Search

Several computational studies on different water models reported evidence of a phase transition in supercooled conditions between two liquid states of water differing in density: the high-density liquid (HDL) and the low-density liquid (LDL). Yet, conclusive experimental evidence of the existence of a phase transition between the two liquid water phases could not be obtained due to fast crystallization in the region where the phase transition should occur. For the same reason, the investigation of possible transition mechanisms between the two phases is committed to computational investigations. In this work, we simulate an out-of-equilibrium temperature-induced transition from the LDL to the HDL-like state in the TIP4P/2005 water model. To structurally characterize the system relaxation, we use the node total communicability (NTC) we recently proposed as an effective order parameter to discriminate the two liquid phases differing in density. We find that the relaxation process is compatible with a spinodal-like scenario. We observe the formation of HDL-like domains in the LDL phase and we characterize their fluctuating behavior and subsequent coarsening and stabilization. Furthermore, we find that the formation of stable HDL-like domains is favored in the regions where the early formation of small patches of highly connected HDL-like molecules (i.e., with very high NTC values) is observed. Besides characterizing the LDL- to HDL-like relaxation from a structural point of view, these results also show that the NTC order parameter can serve as an early-time predictor of the regions from which the transition process initiates. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a cluster of risk factors, including abdominal obesity, insulin resistance, hypertension, dyslipidemia (intended as an increase in triglyceride levels and a reduction in HDL cholesterol levels), and elevated fasting glucose, that increase the risk of cardiovascular disease and type 2 diabetes. With the rising prevalence of metabolic syndrome, effective dietary interventions are essential in reducing these health risks. The Mediterranean diet, rich in fruits, vegetables, whole grains, legumes, nuts, and olive oil and moderate in fish and poultry, has shown promise in addressing metabolic syndrome and its associated components. This diet's anti-inflammatory and antioxidant properties, primarily due to its unsaturated fats, polyphenols, and fiber, have improved blood pressure, lipid levels, and insulin sensitivity. Adherence to the Mediterranean diet has been linked to reductions in central obesity and insulin resistance, both key elements in managing metabolic syndrome. Regarding lipid management, the Mediterranean diet lowers triglyceride levels and low-density lipoprotein (LDL) cholesterol while raising high-density lipoprotein (HDL) cholesterol, enhancing lipid profiles. It also helps regulate blood glucose levels, reducing the likelihood of developing type 2 diabetes. Additionally, the diet promotes weight loss and improves body composition, particularly by decreasing visceral fat, a primary driver of metabolic syndrome according to IDF classification. The Mediterranean diet offers a holistic approach to managing metabolic syndrome and reducing the risk of related chronic diseases. Its positive impact on metabolic health, combined with lifestyle changes like increased physical activity, provides a sustainable method for addressing the global burden of this syndrome. This review aimed to summarize the positive effects of the Mediterranean diet on the component of the metabolic syndrome with subsequent positive effects on cardiometabolic risk profile. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation is associated with several comorbidities, particularly cognitive impairment and dementia, especially in older patients. Non‐vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) were used to prevent thromboembolic events. However, data on the real benefit of these drugs on cognitive function decline remains controversial. In this study we evaluated the effect of NOACs compared to VKAs on the absolute and relative decline in cognitive function over time. Methods: Nine hundred and eighty‐three older patients with nonvalvular AF were enrolled (76 ± 6 years; 291 on VKAs and 692 on NOACs). The cognitive function was assessed with Mini Mental State examination (MMSE) score. The between‐arms difference of cognitive evolution over time was investigated by Linear Mixed Models and group‐based trajectory model analyses. Results: In the whole multicenter observational study, after a long follow‐up of 7.2 ± 3.4 years, the patients of the NOACs versus VKAs group had lowest absolute reduction of the MMSE score between baseline and follow‐up (−0.3 ± 0.03 vs.−1.7 ± 0.1, p < 0.001). After stratification into five subgroups according to trajectories of MMSE score over time, the probability to belong to trajectories with lower decline in cognitive functions was higher in patients on NOACs than in those on VKAs (3.93–13.88 times). Conclusion: In older patients with atrial fibrillation, the use of NOACs was associated with a smaller decline of cognitive function over time compared to the VKAs, regardless that patients in the NOACs group were older and with a higher burden of comorbidities. [ABSTRACT FROM AUTHOR]

We investigate the potential of surface plasmon polaritons at noble metal interfaces for surface-enhanced chiroptical sensing of dilute chiral drug solutions with nl volume. The high quality factor of surface plasmon resonances in both Otto and Kretschmann configurations enables the enhancement of circular dichroism differenatial absorption thanks to the large near-field intensity of such plasmonic excitations. Furthermore, the subwavelength confinement of surface plasmon polaritons is key to attain chiroptical sensitivity to small amounts of drug volumes placed around ≃100 nm by the metal surface. Our calculations focus on reparixin, a pharmaceutical molecule currently used in clinical studies for patients with community-acquired pneumonia, including COVID-19 and acute respiratory distress syndrome. Considering realistic dilute solutions of reparixin dissolved in water with concentration ≤ 5 mg/ml and nl volume, we find a circular-dichroism differential absorption enhancement factor of the order ≃20 and chirality-induced polarization distortion upon surface plasmon polariton excitation. Our results are relevant for the development of innovative chiroptical sensors capable of measuring the enantiomeric imbalance of chiral drug solutions with nl volume. [ABSTRACT FROM AUTHOR]

In this paper, we apply a theoretical model for fluid state thermodynamics to investigate simulated water in supercooled conditions. This model, which we recently proposed and applied to sub- and super-critical fluid water [Zanetti-Polzi et al., J. Chem. Phys. 156(4), 44506 (2022)], is based on a combination of the moment-generating functions of the enthalpy and volume fluctuations as provided by two gamma distributions and provides the free energy of the system as well as other relevant thermodynamic quantities. The application we make here provides a thermodynamic description of supercooled water fully consistent with that expected by crossing the liquid–liquid Widom line, indicating the presence of two distinct liquid states. In particular, the present model accurately reproduces the Widom line temperatures estimated with other two-state models and well describes the heat capacity anomalies. Differently from previous models, according to our description, a cluster of molecules that extends beyond the first hydration shell is necessary to discriminate between the statistical fluctuation regimes typical of the two liquid states. [ABSTRACT FROM AUTHOR]

