Emerging and re-emerging infectious disease in otorhinolaryngology (ENT) are an area of growing epidemiological and clinical interest. The aim of this section is to comprehensively report on the ...epidemiology of key infectious disease in otorhinolaryngology, reporting on their burden at the national and international level, expanding of the need of promoting and implementing preventive interventions, and the rationale of applying evidence-based, effective and cost- effective diagnostic, curative and preventive approaches. In particular, we focus on i) ENT viral infections (HIV, Epstein-Barr virus, Human Papilloma virus), retrieving the available evidence on their oncogenic potential; ii) typical and atypical mycobacteria infections; iii) non-specific granulomatous lymphadenopathy; iv) emerging paediatric ENT infectious diseases and the prevention of their complications; v) the growing burden of antimicrobial resistance in ENT and the strategies for its control in different clinical settings. We conclude by outlining knowledge gaps and action needed in ENT infectious diseases research and clinical practice and we make references to economic analysis in the field of ENT infectious diseases prevention and care.
Biodiesel fuel production remains one of the most promising alternatives to non-renewable fossil fuels such as conventional oil and diesel. However, many challenges persist in its production ...particularly related to the tedious purification processes, high cost of production and unsustainable practices. Heterogenous metal-based catalysts can address these issues while having the added advantage of being recoverable and reusable; however, they can require a high catalyst loading and can be susceptible to metal leaching. Here we show the hydrothermal reaction of glycine and citric acid to prepare a heterogeneous carbon dot catalyst for the transesterification of canola oil to produce biodiesel. We report biodiesel conversions of ≥97% at 150 °C and 1 wt% catalyst loading. Moreover, we demonstrate the stability and reusability of the nanocatalyst with sustained catalytic efficiency for at least five reaction cycles. This cost-efficient and effective heterogeneous catalyst can have positive economic and environmental repercussions that can further drive academic and industrial research in this burgeoning area.
Biodiesel fuel production remains one of the most promising alternatives to non-renewable fossil fuels such as conventional oil and diesel.
Studies of vaccine effectiveness (VE) rely on accurate identification of vaccination and cases of vaccine-preventable disease. In practice, diagnostic tests, clinical case definitions and vaccination ...records often present inaccuracies, leading to biased VE estimates. Previous studies investigated the impact of non-differential disease misclassification on VE estimation.
We explored, through simulation, the impact of non-differential and differential disease- and exposure misclassification when estimating VE using cohort, case-control, test-negative case-control and case-cohort designs. The impact of misclassification on the estimated VE is demonstrated for VE studies on childhood seasonal influenza and pertussis vaccination. We additionally developed a web-application graphically presenting bias for user-selected parameters.
Depending on the scenario, the misclassification parameters had differing impacts. Decreased exposure specificity had greatest impact for influenza VE estimation when vaccination coverage was low. Decreased exposure sensitivity had greatest impact for pertussis VE estimation for which high vaccination coverage is typically achieved. The impact of the exposure misclassification parameters was found to be more noticeable than that of the disease misclassification parameters. When misclassification is limited, all study designs perform equally. In case of substantial (differential) disease misclassification, the test-negative design performs worse.
Misclassification can lead to significant bias in VE estimates and its impact strongly depends on the scenario. We developed a web-application for assessing the potential (joint) impact of possibly differential disease- and exposure misclassification that can be modified by users to their own study scenario. Our results and the simulation tool may be used to guide better design, conduct and interpretation of future VE studies.
Biodiesel remains one of the most promising sustainable alternatives to fossil fuel-derived energy; however, current process limitations and steep production costs associated with the use of ...homogeneous catalysts have limited global-wide acceptance and adoption. While heterogeneous catalysts have been put forth as suitable alternatives, they suffer from numerous drawbacks including high metal content and cost. As such, the search for novel and inexpensive alternatives is currently underway. Graphitic carbon nitride macrostructures have been widely investigated for photocatalytic applications yet their role in driving chemically-catalyzed reactions remains relatively unexplored. Herein, we synthesized and investigated the use of bulk, fiber, acid- and thermal-treated carbon nitrides as heterogeneous catalysts for the transesterification of canola oil to biodiesel. A conversion of 96% was achieved using 1 wt% catalyst loading, a low oil to methanol ratio of 1:24 and a reaction temperature and time of 150 °C and 3 h, respectively. Carbon nitrides offer a high thermal stability, cost effective and metal-free alternative to the many proposed metal-containing heterogeneous catalysts for biodiesel production, while maintaining high biodiesel conversions of >90%.
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•Carbon nitrides are a promising metal-free alternative heterogeneous catalyst in transesterification reactions.•Surface chemistry and morphology can be tuned to maximize catalytic efficiency.•Oxygen-rich surface chemistry is essential for efficient transesterification catalysts.
Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is ...often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR).
We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min.
237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable.
Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.
Biodiesel remains one of the most promising alternatives to replace fossil fuel‐derived petrodiesel. Nonetheless, conventional biodiesel synthesis relies on homogeneous alkali‐based catalysts that ...involve long and tedious purification steps , increasing biodiesel production costs. Heterogeneous catalysts have emerged as promising alternatives to circumvent these drawbacks, as they can easily be recovered and reused. Herein, polymeric carbon nitride dots and nanosheets are synthesized through a solid‐phase reaction between urea and sodium citrate. Their morphology and surface chemistry are tuned by varying the precursor's ratio, and the materials are investigated as catalysts in the transesterification reaction of canola oil to biodiesel. A conversion of > 98% is achieved using a 5 wt% catalyst loading, oil to methanol ratio of 1:36 at 90 °C for 4 h, with the performance maintained over at least five reuse cycles. In addition, the effect of the transesterification reaction parameters on the reaction kinetics is evaluated, which follows a pseudo‐first‐order (PFO) regime. Combined with a deep understanding of the catalyst's surface, these results have allowed us to propose a reaction mechanism similar to the one observed for homogenous alkali catalysts. These carbon nitride‐based nanoparticles offer a metal‐free and cost‐effective alternative to conventional homogeneous and metal‐based heterogeneous catalysts.
