Melatonin Enhances Neural Differentiation of Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ASCs) are adult multipotent stem cells, able to differentiate toward neural elements other than cells of mesodermal lineage. The aim of this research was to test ASC neural differentiation using melatonin combined with conditioned media (CM) from glial cells. Isolated from the lipoaspirate of healthy donors, ASCs were expanded in a basal growth medium before undergoing neural differentiation procedures. For this purpose, CM obtained from olfactory ensheathing cells and from Schwann cells were used. In some samples, 1 µM of melatonin was added. After 1 and 7 days of culture, cells were studied using immunocytochemistry and flow cytometry to evaluate neural marker expression (Nestin, MAP2, Synapsin I, GFAP) under different conditions. The results confirmed that a successful neural differentiation was achieved by glial CM, whereas the addition of melatonin alone did not induce appreciable changes. When melatonin was combined with CM, ASC neural differentiation was enhanced, as demonstrated by a further improvement of neuronal marker expression, whereas glial differentiation was attenuated. A dynamic modulation was also observed, testing the expression of melatonin receptors. In conclusion, our data suggest that melatonin's neurogenic differentiation ability can be usefully exploited to obtain neuronal-like differentiated ASCs for potential therapeutic strategies.

Whooping Cough Cases Increase in Central Italy after COVID-19 Pandemic.

Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B. pertussis prevalence in pediatric patients admitted to the Reference Italian Pediatric Hospital, located in Rome, from January 2015 to July 2023. A total of 5464 tests for B. pertussis were performed during the study period, and 6.9% were positive. At the time of the COVID-19 pandemic, there was a sharp decrease in the presence of B. pertussis, which reappeared only in August 2023, recording five new cases. All five children presented with paroxysmal cough 5 to 10 days before admission. Four patients had other mild respiratory symptoms and moderate B. pertussis DNA levels (Ct mean: 26). Only one child, with very high B. pertussis DNA levels (Ct: 9), presented with severe respiratory failure. The patients with mild/moderate infection achieved clinical recovery while the patient with the severe manifestation died of cardiac arrest. These observations highlight the reemergence of pertussis even in vaccinated countries and its association with morbidity and mortality especially in young children. This emphasizes the importance of rapid diagnosis to immediately implement appropriate treatment and monitoring of immune status.

Presence and Significance of Multiple Respiratory Viral Infections in Children Admitted to a Tertiary Pediatric Hospital in Italy.

Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still controversial. This study aimed to investigate the type of viral mono- and co-infections by also evaluating viral correlations in 3525 respiratory samples from 3525 pediatric in/outpatients screened by the Allplex Respiratory Panel Assays and with a Severe Acute Respiratory Syndrome-COronaVirus 2 (SARS-CoV-2) test available. Overall, viral co-infections were detected in 37.8% of patients and were more frequently observed in specimens from children with lower respiratory tract infections compared to those with upper respiratory tract infections (47.1% vs. 36.0%, p = 0.003). SARS-CoV-2 and influenza A were more commonly detected in mono-infections, whereas human bocavirus showed the highest co-infection rate (87.8% in co-infection). After analyzing viral pairings using Spearman's correlation test, it was noted that SARS-CoV-2 was negatively associated with all other respiratory viruses, whereas a markedly significant positive correlation (p < 0.001) was observed for five viral pairings (involving adenovirus/human bocavirus/human enterovirus/metapneumoviruses/rhinovirus). The correlation between co-infection and clinical outcome may be linked to the type of virus(es) involved in the co-infection rather than simple co-presence. Further studies dedicated to this important point are needed, since it has obvious implications from a diagnostic and clinical point of view.

Acute Hepatitis of Unknown Origin in Children: Analysis of 17 Cases Admitted to the Bambino Gesù Children's Hospital in Rome.