Introduction: Penile metastases (PMs) are a rare clinical presentation mainly related to advanced stages of disease. Considering the low incidence, an optimal treatment approach has not yet been defined; surgery, chemotherapy, and radiotherapy (RT) are different options used in the vast majority with palliative intent. The advances in modern RT can represent an innovative tool in PM management and a curative option. This paper aimed to report the case of a PM patient treated with stereotactic body radiotherapy (SBRT) and perform a systematic literature review of current evidence on the RT approach to PM. Case Presentation: We reported the case of an 80-year-old patient with PM from primary bladder cancer. Following the surgical approach for the primary tumor, evidence of PM was shown, and the patient was admitted to SBRT treatment on PM after an adjuvant RT course on the pelvis. A 25 Gy in 5-fraction SBRT treatment was performed, and a complete clinical response was shown at the first follow-up. A PubMed/MEDLINE and Embase systematic review was carried out. The search strategy terms were [("penile metastasis"/exp OR "penile metastasis" OR (penile AND ("metastasis"/exp OR metastasis))) AND ("radiotherapy"/exp OR radiotherapy)] and only original articles up to October 24, 2023 were considered. Conclusion: A total of 174 studies were obtained using the previously mentioned search strategy, and the analysis was performed on 15 papers obtained following the complete selection process. All reported evidence was focused on the palliative approach of PM, showing good results in terms of symptom control. The potential role of modern RT in the management of PM has yet to be defined. The reported case showed the feasibility and the clinical impact of SBRT in PM treatment. [ABSTRACT FROM AUTHOR]

The improvement of the extra virgin olive oil (EVOO) extraction process involves the proper management of endogenous enzymes of the olive fruit and all the technological conditions that can affect their activities. Coratina and Peranzana cultivars were processed to assess the influence of different technologies for fruit breaking (crushing and stoning) with and without controlled oxygen addition during this critical phase. The study of volatile compounds revealed that the enzymes that are responsible for their genesis during the technological process were significantly affected by oxygen addition in both the systems of fruit crushing. The results from the stoning technology proved that the quality improvement was a consequence of the prevention of the seed breaking and the oxidation catalyzed by the olive stone enzymes. In Peranzana EVOOs, it was possible to increase the aldehyde concentration up to 97% using stoning technology with a 0.2 L/min oxygen addition compared with traditional crushing. At the same time, non-significant reductions in phenolic compounds were detected when comparing crushing and stoning with and without the addition of oxygen, and similar trends were observed for the two studied cultivars. The sensory analyses confirmed the differences in phenolic and volatile composition detected in the EVOO samples. [ABSTRACT FROM AUTHOR]

Acrylamide (AA) is a contaminant resulting from the Maillard reaction and classified by the International Agency for Research on Cancer (IARC) as a probable carcinogen in Group 2A, with proven neurotoxic effects on humans. European Union (EU) Regulation No. 2017/2158 is currently in force, which establishes measures meant to reduce AA levels in food and sets reference values, but not legal limits, equal to 40 and 150 μg/kg AA in processed cereal-based foods intended for infants and young children and in biscuits and rusks, respectively. For this reason, sixty-two baby foods were analyzed using ultra-high performance liquid chromatography with diode array detector and quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q-TOF/MS) to check whether industries were complying with these values, even though AA control is not legally mandatory. In total, 14.5% of the samples exceeded the reference values; these were homogenized chicken products (211.84 ± 16.53, 154.32 ± 12.71, 194.88 ± 7.40 μg/kg), three biscuits (276.36 ± 0.03, 242.06 ± 0.78, 234.78 ± 4.53 μg/kg), a wheat semolina (46.07 ± 0.23 μg/kg), a homogenized product with plaice and potatoes (45.52 ± 0.28 μg/kg), and a children's snack with milk and cocoa (40.95 ± 0.32 μg/kg). Subsequently, the daily intake of AA was estimated, considering the worst-case scenario, as provided by the consumption of homogenized chicken products and biscuits. The results are associated with margins of exposure (MOEs) that are not concerning for neurotoxic effects but are alarming for the probable carcinogenic effects of AA. [ABSTRACT FROM AUTHOR]

Estimating the kinetics of electron transfer (ET) processes in biologically relevant systems using theoretical‐computational methods remains a formidable task. This challenge arises from the inherent complexity of these systems, which makes it impractical to apply a fully quantum‐mechanical treatment. Hybrid quantum mechanical/classical mechanical computational approaches have been devised to enable the explicit simulation of electron transfer kinetics. This concept article focuses on a specific theoretical‐computational method employed in this context, namely the Perturbed Matrix Method (PMM), which has the merit of being able to include large‐scale conformational effects in the ET kinetics and potential multiple, alternative, ET channels. We describe its underlying physical principles, examine its advantages and limitations, and offer insights into its applications. Examples of the approach are discussed in the context of estimating photo‐induced electron transfer kinetics in proteins. The non‐exponential behavior observed in the presented case studies mainly arises from an active coupling with the environment fluctuations, but also partly stems from the presence of branching ET pathways. [ABSTRACT FROM AUTHOR]

Background: A randomized clinical trial to evaluate the effect of a Mediterranean-style diet on vascular health indices such as endothelial function indices, serum lipid and ceramide plasma and some adipokine serum levels. We recruited all consecutive patients at high risk of cardiovascular diseases admitted to the Internal Medicine and Stroke Care ward at the University Hospital of Palermo between September 2017 and December 2020. Materials and methods: The enrolled subjects, after the evaluation of the degree of adherence to a dietary regimen of the Mediterranean-style diet, were randomised to a Mediterranean Diet (group A) assessing the adherence to a Mediterranean-style diet at each follow up visit (every three months) for the entire duration of the study (twelve months) and to a Low-fat diet (group B) with a dietary "counselling" starting every three months for the entire duration of the study (twelve months).The aims of the study were to evaluate: the effects of adherence to Mediterranean Diet on some surrogate markers of vascular damage, such as endothelial function measured by means of the reactive hyperaemia index (RHI) and augmentation index (AIX), at the 6-(T1) and 12-month (T2) follow-ups; the effects of adherence to Mediterranean Diet on the lipidaemic profile and on serum levels of ceramides at T1 and T2 follow-ups; the effects of adherence to Mediterranean Diet on serum levels of visfatin, adiponectin and resistin at the 6- and 12-month follow-ups. Results: A total of 101 patients were randomised to a Mediterranean Diet style and 52 control subjects were randomised to a low-fat diet with a dietary "counselling". At the six-month follow-up (T1), subjects in the Mediterranean Diet group showed significantly lower mean serum total cholesterol levels, and significantly higher increase in reactive hyperaemia index (RHI) values compared to the low-fat diet group. Patients in the Mediterranean Diet group also showed lower serum levels of resistin and visfatin at the six-month follow-up compared to the control group, as well as higher values ​​of adiponectin, lower values of C24:0, higher values of C22:0 and higher values of the C24:0/C16:0 ratio. At the twelve-month follow-up (T2), subjects in the Mediterranean Diet group showed lower serum total cholesterol levels and lower serum LDL cholesterol levels than those in the control group. At the twelve-month follow-up, we also observed a further significant increase in the mean RHI in the Mediterranean Diet group, lower serum levels of resistin and visfatin, lower values of C24:0 and of C:18:0,and higher values of the C24:0/C16:0 ratio. Discussion: The findings of our current study offer a further possible explanation with regard to the beneficial effects of a higher degree of adherence to a Mediterranean-style diet on multiple cardiovascular risk factors and the underlying mechanisms of atherosclerosis. Moreover, these findings provide an additional plausible interpretation of the results from observational and cohort studies linking high adherence to a Mediterranean-style diet with lower total mortality and a decrease in cardiovascular events and cardiovascular mortality. Trial registration: ClinicalTrials.gov Identifier: NCT04873167. https://classic.clinicaltrials.gov/ct2/show/NCT04873167. [ABSTRACT FROM AUTHOR]

