ABSTRACT
In this work, we synthesize a series of push-pull compounds bearing naphthalimide as the electron acceptor and tetraphenylethylene (TPE)/triphenylamine (TPA)/phenothiazine (PTZ) as the electron rich/electron donor units. These moieties are arranged in highly conjugated quadrupolar structures. The structure-property relationships are investigated through a joint experimental time-resolved spectroscopic and computational TD-DFT study. The femtosecond transient absorption and fluorescence up-conversion experiments reveal ultrafast photoinduced intramolecular charge transfer. This is likely the key factor leading to efficient spin-orbit CT-induced intersystem crossing for the TPA- and PTZ-derivatives as well as to small singlet-to-triplet energy gap. Consequently, evidence for a delayed fluorescence component is found together with the main prompt emission in the fluorescence kinetics both in solution and in thin film. The weight of the Thermally Activated Delayed Fluorescence (TADF) is greatly enhanced when these fluorophores are used as guests in solid-state host matrices. TADF is interestingly revealed in the orange-red region of the visible. Such long wavelength emission is here observed with surprisingly large fluorescence quantum yields, thanks to the conjugation enhancement achieved in these newly synthesized structures relative to previous studies. Our findings may be thus promising for the future development of efficient third generation TADF-based OLEDs.
ABSTRACT
Cognitive and psychiatric disorders are well documented across the lifetime of patients with inborn errors of metabolism (IEMs). Gut microbiota impacts behavior and cognitive functions through the gut-brain axis (GBA). According to recent research, a broad spectrum of GBA disorders may be influenced by a perturbed Tryptophan (Trp) metabolism and are associated with alterations in composition or function of the gut microbiota. Furthermore, early-life diets may influence children's neurodevelopment and cognitive deficits in adulthood. In Phenylketonuria (PKU), since the main therapeutic intervention is based on a life-long restrictive diet, important alterations of gut microbiota have been observed. Studies on PKU highlight the impact of alterations of gut microbiota on the central nervous system (CNS), also investigating the involvement of metabolic pathways, such as Trp and kynurenine (KYN) metabolisms, involved in numerous neurodegenerative disorders. An alteration of Trp metabolism with an imbalance of the KYN pathway towards the production of neurotoxic metabolites implicated in numerous neurodegenerative and inflammatory diseases has been observed in PKU patients supplemented with Phe-free amino acid medical foods (AA-MF). The present review investigates the possible link between gut microbiota and the brain in IEMs, focusing on Trp metabolism in PKU. Considering the evidence collected, cognitive and behavioral well-being should always be monitored in routine IEMs clinical management. Further studies are required to evaluate the possible impact of Trp metabolism, through gut microbiota, on cognitive and behavioral functions in IEMs, to identify innovative dietetic strategies and improve quality of life and mental health of these patients.
Subject(s)
Brain-Gut Axis , Phenylketonurias , Child , Humans , Tryptophan , Quality of Life , CognitionABSTRACT
A series of new naphthalimide and phenothiazine-based push-pull systems (NPI-PTZ1-5), in which we structurally modulate the oxidation state of the sulfur atom in the thiazine ring, i.e., S(II), S(IV), and S(VI), was designed and synthesized by the Pd-catalyzed Sonogashira cross-coupling reaction. The effect of the sulfur oxidation state on the spectral, photophysical, and electrochemical properties was investigated. The steady-state absorption and emission results show that oxygen functionalization greatly improves the optical (absorption coefficient and fluorescence efficiency) and nonlinear optical (hyperpolarizability) features. The cyclic voltammetry experiments and the quantum mechanical calculations suggest that phenothiazine is a stronger electron donor unit relative to phenothiazine-5-oxide and phenothiazine-5,5-dioxide, while the naphthalimide is a strong electron acceptor in all cases. The advanced ultrafast spectroscopic measurements, transient absorption, and broadband fluorescence up conversion give insight into the mechanism of photoinduced intramolecular charge transfer. A planar intramolecular charge transfer (PICT) and highly fluorescent excited state are populated for the oxygen-functionalized molecules NPI-PTZ2,3 and NPI-PTZ5; on the other hand, a twisted intramolecular charge transfer (TICT) state is produced upon photoexcitation of the oxygen-free derivatives NPI-PTZ1 and NPI-PTZ4, with the fluorescence being thus significantly quenched. These results prove oxygen functionalization as a new effective synthetic strategy to tailor the photophysics of phenothiazine-based organic materials for different optoelectronic applications. While oxygen-functionalized compounds are highly fluorescent and promising active materials for current-to-light conversion in organic light-emitting diode devices, oxygen-free systems show very efficient photoinduced ICT and may be employed for light-to-current conversion in organic photovoltaics.