This study described 17 cases of children admitted to the Bambino Gesù Children's Hospital with acute hepatitis of unknown origin between mid-April and November 2022. Following the World Health Organization's working case definition of probable cases, 17 children, with a median age of 2.1 years (interquartile range: 1.0-7.1), presenting with acute hepatitis non-AE, with serum transaminase >500 IU/L, were included in the study. A pre-specified set of microbiological tests was performed on different biological specimens for all pediatric patients. All patients resulted negative for the common hepatotropic viruses. The most common pathogen detected in blood specimens was human-herpes-virus-7 (52.9%). Adenovirus was detected more frequently in stool specimens (62.5%) than in respiratory (20.0%) or blood samples (17.6%). Regarding Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, one child tested positive two days after admission, while antibodies against spike and nucleoprotein were present in 82.3% of patients. A co-pathogen detection was observed in 94.1% of children. Overall, 16 children recovered without clinical complications, while one patient required liver transplantation. In these cases of acute hepatitis of unknown origin, adenovirus was mainly detected in stool samples. A co-pathogen detection was also frequently observed, suggesting that the etiology of this acute hepatitis is most probably multifactorial.

The Therapeutic Trip of Melatonin Eye Drops: From the Ocular Surface to the Retina.

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous topical administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts. Moreover, it provides data suggesting that the topical administration of melatonin as eye drops is a real possibility, utilizing nanotechnological formulations that could improve its solubility and permeation through the eye. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

Behavioral Therapy for People With Diabetes Who Smoke: A Scoping Review.

BACKGROUND: Tobacco smoking exacerbates diabetes-related complications; its prevalence is notwithstanding substantial. Persons with diabetes face a number of barriers and challenges to quitting such as multiple lifestyle restrictions; tailored interventions are required for smoking cessation. OBJECTIVE: To identify research on behavioral interventions for smoking cessation in diabetes. METHODS: Studies had to be randomized controlled trials, quasiexperimental or systematic reviews. The behavioral interventions included were: the 5As, Cognitive-Behavioral Therapy, Motivational Interviewing, Contingency Management, Health Coaching and Counselling, as compared to standard care. The outcomes were self-reported and/or biochemically verified smoking cessation. CINAHL Complete, MEDLINE Complete, the Cochrane databases of systematic reviews and randomized controlled trials, PsychInfo and PubMed Central were searched until July, 2023. Keywords used included diabetes, smoking cessation and each of the behavioral interventions included. RESULTS: 1615 papers were identified. Three studies on the 5As/brief advice, 4 on Motivational Intervention and 1 on counseling were retained. The results on the 5As and Motivational Interviewing were conflicting. More intensive interventions appear to be more successful in achieving smoking cessation in smokers with diabetes. CONCLUSIONS: Future research should focus on the continued development and evaluation of structured smoking cessation interventions based on the 5As, Motivational interviewing and Cognitive Behavioral Therapy.

Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multi-centre case-control study.

BACKGROUND: In high-resource settings the survival of immunocompromised (IC) children has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools and outcome of IC children with TB in Europe. METHODS: Multicentre, matched case-control study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), capturing TB cases <18 years diagnosed 2000-2020. RESULTS: 417 TB cases were included, comprising 139 children with IC (HIV, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions) and 278 non-IC children as controls. Non-respiratory TB was more frequent among cases than controls (32.4% vs. 21.2%; p = 0.013). IC patients had an increased likelihood of presenting with severe disease (57.6% vs. 38.5%; p < 0.001; OR [95% CI]: 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs. 6.0%; p < 0.001) and QuantiFERON-TB Gold assay (30.0% vs. 7.3%; p < 0.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs. 49.3%; p = 0.083). Although the mortality in IC children was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs. 6.1%; p = 0.004). CONCLUSIONS: IC children with TB disease in Europe have increased rates of non-respiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in IC patients, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

Molecular characterization of SARS-CoV-2 Omicron clade and clinical presentation in children.