Water's anomalous behavior is often explained using a two-liquid model, where two types of water, high-density liquid (HDL) and low-density liquid (LDL), can be separated via a liquid–liquid phase transition (LLPT) at low temperature. Mixtures of water and the ionic liquid hydrazinium trifluoroacetate were suggested to also show an LLPT but with the advantage that there is no rapid ice crystallization hampering its observation. It remains controversial whether these solutions exhibit an LLPT or are instead associated with complex phase separation phenomena. We here show detailed low-temperature calorimetry and diffraction experiments on aqueous solutions containing hydrazinium trifluoroacetate and other similar ionic liquids, all at a solute mole fraction of x = 0.175. Hydrazinium trifluoroacetate, ammonium trifluoroacetate, ethylammonium trifluoroacetate and hydrazinium pentafluoropropionate all boast exothermic transitions unrelated to crystallization as well as remarkable structural changes upon cooling into the glassy state. We propose a model inspired by micelle formation and decomposition in surfactant solutions, which is complemented by MD simulations and allows rationalizing the rich phase behavior of our mixtures during cooling. The fundamental aspect of the model is the hydrophobic nature of fluorinated anions that enables aggregation, which is reversed upon cooling and culminates in the remarkable exothermic first-order transition observed at low temperature. That is, we assign the first-order transition not to an LLPT but to phase-separations similar to the ones when falling below the Krafft temperature. All other solutions merely show simple vitrification behavior. Still, they exhibit distinct differences in liquid fragility, which is decreased continuously with decreasing hydrophobicity of the anions. This might enable the systematic tuning of ionic liquids with the goal of designing aqueous solutions of specific fragility. [ABSTRACT FROM AUTHOR]

We propose in this paper a theoretical model for fluid state thermodynamics based on modeling the fluctuation distributions and, hence, the corresponding moment generating functions providing the free energy of the system. Using the relatively simple and physically coherent gamma model for the fluctuation distributions, we obtain a complete theoretical equation of state, also giving insight into the statistical/molecular organization and phase or pseudo-phase transitions occurring under the sub- and super-critical conditions, respectively. Application to sub- and super-critical fluid water and a comparison with the experimental data show that this model provides an accurate description of fluid water thermodynamics, except close to the critical point region where limited but significant deviations from the experimental data occur. We obtain quantitative evidence of the correspondence between the sub- and super-critical thermodynamic behaviors, with the super-critical water pseudo-liquid and pseudo-gas phases being the evolution of the sub-critical water liquid and gas phases, respectively. Remarkably, according to our model, we find that for fluid water the minimal subsystem corresponding to either the liquid-like or the gas-like condition includes an infinite number of molecules in the sub-critical regime (providing the expected singularities due to macroscopic phase transitions) but only five molecules in the super-critical regime (coinciding with the minimal possible hydrogen-bonding cluster), thus suggesting that the super-critical regime be characterized by the coexistence of nanoscopic subsystems in either the pseudo-liquid or the pseudo-gas phase with each subsystem fluctuating between forming and disrupting the minimal hydrogen-bonding network. [ABSTRACT FROM AUTHOR]

The most intriguing hypothesis explaining many water anomalies is a metastable liquid–liquid phase transition (LLPT) at high pressure and low temperatures, experimentally hidden by homogeneous nucleation. Recent infrared spectroscopic experiments showed that upon addition of hydrazinium trifluoroacetate to water, the supercooled ionic solution undergoes a sharp, reversible LLPT at ambient pressure, possible offspring of that in pure water. Here, we calculate the temperature-dependent signature of the OH-stretching band, reporting on the low/high density phase of water, in neat water and in the same experimentally investigated ionic solution. The comparison between the infrared signature of the pure liquid and that of the ionic solution can be achieved only computationally, providing insight into the nature of the experimentally observed phase transition and allowing us to investigate the effects of ionic compounds on the high to low density supercooled liquid water transition. We show that the experimentally observed crossover behavior in the ionic solution can be reproduced only if the phase transition between the low- and high-density liquid states of water is coupled to a mixing–unmixing transition between the water component and the ions: at low temperatures, water and ions are separated and the water component is a low density liquid. At high temperatures, water and ions get mixed and the water component is a high-density liquid. The separation at low temperatures into ion-rich and ion-poor regions allows unveiling the polyamorphic nature of liquid water, leading to a crossover behavior resembling that observed in supercooled neat water under high pressure. [ABSTRACT FROM AUTHOR]

Recent advances in the olive oil sector aim to develop sustainable strategies for the valorisation of mechanical extraction co-products as a rich source of bioactive compounds with antioxidant and antimicrobial activities. In this work, we studied the effectiveness of a phenolic extract (PE) from olive vegetation water (OVW) as a new antioxidant of natural origin for improving the quality and extending the secondary shelf life (SSL) of a fresh basil pesto sold as a served loose product at the deli counter, simulating the storage conditions after packaging, opening, and serving. For that, the PE was mixed with the oily phase of fresh pesto in two different concentrations and compared to a control pesto (CTRL) made with the addition of common additives (ascorbic acid (E300) and sorbic acid (E200)). The physicochemical parameters, phenolic and volatile composition, sensory profiles, and antioxidant capacity of the experimental pesto samples were evaluated after opening. The results proved that the enrichment with the PE improved the stability of the pesto and, hence, its overall quality. The PE provided higher protection than the CTRL against primary and secondary oxidation at both concentrations tested and delayed the accumulation of the volatile compounds responsible for the 'rancid' off-flavour up to 7 days after first opening, while also preserving higher levels of the pesto phytonutrients (such as the rosmarinic, caffeic, and chicoric acids and α-tocopherol). These results show that the generation of food waste in households, catering chains, retail, and/or restaurants can be reduced, improving the sustainability of the food industry and the competitiveness of the olive oil sector. [ABSTRACT FROM AUTHOR]

We study how participation in various social protection schemes can mitigate the negative relationship between adverse rainfall shocks and agricultural production, thus acting as a tool for climate change adaptation. We use panel data from Ethiopia, analyzing the influence of these programs on the technical efficiency of smallholder farmers and how these effects on agricultural production change in the presence adverse rainfall shocks. We find heterogeneous effects of social protection. Public works are negatively associated with productive efficiency, especially in the presence of negative shocks. Recipients of free food display higher sales and profits while cash transfers are more neutral to production and positively associated with farming profitability. [ABSTRACT FROM AUTHOR]

