Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome

Long Coronavirus disease-19 (COVID-19) refers to the persistence of symptoms related to the infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This condition is described as persistent and can manifest in various combinations of signs and symptoms, such as fatigue, headache, dyspnea, depression, cognitive impairment, and altered perception of smells and tastes. Long COVID-19 may be due to long-term damage to different organs-such as lung, brain, kidney, and heart-caused by persisting viral-induced inflammation, immune dysregulation, autoimmunity, diffuse endothelial damage, and micro thrombosis. In this review, we discuss the potential and biologically plausible role of some vitamins, essential elements, and functional foods based on the hypothesis that an individual's dietary status may play an important adjunctive role in protective immunity against COVID-19 and possibly against its long-term consequences

A simple blood tests, such as complete blood count, can predict calcification grade of Abdominal Aortic Aneurysm.

Objective. The pathogenesis of abdominal aortic aneurysm (AAA) is complex and different factors, including calcification, are linked to increased complications. This study was conducted in order to verify if classical risk factors for AAA and cell blood count parameter could help in the identification of calcification progression of the aneurysm. Design. Risk factors were collected and cell blood count was performed in patients with AAA and patients were analyzed for the presence of aorta calcification using CT angiography. Results. We found no association of calcification grade with risk factors for AAA but we found a strong association between MCV, MCH, and calcification grade. Instead, no association was found with the other parameter that we analyzed. Conclusions. In this study, we demonstrate that biomarkers such as MCV and MCH could have potential important information about AAA calcification progression and could be useful to discriminate between those patients that should undergo a rapid imaging, thus allowing prompt initiation of treatment of suspicious patients that do not need imaging repetition

Potential protective effects of melatonin against UV-A irradiation on fibroblast cell line

The sun’s radiation that reaches Earth contains ultraviolet (UV) wavelights made up of a combination of UV-A (95%) and UV-B (5%) radiations. Chronic sun exposure is responsible for long term clinical skin changes such as photoaging, photodamage and photocancers. Moreover, inflammation is mostly due to UV-A which stimulates the production of reactive oxygen species (ROS) inducing also photoaging (Mouchet et al., 2010; Marionnet et al., 2010). In order to protect themselves against oxidative stress, skin cells developed several defense systems, including ROS and metal ions scavengers and a battery of detoxifying and repair enzymes (Bickers and Athar, 2006). In addition, UV-A can also directly influence the structure of nucleic acids, breaking the chain or changing the nucleotide sequence. Altogether these perturbations of cells homeostasis advantages a significant up-regulation of oxidative and inflammatory responsive genes. In this study, we focused our attention on prevention of photodamage, choosing melatonin as antioxidant agent. Melatonin is a neuroendocrine mediator with pleiotropic bioactivities such as hormonal, neurotransmitter, immunomodulator and biological modifier actions. Its antioxidant activity is the result of two different but synergic actions: a direct, due to its ability to act as a free radical scavenger and an indirect due to the up-regulation of antioxidant enzymes (Fischer et al., 2008). The aim of the present study was to analyze the impact of pre-treatment of murine fibroblasts cells (NIH-3T3) with melatonin (10-3 M- kindly provided by Chronolife S.r.l., Roma, Italy) later irradiated by UV-A irradiation (15 J/ cm2) evaluating the changes of fibroblast microenvironment conditions. We observed that UV-A irradiation caused matrix restructuration and alteration, oxidative stress and inflammation; while melatonin pre-treatment suppresses UV-A induced photodamage. Collectively, these results suggest that melatonin provides relevant protective effects against UV-A irradiation. A new chapter of melatonin in dermato-endocrine research could be open

Pediatric obesity and severe asthma: Targeting pathways driving inflammation

Asthma affects more than 300 million people of all ages worldwide, including about 10-15% of school-aged children, and its prevalence is increasing. Severe asthma (SA) is a particular and rare phenotype requiring treatment with high-dose inhaled corticosteroids plus a second controller and/or systemic glucocorticoid courses to achieve symptom control or remaining "uncontrolled" despite this therapy. In SA, other diagnoses have been excluded, and potential exacerbating factors have been addressed. Notably, obese asthmatics are at higher risk of developing SA. Obesity is both a major risk factor and a disease modifier of asthma in children and adults: two main "obese asthma" phenotypes have been described in childhood with high or low levels of Type 2 inflammation biomarkers, respectively, the former characterized by early onset and eosinophilic inflammation and the latter by neutrophilic inflammation and late-onset. Nevertheless, the interplay between obesity and asthma is far more complex and includes obese tissue-driven inflammatory pathways, mechanical factors, comorbidities, and poor response to corticosteroids. This review outlines the most recent findings on SA in obese children, particularly focusing on inflammatory pathways, which are becoming of pivotal importance in order to identify selective targets for specific treatments, such as biological agents

