents

Parenting can be considered as being an all-encompassing network of development for children. Children learn about eating not only through their own experiences but also by watching others. Mothers and children show similar patterns of food acceptance and food preferences. Children’s intake of fruit and vegetables was positively related to parents’ intake of fruit and vegetables. The current study used self-reported data from parents/primary caregivers' children aged 3–18 covering sociodemographic characteristics, feeding style dimensions (‘control overeating’, ‘emotional feeding’, ‘encouragement to eat’ and ‘instrumental feeding’) and parenting style dimensions (‘involvement’ and ‘strictness’). The results suggest, that in general, parents were inclined to encourage balance and variety in the food intake of their children, modeling healthy eating behavior, as well as monitoring the food intake of children while restricting unhealthy foods. Further research is needed into whether parents’ diets affect children’s food choices feeding

Personalized Feedback on Staff Dose in Fluoroscopy-Guided Interventions: A New Era in Radiation Dose Monitoring

Radiation safety and protection are a key component of fluoroscopy-guided interventions. We hypothesize that providing weekly personal dose feedback will increase radiation awareness and ultimately will lead to optimized behavior. Therefore, we designed and implemented a personalized feedback of procedure and personal doses for medical staff involved in fluoroscopy-guided interventions. Medical staff (physicians and technicians, n = 27) involved in fluoroscopy-guided interventions were equipped with electronic personal dose meters (PDMs). Procedure dose data including the dose area product and effective doses from PDMs were prospectively monitored for each consecutive procedure over an 8-month period (n = 1082). A personalized feedback form was designed displaying for each staff individually the personal dose per procedure, as well as relative and cumulative doses. This study consisted of two phases: (1) 1-5th months: Staff did not receive feedback (n = 701) and (2) 6-8th months: Staff received weekly individual dose feedback (n = 381). An anonymous evaluation was performed on the feedback and occupational dose. Personalized feedback was scored valuable by 76% of the staff and increased radiation dose awareness for 71%. 57 and 52% reported an increased feeling of occupational safety and changing their behavior because of personalized feedback, respectively. For technicians, the normalized dose was significantly lower in the feedback phase compared to the prefeedback phase: [median (IQR) normalized dose (phase 1) 0.12 (0.04-0.50) A mu Sv/Gy cm(2) versus (phase 2) 0.08 (0.02-0.24) A mu Sv/Gy cm(2), p = 0.002]. Personalized dose feedback increases radiation awareness and safety and can be provided to staff involved in fluoroscopy-guided interventions

Management of Preschool Wheezing: Guideline from the Emilia-Romagna Asthma (ERA) Study Group

Preschool wheezing should be considered an umbrella term for distinctive diseases with different observable and measurable phenotypes. Despite many efforts, there is a large gap in knowledge regarding management of preschool wheezing. In order to fill this lack of knowledge, the aim of these guidelines was to define management of wheezing disorders in preschool children (aged up to 5 years). A multidisciplinary panel of experts of the Emilia-Romagna Region, Italy, addressed twelve different key questions regarding the management of preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes) and systematic reviews have been conducted on PubMed to answer these specific questions, with the aim of formulating recommendations. The GRADE approach has been used for each selected paper, to assess the quality of the evidence and the degree of recommendations. These guidelines represent, in our opinion, the most complete and up-to-date collection of recommendations on preschool wheezing to guide pediatricians in the management of their patients, standardizing approaches. Undoubtedly, more research is needed to find objective biomarkers and understand underlying mechanisms to assess phenotype and endotype and to personalize targeted treatment

Universal surface-enhanced Raman tags : individual nanorods for measurements from the visible to the infrared (514 – 1064 nm)

Surface-enhanced Raman scattering (SERS) is a promising imaging modality for use in a variety of multiplexed tracking and sensing applications in biological environments. However, the uniform production of SERS nanoparticle tags with high yield and brightness still remains a significant challenge. Here, we describe an approach based on the controlled co-adsorption of multiple dye species onto gold nanorods to create tags that can be detected across a much wider range of excitation wavelengths (514 – 1064 nm) compared to conventional approaches that typically focus on a single wavelength. This was achieved without the added complexity of nanoparticle aggregation or growing surrounding metallic shells to further enhance the surface-enhanced resonance Raman scattering (SERRS) signal. Correlated Raman and scanning electron microscopy mapping measurements of individual tags were used to clearly demonstrate that strong and reproducible SERRS signals at high particle yields (>92 %) were readily achievable. The polyelectrolyte-wrapped nanorod-dye conjugates were also found to be highly stable as well as non-cytotoxic. To demonstrate the use of these universal tags for the multimodal optical imaging of biological specimens, confocal Raman and fluorescence maps of stained immune cells following nanoparticle uptake were acquired at several excitation wavelengths and compared with dark-field images. The ability to colocalize and track individual optically encoded nanoparticles across a wide range of wavelengths simultaneously will enable the use of SERS alongside other imaging techniques for the real-time monitoring of cell-nanoparticle interactions

Unfolding dermatologic spectrum of Behçet’s disease in Italy: real-life data from the International AIDA Network Behçet’s disease Registry

Behçet’s disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care