Since its emergence, SARS-CoV-2 Omicron clade has shown a marked degree of variability and different clinical presentation compared with previous clades. Here we demonstrate that at least four Omicron lineages circulated in children since December 2021, and studied until November 2022: BA.1 (33.6%), BA.2 (40.6%), BA.5 (23.7%) and BQ.1 (2.1%). At least 70% of infections concerned children under 1 year, most of them being infected with BA.2 lineages (n = 201, 75.6%). Looking at SARS-CoV-2 genetic variability, 69 SNPs were found to be significantly associated in pairs, (phi < - 0.3 or > 0.3 and p-value < 0.001). 16 SNPs were involved in 4 distinct clusters (bootstrap > 0.75). One of these clusters (A23040G, A27259C, T23617G, T23620G) was also positively associated with moderate/severe COVID-19 presentation (AOR [95% CI] 2.49 [1.26-4.89] p-value: 0.008) together with comorbidities (AOR [95% CI] 2.67 [1.36-5.24] p-value: 0.004). Overall, these results highlight the extensive SARS-CoV-2 Omicron circulation in children, mostly aged < 1 year, and provide insights on viral diversification even considering low-abundant SNPs, finally suggesting the potential contribution of viral diversification in affecting disease severity.

Options for Topical Treatment of Oxidative Eye Diseases with a Special Focus on Retinopathies.

Antioxidants, usually administered orally through the systemic route, are known to counteract the harmful effects of oxidative stress on retinal cells. The formulation of these antioxidants as eye drops might offer a new option in the treatment of oxidative retinopathies. In this review, we will focus on the use of some of the most potent antioxidants in treating retinal neuropathies. Melatonin, known for its neuroprotective qualities, may mitigate oxidative damage in the retina. N-acetyl-cysteine (NAC), a precursor to glutathione, enhances the endogenous antioxidant defense system, potentially reducing retinal oxidative stress. Idebenone, a synthetic analogue of coenzyme Q10, and edaravone, a free radical scavenger, contribute to cellular protection against oxidative injury. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, possesses anti-inflammatory and antioxidant effects that could be beneficial in cases of retinopathy. Formulating these antioxidants as eye drops presents a localized and targeted delivery method, ensuring effective concentrations reach the retina. This approach might minimize systemic side effects and enhance therapeutic efficacy. In this paper, we also introduce a relatively new strategy: the alkylation of two antioxidants, namely, edaravone and EGCG, to improve their insertion into the lipid bilayer of liposomes or even directly into cellular membranes, facilitating their crossing of epithelial barriers and targeting the posterior segment of the eye. The synergistic action of these antioxidants may offer a multifaceted defense against oxidative damage, holding potential for the treatment and management of oxidative retinopathies. Further research and clinical trials will be necessary to validate the safety and efficacy of these formulations, but the prospect of antioxidant-based eye drops represents a promising avenue for future ocular therapies.

Presence of neutralizing SARS-CoV-2 antibodies in asymptomatic population of N'Djamena, Chad.

INTRODUCTION: Neutralizing antibodies (NAbs) are an important specific defence against viral infections, as these antibodies bind to specific receptor(s) and block the viral entry. NAbs assessments are therefore useful in determining individual or herd immunity to SARS-CoV-2. This study aims to deepen the investigation by assessing the positivity rate of neutralizing anti-spike antibodies to understand the real protection of the studied population against SARS-CoV-2. METHODS: This study involved 260 plasma samples from a larger cohort of 2,700 asymptomatic volunteer donors, enrolled between August and October 2021 in health facilities of N'Djamena. In this study four different kits and techniques including the pseudotype assay have been used and compared with detect the SARS-CoV-2 antibodies. Pseudotyped vesicular stomatitis virus (VSV), was used both the identify and measure the NAbs that to evaluate the performance of two cheaper and easy to use commercial kits, specific for the detection of receptor-binding domain antibodies (anti-RBD) against the SARS-CoV-2 spike protein. RESULTS: The VSV spike neutralization assay showed that 59.0% (n = 59) samples were positive for NAbs with titers ranging from 1:10 to 1:4800. While 23 out the 41 negative NAbs samples were detected positive using anti-RBD (Abbott) test. Furthermore, a direct and significant strong correlation was found between NAbs and anti-RBD, specifically with Abbott kit. Taken together, the Roche and Abbott methods indicated agreement at the high concentrations of antibodies with the VSV-pseudovirus method. Abbott and Roche indicated a good sensitivity, but the Abbott system test appeared to have better specificity than the Roche test. CONCLUSION: Our findings indicated a high presence of NAbs against SARS-CoV-2 spike protein among asymptomatic individuals in N'Djamena. This could be one of the reasons for the low severity of Covid-19 observed in this area, given the key role of NAbs in blocking SARS-CoV-2 infection.

