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Despite constant medical evolution, the reimbursement policy of Portuguese National Health Service (NHS) for the study and risk stratification of coronary heart disease has remained unchanged for several decades. Lack of adjustment to contemporary clinical practice has long been evident. However, the recent publication of the European Guidelines for diagnosis and treatment of chronic coronary syndromes further highlighted this gap and the urgent need for a change. Prompted by these Guidelines, the Working Group on Nuclear Cardiology, Cardiac Magnetic Resonance and Cardiac CT, the Working Group on Echocardiography and the Working Group on Stress Pathophysiology and Cardiac Rehabilitation of the Portuguese Society of Cardiology, began a process of joint reflection on the current limitations and how these recommendations could be applied in Portugal. To this end, the authors suggest that the new imaging methods (stress echocardiogram, cardiac computed tomography and cardiac magnetic resonance), should be added to exercise treadmill stress test and myocardial perfusion scintigraphy in the available exam portfolio within the Portuguese NHS. This change would allow full adoption of European guidelines and a better use of tests, according to clinical context, availability and local specificities. The adoption of clinical guidance standards, based on these assumptions, would translate into a qualitative improvement in the management of these patients and would promote an effective use of the available resources, with potential health and financial gains.

Introduction: Direct oral anticoagulants (DOACs) changed the landscape of atrial fibrillation (AF) treatment, but also brought with them new challenges in terms of accessibility and compliance. The purpose of this study was to assess adherence to DOACs, and its determinants in a population of AF patients. Methods: Single-center retrospective study including all patients with non-valvular AF treated with a DOAC from the outpatient general cardiology list at a tertiary center, whose first DOAC prescription was between 1 April 2016 and August 2018. The number of pharmacy refills from the day of first prescription to 31 August 2018 was counted (by means of an electronic prescription platform). Medication refill adherence (MRA) was calculated by dividing the total days' supply by the number of days under therapy. Non-compliance was defined as MRA

Ginger (from the rizhome of Zingiber officinale Roscoe) has been widely used in ethnomedicine for the cure of several ailments. Main active ingredients include phenolic compounds named gingerols. In modern phytotherapy, ginger preparations are predominantly used to counteract nausea and vomiting in pregnant women. However, a number of other pharmacological actions of potential therapeutic interest, which might broaden the spectrum of its clinical use, have been reported. This focused review aims at giving a shot on the antinflammatory, analgesic, and metabolic actions of Zingiber officinale preparations, with a discussion on the clinical applications in knee osteoarthritis, dysmenorrhea, type-2 diabetes, hyperlipidemia, overweight, and obesity., info:eu-repo/semantics/publishedVersion

Background Reductions in substance use are associated with positive long‐term treatment outcomes such as psychosocial functioning; substance use–related consequences; and mental, physical, and neurobiological health. Therefore, nonabstinent clinical trial endpoints have received growing attention from substance abuse treatment experts. Regional brain tissue volumes in alcoholism treatment seekers increase during abstinence, in parallel to cognitive performance. Methods We examined the relationships of drinking levels in those who did not maintain abstinence after treatment with magnetic resonance imaging‐derived gray matter (GM) volumes measured 8 months after baseline assessments while in outpatient treatment. The complex drinking behavior during the interval was operationalized as World Health Organization risk drinking levels (WHO‐RDL), derived from the number of standard alcoholic drinks per day. We compared the volumes of addiction‐relevant cortical and subcortical brain regions at long‐term follow‐up among abstainers and 2 groups of relapsers with low and higher WHO‐RDL. Results We found that: (i) relapsers with low WHO‐RDL at follow‐up, who as a group had reduced their risk levels by 2.8 units (by consuming 10 drinks per day, relapsers with low WHO‐RDL at follow‐up tended to perform better than those with higher WHO‐RDL on cognitive domains of working memory and visuospatial skills assessed over the recovery interval. Conclusions Nonabstinent recovery is characterized by addiction‐relevant GM volumes comparable to those of complete abstainers. The WHO‐RDL has meaningful structural neuroimaging correlates potentially suitable as cognitively relevant biomarkers of treatment response and general brain health, perhaps even as objective clinical trial endpoints., Non‐abstinent recovery after treatment for alcohol use disorder (AUD) has been shown to be beneficial for psychological and physical health. Here, researchers demonstrate by MRI that non‐abstinent recovery also benefits frontal gray matter volume, a brain region important for cognitive control. Treated AUD individuals have smaller volumes than healthy controls (CON), but the volumes are similar for total abstainers (ABST) and relapsers with low drinking severity (WHO low). Only severe relapsers (WHO higher) show dramatically less frontal gray matter.

Cigarette smoking is associated with neurocognitive dysfunction in various populations, including those seeking treatment for an alcohol use disorder (AUD). This study compared the rate and extent of recovery on measures of processing speed, executive functions, general intelligence, visuospatial skills and working memory in treatment-seeking alcohol dependent individuals (ALC) who were never-smokers (nvsALC), former-smoker (fsALC), and active smokers (asALC), over approximately 8 months of abstinence from alcohol. Methods: ALC participants were evaluated at approximately 1 month of abstinence (AP1; n = 132) and reassessed after 8 months of sobriety (AP2; n = 54). Never-smoking controls (CON; n = 33) completed a baseline and follow-up (n = 19) assessment approximately 9 months later. Domains evaluated were executive functions, general intelligence, processing speed, visuospatial skills and working memory; a domain composite was formed from the arithmetic average of the foregoing domains. nvsALC showed greater improvement than fsALC, asALC and CON on most domains over the AP1-AP2 interval. fsALC demonstrated greater recovery than asALC on all domains except visuospatial skills; fsALC also showed greater improvements than CON on general intelligence, working memory and domain composite. asALC did not show significant improvement on any domain over the AP1-AP2 interval. At 8 months of abstinence, asALC were inferior to CON and nvsALC on multiple domains, fsALC performed worse than nvsALC on several domains, but nvsALC were not different from CON on any domain. Our results provide robust evidence that smoking status influenced the rate and extent of neurocognitive recovery between 1 and 8 months of abstinence in this ALC cohort. Chronic smoking in AUD likely contributes to the considerable heterogeneity observed in neurocognitive recovery during extended abstinence. The findings provide additional strong support for the benefits of smoking cessation and the increasing clinical movement to offer smoking cessation resources concurrent with treatment for AUD.

To better understand nutrition, food chemistry, and medicine, it is important to investigate biologically active constituents, which requires a detailed knowledge and coverage of the composition of compounds of nutritional and nutraceutical character [...]

