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Phosphodiesterase 4 (PDE4) enzymes catalyze cyclic adenosine monophosphate (cAMP) hydrolysis and are involved in a variety of physiological processes, including brain function, monocyte and macrophage activation, and neutrophil infiltration. Among different PDE4 isoforms, Phosphodiesterases 4D (PDE4Ds) play a fundamental role in cognitive, learning and memory consolidation processes and cancer development. Selective PDE4D inhibitors (PDE4Dis) could represent an innovative and valid therapeutic strategy for the treatment of various neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's, and Lou Gehrig's diseases, but also for stroke, traumatic brain and spinal cord injury, mild cognitive impairment, and all demyelinating diseases such as multiple sclerosis. In addition, small molecules able to block PDE4D isoforms have been recently studied for the treatment of specific cancer types, particularly hepatocellular carcinoma and breast cancer. This review overviews the PDE4DIsso far identified and provides useful information, from a medicinal chemistry point of view, for the development of a novel series of compounds with improved pharmacological properties. [ABSTRACT FROM AUTHOR]

The impact of COVID-19 on the economy was devastating. Small businesses typically have few resources to fight against such adversity. Many businesses remained closed for some time during the pandemic period, resulting in significant consequences for people in terms of jobs, income and life. The objective of this research is to identify the factors that contributed to increasing company failures during the pandemic. Furthermore, this study aims to verify whether the size of the companies, the sectors of economic activity in which they operate and their geographic location influence enterprise failure. This article analyzes the survival of 8931 small businesses from 2017 to 2023, in Rio Grande do Sul, Brazil. The study applied a survival analysis using the Kaplan–Meier procedure, complemented with the Cox procedure, to determine the effects of the size of companies, sector activity and location on the survival time. The results indicate that survival is much higher in small companies with large revenues that are located in the Campaign and West Frontier regions, as well as in the Northeast, North, Production, South, Taquari, and Rio Pardo Valleys regions, whereas the survival rates were extremely lower in the commercial sector and in financial intermediation activities. In the second analysis restricted to the commerce sector, the data highlighted the retail activities, accommodation and food activities sectors as the most affected in terms of overall survival. The results indicated that the survival of small business remained relatively strong during the COVID-19 pandemic, signaling the pertinent support from the government. The smallest business with revenues under USD 15,576 (BRL 81,000) per year were the most affected, with only 39% survival after 7 years. Some activities and some regions suffered more than others, emphasizing the need for special attention from authorities in future catastrophes. [ABSTRACT FROM AUTHOR]

Even at low temperatures, metal nanoparticles (NPs) possess atomic dynamics that are key for their properties but challenging to elucidate. Recent experimental advances allow obtaining atomic‐resolution snapshots of the NPs in realistic regimes, but data acquisition limitations hinder the experimental reconstruction of the atomic dynamics present within them. Molecular simulations have the advantage that these allow directly tracking the motion of atoms over time. However, these typically start from ideal/perfect NP structures and, suffering from sampling limits, provide results that are often dependent on the initial/putative structure and remain purely indicative. Here, by combining state‐of‐the‐art experimental and computational approaches, how it is possible to tackle the limitations of both approaches and resolve the atomistic dynamics present in metal NPs in realistic conditions is demonstrated. Annular dark‐field scanning transmission electron microscopy enables the acquisition of ten high‐resolution images of an Au NP at intervals of 0.6 s. These are used to reconstruct atomistic 3D models of the real NP used to run ten independent molecular dynamics simulations. Machine learning analyses of the simulation trajectories allow resolving the real‐time atomic dynamics present within the NP. This provides a robust combined experimental/computational approach to characterize the structural dynamics of metal NPs in realistic conditions. [ABSTRACT FROM AUTHOR]