A multicenter prospective randomized controlled trial investigating the effects of combustion-free nicotine alternatives on cardiovascular risk factors and metabolic parameters in individuals with type 2 diabetes who smoke: the DiaSmokeFree study protocol.

Stopping smoking is crucial for public health and especially for individuals with diabetes. Combustion-free nicotine alternatives like e-cigarettes and heated tobacco products are increasingly being used as substitutes for conventional cigarettes, contributing to the decline in smoking prevalence. However, there is limited information about the long-term health impact of those products in patients with diabetes. This randomized controlled trial aims to investigate whether switching from conventional cigarettes to combustion-free nicotine alternatives will lead to a measurable improvement in cardiovascular risk factors and metabolic parameters over a period of 2 years in smokers with type 2 diabetes. The multicenter study will be conducted in seven sites across four countries. A total of 576 smokers with type 2 diabetes will be randomly assigned (1:2 ratio) to either standard of care with brief cessation advice (Control Arm) or combustion-free nicotine alternatives use (Intervention Arm). The primary end point is the change in the proportion of patients with metabolic syndrome between baseline and the 2-year follow-up. Additionally, the study will analyze the absolute change in the sum of the individual factors of metabolic syndrome at each study time point. Patient recruitment has started in September 2021 and enrollment is expected to be completed by December 2023. Results will be reported in 2026. This study may provide valuable insights into cardiovascular and metabolic health benefits or risks associated with using combustion-free nicotine alternatives for individuals with type 2 diabetes who are seeking alternatives to tobacco cigarette smoking. The study protocol, informed consent forms, and relevant documents were approved by seven ethical review boards. Study results will be disseminated through articles published in high-quality, peer-reviewed journals and presentations at conferences.

Respiratory syncytial virus: can we still believe that after pandemic bronchiolitis is not a critical issue for public health?

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. Since the beginning of the COVID-19 pandemic, non-pharmacological interventions were applied, interfering with the circulation of most respiratory viruses, including RSV. The aim of this study is to analyze the RSV infection trend among hospitalized infants during the actual epidemic season (2022-2023) in comparison with the last pre-pandemic season (2018-2019), in order to outline whether significant differences emerge due to COVID-19 pandemia. We retrospectively reviewed medical data on infants hospitalized at the Bambino Gesù Children's Hospital with diagnosis of bronchiolitis in the current epidemic season and in the last pre-pandemic season, 2018-2019. RSV remains the main etiological agent of bronchiolitis in terms of frequency and severity of infections in the ongoing epidemic season. The first RSV case of the 2022-2023 season was detected at week 42 vs week 47 in the 2018-2019 season. The length of epidemic season was of 17 weeks in 2022-2023 vs 18 weeks in 2018-2019. Comparing the two seasons, age at admission was significantly higher in the current season (median age 2022-2023 65 days vs median age 2018-2019 58 days), but the disease severity was similar.       Conclusions: The 2022-2023 bronchiolitis season in Italy started earlier than the usual pre-pandemic seasons but seasonality pattern may be going back to the pre-pandemic one. This season was not more severe than the previous ones. The impact of RSV disease on health care systems and costs remains a critical issue. What is Known: • RSV is one of the major leading causes of hospitalization among children aged less than 3 months. SarsCOV2 pandemic interfered with the seasonal circulation of most respiratory viruses, Including RSV. What is New: • The 2022-2023 bronchiolitis season in Italy started and peaked earlier than the usual pre-pandemic seasons but seasonality pattern may be realigning to the pre-pandemic one. The impact of RSV disease on health care systems and costs is concerning.

Influenza viruses circulation in a tertiary care children hospital in Rome: a comparison between 2022 and the previous 5 years.