The by-products/wastes from agro-food and in particular the fruit industry represents from one side an issue since they cannot be disposed as such for their impact on the environment but they need to be treated as a waste. However, on the other side, they are a source of bioactive healthy useful compounds which can be recovered and be the starting material for other products in the view of sustainability and a circular economy addressing the global goal of zero waste in the environment. An updated view of the state of art of the research on fruit wastes is here given under this perspective. The topic is defined as follows: (i) literature quantitative analysis of fruit waste/by-products, with particular regards to linkage with health; (ii) an updated view of conventional and innovative extraction procedures; (iii) high-value added compounds obtained from fruit waste and associated biological properties; (iv) fruit wastes presence and relevance in updated databases. Nowadays, the investigation of the main components and related bioactivities of fruit wastes is being continuously explored throughout integrated and multidisciplinary approaches towards the exploitation of emerging fields of application which may allow to create economic, environmental, and social value in the design of an eco-friendly approach of the fruit wastes., info:eu-repo/semantics/publishedVersion

Great attention has been given in recent years to the relationships between metrology, agriculture, and food. This study aims at providing an analysis of the literature regarding the relationships between metrology, agriculture, and food. The Scopus online database has been used to extract bibliometric data throughout the search string: TITLE-ABS-KEY (Metrology* AND Agriculture* OR Food*), and the VOSviewer bibliometric software was used to visualize results as bubble maps. The novelty character of this perspective paper is to indicate and point out the main research themes/lines addressing the relationships between metrology, agriculture, and food by analyzing: (i) the authors of the published papers; (ii) the type of paper; (iii) the countries and institutions where the research is developed. Bibliometrics allows one to holistically examine entire scientific areas or sub-fields to get new qualitative and quantitative insights. These results represent a useful tool for identifying emerging research directions, collaboration networks, and suggestions for more in-depth literature searches., This research received no external funding., info:eu-repo/semantics/publishedVersion

Biodiversity strengthens the productivity of any ecosystem (agricultural land, forest, lake, etc.). The loss of biodiversity contributes to food and energy insecurity; increases vulnerability to natural disasters, such as floods or tropical storms; and decreases the quality of both life and health. Wild and managed bees play a key role in maintaining the biodiversity and in the recovery and restoration of degraded habitats. The novelty character of this perspective is to give an updated representation of bee products biodiversity, sustainability, and health relationship. The role of bees as bioindicators, their importance in the conservation of biodiversity, their ecosystem services, and the variety of the bee products are described herein. An overview of the main components of bee products, their biological potentials, and health is highlighted and detailed as follows: (i) nutritional value of bee products, (ii) bioactive profile of bee products and the related beneficial properties; (iii) focus on honey and health through a literature quantitative analysis, and (iv) bee products explored through databases. Moreover, as an example of the interconnection between health, biodiversity, and sustainability, a case study, namely the Cellulose Park, realized in Rome (Italy), is presented here. This case study highlights how bee activities can be used to assess and track changes in the quality of agricultural ecosystemshive products could be valid indicators of the quality and health of the surrounding environment, as well as the changes induced by the biotic and abiotic factors that impact the sustainability of agricultural production and biodiversity conservation in peri-urban areas., (undefined), info:eu-repo/semantics/publishedVersion

This review offers a systematic discussion about nanotoxicology and nanosafety associated with nanomaterials during manufacture and further biomedical applications. A detailed introduction on nanomaterials and their most frequently uses, followed by the critical risk aspects related to regulatory uses and commercialization, is provided. Moreover, the impact of nanotoxicology in research over the last decades is discussed, together with the currently available toxicological methods in cell cultures (in vitro) and in living organisms (in vivo). A special focus is given to inorganic nanoparticles such as titanium dioxide nanoparticles (TiO2NPs) and silver nanoparticles (AgNPs). In vitro and in vivo case studies for the selected nanoparticles are discussed. The final part of this work describes the significance of nano-security for both risk assessment and environmental nanosafety. “Safety-by-Design” is defined as a starting point consisting on the implementation of the principles of drug discovery and development. The concept “Safety-by-Design” appears to be a way to “ensure safety”, but the superficiality and the lack of articulation with which it is treated still raises many doubts. Although the approach of “Safety-by-Design” to the principles of drug development has helped in the assessment of the toxicity of nanomaterials, a combination of scientific efforts is constantly urgent to ensure the consistency of methods and processes. This will ensure that the quality of nanomaterials is controlled and their safe development is promoted. Safety issues are considered strategies for discovering novel toxicological-related mechanisms still needed to be promoted., This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the projects M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

Mycotoxin contamination continues to be a food safety concern globally, with the most toxic being aflatoxins. On-farm aflatoxins, during food transit or storage, directly or indirectly result in the contamination of foods, which affects the liver, immune system and reproduction after infiltration into human beings and animals. There are numerous reports on aflatoxins focusing on achieving appropriate methods for quantification, precise detection and control in order to ensure consumer safety. In 2012, the International Agency for Research on Cancer (IARC) classified aflatoxins B1, B2, G1, G2, M1 and M2 as group 1 carcinogenic substances, which are a global human health concern. Consequently, this review article addresses aflatoxin chemical properties and biosynthetic processes; aflatoxin contamination in foods and feeds; health effects in human beings and animals due to aflatoxin exposure, as well as aflatoxin detection and detoxification methods., (undefined), info:eu-repo/semantics/publishedVersion

The latest advances in pharmaceutical technology are leading to the development of cutting edged approaches to produce what is now known as the “Holy Grail” of medicine—nanopharmaceutics. Over the latest decade, the pharmaceutical industry has made important contributions to the scale up of these new products. To ensure their quality, efficacy, and safety for human use, clinical trials are mandatory. Yet, regulation regarding nanopharmaceuticals is still limited with a set of guidelines being recently released with respect to compliance with quality and safety. For the coming years, updates on regulatory issues about nanopharmaceuticals and their use in clinical settings are expected. The use of nanopharmaceuticals in clinical trials depends on the approval of the production methods and assurance of the quality of the final product by implementation and verification of the good manufacturing practices (GMP). This review addresses the available legislation on nanopharmaceuticals within the European Union (EU), the GMP that should be followed for their production, and the current challenges encountered in clinical trials of these new formulations. The singular properties of nanopharmaceuticals over their bulk counterparts are associated with their size, matrix composition, and surface properties. To understand their relevance, four main clinical trial guidelines, namely, for intravenous iron-based nanopharmaceuticals, liposomal-based nanopharmaceuticals, block copolymer micelle-based nanopharmaceuticals, and related to surface coating requirements, are described here., The financial support was received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the projects M‐ERA‐NET‐0004/2015‐PAIRED and UIDB/04469/2020 (strategic fund), co‐financed by FEDER, under the Partnership Agreement PT2020. Authors thank the support of the project: Nutraceutica come supporto nutrizionale nel paziente oncologico; CUP: B83D18000140007., info:eu-repo/semantics/publishedVersion