O treinamento funcional e corrida de rua têm conquistado muitos adeptos nos últimos tempos, como forma de variar a prática esportiva. Entretanto, estudos de perfil nutricional do público feminino que pratica estas modalidades de exercício físico ainda são escassos. Portanto, o presente trabalho teve como objetivo avaliar o consumo alimentar, a composição corporal e o estado nutricional de mulheres praticantes de corrida de rua e treinamento funcional da cidade de Itaqui-RS. Foram avaliadas 12 mulheres praticantes de treinamento funcional e/ou corrida de rua, sendo mensurados e classificados seu IMC, circunferência da cintura e percentual de gordura corporal. O consumo alimentar foi avaliado a partir do recordatório de 24horas. Observou-se uma distribuição equilibrada de macronutrientes, porém constatou-se se um déficit médio de 520 kcal, considerando as recomendações para prática de exercícios físicos. A maioria das participantes encontrava-se em eutrofia ou sobrepeso (41,66% para ambas classificações) e 66,66% apresentaram percentual de gordura elevado. O risco aumentado de complicações metabólicas foi observado em 50% das mulheres e risco substancialmente aumentado em 41,66%. Concluiu-se que, apesar de se tratar de um grupo de mulheres fisicamente ativas, o consumo energético estava deficitário e havia risco de agravos à saúde em função do excesso de peso, do alto percentual de gordura corporal e da alta circunferência da cintura. Uma vez que 100% das participantes da pesquisa não estavam sob acompanhamento nutricional, os resultados reforçam a necessidade de orientações nutricionais com vistas à saúde e desempenho físico.

Il monastero femminile di San Zaccaria di Venezia, fondato nel IX secolo, adotta intorno alla metà del XII secolo le consuetudini di Cluny. Questo contributo vuole dimostrare che la decisione, riconfermata più volte nel corso del tempo, contribuisce al rilancio del cenobio dopo un periodo di difficoltà, e anche se non comporta il formale collegamento del cenobio alla congregazione borgognona, lo proietta per la prima volta in una dimensione sovralocale. Tale proiezione è ben visibile circa cinquant’anni più tardi, quando le monache si presentano a Verona e trattano con il podestà e le autorità veronesi una questione patrimoniale che ha importantissime implicazioni di natura politico-territoriale per entrambe le città.

The need for specific documents in terms of environment and landscape has its origin in late Eighties, when in Italy both at European and Regional level several dispositions related to the improvement of the landscape quality came out to guarantee the compatibility of territorial transformations. Within this traditional context, how innovative, mainly BIM-oriented, technologies can be useful in offering new ways of interpretation for the landscape planning and safeguarding? The aim of the present work is to read and translate landscape elements using digital BIMoriented platforms, in order to develop an optimized procedure to collect/organize/implement data and define guidelines for landscape and visual impact assessment; furthermore, the aim is to understand the limits that are still present within available tools. After having read the features of the territory another key point is the creation of digital parametric libraries to represent environmental mitigation works. As far as visual mitigation works are concerned, visibility analysis of the infrastructure is possible through Virtual and Mixed Reality. Once the modeling of specific components is performed, they can be located within the contextual model, where outputs related to the “whole” can be extracted and updated afterwards. New digital technologies and techniques undoubtedly offer new interpretation scenarios of the landscape evolution; nevertheless, there are still strong limits related to the interactions among these tools. The present work provides a valid methodology to involve landscape and urban planning in the BIM process. The research also proposes a series of BIM oriented tools and software to develop a typical output (landscape report) required during the design process, useful for landscape architects.DOI: https://doi.org/10.20365/disegnarecon.22.2019.25

Increasing nanoparticle size usually increases the stability of ordered phases within them. In contrast, the authors show here that the L11 ordered phase only forms in AgPt nanoparticles smaller than 2.5 nm because the segregation of a monolayer Ag shell constrains the nanophase which becomes unstable at larger sizes.

# Objective Fear of hypoglycemia for children with diabetes influences parental life and could increase parental stress. The present study aimed to explore the association between resilience, the self-perception of the parental role, and fear of hypoglycemia in mothers of children with type I diabetes (T1DM). # Methods Ninety mothers (mean age: 44.20 years) of children with a T1DM diagnosis (mean age: 11.48 years) were recruited from an association for parents and completed an online self-report questionnaire packet that includes: Fear of Hypoglycemia Survey, Self-Perception of the Parental Role and Resilience Scale for Adults. Participants were recruited in 2017. Data collection lasted 10 months. Data analysis was performed using the SPSS statistical package, version 22, and the PROCESS macro program by Hayes. # Results The analysis of the mediation model shows that resilience assumes a mediational role in the relationships between the parental role and preoccupation with hypoglycemia. In particular, the mother's perceived competence and role balance can influence the development and increase of the mother's resilience, which in turn can allow a decrease in the mother’s worry about the possible hypoglycemic episode of her child. # Conclusion The findings suggest that resilience is a significant topic to focus on in interventions designed to increase the self-perception of the parental role and reduce fear of hypoglycemia in mothers

Questo intervento analizza il libro The Lands of Saint Ambrose. Monks and Society in Early Medieval Milan di Ross Balzaretti, concentrandosi sul tema dei rapporti tra il monastero di Sant’Ambrogio e le élites laiche ed ecclesiastiche attive a Milano tra VIII e X secolo.