BACKGROUND: Influenza surveillance aims to determine onset, duration and intensity of the seasonal Influence-like Illness (ILI); data collection begins in the week 42 of a year and ends in the week 17 of the following year. In this observational study, we report the experience of a tertiary care children hospital in Rome about Influenza viruses circulation during the calendar year 2022 (January-December) in comparison with the previous five years (2017-2021), with a special focus on the weeks 18-41, usually not under surveillance. METHODS: This retrospective study involved 36782 respiratory samples referred to 21354 patients (pts), median age 2.63 years, admitted with respiratory symptoms at Bambino Gesù Children's Hospital in the years 2017-2022. Respiratory viruses were detected by molecular Allplex™ Respiratory Panel Assays (Seegene, Korea). RESULTS: Regarding the pre pandemic years, 2017-2019, distribution of Flu positive patients focused in the first weeks of the year (weeks 1-17). During the pandemic period, Flu was not detected. In 2022, 239 Flu viruses were identified: 37 FluA (weeks 1-17), 29 FluA (weeks 18-41) and 168 FluA and 5 FluB (weeks 42-52). For the year 2022, during the non-epidemic period, the number of Flu viruses detected corresponded to 12.1% of total Flu detected, respect to 0-1.7% for the previous five years (p < 0.001). CONCLUSIONS: When compared with pre SARS-CoV-2 pandemic years, our data show a significant increase in Influenza cases during weeks 18-41/2022 and reveal an unexpected summer circulation of these viruses: just weeks 26-30 showed to be influenza virus free. A national year-round Flu surveillance could be useful to understand if changing in influenza epidemiology is transitional or likely to persist in the following years.

Spatially Resolved Quantitation of Drug in Skin Equivalents Using Mass Spectrometry Imaging (MSI).

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has seen a growing interest as a leading technique in the pharmaceutical industry for mapping label-free exogenous and endogenous species in biological tissues. However, the use of MALDI-MSI to perform spatially resolved absolute quantitation of species directly in tissues is still challenging, and robust quantitative mass spectrometry imaging (QMSI) methods need to be developed. In this study, we describe the microspotting technique for analytical and internal standard deposition, matrix sublimation, powerful QMSI software, and mass spectrometry imaging setup to obtain absolute quantitation of drug distribution in 3D skin models.

Adipose-Derived Mesenchymal Stromal Cells: A Tool for Bone and Cartilage Repair.

The osteogenic and chondrogenic differentiation ability of adipose-derived mesenchymal stromal cells (ASCs) and their potential therapeutic applications in bone and cartilage defects are reported in this review. This becomes particularly important when these disorders can only be poorly treated by conventional therapeutic approaches, and tissue engineering may represent a valuable alternative. Being of mesodermal origin, ASCs can be easily induced to differentiate into chondrocyte-like and osteocyte-like elements and used to repair damaged tissues. Moreover, they can be easily harvested and used for autologous implantation. A plethora of ASC-based strategies are being developed worldwide: they include the transplantation of freshly harvested cells, in vitro expanded cells or predifferentiated cells. Moreover, improving their positive effects, ASCs can be implanted in combination with several types of scaffolds that ensure the correct cell positioning; support cell viability, proliferation and migration; and may contribute to their osteogenic or chondrogenic differentiation. Examples of these strategies are described here, showing the enormous therapeutic potential of ASCs in this field. For safety and regulatory issues, most investigations are still at the experimental stage and carried out in vitro and in animal models. Clinical applications have, however, been reported with promising results and no serious adverse effects.

Comparison of Vitamin D and Resveratrol Performances in COVID-19.

Over the last few years, we have experienced the infection generated by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) often resulting in an exaggerated immune reaction and systemic inflammation. The preferred treatments against SARS-CoV-2 were those that mitigated immunological/inflammatory dysfunction. A variety of observational epidemiological studies have reported that vitamin D deficiency is often a crucial factor in many inflammatory diseases and autoimmune diseases, as well as the susceptibility to contract infectious diseases, including acute respiratory infections. Similarly, resveratrol regulates immunity, modifying the gene expression and the release of proinflammatory cytokines in the immune cells. Therefore, it plays an immunomodulatory role that can be beneficial in the prevention and development of non-communicable diseases associated with inflammation. Since both vitamin D and resveratrol also act as immunomodulators in inflammatory pathologies, many studies have paid particular attention to an integrated treatment of either vitamin D or resveratrol in the immune reaction against SARS-CoV-2 infections. This article offers a critical evaluation of published clinical trials that have examined the use of vitamin D or resveratrol as adjuncts in COVID-19 management. Furthermore, we aimed to compare the anti-inflammatory and antioxidant properties linked to the modulation of the immune system, along with antiviral properties of both vitamin D and resveratrol.