Burn wounds are highly debilitating injuries, with significant morbidity and mortality rates worldwide. In association with the damage of the skin integrity, the risk of infection is increased, posing an obstacle to healing and potentially leading to sepsis. Another limitation against healing is associated with antibiotic resistance mainly due to the use of systemic antibiotics for the treatment of localized infections. Nanotechnology has been successful in finding strategies to incorporate antibiotics in nanoparticles for the treatment of local wounds, thereby avoiding the systemic exposure to the drug. This review focuses on the most recent advances on the use of nanoparticles in wound dressing formulations and in tissue engineering for the treatment of burn wound infections., The authors would like to thank the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project references M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020, co-financed by FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

Featured Application: The loading of pharmaceuticals and cosmeceuticals into nanomaterials is discussed as new formulations for potential treatment of age-related skin problems. Topical administration of active ingredients formulated as nanopharmaceuticals and nanonutraceuticals is discussed.Abstract: Skin aging is described as dermatologic changes either naturally occurring over the course of years or as the result of the exposure to environmental factors (e.g., chemical products, pollution, infrared and ultraviolet radiations). The production of collagen and elastin, the main structural proteins responsible for skin strength and elasticity, is reduced during aging, while their role in skin rejuvenation can trigger a wrinkle reversing effect. Elasticity loss, wrinkles, dry skin, and thinning are some of the signs that can be associated with skin aging. To overcome skin aging, many strategies using natural and synthetic ingredients are being developed aiming to reduce the signs of aging and/or to treat age-related skin problems (e.g., spots, hyper- or hypopigmentation). Among the different approaches in tissue regeneration, the use of nanomaterials loaded with cosmeceuticals (e.g., phytochemicals, vitamins, hyaluronic acid, and growth factors) has become an interesting alternative. Based on their bioactivities and using different nanoformulations as efficient delivery systems, several cosmeceutical and pharmaceutical products are now available on the market aiming to mitigate the signs of aged skin. This manuscript discusses the state of the art of nanomaterials commonly used for topical administration of active ingredients formulated in nanopharmaceuticals and nanocosmeceuticals for skin anti-aging., The authors acknowledge the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the projects M-ERANET/0004/2015-PAIRED and UIDB/04469/2020 (strategic fund) co-financed by FEDER, under the Partnership Agreement PT2020. The FCT grant to CMG (SFRH/BD/145855/2019) and project PEst-OE/UID/AGR/04033/2019 (CITAB strategic fund) are also acknowledged. The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007., info:eu-repo/semantics/publishedVersion

Due the implementation of nanotechnologies in the pharmaceutical industry over the last few decades, new type of cutting-edge formulationsnanopharmaceuticshave been proposed. These comprise pharmaceutical products at the nanoscale, developed from different types of materials with the purpose to, e.g., overcome solubility problems of poorly water-soluble drugs, the pharmacokinetic and pharmacodynamic profiles of known drugs but also of new biomolecules, to modify the release profile of loaded compounds, or to decrease the risk of toxicity by providing site-specific delivery reducing the systemic distribution and thus adverse side effects. To succeed with the development of a nanopharmaceutical formulation, it is first necessary to analyze the type of drug which is to be encapsulated, select the type matrix to load it (e.g., polymers, lipids, polysaccharides, proteins, metals), followed by the production procedure. Together these elements have to be compatible with the administration route. To be launched onto the market, the selected production method has to be scaled-up, and quality assurance implemented for the product to reach clinical trials, during which in vivo performance is evaluated. Regulatory issues concerning nanopharmaceutics still require expertise for harmonizing legislation and a clear understanding of clinically compliant production methods. The first part of this study addressing Nanopharmaceutics: Part IClinical trials legislation and Good Manufacturing Practices (GMP) of nanotherapeutics in the EU has been published in Pharmaceutics. This second part complements the study with the discussion about the production scales and clinically compliant production methods of nanopharmaceutics., The financial support was received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the projects M‐ERA‐NET‐0004/2015‐PAIRED and UIDB/04469/2020 (strategic fund), co‐financed by FEDER, under the Partnership Agreement PT2020. Authors thank the support of the project: Nutraceutica come supporto nutrizionale nel paziente oncologico; CUP: B83D18000140007., info:eu-repo/semantics/publishedVersion

Forest ecosystems are an important biodiversity environment resource for many species. Forests and trees play a key role in food production and have relevant impact also on nutrition. Plants and animals in the forests make available nutrient-rich food sources, and can give an important contributions to dietary diversity, quality, and quantity. In this context, the Special Issue, entitled “Forest, Food and Nutrition”, is focused on the understanding of the intersection and linking existing between forests, food, and nutrition.

Fish is a nutrient-rich food but, at the same time, consumption of fish is a possible source of exposure to heavy metals. Since many coastal Mediterranean areas suffer from great anthropomorphic pressure, the aim of this study was to assess the level of potentially toxic inorganic elements in different fish samples from the coastal zone of Southern Italy (Gela) where there is a high mortality rate linked to cancer disease and congenital malformations. The presence of mercury, cadmium, lead, nickel, arsenic, vanadium, and chromium was measured by inductively coupled plasma-mass spectrometry (ICP-MS). The risk assessment was evaluated in terms of estimated daily intake by calculating the amount of potentially toxic elements that an average individual adult weighing 60 kg would ingest. Moreover the non-carcinogenic risk was estimated by target hazard quotient (THQ). The study evidenced significant contamination by inorganic elements, especially cadmium, which can be linked to industrial pollution. The THQ indexes, as indicators of human health, suggest that the consumption of fish from the study area is not free of risk.

Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chronic inflammation. The development of new therapies capable of combating vision loss involves knowledge of inflammatory retinal changes. Studies in animal models and patients with diabetes have shown a high expression of the inflammatory molecules that are involved in the progression of diabetic retinopathy. Uveal melanoma is an eye tumour that remains highly deadly, because despite the correct treatment, it still causes metastasis in about 50% of patients. This type of tumour has the ability to produce and store melanin, which may result in resistance to therapy. Over time there has been development of new therapies for this disease, such as radiotherapy and surgical resection. In this review, we discuss diabetic retinopathy and ocular melanoma, their relationship with angiogenesis and the current anti-angiogenic therapies for their treatment., The authors acknowledge the financial support received from the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project references M-ERANET/0004/2015-PAIRED, UIDB/04469/2020 (strategic fund) and UID/AGR/04033/2019 (CITAB), co-financed by FEDER, under the Partnership Agreement PT2020. The authors also acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007., info:eu-repo/semantics/publishedVersion

The relationship between wine polyphenols and health has been receiving growing scientific attention in the last few years. To confirm this point, the proposed paper identifies the major contributors to academic journals regarding the relationships between wine polyphenols and health. The endpoints of the proposed study are to provide a comprehensive overview and analysis of the literature regarding the relationships between wine polyphenol and health based on a bibliometric analysis. Bibliometric data were extracted from the Scopus online database using the search string TITLE-ABS-KEY (wine AND polyphenol* AND health OR (french paradox OR cardiovascular disease* OR atherosclerosis OR microbiota) and analyzed using the VOSviewer bibliometric software to generate bubble maps and to visualize the obtained results. This perspective paper analyzes: (i) the research themes addressing the relationships between wine polyphenols and health; (ii) the major contributors origin, e.g., country and/or regions; (iii) the institutions where the research is based; (iv) the authors; and (v) the type of paper. These results represent a useful tool to identify emerging research directions, collaboration networks, and suggestions for more in-depth literature searches., Antimicrobial and antioxidant activities of a Portuguese honey harvested over two consecutive years., info:eu-repo/semantics/publishedVersion

Many plants have been known for centuries to have medicinal importance with potential beneficial effects on health. Phytotherapeutic compounds are well known to play a globally significant role, in particular in the management and treatment of various chronic diseases. Among these, diabetes can cause long term damage to the body other than having a relevant economic burden on society being among the costliest chronic diseases. This motivated the focus of the proposed Special Issue, intended to develop and exploit the potential role of plants in the management and treatment of diabetes. The main topics included are: (i) description and use of medicinal plants for diabetes management; (ii) the elucidation and delineation of their main components, properties (anti-hyperglycaemic, hypoglicaemic, anti-infiammatory, apoptotic agents, etc.), (iii) the mechanism of action (in vitro and in vivo studies); (iv) formulation of nutraceuticals, botanicals, and dietary supplements useful as tools as an alternative or support to anti-diabetic pharmacological therapies; (v) development of new markers.

This study assessed the periodontal conditions of type 2 diabetes (T2DM) patients attending an Outpatient Center in North Italy and explored the associations between metabolic control and periodontitis. Periodontal health of 104 T2DM patients (61 men and 43 women, mean age of 65.3 ± 10.1 years) was assessed according to CDC/AAP periodontitis case definitions and Periodontal Inflamed Surface Area (PISA) Index. Data on sociodemographic factors, lifestyle behaviors, laboratory tests, and glycated hemoglobin (HbA1c) levels were collected by interview and medical records. Poor glycemic control (HbA1c ≥ 7%), family history of T2DM, and C-reactive protein levels were predictors of severe periodontitis. An increase in HbA1c of 1% was associated with a rise in PISA of 89.6 mm2. On the other hand, predictors of poor glycemic control were severe periodontitis, waist circumference, unbalanced diet, and sedentary lifestyle. A rise in PISA of 10 mm2 increased the odds of having HbA1c ≥ 7% by 2%. There is a strong bidirectional connection between periodontitis and poor glycemic control. The inflammatory burden posed by periodontitis represents the strongest predictor of poor glycemic control.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Whether SARS-CoV-2 can trigger an autoimmune reaction against platelets and red blood cells remains unclear. Herein, we report a case of COVID-19 pneumonia associated with severe immune thrombocytopenia and hemolytic anemia. An 83-year-old woman was admitted to the hospital because of both dyspnea and diffuse mucocutaneous bleeding. Exams revealed hemolytic anemia (HA), severe immune thrombocytopenia (ITP), and bilateral pneumonia. Molecular testing confirmed a diagnosis of COVID-19 pneumonia. Thrombocytopenia did not respond to first-line treatment with immunoglobulin, corticosteroids, and platelet transfusions. Addition to therapy of the thrombopoietin receptor agonist, eltrombopag, resulted in full recovery. COVID-19 can be associated with ITP and HA. There are neither guidelines nor clinical experience on the treatment of COVID-19-associated ITP and our case, showing complete response to eltrombopag, may help clinicians in their practice during the COVID-19 pandemic. Plain language summary The case of an 83-year-old woman with COVID-19 pneumonia associated with two severe blood diseases that cause platelet and red cell destruction Coronavirus disease 2019 (COVID-19) is caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We do not know exactly whether this virus can stimulate our immune system to react against platelets and red blood cells. Herein, we report a case of COVID-19 pneumonia associated with two severe blood diseases, immune thrombocytopenia, which causes platelet destruction, and hemolytic anemia, which causes red cell destruction. An 83-year-old woman was admitted to the hospital because of both difficulty in breathing and diffuse bleeding in mucosae and skin. Exams revealed hemolytic anemia, severe immune thrombocytopenia, and pneumonia in both lungs. Molecular testing confirmed a diagnosis of COVID-19 pneumonia. The first treatment with immunoglobulin, corticosteroids, and platelet transfusions was not enough to cure thrombocytopenia; the addition of eltrombopag which acts on the thrombopoietin receptor agonist resulted in full recovery. COVID-19 can be present together with immune thrombocytopenia and hemolytic anemia. As there are no guidelines on the treatment of immune thrombocytopenia in patients with COVID-19 and the clinical experience is limited, the complete response achieved with eltrombopag may help clinicians in their practice during the COVID-19 pandemic.

The article shows new designed cermets and processes concerning primary to applications as thermal insulation materials with low emissivity. A new projected microstructure was obtained where dense regions (micropellets) rest inside the main porous pellet. The feature resembles a frozen hypercube, therefore such architecture is called hyper-pellet/ cermet. The processing method to obtain the hyper-cermet is based on sequential tape castings and sintering techniques. Ni-zirconia lamellae were prepared by a special mechanochemical process followed by sintering, which remain inside the main pellets as a dense region. The whole pellet is turned to be porous by employing pore-forming additives. All the constituents and porosity shapes are aligned along the disc/ flake planes. Thermal conductivity is estimated for the materials up to 800 °C by a flash diffusivimeter. Ceramographic analyses show graded density regions with directional constituents and pores. Applications of such materials are foreseen as temperature insulation materials and thermal radiation shields.