This paper addresses the topic of work-life interferences in academic contexts. More specifically, it focuses on early career researchers in the Italian university system. The total availability required from those who work in the research sector is leading to significant transformations of the temporalities of work, especially among the new generation of researchers, whose condition is characterized by a higher degree of instability and uncertainty. Which are the experiences of the early career researchers in an academic context constituted by a growing competition for permanent positions and, as a consequence, by a greatly increased pressure? Which are the main gender differences? In what elements do Science, Technology, Engineering and Mathematics disciplines differ from Social Sciences and Humanities? The collected narratives reveal how the ongoing process of precarization is affecting both the everyday working activities and the private and family lives of early career researchers, with important consequences also on their future prospects.

Increasing evidence point out the important roles of ion channels in the physiopathology of cancers, so that these proteins are now considered as potential new therapeutic targets and biomarkers in this disease. Indeed, ion channels have been largely described to participate in many hallmarks of cancers such as migration, invasion, proliferation, angiogenesis, and resistance to apoptosis. At the molecular level, the development of cancers is characterised by alterations in transduction pathways that control cell behaviors. However, the interactions between ion channels and cancer-related signaling pathways are poorly understood so far. Nevertheless, a limited number of reports have recently addressed this important issue, especially regarding the interaction between ion channels and one of the main driving forces for cancer development: the Wnt/β-catenin signaling pathway. In this review, we propose to explore and discuss the current knowledge regarding the interplay between ion channels and the Wnt/β-catenin signaling pathway in cancers.

Background: The world, and Italy on the front lines, has experienced a major medical emergency due to the novel coronavirus outbreak. Cancer patients are one of the potentially most vulnerable cohorts of people, but data about their management are still few.Patients and Methods: In this monocentric retrospective study we included all SARS-CoV-2 oncological patients accepted, between March 27th and April 19th 2020, at the Onco-COVID Unit at San Luigi Gonzaga Hospital, one of the few Italian oncological-COVID wards. Data were obtained from medical records.Results: Eighteen cancer patients with COVID-19 were included. The mean (±SD) age of patients was 67 ± 14 years, 89% were men. Seven (39%) developed infection in communities and 11 (61%) during hospitalization. Lung cancer was the most frequent type of cancer (10, 56%). Seven patients (39%) were symptomatic for COVID-19 at the time of diagnosis and symptoms began 2 (±2) days before. The most common were shortness of breath and diarrhea. Fever was present in 5 patients (28%). Among the 11 asymptomatic patients, 8 (73%) became symptomatic during the hospitalization (mean time of symptoms onset 4 days ±4). Six patients (33%) were on active anti-tumor treatment: 2 (33%) received anti-tumor therapy within 2 weeks before the infection diagnosis and 2 (33%) continued oncological treatment after SARS-CoV-2 positivity. Eight (44%) patients died within a mean of 12 days (±8) from the infection diagnosis.Conclusions: Our series confirms the high mortality among cancer patients with COVID-19. The presence of asymptomatic cases evidences that typical symptoms and fever are not the only parameters to suspect the infection. The Onco-Covid unit suggests the importance of a tailored and holistic approach, even in this difficult situation.

This research aims at evaluating the effects of the dietary addition of a supplement containing 75% of chestnut tannins (CT) on growth performance, slaughter traits (Experiment 1) and on nutrient utilisation (Experiment 2) of Italian heavy pigs. Exp. 1 compared a control (C) diet with diets containing 0.15 or 0.30% of CT supplement. Forty-two barrows (91 ± 6 kg of BW) were divided into pairs and kept in 21 partially-slatted pens equipped with individual feeding (7 pens/diet). Animals were slaughtered at a BW of 174 ± 6 kg. The CT inclusion did not modify the performance and the slaughter traits but lowered the intensity of red colour (p

Chronic hepatitis B virus (HBV) infection is a global health problem that presents as a spectrum of liver disease, reflecting an interplay between the virus and the host immune system. HBV genomes exist as episomal covalently closed circular DNA (cccDNA) or chromosomal integrants. The relative contribution of these genomes to the viral transcriptome in chronic hepatitis B (CHB) is not well-understood. We developed a qPCR method to estimate the abundance of HBV cccDNA- and integrant-derived viral transcripts and applied this to a cohort of patients diagnosed with CHB in the HBe antigen negative phase of disease. We noted a variable pattern of HBV transcripts from both DNA templates, with preS1/S2 mRNAs predominating and a significant association between increasing age and the expression of integrant-derived mRNAs, but not with inflammatory status. In contrast, cccDNA-derived transcripts were associated with markers of liver inflammation. Analysis of the inflammatory hepatic transcriptome identified 24 genes significantly associated with cccDNA transcriptional activity. Our study uncovers an immune gene signature that associates with HBV cccDNA transcription and increases our understanding of viral persistence.