Background: The autonomic nervous system is linked to hyperdynamic circulation in cirrhosis and several studies have highlighted the crucial role that systemic inflammation elicits in altering sympathovagal equilibrium with the consequent reduction in heart rate variability (HRV). To investigate the correlation between time‐domain HRV parameters, serum cytokines concentrations and portal hypertension, we studied a cohort of patients with cirrhosis, accounting for etiology and treatments. Methods: In this cross‐sectional, observational cohort study, 107 outpatients with non‐alcoholic cirrhosis were assessed consecutively by abdominal ultrasound and by upper gastrointestinal endoscopy to search for esophagogastric varices. 24‐h electrocardiogram Holter monitoring with time‐domain HRV measurement (square root of the mean of successive differences of Normal‐to‐Normal [NN] [RMSSD], standard deviation or the square root of variance [SDNN] and standard deviation of the means of the NN intervals calculated over a 5‐min period [SDANN]) was performed and serum concentrations of osteopontin (OPN), interleukin (IL)‐22, IL‐6, IL‐1Ra and IL‐17 were obtained in all patients. Results: IL‐6, OPN, IL‐22 and IL‐1Ra concentrations in cirrhotic patients were associated with disease severity expressed by Child‐Pugh and MELD score, to some portal hypertension's indirect signs and some of its complications. A significant increase in systemic concentrations of OPN in patients with hepatocellular carcinoma was encountered. SDANN and SDNN values were indirectly related to serum levels of IL‐6, OPN, IL‐1Ra and IL‐22. Conclusions: This study underlines the interaction between the alteration of the ANS and the activation of inflammatory pathways that characterize cirrhosis taking into account clinical characteristics and treatments. [ABSTRACT FROM AUTHOR]

Infrared spectroscopy is a widely used technique to characterize protein structures and protein mediated processes. While the amide I band provides information on proteins' secondary structure, amino acid side chains are used as infrared probes for the investigation of protein reactions and local properties. In this paper, we use a hybrid quantum mechanical/classical molecular dynamical approach based on the perturbed matrix method to compute the infrared band due to the C=O stretching mode of amide-containing side chains. We calculate, at first, the infrared band of zwitterionic glutamine in water and obtain results in very good agreement with the experimental data. Then, we compute the signal arising from glutamine side chains in a microcrystal of the yeast prion Sup35-derived peptide, GNNQQNY, with a fibrillar structure. The infrared bands obtained by selective isotopic labeling of the two glutamine residues, Q4 and Q5, of each peptide were experimentally used to investigate the local hydration in the fibrillar microcrystal. The experimental spectra of the two glutamine residues, which experience different hydration environments, feature different spectral signals that are well reproduced by the corresponding calculated spectra. In addition, the analysis of the simulated spectra clarifies the molecular origin of the experimentally observed spectroscopic differences that arise from the different local electric field experienced by the two glutamine residues, which is, in turn, determined by a different hydrogen bonding pattern. [ABSTRACT FROM AUTHOR]

Background: SARS- CoV-2 virus has had dramatic consequences worldwide being able to cause acute respiratory distress syndrome (ARDS), massive thrombosis and pulmonary embolism and, finally, patients' death. In COVID-19 infection, platelets have a procoagulant phenotype that can cause thrombosis in the pulmonary and systemic vascular network. Aspirin is a well-known anti-platelet drug widely used for the prevention of cardiovascular events and systematic reviews suggest a possible benefit of low-dose aspirin (LDA) use in the prevention and treatment of ARDS in patients with COVID-19 infection. However, several studies are available in the literature which do not support any benefits and no association with the patients' outcome. Therefore, currently available data are inconclusive. Materials and patients: Data from the nationwide cohort multicenter study of the Italian Society of Internal Medicine (SIMI) were analyzed. We conducted a propensity score-matched cohort analysis to investigate the impact of chronic assumption of LDA on mortality of adult COVID-19 patients admitted in Internal Medicine Units (IMU). Data from 3044 COVID-19 patients who referred to 41 Italian hospitals between February 3rd to May 8th 2020 were analyzed. A propensity score-matched analysis was conducted using the following variables: age, sex, hypertension, hyperlipidemia diabetes, atrial fibrillation, cerebrovascular disease, COPD, CKD and stratified upon LDA usage, excluding anticoagulant treatment. After matching, 380 patients were included in the final analysis (190 in LDA group and 190 in no-LDA group). Results: 66.2% were male, median age was 77 [70–83]. 34.8% of the population died during the hospitalization. Cardiovascular diseases were not significantly different between the groups. After comparison of LDA and no-LDA subgroups, we didn't record a significant difference in mortality rate (35.7% vs 33.7%) duration of hospital stay and ICU admission. In a logistic regression model, age (OR 1.05; 95% CI 1.01–1.09), FiO2 (OR 1.024; 95% CI 1.03–1.04) and days between symptoms onset and hospitalization (OR 0.93; 95% CI 0.87–0.99) were the only variables independently associated with death. [ABSTRACT FROM AUTHOR]

Background: The addition of organic solvents to an aqueous medium for enzymatic reactions offers several advantages, as they can increase the solubility of substrates but can also lead to enzyme inactivation and/or aggregation. Results: The effect of adding 30% of several water‐soluble organic solvents on the catalytic activity of lipase B from Candida antarctica (CalB) was studied and the results showed that the highest activity was obtained with the addition of t‐butanol. t‐Butanol and acetonitrile were selected and the kinetic parameters, determined to deepen their effect on CalB activity, showed that the addition of acetonitrile improved the enzyme–substrate affinity, while water–t‐butanol mixtures led to a more than ninefold increase in kcat. To rationalize at a molecular level the kinetic results, molecular dynamic simulations were performed. Analysis of the accessibility of the active‐site cavity, solvent occupancy in the site and in the oxyanion hole, and the stability of the catalytic triad in the two solvent mixtures, provided insight into their effects on the catalytic properties of CalB. Conclusion: The lower occupancy in the oxyanion hole of water molecules and a shorter residence time in the active site of acetonitrile molecules in the acetonitrile–water mixture contribute to the higher enzyme–substrate affinity found experimentally. Conversely, the higher kcat in the t‐butanol mixture is explained by the higher stability of the catalytic triad and by an increase in the nucleophilicity of the catalytic serine due to the persistent presence of t‐butanol molecules in the active site. © 2023 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Background: The favorable role of SBRT for lymph-nodal oligometastases from prostate cancer has been reported by several retrospective and prospective experiences, suggesting a more indolent natural history of disease when compared to patients with bone oligometastases. This retrospective multicenter study evaluates the outcomes of a cohort of patients treated with stereotactic body radiotherapy for lymph-nodal oligometastases. Methods: Inclusion criteria were up to five lymph-nodal oligometastases detected either with Choline-PET or PSMA-PET in patients naïve for ADT or already ongoing with systemic therapy and at least 6 Gy per fraction for SBRT. Only patients with exclusive lymph-nodal disease were included. The primary endpoint of the study was LC; a toxicity assessment was retrospectively performed following CTCAE v4.0. Results: A total of 100 lymph-nodal oligometastases in 69 patients have been treated with SBRT between April 2015 and November 2022. The median age was 73 years (range, 60–85). Oligometastatic disease was mainly detected with Choline-PET in 47 cases, while the remaining were diagnosed using PSMA-PET, with most of the patients treated to a single lymph-nodal metastasis (48/69 cases), two in 14 cases, and three in the remaining cases. The median PSA prior to SBRT was 1.35 ng/mL (range, 0.3–23.7 ng/mL). Patients received SBRT with a median total dose of 35 Gy (range, 30–40 Gy) in a median number of 5 (range, 3–6) fractions. With a median follow-up of 16 months (range, 7–59 months), our LC rates were 95.8% and 86.3% at 1 and 2 years. DPFS rates were 90.4% and 53.4%, respectively, at 1 and 2 years, with nine patients developing a sequential oligometastatic disease treated with a second course of SBRT. Polymetastatic disease-free survival (PMFS) at 1 and 2 years was 98% and 96%. Six patients needed ADT after SBRT for a median time of ADT-free survival of 15 months (range, 6–22 months). The median OS was 16 months (range, 7–59) with 1- and 2-year rates of both 98%. In multivariate analysis, higher LC rates and the use of PSMA-PET were related to improved DPFS rates, and OS was significantly related to a lower incidence of distant progression. No G3 or higher adverse events were reported. Conclusions: In our experience, lymph-nodal SBRT for oligometastatic prostate cancer is a safe and effective option for ADT delay with no severe toxicity. [ABSTRACT FROM AUTHOR]