Reversed Mirror Therapy (REMIT) after Stroke-A Proof-of-Concept Study.

In mirror training (MIT), stroke patients strive to move their hands while looking at the reflected image of the unaffected one. The recruitment of the mirror neurons and visual-proprioceptive conflict are expected to facilitate the paretic voluntary movement. Here, a reversed MIT (REMIT) is presented, which requires moving hands while looking at the reflected image of the paretic one, giving the illusion of being unable to move the unimpaired hand. This study compares MIT and REMIT on post-stroke upper-limb recovery to gain clues on the mechanism of action of mirror therapies. Eight chronic stroke patients underwent two weeks of MIT and REMIT (five sessions each) in a crossover design. Upper-limb Fugl-Meyer, Box and Block and handgrip strength tests were administered at baseline and treatments end. The strength of the mirror illusion was evaluated after each session. MIT induced a larger illusory effect. The Fugl-Meyer score improved to the same extent after both treatments. No changes occurred in the Box and Block and the handgrip tests. REMIT and MIT were equally effective on upper-limb dexterity, challenging the exclusive role of mirror neurons. Contrasting learned nonuse through an intersensory conflict might provide the rationale for both forms of mirror-based rehabilitation after stroke.

Pediatric COVID-TB: A Clinical Perspective Based on the Analysis of Three Cases.

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are currently two major causes of death among infectious diseases. Active tuberculosis and a history of tuberculosis appear to be associated with an increased risk of COVID-19. This coinfection, named COVID-TB, was never described in previously healthy children. We report three cases of pediatric COVID-TB. We describe three girls affected by tuberculosis, who tested positive for SARS-CoV-2. The first patient is a 5-year-old girl who was hospitalized for recurrent TB lymphadenopathy. As she never had any complications related to the concomitant infection with SARS-CoV-2, she received TB treatment. The second case is a 13-year-old patient with a history of pulmonary and splenic tuberculosis. She was admitted to the hospital due to deteriorating respiratory dynamics. She was already undergoing treatment for TB, but in the absence of improvement, she also required treatment for COVID-19. Slowly, the general condition improved until discharge. The last patient, a 10-year-old girl, was hospitalized for supraclavicular swelling. The investigations showed disseminated TB characterized by lung and bone involvement without COVID-19-related complications. She was treated with antitubercular and supportive therapy. Based on the data obtained from the adult population and our small experience, a pediatric patient with COVID-TB infection should be considered potentially at risk of worse clinical outcomes; for this reason, we suggest close observation, careful clinical management, and consideration of targeted anti-SARS-CoV-2 therapies.

Treatment Options for Hepatitis A and E: A Non-Systematic Review.

Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal-oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results.

Chitinase Signature in the Plasticity of Neurodegenerative Diseases.

Several reports have pointed out that Chitinases are expressed and secreted by various cell types of central nervous system (CNS), including activated microglia and astrocytes. These cells play a key role in neuroinflammation and in the pathogenesis of many neurodegenerative disorders. Increased levels of Chitinases, in particular Chitotriosidase (CHIT-1) and chitinase-3-like protein 1 (CHI3L1), have been found increased in several neurodegenerative disorders. Although having important biological roles in inflammation, to date, the molecular mechanisms of Chitinase involvement in the pathogenesis of neurodegenerative disorders is not well-elucidated. Several studies showed that some Chitinases could be assumed as markers for diagnosis, prognosis, activity, and severity of a disease and therefore can be helpful in the choice of treatment. However, some studies showed controversial results. This review will discuss the potential of Chitinases in the pathogenesis of some neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, to understand their role as distinctive biomarkers of neuronal cell activity during neuroinflammatory processes. Knowledge of the role of Chitinases in neuronal cell activation could allow for the development of new methodologies for downregulating neuroinflammation and consequently for diminishing negative neurological disease outcomes.