Polymeric carbon nitride dots and nanosheets are prepared through a solid‐phase reaction between urea and sodium citrate. These heterogeneous catalysts are used to catalyze the transesterification reaction of canola oil to a biofuel namely biodiesel achieving > 98% conversion over multiple catalytic cycles and using only a 5 wt% catalyst loading.
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal ...antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices.
We built a retroprospective cohort study including 30 non-selected patients with laCSCC (25) and mCSCC (five) treated with cemiplimab from August 2019 to November 2020. Clinical outcomes, toxicity profile, and correlations with disease, patients, and peripheral blood parameters are explored.
The median age was 81 years (range, 36-95), with 24 males and five patients having an immunosuppressive condition, while the frailty prevalence was 83% based on index derived from age, Eastern Cooperative Oncology Group performance status, and Charlson Comorbidity Index. We reported 23 responses (76.7%) with nine complete responses (30%). A statistically significant higher response rate was observed in head and neck primary tumors and in patients with hemoglobin level >12 g/dl. No difference was observed with respect to frailty, median age, sex, and body mass index. The baseline low neuthophil/lymphocyte ratio and low platelet/lymphocyte ratio resulted to be also correlated with a better response. Moreover, lymphocyte, neutrophil, and monocyte behaviors had an opposite trend in responders and non-responders. An overall response was reported in four of five immunosuppressed patients. Seventeen patients (57.6%) have an ongoing response and are still alive. Six responders had interrupted treatment (two for toxicity and four for personal choice) but maintained their response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in seven patients (23.3%) and skin toxicity in 10 patients (33.3%), including pruritus in six patients, rash in three patients, and bullous erythema in one patient.
In our real-life experience, cemiplimab showed a high antitumor activity with acceptable safety profile similar to those in trials with selected patients. Moreover, its antitumor activity resulted to be not impaired in very elderly patients and in those with immunocompromised status.
Cardiac fibrosis represents a key element in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), a condition highly prevalent amongst geriatric patients, especially if ...diabetic. The microRNA 181c (miR-181c) has been shown to be associated with the response to exercise training in HFpEF patients and has been also linked to diabetic cardiovascular complications. However, the underlying mechanisms have not been fully elucidated.
To measure circulating miR-181c in elderly patients with HFpEF and diabetes mellitus (DM) and identify gene targets pathophysiologically relevant in HFpEF.
We quantified circulating miR-181c in frail older adults with a confirmed diagnosis of HFpEF and DM, and, as control, we enrolled age-matched subjects without HFpEF and without DM. We validated in human cardiac fibroblasts the molecular mechanisms linking miR-181c to a pro-fibrotic response.
51 frail patients were included :34 patients with DM and HFpEF and 17 age-matched controls. We observed that miR-181c was significantly upregulated (p < 0.0001) in HFpEF patients vs controls. We confirmed in vitro that miR-181c is targeting PRKN and SMAD7.
We demonstrate that miR-181c levels are significantly increased in frail elderly adults with DM and HFpEF and that miR-181c targets PRKN and SMAD7 in human cardiac fibroblasts.
•We measured circulating levels of miR-181c in frail older adults with a confirmed diagnosis of HFpEF and diabetes.•We observed that miR-181c levels were upregulated in HFpEF patients compared to age-matched control subjects.•We demonstrated that miR-181c targets PRKN and SMAD7 in human cardiac fibroblasts.
Endothelial dysfunction represents a key mechanism underlying heart failure with preserved ejection fraction (HFpEF), diabetes mellitus (DM), and frailty. However, reliable biomarkers to monitor ...endothelial dysfunction in these patients are lacking. In this study, we evaluated the expression of a panel of circulating microRNAs (miRs) involved in the regulation of endothelial function in a population of frail older adults with HFpEF and DM treated for 3 months with empagliflozin, metformin, or insulin. We identified a distinctive pattern of miRs that were significantly regulated in HFpEF patients compared to healthy controls and to HFpEF patients treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin. Three miRs were significantly downregulated (miR-126, miR-342-3p, and miR-638) and two were significantly upregulated (miR-21 and miR-92) in HFpEF patients compared to healthy controls. Strikingly, two of these miRs (miR-21 and miR-92) were significantly reduced in HFpEF patients after the 3-month treatment with empagliflozin, whereas no significant differences in the profile of endothelial miRs were detected in patients treated with metformin or insulin. Taken together, our findings demonstrate for the first time that specific circulating miRs involved in the regulation of endothelial function are significantly regulated in frail HFpEF patients with DM and in response to SGLT2 inhibition. SIGNIFICANCE STATEMENT: We have identified a novel microRNA signature functionally involved in the regulation of endothelial function that is significantly regulated in frail patients with HFpEF and diabetes. Moreover, the treatment with the SGLT2 inhibitor empagliflozin caused a modification of some of these microRNAs in a direction that was opposite to what observed in HFpEF patients, indicating a rescue of endothelial function. Our findings are relevant for clinical practice inasmuch as we were able to establish novel biomarkers of disease and response to therapy.
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