The quality of commercially available extra-virgin olive oils (VOOs) of different chemical compositions was evaluated as a function of storage (12 months), simulating market storage conditions, to find reliable and early markers of the virgin olive oil (VOOs) quality status in the market. By applying a D-optimal design using the Most Descriptive Compound (MDC) algorithm, 20 virgin olive oils were selected. The initial concentrations of oleic acid, hydrophilic phenols, and α-tocopherol in the 20 VOOs ranged from 58.2 to 80.5%, 186.7 to 1003.2 mg/kg, and 170.7–300.6 mg/kg, respectively. K270, ∆K, (E, E)-2.4-decadienal and (E)-2-decenal, and the oxidative form of the oleuropein aglycon (3,4-DHPEA-EA-OX) reflected the VOO quality status well, with 3,4-DHPEA-EA-OX being the most relevant and quick index for simple monitoring of the "extra-virgin" commercial shelf-life category. Its HPLC-DAD evaluation is easy because of the different wavelength absorbances of the oxidized and non-oxidized form (3,4-DHPEA-EA), respectively, at 347 and 278 nm. [ABSTRACT FROM AUTHOR]

This study examined the accuracy of English-speaking learners of Spanish in storing L2 sounds within cognates and noncognates, specifically in words containing 〈g〉 and 〈h〉, which have differing cross-linguistic phoneme-grapheme correspondences. In the first task, participants heard Spanish words with target-like pronunciations of 〈g〉 and 〈h〉 or inaccurate pronunciations with an English-like phonemic substitution for these graphemes, and they decided whether or not they were words. The second task had participants decide between the two pronunciations of each Spanish word and select the accurate pronunciation. The findings in both tasks showed that for L2 learners, 〈h〉 cognate words had less accurate phonological representations compared to all other conditions, possibly due to the greater consistency in phoneme-grapheme correspondence for 〈h〉 in English. These results show that cognate status and orthographic (in)congruity interact to influence the accuracy of L2 lexical encoding. [ABSTRACT FROM AUTHOR]

Metamorphic, or fold-switching, proteins feature different folds that are physiologically relevant. The human chemokine XCL1 (or Lymphotactin) is a metamorphic protein that features two native states, an α - β and an all - β fold, which have similar stability at physiological condition. Here, extended molecular dynamics (MD) simulations, principal component analysis of atomic fluctuations and thermodynamic modeling based on both the configurational volume and free energy landscape, are used to obtain a detailed characterization of the conformational thermodynamics of human Lymphotactin and of one of its ancestors (as was previously obtained by genetic reconstruction). Comparison of our computational results with the available experimental data show that the MD-based thermodynamics can explain the experimentally observed variation of the conformational equilibrium between the two proteins. In particular, our computational data provide an interpretation of the thermodynamic evolution in this protein, revealing the relevance of the configurational entropy and of the shape of the free energy landscape within the essential space (i.e., the space defined by the generalized internal coordinates providing the largest, typically non-Gaussian, structural fluctuations). [ABSTRACT FROM AUTHOR]

Photosystem‐II (PSII) is a multi‐subunit protein complex that harvests sunlight to perform oxygenic photosynthesis. Initial light‐activated charge separation takes place at a reaction centre consisting of four chlorophylls and two pheophytins. Understanding the processes following light excitation remains elusive due to spectral congestion, the ultrafast nature, and multi‐component behaviour of the charge‐separation process. Here, using advanced computational multiscale approaches which take into account the large‐scale configurational flexibility of the system, we identify two possible primary pathways to radical‐pair formation that differ by three orders of magnitude in their kinetics. The fast (short‐range) pathway is dominant, but the existence of an alternative slow (long‐range) charge‐separation pathway hints at the evolution of redundancy that may serve other purposes, adaptive or protective, related to formation of the unique oxidative species that drives water oxidation in PSII. [ABSTRACT FROM AUTHOR]

Photosystem‐II (PSII) is a multi‐subunit protein complex that harvests sunlight to perform oxygenic photosynthesis. Initial light‐activated charge separation takes place at a reaction centre consisting of four chlorophylls and two pheophytins. Understanding the processes following light excitation remains elusive due to spectral congestion, the ultrafast nature, and multi‐component behaviour of the charge‐separation process. Here, using advanced computational multiscale approaches which take into account the large‐scale configurational flexibility of the system, we identify two possible primary pathways to radical‐pair formation that differ by three orders of magnitude in their kinetics. The fast (short‐range) pathway is dominant, but the existence of an alternative slow (long‐range) charge‐separation pathway hints at the evolution of redundancy that may serve other purposes, adaptive or protective, related to formation of the unique oxidative species that drives water oxidation in PSII. [ABSTRACT FROM AUTHOR]