There is a general consensus on the importance of the nomenclature, description, and classification of foods and food groups due to the significant impact in nutritional field, especially in the epidemiological one. Particular attention should be addressed towards composite dishes and food preparations that are widely consumed by the population. In this work, 49 Italian composite dishes were selected, described, classified, and coded according to two types of classification and description systems. LanguaL™ is a multi-faceted food categorization system that addresses the requisite of flexibility in terms of food description, allowing description and categorization at different levels of detail. FoodEx2 represents a system of flexible combinations of classifications categories and descriptors based on a hierarchical system for different food safety-related domains. Dishes from different Italian regions were selected according to the EuroFIR Network and the QUALIFU-SIAGRO project, supported by the Italian Ministry of Agricultural, Food and Forestry Policies and Tourism. For each recipe, ingredients, amount and preparations methods were defined. Accuracy of the description of food items becomes very important to ensure a correct link between different Food Composition Tables and/or Food Consumption Databases. All recipes were described and codified by LanguaL™ and FoodEx2 and will be used to update the Italian Food Composition Tables of the CREA Research Centre for Food and Nutrition and further of the international European Food Data Platform: FoodExplorer™ developed by EuroFIR.

Italian food is very popular around the world, but the knowledge of the proximate composition of traditional composite dishes consumed in Italy is limited. This is mainly due to the large regional variety and complexity of such dishes. The present study provides new analytical data in order to fill this gap. Thirty dishes from different regions in Italy were selected including main courses, side dishes and desserts. For each dish, samples were prepared and then analyzed to determine the nutrient composition in terms of moisture, protein, fat, starch, sugars, dietary fibre and energy value. The nutrients varied between the dishes as can be expected. Moreover, to assess their specific nutritional quality, in terms of adequacy or deficit, the nutrients of one portion of every dish were compared with the Dietary References Values (DRVs) for the Italian population. Our results provide an important update of the national Food Composition Database (FCDB) of the CREA Research Centre for Food and Nutrition. The new data widen the nutritional knowledge of a variety of traditional Italian dishes and provide dietary information to health workers, the food industry and consumers.

Background Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure primarily focused on cortical volumes. Much less is known about the effects of smoking on cortical thickness. Smokers and Non-smokers were compared on regional cortical thickness. We predicted smokers would demonstrate greater age-related thinning localized to anterior frontal regions that serve as nodes for the executive, salience, and emotional regulation networks (ESER regions) and those demonstrating significant atrophy in early Alzheimer’s Disease (AD regions). Methods Non-smokers (n = 41) and smokers (n = 41), 22–70 years of age, completed a 4 T MRI study. Regional cortical thickness was quantitated via FreeSurfer. In smokers, associations between smoking severity, decision-making, impulsivity, and regional cortical thickness were examined. Results Smokers demonstrated cortical thinning in the medial and lateral OFC, insula, entorhinal, fusiform, middle temporal, and Composite AD regions. In Smokers, greater pack-years were associated with thinner lateral OFC, middle temporal, inferior parietal, fusiform, precuneus, and Composite AD regions. In Smokers, poorer decision-making/greater risk taking was related to thinner cortices in caudal ACC, rostral middle frontal and superior frontal gyri, and Composite ESER. Higher self-reported impulsivity was associated with thinner rostral and caudal ACC. Conclusions This study provides additional evidence that cigarette smoking is associated with thinner cortices in regions implicated in the development and maintenance of substance use disorders and in regions demonstrating significant atrophy in early AD. The novel structure-function relationships in Smokers further our understanding of the neurobiological substrates potentially underlying the neuropsychological abnormalities documented in smokers.

The demand for nuclear fuel for research reactors is increasing worldwide. However, some nuclear fuel factories have small production volumes. There is a gap in the literature regarding how to expand capacity of those facilities in a safe and reliable way. Thus, the purpose of this work is to propose and validate a conceptual model to increase the production capacity of these factories. We addressed factories that produce plate-type fuel elements loaded with LEU U3Si2-Al, which are typically used in nuclear research reactors. We collected data from a real nuclear fuel plant and applied the model to that data, i.e., we set up a case study. We developed two different strategies for the use of the model, thus generating several production scenarios. Each scenario is an experiment of the different possibilities to enlarge the capacity. We applied discrete events simulation in order to cover all production scenarios. Our tests indicated significant increases in productive capacity, thus showing that the model has fully achieved its proposed objective. One of the main conclusions that we point out is the model’s effectiveness. That effectiveness was demonstrated by using the model in two different strategies and obtaining increases in capacity with both of them.

The hepatitis delta virus (HDV) is a small RNA virus that encodes a single protein and which requires the hepatitis B virus (HBV)-encoded hepatitis B surface antigen (HBsAg) for its assembly and transmission. HBV/HDV co-infections exist worldwide and show a higher prevalence among selected groups of HBV-infected populations, specifically intravenous drug users, practitioners of high-risk sexual behaviours, and patients with cirrhosis and hepatocellular carcinoma. The chronic form of HDV-related hepatitis is usually severe and rapidly progressive. Patterns of the viral infection itself, including the status of co-infection or super-infection, virus genotypes (both for HBV and HDV), and persistence of the virus' replication, influence the outcome of the accompanying and manifested liver disease. Unfortunately, disease severity is burdened by the lack of an effective cure for either virus type. For decades, the main treatment option has been interferon, administered as mono-therapy or in combination with nucleos(t)ide analogues. While its efficacy has been reported for different doses, durations and courses, only a minority of patients achieve a sustained response, which is the foundation of eventual improvement in related liver fibrosis. The need for an efficient therapeutic alternative remains. Research efforts towards this end have led to new treatment options that target specific steps in the HDV life cycle; the most promising among these are myrcludex B, which inhibits virus entry into hepatocytes, lonafarnib, which inhibits farnesylation of the viral-encoded L-HDAg large hepatitis D antigen, and REP-2139, which interferes with HBsAg release and assembly.

The family Cactaceae (commonly known as cactus) comprises plants with a wide applications in traditional folk medicine as well as in food and pharmaceutical industries. Among the geographically spread species in Africa, America, and the Mediterranean basin, Opuntia spp. has received particular attention attributed to its valuable functional and therapeutic compounds. Phenolic acids, antioxidants, biopeptides, pigments, soluble fibers are among those compounds of pharmaceutical and nutritional value. This chapter aims to comprehensively review recent studies and methodologies used to identify these compounds in the various parts of the plant and the biomass wasted during cultivation and fruit processing.