Vascular oxidative stress-induced senescence is minimized by melatonin intake in ApoE-deficient mice

Aging is a natural process that produces deleterious changes in all tissues of the organism. One leading theory about the cause of aging suggest that oxidative stress play a fundamental role in pathogenesis. Oxidative stress induces intracellular damage that affects all biological components, including, DNA, lipids, sugars and proteins. Therefore, the imbalance between intracellular reactive oxygen species (ROS) and antioxidant defence mechanisms results in harmful oxidative stress. One of the most widely considered strategies for preventing aging and for treating age-related disease is the use of natural anti-oxidant agents, such as melatonin and resveratrol. Melatonin is a potent endogenous anti-oxidant neurohormone, which acts through various mechanisms to ameliorate the toxic effects of ROS. However, little is known about the mechanisms of signalling pathways through which melatonin acts to reverse the effects of ROS. In the present study we treated ApoE-deficient mice, a well-known senescence model, from 6th week to 15th week of life, with a specific melatonin formulation: Armonia Retard (kindly provided by Nathura s.r.l, Reggio Emilia, Italy), with an extended-release pharmacokinetic, at different progressive doses 0.04, 0.1, 10 mg/kg/day. We used the same treatment in C57BL6 mice, as control group. Vascular alterations were evaluated in aorta by morphology and immunofluorescence analysis was focused on pleiotropic inflammatory markers, such as interleukins (IL) 6 and 10, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α). We observed in ApoE-deficient mice endothelial cell detachment and  IL-6, IL-10, iNOS and TNF-α overexpression. Melatonin treatment improved not only the endothelial damage, but also the overall vascular cytoarchitecture and reduced inflammation and macrophages infiltration. In particular, melatonin Retard at the highest dose, recovered all the above markers to the levels of C57BL6 mice. These results outline the anti-inflammatory and anti-oxidant properties of melatonin and its beneficial anti-aging and anti-atherosclerotic effects, especially in extended-release formulation

Sirtuin 6 localization at cortical brain level of young diabetic mice

The metabolic syndrome, characterized by visceral obesity, dyslipidaemia, hyperglycaemia and hypertension, has become one of the major public-health challenges worldwide and it is strictly associated with the development of type II diabetes and neurodegenerative diseases (Alberti et al. 2005; Panza et al. 2010). Increased metabolic flux to the brain during overnutrition can orchestrate stress response, blood-brain barrier alteration, microglial cells activation and neuroinflammation (Nerurkar et al., 2011). The protein sirtuin family is a class of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that act on a variety of targets and so play a key role in central physiological regulation (Sebastian et al., 2012; Wang et al., 2012). To assess the physiopathological significance of sirtuin6 (SIRT6) at brain cortical level, we analysed its specific expression and subcellular localization in young db/db mice, animal model of type II diabetes mellitus, and respective control lean mice. In particular, we analysed the cytoarchitecture of the brain cortex, evaluated SIRT6 expression and its localization by immunohistochemistry comparing young db/db mice to lean control mice, distinguishing among the six cortical layers and between motor and somatosensory cortex. We observed that SIRT6 is mainly localized in the nucleus of both lean and db/db mice. Diabetic mice showed few SIRT6 positive cells respect to lean control mice in all cortical layers without significant differences between motor and somatosensory cortex. No morphological alteration have been find. In conclusion, our findings contribute to further understand SIRT6 protein expression in the early steps of type II diabetes mellitus and suggest its implication in the pathogenic processes of diabetes mellitus and diabetes–induced neurodegeneration