Background: The cardiovascular risk (CVD) in patients with rheumatoid arthritis (RA) is 1.5–2 times higher than that in individuals of the same age and sex. Aims: To analyse the degree of endothelial dysfunction, the atherogenic immunoinflammatory serum background and the relationships among some vascular indices, cardiovascular comorbidities, and cognitive performance in subjects with RA. Patients and methods: All consecutive patients with a rheumatoid arthritis diagnosis admitted to the Rheumatology Ward of "Policlinico Paolo Giaccone" Hospital of Palermo were enrolled from July 2019 to September 2020. We evaluated our patients' cognitive functions by administering the Mini-Mental State Examination (MMSE). Reactive Hyperaemia Index (RHI) was evaluated for assessment of endothelial function. Serum levels of angiopoietin 2, osteopontin and pentraxin 3 were assessed by blood collection. Results: Fifty-eight consecutive patients with RA and 40 control subjects were analysed. RA patients showed significantly lower mean RHI values, significantly higher mean Augmentation Index (AIX) values and significantly lower mean Mini-Mental State Examination (MMSE) score values than the control group. Patients with rheumatoid arthritis also showed higher mean serum values of pentraxin 3 and angiopoietin 2 than healthy controls. Multivariate logistic regression analysis showed a significant association between pentraxin 3 and angiopoietin 2 and the presence of RA. Discussion: Angiopoietin 2 and pentraxin 3 could be considered surrogate biomarkers of endothelial activation and vascular disease, as they could play an essential role in the regulation of endothelial integrity and inflammation. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer (BC) is one of the most common tumors; better screening policies and multidisciplinary approach allow personalized treatment. Radiotherapy (RT) plays a central role in the multimodal approach in BC, and recent evidence has shown the non-inferiority of hypofractionated treatments. The aim of this study was to describe the feasibility and validity of stereotactic RT (SBRT) in BC in a neoadjuvant and exclusive setting. Methods: A PubMed/MEDLINE and Embase systematic review was conducted to assess the role of radiomics in BC. The search strategy was "breast [All Fields] AND "stereotactic" [All Fields] AND "radiotherapy" [All Fields]" and only original articles referred to BC in humans in the English language were considered. Results: A total of 2,149 studies were obtained using the mentioned search strategy on PubMed and Embase. After the complete selection process, a total of 12 papers were considered eligible for the analysis of the results. SBRT in BC was described in 8 studies regarding neoadjuvant approach and 4 papers regarding exclusive approach. Conclusions: Relative low toxicity rates, the reduced treatment volumes in the neoadjuvant setting, and the possibility to replace surgery when not feasible in exclusive setting resulted to be main advantages for SBRT in BC. Current evidence shows that both the neoadjuvant and the definitive settings seem to be promising clinical scenarios for SBRT, especially for EBC. [ABSTRACT FROM AUTHOR]

We present findings from a study of the local-economy impacts of Lesotho's Child Grants Programme and of a multi-faceted rural development intervention. We designed a micro-data parameterised general equilibrium model and used it to simulate the direct and indirect impacts of the two interventions, considering income and production spillovers. The Child Grants Programme, alone and in combination with the rural development programme, generates total discounted benefits that exceed discounted programme costs. Local-economy spillovers amplify the benefit-cost ratio of both cash transfers and productive interventions. By better integrating with outside markets, it is possible to attain substantial cost-effective income gains for local economies. [ABSTRACT FROM AUTHOR]

Introduction: Autonomic nervous system activity in cirrhotic portal hypertension is linked to hyperdynamic circulation. Heart rate variability (HRV) is a validated noninvasive method to assess the sympathovagal balance. To investigate the correlation between HRV parameters and degree of portal hypertension, we studied a cohort of patients with cirrhosis accounting for etiology and treatments. Patients and Methods: In this cross-sectional, observational cohort study, 157 outpatients of both sex with nonalcoholic cirrhosis were assessed by upper gastrointestinal endoscopy to search for esophagogastric varices. Twenty-four-hour electrocardiogram Holter monitoring with 3 HRV parameters measurement [SD of the NN intervals, root mean square successive difference of NN intervals, and SD of the averages of NN intervals (SDANN)] according to time-domain analysis were performed in all patients. Sixteen patients with large esophagogastric varices underwent measurements of the HVPG and assessment of HRV parameters at baseline and after 45 days on carvedilol. Results: The liver dysfunction, expressed by Child-Pugh class or MELD score, was directly related to root mean square successive difference of NN intervals and inversely related to SDANN. Presence of ascites was inversely related to SDANN and to SD of the NN intervals. Treatment with carvedilol had an inverse relation with SDANN. Presence and size of esophagogastric varices had an inverse relation to SDANN and SD of the NN intervals. Upon multivariate analysis the associations between SDANN and Child-Pugh class, size of varices and ascites were confirmed. In the subgroup of 16 patients undergoing HVPG measurement, pressure gradient was unrelated to heart rate and HRV parameters. Conclusions: Time-domain HRV parameters in patients with cirrhosis, confirm the autonomic nervous system alteration, and their correlation to the degree of portal hypertension suggesting a role of the ANS in hepatic decompensation. [ABSTRACT FROM AUTHOR]

Thalassemia is a Mendelian inherited blood disease caused by α- and β-globin gene mutations, known as one of the major health problems of Mediterranean populations. Here, we examined the distribution of α- and β-globin gene defects in the Trapani province population. A total of 2,401 individuals from Trapani province were enrolled from January 2007 to December 2021, and routine methodologies were used for detecting the α- and β-globin genic variants. Appropriate analysis was also performed. Eight mutations in the α globin gene showed the highest frequency in the sample studied; three of these genetic variants represented the 94% of the total α-thalassemia mutations observed, including the −α3.7 deletion (76%), and the tripling of the α gene (12%) and of the α2 point mutation IVS1-5nt (6%). For the β-globin gene, 12 mutations were detected, six of which constituted 83.4% of the total number of β-thalassemia defects observed, including codon β039 (38%), IVS1.6 T > C (15.6%), IVS1.110 G > A (11.8%), IVS1.1 G > A (11%), IVS2.745 C > G (4%), and IVS2.1 G > A (3%). However, the comparison of these frequencies with those detected in the population of other Sicilian provinces did not demonstrate significant differences, but it contrarily revealed a similitude. The data presented in this retrospective study help provide a picture of the prevalence of defects on the α and β-globin genes in the province of Trapani. The identification of mutations in globin genes in a population is required for carrier screening and for an accurate prenatal diagnosis. It is important and necessary to continue promoting public awareness campaigns and screening programs. [ABSTRACT FROM AUTHOR]

Liquid water, besides being fundamental for life on Earth, has long fascinated scientists due to several anomalies. Different hypotheses have been put forward to explain these peculiarities. The most accredited one foresees the presence in the supercooled region of two phases at different densities: the low-density liquid phase and the high-density liquid phase. In our previous work [Faccio et al. (2022), J. Mol. Liq. , 355 , 118922], we showed that it is possible to identify these two forms in water networks through a computational approach based on molecular dynamics simulation and on the calculation of the total communicability of the associated graph, in which the nodes correspond to water molecules and the edges represent the connections (interactions) between molecules. In this article, we present a more in-depth investigation of the application of graph-theory based approaches to the analysis of the structure of water networks. In particular, we investigate different connectivity and centrality measures and we report on the use of a variety of global metrics aimed at giving a topological and geometrical characterization of liquid water. [ABSTRACT FROM AUTHOR]

I teach an upper-division Spanish pronunciation course, which has several objectives: to raise students' awareness of their pronunciation and help them improve it; to guide students toward an appreciation of the difference between intelligibility, comprehensibility, and accentedness and the pronunciation features that are most likely to map onto each dimension of speech; and to introduce students to regional variation in Spanish pronunciation. The goals of this class are for students to be able to talk about basic principles of phonetics and phonology with appropriate terminology, explain how Spanish sounds are articulated and how they are different from English sounds, describe and recognize regional and social variation in Spanish pronunciation, recognize and apply sound-spelling correspondences in their own pronunciation and listening comprehension, use Praat to analyze their own speech and that of others, and recognize features of non-native pronunciation and apply strategies to reduce them. I created a map task to practice various Spanish sound-spelling correspondences that can be difficult for English speakers. I use these two resources to showcase variation in pronunciation and to help students improve their own pronunciation. [Extracted from the article]