Background Non-alcoholic fatty liver disease (NAFLD) is a spectrum of pathologies characterized by liver damage without history of excessive alcohol intake. Advanced fibrosis, generally detected by transient elastography (TE), is the most significant predictor of poor prognosis and mortality among these patients. This study aimed at assessing the accuracy of five noninvasive methods, compared to TE, for the evaluation of severity of liver fibrosis in patients with NAFLD. Methods The cohort included 41 patients, in whom the result of TE was compared to AST/ALT ratio, BARD Score (Body Mass Index, AST/ALT ratio, diabetes), AST To Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4 Index) and NAFLD Fibrosis Score (NFS). Results The severity of fibrosis, assessed by TE, was the following: F0 (absence of fibrosis): 17%, F1 (mild): 39%, F2 (moderate): 17%, F3 (advanced): 10%, F4 (cirrhosis): 17%. Performances of the diagnostic scores were: 49% for AST/ALT ratio, 68% for BARD Score, 73% for APRI, 59% and 71% for the lower and upper cut-off of FIB-4 Index, 61% and 76% for the lower and upper cut-off of NFS. Conclusions Considering the scores compared to TE, AST/ALT ratio was not enough sensitive, while BARD Score had better diagnostic performance and APRI had a superior accuracy than the formers. However, FIB-4 and NFS were the most useful tests and their performance could be improved through the use of a single cut-off. These findings demonstrated that the most accurate scores, compared to TE, were NFS and FIB-4.

Plant species are fundamental source of nectar in beekeeping since bees access nectar and pollen from flowers. Consequently, bee products are strongly linked to the bee foraging flora source, and, depending on this, they acquire defined features, including their health and medicinal properties. Medicinal plants contribute greatly to increase the beneficial properties of bee products, such as honey, pollen, royal jelly, and propolis. Bee products represent a potential source of natural antioxidants that can counteract the effects of oxidative stress underlying the pathogenesis of many diseases. The antioxidant properties of bee products have been widely studied and there is an abundance of information available in the literature. Notwithstanding, the uniqueness of the presented perspective is to provide an updated overview of the antioxidant properties of bee products derived from medicinal plants as beekeeping sources. This topic is divided and discussed in the text in different sections as follows: (i) beekeeping and the impacts of environmental factors; (ii) an overview of the role of medicinal plants for bee products; (iii) definition and categorization of the main medicinal bee plants and related bee products; (iv) the study approach of the antioxidant properties; (v) the conventional and innovative assays used for the measurement of the antioxidant activity; and (vi) the antioxidant properties of bee products from medicinal plants., info:eu-repo/semantics/publishedVersion

Background and aim Prophylactic implantation of an implantable cardioverter-defibrillator (ICD) is class 1 recommendation for heart failure (HF) patients with reduced ejection fraction (HFrEF) even though its proven advantage is weaker among nonischemic aetiology. In fact, in an era where both optimal medical therapy (OMT) and cardiac resynchronization therapy (CRT) significantly reduce sudden cardiac death (SCD), it is questionable whether ICD still have additional value. The aim of this study was to assess the current benefit of ICDs in preventing sudden cardiac death through resuscitated cardiac arrest (RCA), appropriate therapy for sustained ventricular tachycardia (VT) or fibrillation (VF) in a contemporary population of idiopathic HFrEF patients. Methods Single-centre retrospective study of consecutive symptomatic (NYHA class II to IV) idiopathic HFrEF patients with an ICD (either alone or in association with CRT), and remote monitoring with the corresponding software (MerlinTM, LatitudeTM, CarelinkTM, MicroPortTM or BiotronikTM) to assure appropriate event supervising. Idiopathic aetiology was assumed after excluding other probable causes. Coronary angiogram was required to exclude ischemic aetiology. Only those with prophylactic ICD implantation were included. RCA was defined as collapse with clinical signs of cardiac arrest and VF or VT appropriately terminated by ICD. In order to be sustained, VT episode had to have last at least 30 seconds. Results From 781 remote monitoring controlled patients, a total of 187 consecutive symptomatic idiopathic HFrEF patients with an ICD (125 men, mean age 64±18 years) were enrolled. Patients were on optimal medical therapy (ACEi/ARB: n=168, 90%; BB: n=154, 82%; mineralocorticoid antagonists: n=91, 49%; CRT: n=130, 70%; see Table). After a median follow-up of 99 months (IQR 62.2), RCA occurred in 10.7% (n=20) and 36.9% (n=69) had appropriately terminated VT. Both left ventricular ejection fraction (LVEF) improvement and CRT implantation did not independently reduce the incidence of RCA and VT requiring ICD therapy (OR, 1.02; 95% CI, 0.99–1.05; P=0.146 and OR, 0.85; 95% CI, 0.34–2.13; P=0.728; respectively). All cause mortality was 20 (10.7%). Inappropriate therapy was given as shocks to 41 patients (21.9%) and as antitachycardia pacing (ATP) to 30 (16%), opposing with appropriately given therapy to 43 (23%) and 63 (33.7%) patients, respectively (see Figure), contributing to a net clinical benefit (NCB) of 18.8%, favouring ICD implantation. Conclusion In this contemporaneous real-world population of symptomatic idiopathic HFrEF patients, episodes of impending cardiac death were frequent. Prophylactic ICD implantation seems to have added further benefit reducing SCD on top of optimal medical therapy, LVEF improvement and coexisting CRT. Funding Acknowledgement Type of funding source: None

Background Catheter ablation (CA), has gained wider acceptance as an attractive option for treating symptomatic AF. Although traditionally seen as a safe procedure, there is limited and conflicting data on procedure-related early morbimortality, with new evidence suggesting early mortality may be as high as 0.5%-1%. Purpose We aimed to assess the rates of early and late morbimortality of post-atrial fibrillation (AF) ablation in high-volume centers. Methods Prospective registry of 2 high-volume ablation centers, comprising 3722 consecutive patients (mean age 61.1±11.2, 66.4% male, n=2471), who underwent AF ablation from 2005 to 2019. Early mortality was defined as death during initial admission or during the first 45 days after ablation. Median follow-up time was 5.4 years. Results Most patients were treated with radiofrequency (97%) while 3% were treated with cryoablation. Early mortality was 0.08% (n=3), with a median time from ablation to death of 22 days. Cumulative mortality at 3, 6 and 12 months was 0.08%, 0.16% and 0.19%, respectively. At 3 and 5 years, mortality remained low at 0.48% and 0.73%, respectively. Early mortality was higher among patients who had suffered procedural complications (fistula and stroke, p Conclusion Early mortality following ablation is very low ( AF catheter ablation morbimort Funding Acknowledgement Type of funding source: None