Sirtuin 6 localization at cortical brain level of young diabetic mice

The metabolic syndrome, characterized by visceral obesity, dyslipidaemia, hyperglycaemia and hypertension, has become one of the major public-health challenges worldwide and it is strictly associated with the development of type II diabetes and neurodegenerative diseases (Alberti et al. 2005; Panza et al. 2010). Increased metabolic flux to the brain during overnutrition can orchestrate stress response, blood-brain barrier alteration, microglial cells activation and neuroinflammation (Nerurkar et al., 2011). The protein sirtuin family is a class of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that act on a variety of targets and so play a key role in central physiological regulation (Sebastian et al., 2012; Wang et al., 2012). To assess the physiopathological significance of sirtuin6 (SIRT6) at brain cortical level, we analysed its specific expression and subcellular localization in young db/db mice, animal model of type II diabetes mellitus, and respective control lean mice. In particular, we analysed the cytoarchitecture of the brain cortex, evaluated SIRT6 expression and its localization by immunohistochemistry comparing young db/db mice to lean control mice, distinguishing among the six cortical layers and between motor and somatosensory cortex. We observed that SIRT6 is mainly localized in the nucleus of both lean and db/db mice. Diabetic mice showed few SIRT6 positive cells respect to lean control mice in all cortical layers without significant differences between motor and somatosensory cortex. No morphological alteration have been find. In conclusion, our findings contribute to further understand SIRT6 protein expression in the early steps of type II diabetes mellitus and suggest its implication in the pathogenic processes of diabetes mellitus and diabetes–induced neurodegeneration

Acute cough in children and adolescents: A systematic review and a practical algorithm by the Italian Society of Pediatric Allergy and Immunology

The current systematic review presented and discussed the most recent studies on acute cough in pediatric age. After that, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to pediatric patients, such as infants, children, and adolescents, with acute cough. An acute cough is usually consequent to upper respiratory tract infections and is self-resolving within a few weeks. However, an acute cough may be bothersome, and therefore remedies are requested, mainly by the parents. An acute cough may significantly affect the quality of life of patients and their family.Several algorithms for the management of acute cough have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, and, also, in accordance to the Italian National Health System, which regularly follows the child from birth to all lifelong. Based on our findings, infants from 6 months, children, and adolescents with acute cough without cough pointers can be safely managed using well-known medications, preferably non-sedative agents, such as levodropropizine and/or natural compounds, including honey, glycerol, and herb-derived components

Chronic cough in childhood: A systematic review for practical guidance by the Italian Society of Pediatric Allergy and Immunology

The current systematic review presented and discussed the most recent studies on pediatric chronic cough. In addition, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to a pediatric patient with chronic cough.Several algorithms on chronic cough management have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, from birth until adulthood. Based on our findings, children and adolescents with chronic cough without cough pointers can be safely managed, initially using the watchful waiting approach and, successively, starting empirical treatment based on cough characteristics. Unlike other algorithms that suggest laboratory and instrumental investigations as a first step, this review highlighted the importance of a "wait and see" approach, consisting of parental reassurance and close clinical observation, also due to interprofessional collaboration and communication between general practitioners and specialists that guarantee better patient management, appropriate prescription behavior, and improved patient outcome. Moreover, the neonatal screening program provided by the Italian National Health System, which intercepts several diseases precociously, allowing to treat them in a very early stage, helps and supports a "wait and see" approach.Conversely, in the presence of cough pointers or persistence of cough, the patient should be tested and treated by the specialist. Further investigations and treatments will be based on cough etiology, aiming to intercept the underlying disease, prevent potentially irreversible tissue damage, and improve the general health of patients affected by chronic cough, as well as the quality of life of patients and their family. Further high-quality randomized controlled trials are needed to validate this algorithm's performance in real clinical practice

Different ways to manage Indocyanine green fluorescence to different purposes in liver surgery. A systematic review.

Fluorescent properties of indocyanine green (ICG) for hepatic tumor identification and features have been recently studied. The aim is to review the published data on the use of ICG enhanced fluorescence surgery during liver resection. A systematic search of literature was performed using MEDLINE, EMBASE, Cochrane and Web of Science libraries. For all eligible studies, the following data were extracted: study design, number of cases, management of indocyanine green (dose, time and method of administration), type of surgery, outcome variables, false positive and accuracy value, if reported. For statistical analysis, it was considered significant P<0.05, when published. 19 articles were fully analyzed and data were extracted. A total of 718 cases were globally analyzed as study group. No side effects of ICG were reported in any articles. 12 prospective observational, 1 randomized and 2 case-control studies were found. Three case reports and one experimental on animal model were also included. Detection of superficial lesions, segmental staining, biliary anatomy investigation (biliary leakage detection, biliary tree anatomy) were the main clinical application of fluorescence liver guided surgery. The overall quality of the data currently available is limited but the role of fluorescence guided liver surgery seems promising