Background: COVID-19 is associated with higher morbidity and mortality in patients with chronic liver diseases (CLDs). However, our understanding of the long-term outcomes of COVID-19 in patients with CLD is limited. Methods: We conducted a multicenter, observational cohort study of adult patients with CLD who were diagnosed with COVID-19 before May 30, 2020, to determine long-term clinical outcomes. We used a control group of patients with CLD confirmed negative for COVID-19. Results: We followed 666 patients with CLD (median age 58 years, 52.8% male) for a median of 384 (interquartile range: 31-462) days. The long-term mortality was 8.1%; with 3.6% experiencing delayed COVID-19-related mortality. Compared to a propensity-matched control group of patients with CLD without COVID-19 (n= 1332), patients with CLD with COVID-19 had worse long-term survival [p< 0.001; hazards ratio (HR): 1.69; 95% CI: 1.19-2.41] and higher rate of hospitalization (p< 0.001, HR: 2.00, 1.62-2.48) over a 1-year follow-up period. Overall, 29.9% of patients reported symptoms of long-COVID-19. On multivariable analysis, female sex (p= 0.05, HR: 2.45, 1.01-2.11), Hispanic ethnicity (p =0.003, HR: 1.94, 1.26-2.99), and severe COVID-19 requiring mechanical ventilation (p =0.028, HR: 1.74, 1.06-2.86) predicted long-COVID-19. In survivors, liver-related laboratory parameters showed significant improvement after COVID-19 resolution. COVID-19 vaccine status was available for 72% (n =470) of patients with CLD and history of COVID-19, of whom, 70% (n =326) had received the COVID-19 vaccine. Conclusions: Our large, longitudinal, multicenter study demonstrates a high burden of long-term mortality and morbidity in patients with CLD and COVID-19. Symptoms consistent with long-COVID-19 were present in 30% of patients with CLD. These results illustrate the prolonged implications of COVID-19 both for recovering patients and for health care systems. [ABSTRACT FROM AUTHOR]

Artemisia arborescens (Vaill.) L. is a perennial shrubby plant growing along the coastal strips of the Mediterranean region. It is used in traditional medicine. Its essential oil and solvent extracts exhibit a very interesting chemotherapeutic potential, which makes this plant useful in maintaining human health. The goal of this study was to determine the phytochemical composition of the petroleum ether and methanol extracts, as well as to evaluate anticancer activities and antimicrobial and biofilm formation reduction. Thirty-nine phytochemical compounds in negative ion mode and 25 in positive ion mode were identified by HPLC-ESI-QTOF-MS. All four extracts reduced the viability of human MDA-MB231 and HCT116 cancer cells suggesting a similar cytotoxic efficacy of the different extracts in MDA-MB231 and more pronounced antiproliferative effects on HCT116 cells treated with HPEE and CPEE. Antimicrobial activity was exhibited by the hot petroleum ether extract against all tested bacteria (MIC 0.15–2.5 mg/mL), except for S. agalactiae. Both methanol extracts showed activity against C. albicans with a MIC value of 2.5 mg/mL, and a lack of antibacterial activity. To whom concern the anti-biofilm activity, hot methanol extract shows the highest activity in inhibiting biofilm formation among all extract. [ABSTRACT FROM AUTHOR]

A new technology used to reduce the temperature of olive paste was applied to the extra virgin olive oil (EVOO) mechanical extraction process. The performance of a cooling crusher that was able to counteract the thermal increase that occurs during olive fruit grinding was analyzed to evaluate the effects on the development of volatile compounds and the concentration of hydrophilic phenols in the final product. The volatile profiles and phenolic fraction of EVOOs extracted from three different cultivars (Coratina, Peranzana, and Moresca) were positively affected by the use of lower temperatures during the crushing phase. The volatile fractions showed increases in the total aldehydes, mainly related to the concentrations of (E)-2-hexenal, and reductions in the total alcohols, mainly due to 1-penten-3-ol, 1-hexanol and (Z)-3-hexen-1-ol contents. The use of a lower temperature reduced the level of oxidative processes, protecting the phenolic compounds in the Moresca and Peranzana EVOOs by 17.8 and 12.1%, respectively. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer in women worldwide, with a high prevalence and incidence, configuring an important issue in cancer epidemiology. Over the years, the combination of primary and secondary prevention programs and multidisciplinary treatment approaches has improved the overall survival (OS) and quality of life (QoL) of patients. However, although treatment pathways should be standardized in evidence-based medicine, clinical practice (real-world evidence) may differ from expected. To improve OS and QoL, having a clear picture of the Patterns of Care actually applied is essential. To this aim, Breast IRRADIATA (Italian Repository of RADIotherapy dATA), a collaborative nationwide project, was developed as a simple tool to probe the current pattern of radiotherapy care in Italy and tested in a feasibility study. This pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of pattern of care radiotherapy directed to other cancers. Aim. Breast IRRADIATA (Italian Repository of RADIotherapy dATA) is a collaborative nationwide project supported by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) and the Italian League Against Cancer (LILT). It focuses on breast cancer (BC) patients treated with radiotherapy (RT) and was developed to create a national registry and define the patterns of care in Italy. A dedicated tool for data collection was created and pilot tested. The results of this feasibility study are reported here. Methods. To validate the applicability of a user-friendly data collection tool, a feasibility study involving 17 Italian Radiation Oncology Centers was conducted from July to October 2021, generating a data repository of 335 BC patients treated between January and March 2020, with a minimum follow-up time of 6 months. A snapshot of the clinical presentation, treatment modalities and radiotherapy toxicity in these patients was obtained. A Data Entry Survey and a Satisfaction Questionnaire were also sent to all participants. Results. All institutions completed the pilot study. Regarding the Data Entry survey, all questions achieved 100% of responses and no participant reported spending more than 10 min time for either the first data entry or for the updating of follow-up. Results from the Satisfaction Questionnaire revealed that the project was described as excellent by 14 centers (82.3%) and good by 3 (17.7%). Conclusion. Current knowledge for the treatment of high-prevalence diseases, such as BC, has evolved toward patient-centered medicine, evidence-based care and real-world evidence (RWE), which means evidence obtained from real-world data (RWD). To this aim, Breast IRRADIATA was developed as a simple tool to probe the current pattern of RT care in Italy. The pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of the pattern of care radiotherapy directed to other cancers. [ABSTRACT FROM AUTHOR]