Background Cardiopulmonary exercise testing (CPET) is recommended in the evaluation of selected patients with Heart Failure (HF). Notwithstanding, its prognostic significance has mainly been ascertained in those with left ventricular ejection fraction (LVEF) Methods We conducted a single-center retrospective study of consecutive patients with HF and LVEF Results Overall, 404 HF patients (mean age 57±11 years, 78.2% male, 55.4% ischemic HF) were included, of whom 321 (79.5%) had HFrEF and 83 (20.5%) HFmrEF. Compared to the former, those with HFmrEF had a significantly higher mean peak oxygen uptake (pVO2) (20.2±6.1 vs 16.1±5.0 mL/kg/min; p35 and EOV identified patients at higher risk for events (all p16.7 and >15.8 mL/kg/min more accurately identified patients at lower risk for the primary endpoint (NPV: 91.2 and 60.5% for HFmrEF and HFrEF, respectively; both p Conclusions CPET is a useful tool in HFmrEF. Both pVO2 and EOV independently predicted the primary endpoint in HFmrEF and HFrEF, contrasting with VE/VCO2, which remained predictive only in latter group. Our findings strengthen the prognostic role of CPET in HF with either reduced or mid-range LVEF. Funding Acknowledgement Type of funding source: None

Background Epicardial adipose tissue (EAT) has been linked to the presence and burden of atrial fibrillation (AF). However, it is still unclear whether this relationship is causal or simply a surrogate marker of other risk factors commonly associated with AF. Purpose The purpose of this study was to assess the relationship between these factors and EAT, and to compare their performance in predicting AF recurrence after an ablation procedure. Methods We assessed 575 consecutive patients (mean age 61±11 years, 62% male) undergoing AF ablation preceded by cardiac CT in a high-volume ablation center. EAT was measured on cardiac CT using a modified simplified method. Patients were divided into 2 groups (above vs. below the median EAT volume). Cox regression was used to assess the relationship between epicardial fat, risk factors, and AF relapse. Results Patients with above-median EAT volume were older (p0.10). Conclusion Classic cardiovascular risk factors are more prevalent in patients with higher amounts of epicardial fat. However, unlike these risk factors, EAT is a powerful predictor of AF recurrence after ablation. These findings suggest that EAT is not merely a surrogate marker, but an important participant in the pathophysiology of AF. EAT, cvrf and AF burden Funding Acknowledgement Type of funding source: None

Isoprenoids have been reported to be the diverse and most abundant natural products with various applications. Microbial approaches have recently attracted much attention for the production of high-level isoprenoid-based biofuels through metabolic engineering efforts and synthetic biology techniques. In this chapter, the recent achievements of metabolic engineering in improving isoprenoid-based biofuel molecules including hemiterpenoids, monoterpenoids, and sesquiterpenoids are reviewed. A perspective discussion on the current situation and potential future of biofuels is also exploited.

We previously reported that at 1-and-4weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12months post treatment. The segmentation method employed did not permit examination of frontal subregions that serve as nodes of the executive, salience and emotional regulation networks; structural abnormalities in these circuits are associated with relapse in those seeking treatment for alcohol use disorders (AUD). The primary goal of this study was to determine if frontal cortical subregion volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared bilateral components of the dorsal prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex and insula volumes, at 1 and 4weeks of abstinence, between individuals who resumed drinking within 12months of treatment (Relapsers) those who showed sustained abstinence over 12months following treatment (Abstainers) and healthy Controls. At 1 and 4weeks of sobriety, Relapsers demonstrated significantly smaller volumes than Controls in 15 of 20 regions of interest, while Abstainers only had smaller volumes than Controls in 5 of 20 regions. In Relapsers, increasing volumes over 1month in multiple frontal subregions and the insula were associated with longer duration of abstinence after treatment. The persistent bilateral frontal and insula volume deficits in Relapsers over 4weeks from last alcohol use may have implications for neurostimulation methods targeting anterior frontal/insula regions, and represent an endophenotype that differentiates those who respond more favorably to available psychosocial and pharmacological interventions.

Lipohypertophy (LH) is the most common skin complication of incorrect injection technique which does not only represent an aesthetic defect but also severely disrupts insulin pharmacokinetics/pharmacodynamics. As a consequence of that, hormone release is delayed and unexplained/unpredictable hypoglycemia occurs, both deteriorating metabolic control while negatively affecting adherence to treatment and quality of life. The economic burden due to unwanted intra-LH injections is accounted for by inappropriately high insulin requirements, increased emergency-related hospitalizations, and loss of work days. Greater attention has to be paid by diabetes care teams to education programs with periodic refreshers to achieve better metabolic control and reduce the economic burden of diabetes.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Although both albuminuria and glomerular filtration rate (GFR) are well-established diagnostic/prognostic biomarkers of DKD, they have important limitations. There is, thus, increasing quest to find novel biomarkers to identify the disease in an early stage and to improve risk stratification. In this review, we will outline the major pitfalls of currently available markers, describe promising novel biomarkers, and discuss their potential clinical relevance. In particular, we will focus on the importance of recent advancements in multi-omic technologies in the discovery of new DKD biomarkers. In addition, we will provide an update on new emerging approaches to explore renal function and structure, using functional tests and imaging.

Heat shock protein 27 (HSP27), an intracellular molecular chaperone, is involved in the pathogenesis of cancer by promoting both tumor cell proliferation and resistance to therapy. HSP27 is also present in the circulation and circulating HSP27 (sHSP27) can elicit an autoimmune response with production of antibodies. Levels of sHSP27 are enhanced in patients with hepatocellular carcinoma (HCC); it is, however, unknown whether changes in HSP27 antibody levels occur in patients with HCC and can be exploited as a circulating biomarker of HCC. Our aim was to assess the potential association between newly diagnosed HCC and serum anti-HSP27 antibody levels. In this cross-sectional study, anti-HSP27 antibody levels were measured in serum samples from 71 HCC patients, 80 subjects with chronic liver disease, and 38 control subjects by immunoenzymatic assay. Anti-HSP27 antibody levels did not differ significantly among groups. However, in patients with chronic active hepatitis/cirrhosis, anti-HSP27 levels were significantly higher in subjects with a positive history of alcoholism (p = 0.03). Our data do not support the hypothesis that anti-HSP27 antibody levels may help identify patients with HCC among subjects with chronic liver disease. However, our finding that alcohol-related liver disease is associated with higher anti-HSP27 levels is novel and deserves further investigations.