The current nutrient recommendations focus on pigs fed ad libitum up to 140 kg in body weight (BW). It remains unclear whether this applies to pigs weighing above 140 kg in BW under different rearing conditions. This study aimed to estimate protein (Pd) and lipid (Ld) depositions and the metabolizable energy (ME), standardized ileal digestible lysine (SID lysine) requirement and partitioning in 224 C21 Goland pigs (90–200 kg in BW). The control pigs (C) received diets limiting ME up to 170 kg in slaughter weight (SW) at 9 months of age (SA); older (OA) pigs had restricted diets limiting ME and SID lysine up to 170 kg in SW at >9 months SA; younger (YA) pigs were fed nonlimited amounts of ME and SID lysine up to 170 kg in SW at 170 kg in SW. The estimated MEm averaged 1.03 MJ/kg0.60. An 11% increase in MEm was observed in OA pigs compared to the controls. Energy restriction had negligible effects on the estimated MEm. The marginal efficiency of SID lysine utilization for Pd averaged 0.725, corresponding to a SID lysine requirement of 9.8 g/100 g Pd.

Abstract The fundamental concept of magnetically confined nuclear fusion devices is the magnetohydrodynamic (MHD) equilibrium: the pressure gradient due to highly energetic charged particles is balanced by the Lorenz force due to strong magnetic fields. Hence, numerical methods for MHD equilibria are also fundamental for fusion engineering applications. We rely here on a finite element method on composite meshes for the simulation of axisymmetric equilibria in tokamaks, torus-shaped nuclear fusion devices. One mesh with Cartesian quadrilaterals covers the domain accessible by the plasma and one mesh with triangles discretizes the region outside the chamber. The two meshes overlap in a narrow region. This approach gives the flexibility to achieve easily and at low cost higher order regularity for the approximation of the principal unknown, the poloidal magnetic flux, while preserving accurate meshing of the geometric details in the exterior. We show that higher order regularity allows to formulate appropriate optimal control problems that help to find a special type of equilibria, called snowflake equilibria, that are a very promising concept to mitigate high heat loads due to plasma escaping particles.

Medici ebrei nella Sardegna Medioevale Il presente lavoro si inserisce in un più ampio progetto di ricerca riguardante la presenza ebraica in Sardegna nel Medioevo, i cui primi risultati sono stati presentati nell’ambito del Convegno internazionale sul tema, svoltosi a Cagliari nel 2008. Ciò che è emerso nel corso della ricerca è il fatto che, grazie alla presenza delle comunità ebraiche nelle maggiori città dell'isola, la Sardegna ha svolto un ruolo centrale negli scambi economici e culturali nel Mediterraneo occidentale. In particolare, essa ha rappresentato un importante centro culturale, al cui interno operavano molti medici e chirurghi di origini ebraiche che divennero protagonisti fondamentali della vita economica, sociale e culturale delle diverse comunità in cui agivano, essendo i loro servizi caldamente richiesti e accolti da illustri personalità. Questo contributo, nell'illustrare lo specifico contesto storico della Sardegna medievale in cui questi medici hanno vissuto e lavorato, si propone di fornire un quadro della vita quotidiana delle varie comunità di appartenenza, attraverso l’analisi di nuove fonti documentarie. Jewish Physicians in Medieval Sardinia This essay is part of a broader research project concerning the Jewish presence in Sardinia during the Middle Ages. What emerged from the research process, is that thanks to the presence of the Jewish community in the island’s cities, Sardinia played a central role in the economic and cultural exchanges within the Mediterranean Sea. In particular, the many doctors and surgeons of Jewish origins operating on this island became fundamental protagonists of the economic, social and cultural life of the different communities in which they worked, their services being warmly requested and welcomed by illustrious personalities. This contribution, while outlining the specific historical context of Medieval Sardinia in which the Jewish doctors lived and worked, sets out to provide a picture of the everyday life in these communities, through the sources relating to these Jews in the medical profession.