Introduction: The most common intracranial neoplasm diagnosed in adults are brain metastases (BrM). The benefit in terms of clinical control and toxicity for stereotactic radiotherapy (SRT) has been investigated for patients with low load of BrM. Aim: The aim of this single-institution experience was to investigate the best dose schedule for five-fraction SRT (FFSRT). Methods: A retrospective analysis of patients treated for BrM with different dose schedules of FFSRT was performed. Local control (LC) and clinical outcomes were evaluated with magnetic resonance imaging at 3, 6, and 9 months. Toxicity data were also collected. Results: A total of 41 patients treated from November 2016 to September 2020 were enrolled in the analysis. Non-small cell lung cancer (51.2%) and breast cancer (24.3%) represented the most frequent primitive tumors. Treatment was performed on 5 consecutive days with prescribed dose ranging from 30 to 40 Gy, prescribed to the 95% isodose line that covered at least 98% of the gross tumor volume. Statistically significant differences (p = 0.025) with higher LC rates for dose schedules >6 Gy for fractions. Toxicity rates were not found to be higher than G1. Conclusion: The results of this retrospective analysis suggest that FFSRT for BrM seems to be safe and feasible. Our results also underline that a total dose lower than 30 Gy in 5 fractions should not be used due to the expected minor LC. [ABSTRACT FROM AUTHOR]

Early data suggest fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics are unknown. We assessed the safety and efficacy of FMT in patients with prior overt HE, comparing five FMT donors. We performed an open‐label study of FMT capsules, administered 5 times over 3 weeks. Primary outcomes were change in psychometric HE score (PHES) and serious adverse events (SAEs). Serial stool samples underwent shallow shotgun metagenomic sequencing. Ten patients completed FMT administration and 6‐month follow‐up. Model for End‐Stage Liver Disease (MELD) score did not change after FMT (14 versus 14, p = 0.51). Thirteen minor adverse events and three serious adverse events (two unrelated to FMT) were reported. One SAE was extended‐spectrum beta‐lactamase Escherichia coli bacteremia. The PHES improved after three doses of FMT (+2.1, p < 0.05), after five doses of FMT (+2.9, p = 0.007), and 4 weeks after the fifth dose of FMT (+3.1, p = 0.02). Mean change in the PHES ranged from −1 to +6 by donor. Two taxa were identified by random forest analysis and confirmed by linear regression to predict the PHES— Bifidobacterium adolescentis (adjusted R2 = 0.27) and B. angulatum (adjusted R2 = 0.25)—both short‐chain fatty acid (SCFA) producers. Patients who responded to FMT had higher levels of Bifidobacterium as well as other known beneficial taxa at baseline and throughout the study. The FMT donor with poorest cognitive outcomes in recipients had the lowest fecal SCFA levels. Conclusion: FMT capsules improved cognition in HE, with an effect varying by donor and recipient factors (NCT03420482). [ABSTRACT FROM AUTHOR]

Purpose: Physical examinations and annual mammography (minimal follow-up) are as effective as laboratory/imaging tests (intensive follow-up) in detecting breast cancer (BC) recurrence. This statement is now challenged by the availability of new diagnostic tools for asymptomatic cases. Herein, we analyzed current practices and circulating tumor DNA (ctDNA) in monitoring high-risk BC patients treated with curative intent in a comprehensive cancer center. Patients and methods: Forty-two consecutive triple negative BC patients undergoing neoadjuvant therapy and surgery were prospectively enrolled. Data from plasma samples and surveillance procedures were analyzed to report the diagnostic pattern of relapsed cases, i.e., by symptoms, follow-up procedures and ctDNA. Results: Besides minimal follow-up, 97% and 79% of patients had at least 1 non-recommended imaging and laboratory tests for surveillance purposes. During a median follow-up of 5.1(IQR, 4.1–5.9) years, 13 events occurred (1 contralateral BC, 1 loco-regional recurrence, 10 metastases, and 1 death). Five recurrent cases were diagnosed by intensive follow-up, 5 by symptoms, and 2 incidentally. ctDNA antedated disseminated disease in all evaluable cases excepted two with bone-only and single liver metastases. The mean time from ctDNA detection to suspicious findings at follow-up imaging was 3.81(SD, 2.68), and to definitive recurrence diagnosis 8(SD, 2.98) months. ctDNA was undetectable in the absence of disease and in two suspected cases not subsequently confirmed. Conclusions: Some relapses are still symptomatic despite the extensive use of intensive follow-up. ctDNA is a specific test, sensitive enough to detect recurrence before other methods, suitable for clarifying equivocal imaging, and exploitable for salvage therapy in asymptomatic BC survivors. [ABSTRACT FROM AUTHOR]

Introduction: Adjuvant radiation therapy (RT) following primary surgery in women affected by early breast cancer (EBC) plays a central role in reducing local recurrences and overall mortality. The FAST‐FORWARD trial recently demonstrated that 1‐week hypofractionated adjuvant RT is not inferior to the standard schedule in terms of local relapse, cosmetic outcomes and toxicity. The aim of this in silico study was to evaluate the dosimetric aspects of a 1‐week RT course, administered through volumetric modulated arc therapy (VMAT), compared with traditional three‐dimensional conformal radiation therapy (3D‐CRT) with tangential fields. Methods: Patients affected by left‐side EBC undergoing adjuvant RT were selected. ESTRO guidelines for the clinical target volume (CTV) delineation and FAST‐FORWARD protocol for CTV to planning target volume (PTV) margin definition were followed. Total prescribed dose was 26 Gy in five fractions. The homogeneity index (HI) and the global conformity index (GCI) were taken into account for planning and dose distribution optimisation purposes. Both 3D‐CRT tangential fields and VMAT plans were generated for each patient. Results: The analysis included 21 patients. PTV coverage comparison between 3D‐CRT and VMAT plans showed significant increases for GCI (P < 0.05) in VMAT technique; no statistically significant differences were observed regarding HI. For organs at risks (OAR), statistically significant increases were observed in terms of skin V103% (P < 0.002) and ipsilateral lung V30% (P < 0.05) with 3D‐CRT and of heart V5% (P < 0.05) with VMAT technique. Conclusions: This in silico study showed that both 3D‐CRT and VMAT are dosimetrically feasible techniques in the framework of 1‐week hypofractionated treatments for left EBC. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 pandemic still represents a global public health emergency, despite the availability of different types of vaccines that reduced the number of severe cases, the hospitalization rate and mortality. The Italian Vaccine Distribution Plan identified healthcare workers (HCWs) as the top-priority category to receive access to a vaccine and different studies on HCWs have been implemented to clarify the duration and kinetics of antibody response. The aim of this paper is to perform a literature review across a total of 44 studies of the serologic response to COVID-19 vaccines in HCWs in Italy and to report the results obtained in a prospective longitudinal study implemented at the Fondazione IRCCS Istituto Nazionale Tumori (INT) of Milan on 1565 HCWs. At INT we found that 99.81% of the HCWs developed an antibody response one month after the second dose. About six months after the first serology evaluation, 100% of the HCWs were still positive to the antibody, although we observed a significant decrease in its levels. Overall, our literature review results highlight a robust antibody response in most of the HCWs after the second vaccination dose. These figures are also confirmed in our institutional setting seven months after the completion of the cycle of second doses of vaccination. [ABSTRACT FROM AUTHOR]