Introduction: Cardiac rehabilitation (CR) programs have a central role in cardiovascular medicine, encompassing a comprehensive framework able to holistically address various facets of cardiovascular disease. However, several obstacles to their optimal application have been reported. Over the years, the Portuguese Society of Cardiology has periodically conducted a national survey on the state of CR in Portugal. Objectives: This study reports the results of the 2019 survey on CR. Methods: In December 2019 a voluntary questionnaire was sent to centers offering CR programs, consisting of several items concerning this intervention. Results: In 2019, 25 centers provided structured CR programs. A total of 2182 patients underwent phase II programs, representing an increase of 13% from the previous survey. Of these, 67.2% were referred due to ischemic heart disease, and 14.5% due to heart failure. Acute coronary syndromes (ACS) comprised 49.3% of referrals, leading to an estimated 9.3% CR coverage. A total of 606 patients participated in phase III programs (a decrease of 37%). Drop-out rates ranged from 0-68%; 91% of centers presented drop-out rates

Chronic cigarette smoking is associated with regional metabolite abnormalities in choline-containing compounds, creatine-containing compounds, glutamate, and N-acetylaspartate. The effects of cigarette smoking on anterior frontal cortical gamma-aminobutyric acid (GABA) concentration is unknown. This study compared chronic smokers (n=33) and non-smokers (n=31) on anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC) GABA+ (the sum of GABA and co-edited macromolecules) concentrations and associations of GABA+ levels in these regions with neurocognition in seven different domains of functioning, decision-making and impulsivity measures. Smokers had significantly lower right DLPFC GABA+ concentration than non-smokers, but groups were equivalent on ACC GABA+ level. Across groups, greater number of days since end of menstrual cycle were related to higher GABA+ level in the ACC, but not right DLPFC GABA+ concentration. In exploratory correlation analyses, higher ACC and right DLPFC GABA+ levels were associated with faster processing speed and better auditory-verbal memory, respectively in the combined group of smokers and non-smokers; in smokers only, higher ACC GABA+ was related to better decision-making and auditory-verbal learning. This study contributes additional novel data on the adverse effects of chronic cigarette smoking on the adult human brain and demonstrated ACC and DLPFC GABA+ concentrations were associated with neurocognition and decision-making/impulsivity in active cigarette smokers. Longitudinal studies on the effects of smoking cessation on regional brain GABA levels, with a greater number of female participants, are required to determine if the observed metabolite abnormalities are persistent or normalize with smoking cessation.

Gastroesophageal reflux disease (GERD) is defined by the presence of symptoms induced by the reflux of the stomach contents into the esophagus. Although clinical manifestations of GERD typically involve the esophagus, extra-esophageal manifestations are widespread and less known. In this review, we discuss extra-esophageal manifestations of GERD, focusing on clinical presentations, diagnosis, and treatment. Common extra-esophageal manifestations of GERD include chronic cough, asthma, laryngitis, dental erosions, and gingivitis. Extra-esophageal involvement can be present also when classic GERD symptoms are absent, making the diagnosis more challenging. Although available clinical studies are heterogeneous and frequently of low quality, a trial with proton pump inhibitors can be suggested as a first-line diagnostic strategy in case of suspected extra-esophageal manifestations of GERD.

Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to humans and animals. Their pharmacological profile results from the structural similarity between lysergic acid-derived compounds and noradrenalin, dopamine, and serotonin neurotransmitters. To reduce their toxicological risk, while increasing their bioavailability, improved delivery systems were proposed. This review discusses the safety aspects of using ergot alkaloids in ocular pharmacology and proposes the development of lipid and polymeric nanoparticles for the topical administration of these drugs to enhance their therapeutic efficacy for the treatment of glaucoma., This work was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) granted to I.B. (88887.368385/2019-00), by the Portuguese Science and Technology Foundation (FCT) and co-financed by FEDER, under the Partnership Agreement PT2020, granted to E.B.S. (UIDB/04469/2020 strategic fund), by the Nutraceutica come supporto nutrizionale nel paziente oncologico, project granted to A.S. (CUP: B83D18000140007), and by Foundation of Research Support of the São Paulo State (FAPESP) for the funded projects 2011/10333-1, 2012/03427-2, and 2018/26069-0 and for the National Council for Scientific and Technological Development (CNPq) granted to W.P.O., info:eu-repo/semantics/publishedVersion

Aims Magnetic resonance imaging (MRI) studies report widespread cortical thinning in individuals with alcohol use disorder (AUD), but did not consider potential effects of pro-atherogenic conditions such as hypertension, type 2 diabetes mellitus, hepatitis C seropositivity and hyperlipidemia on cortical thickness. The conditions are associated with regional cortical thinning in those without AUD. We predicted that individuals with concurrent AUD and pro-atherogenic conditions demonstrate the greatest regional cortical thinning in areas most vulnerable to decreased perfusion. Methods Treatment-seeking individuals with AUD (n = 126) and healthy controls (CON; n = 49) completed a 1.5 T MRI study. Regional cortical thickness was quantitated via FreeSurfer. Individuals with AUD and pro-atherogenic conditions (Atherogenic+), AUD without pro-atherogenic conditions (Atherogenic−) and CON were compared on regional cortical thickness. Results Individuals with AUD showed significant bilateral cortical thinning compared to CON, but Atherogenic+ demonstrated the most widespread and greatest magnitude of regional thinning, while Atherogenic− had reduced thickness primarily in anterior frontal and posterior parietal lobes. Atherogenic+ also showed a thinner cortex than Atherogenic− in lateral orbitofrontal and dorso/dorsolateral frontal cortex, mesial and lateral temporal and inferior parietal regions. Conclusions Our results demonstrate significant bilateral cortical thinning in individuals with AUD relative to CON, but the distribution and magnitude were influenced by comorbid pro-atherogenic conditions. The magnitude of cortical thinning in Atherogenic+ strongly corresponded to cortical watershed areas susceptible to decreased perfusion, which may result in morphometric abnormalities. The findings indicate that pro-atherogenic conditions may contribute to cortical thinning in those seeking treatment for AUD.

Type 1 diabetes (T1D) is a common autoimmune disease that is characterized by insufficient insulin production. The onset of T1D is the result of gene-environment interactions. Sociodemographic and behavioural factors may contribute to T1D, and the gut microbiota is proposed to be a driving factor of T1D. An integrated preventive strategy for T1D is not available at present. This case–control study attempted to estimate the exposure linked to T1D to identify significant risk factors for healthy children. Forty children with T1D and 56 healthy controls were included in this study. Anthropometric, socio-economic, nutritional, behavioural, and clinical data were collected. Faecal bacteria were investigated by molecular methods. The findings showed, in multivariable model, that the risk factors for T1D include higher Firmicutes levels (OR 7.30; IC 2.26–23.54) and higher carbohydrate intake (OR 1.03; IC 1.01–1.05), whereas having a greater amount of Bifidobacterium in the gut (OR 0.13; IC 0.05 – 0.34) was a protective factor for T1D. These findings may facilitate the development of preventive strategies for T1D, such as performing genetic screening, characterizing the gut microbiota, and managing nutritional and social factors.