Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross‐Cycloadditions: DFT‐Supported Homo‐Synergistic Organocatalytic Approach

The discovery of chemical methods enabling the construction of carbocycle‐fused uracils which embody a three‐dimensional and functional‐group‐rich architecture is a useful tool in medicinal chemistry oriented synthesis. In this work, an unprecedented amine‐catalyzed [4+2] cross‐cycloaddition is documented; it involves remotely enolizable 6‐methyluracil‐5‐carbaldehydes and β‐aryl enals, and chemoselectively produces two novel bicyclic and tricyclic fused uracil chemotypes in good yields with a maximum level of enantiocontrol. In‐depth mechanistic investigations and control experiments support an intriguing homo‐synergistic organocatalytic approach, where the same amine organocatalyst concomitantly engages both aldehyde partners in a stepwise eliminative [4+2] cycloaddition, whose vinylogous iminium ion intermediate product may diverge—depending upon conditions—to either bicyclic targets by hydrolysis or tricyclic products by a second homo‐synergistic trienamine‐mediated stepwise [4+2] cycloaddition

Clinical Characteristics and Outcome of Patients with Suspected COVID-19 in Emergency Department (RESILIENCY Study II)

COVID-19 may show no peculiar signs and symptoms that may differentiate it from other infective or non-infective etiologies; thus, early recognition and prompt management are crucial to improve survival. The aim of this study was to describe clinical, laboratory, and radiological characteristics and outcomes of hospitalized COVID-19 patients compared to those with other infective or non-infective etiologies. We performed a prospective study from March 2020 to February 2021. All patients hospitalized for suspected or confirmed COVID-19 were prospectively recruited. All patients were evaluated according to a predefined protocol for diagnosis of suspected SARS-CoV-2 infection. The primary endpoint was evaluation of clinical, laboratory, and radiological characteristics associated or not with COVID-19 etiology at time of hospitalization in an emergency department. A total of 1036 patients were included in the study: 717 (69%) patients with confirmed COVID-19 and 319 (31%) without COVID-19, hospitalized for other causes. The main causes of hospitalization among non-COVID-19 patients were acute heart failure (44%) and bacterial pneumonia (45.8%). Overall, 30-day mortality was 9% among the COVID-19 group and 35% in the non-COVID-19 group. Multivariate analysis showed variables (fever > 3 days, dry cough, acute dyspnea, lymphocytes 250 ng/mL) independently associated with COVID-19 etiology. A decision tree was elaborated to early detect COVID-19 patients in the emergency department. Finally, Kaplan-Meier curves on 30-day survival in COVID-19 patients during the first wave (March-May 2020, n = 289 patients) and the second wave (October-February 2021, n = 428 patients) showed differences between the two study periods (p = 0.021). Patients with confirmed diagnosis of COVID-19 may show peculiar characteristics at time of hospitalization that could help physicians to distinguish from other infective or non-infective etiologies. Finally, a different 30-day mortality rate was observed during different periods of the pandemic

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Wastewater treatment plant based on membrane bioreactors (MBR) in a touristic locality

This paper is focused on a wastewater treatment plant based on MBR in an Italian touristic locality. The plant is designed for 5000 person equivalent (p.e.) in winter and 8200 p.e. in summer; it is made of primary treatments (screen, sand and grit removal, buffer tank, rotary drum screen), predenitrification (220 m3), oxidation (370 m3) with ferric chloride dosage, membrane tank (250 m3) equipped with Kubota plane membrane (total filtration area 3600 m2), deoxygenation tank (115 m3), disinfection with sodium hypochlorite, sludge thickening and dewatering by centrifugation. In 2012, on average basis the plant treated 733 m3d-1 wastewater with 442 mgL-1 COD, 253 mgL-1 BOD, 38.1 mgL-1 TKN; removal efficiencies were 86% for COD, 96% for BOD, 93% for TKN and 74% for total nitrogen. Permeate flux varied in the range 4 \u2013 24 Lm-2h-1 and negative pressure in the range 85 \u2013 300 mbar; membranes were backwashed with sodium hypochlorite once a month

Food Industry Wastewater Treatment Plant based on Flotation and MBBR

This paper deals with a plant that treats wastewater of an Italian food industry. The plant is made of a pumping station, a fine screen, an accumulation tank (182 m3), two parallel dissolved air flotation tanks with lamellae (each with footprint 5.6 m2, projected surface 14.4 m2, volume 3.4 m3), a hybrid MBBR oxidation tank (148 m3) filled with 35% AnoxKaldnesTM polyethylene carriers followed by an activated sludge oxidation tank (292 m3) and a sedimentation tank (surface 33 m2, volume 73 m3); sludge is thickened and dehydrated. On average basis, the plant has treated 152 m3/d wastewater with 9657 mg/L COD, 7848 mg/L BOD and 308 mg/L greases; the primary flotation has removed 64% of COD, 70% of BOD and 65% of greases; the whole plant has removed 97% of COD and 99% of greases, and has a significant residual capacity

Splanchnic Oxygenation at First Enteral Feeding in Preterm Infants: Correlation with Feeding Intolerance

Preterm infants are at risk of developing gastrointestinal complications such as feeding intolerance (FI) and necrotizing enterocolitis. Near-infrared spectroscopy (NIRS) provides continuous monitoring of abdominal oxygenation (ArSO2) and could help to predict gastrointestinal complications in preterm neonates. In this prospective observational study, ArSO2 patterns at first enteral feed were evaluated by NIRS in 61 clinically stable preterm infants. Splanchnic-cerebral oxygenation ratio (SCOR), which is a marker of gut hypoxia, was also calculated. ArSO2 and SCOR were significantly lower both at baseline and after feeding administration in infants who later developed FI (n\u200a=\u200a23). NIRS could help the early prediction of gastrointestinal complications in high-risk preterm infants