ABSTRACT
Marine macroalgae are well known to release a wide spectrum of volatile organic components, the release of which is affected by environmental factors. This paper aimed to identify the essential oil (EO) compounds of the brown algae Cystoseira compressa collected in the Adriatic Sea monthly, from May until August. EOs were isolated by hydrodistillation using a Clavenger-type apparatus and analyzed by gas chromatography coupled with mass spectrometry (GC-MS). One hundred four compounds were identified in the volatile fraction of C. compressa, accounting for 84.37-89.43% of the total oil. Samples from May, June, and July were characterized by a high share of fatty acids (56, 69, and 34% respectively) with palmitic acid being the dominant one, while in the August sample, a high content of alcohols (mainly phytol and oleyl alcohol) was found. Changes in the other minor components, which could be important for the overall aroma and biological activities of the algal samples, have also been noted during the vegetation periods. The results of this paper contribute to studies of algal EOs and present the first report on C. compressa EOs.
Subject(s)
Oils, Volatile/chemistry , Phaeophyceae/chemistry , Seasons , Gas Chromatography-Mass Spectrometry , Oils, Volatile/isolation & purification , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/isolation & purificationABSTRACT
A potential role of dietary lipids in the management of hepatic glycogen storage diseases (GSDs) has been proposed, but no consensus on management guidelines exists. The aim of this study was to describe current experiences with dietary lipid manipulations in hepatic GSD patients. An international study was set up to identify published and unpublished cases describing hepatic GSD patients with a dietary lipid manipulation. A literature search was performed according to the Cochrane Collaboration methodology through PubMed and EMBASE (up to December 2018). All delegates who attended the dietetics session at the IGSD2017, Groningen were invited to share unpublished cases. Due to multiple biases, only data on GSDIII were presented. A total of 28 cases with GSDIII and a dietary lipid manipulation were identified. Main indications were cardiomyopathy and/or myopathy. A high fat diet was the most common dietary lipid manipulation. A decline in creatine kinase concentrations (n = 19, P < .001) and a decrease in cardiac hypertrophy in paediatric GSDIIIa patients (n = 7, P < .01) were observed after the introduction with a high fat diet. This study presents an international cohort of GSDIII patients with different dietary lipid manipulations. High fat diet may be beneficial in paediatric GSDIIIa patients with cardiac hypertrophy, but careful long-term monitoring for potential complications is warranted, such as growth restriction, liver inflammation, and hepatocellular carcinoma development.
Subject(s)
Cardiomyopathies/etiology , Dietary Fats , Glycogen Storage Disease Type III/diet therapy , Cardiomyopathies/physiopathology , Child , Glycogen Storage Disease Type III/complications , Humans , Liver/pathology , Monitoring, Physiologic , Triglycerides/bloodABSTRACT
Doogh is a dairy drinkable fermented product, whose shelf-life and quality is mostly affected by bacteria such as Staphylococcus spp.. This study investigated the antibacterial activity of essential oils (EOs) from Thymus vulgaris L., Mentha piperita L. and Ziziphora tenuior L., alone or in combination, against Staphylococcus aureus in industrial doogh. A three-level and three-variable face centered central composite design experiment was used. Results showed that EOs significantly inhibited S. aureus growth after 1 and 7 days of storage. According to the model, the maximum inhibition was obtained in the presence of 0.2% of EO, independently of the type, and no synergistic or additive effects were observed. Slightly lower S. aureus survivals were observed at the maximum concentration of Z. tenuior EO. In spite of the antimicrobial activity of these EOs, further research is needed to assess their performance in food matrix and, in particular, in dairy product.
Subject(s)
Anti-Bacterial Agents/chemistry , Lamiaceae/chemistry , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Humans , Mentha piperita/chemistry , Microbial Sensitivity Tests , Oils, Volatile/chemistry , Staphylococcal Infections/microbiology , Staphylococcus aureus/pathogenicity , YogurtABSTRACT
The aim of this work was to evaluate the effects of microbial transglutaminase (mTG) and sourdough on gluten-free (GF) flours. Besides deamidation and incorporation of amines, mTG catalyses protein cross-links, modifying dough structure. Sourdough from lactic acid bacteria (LAB) and yeast modifies dough protein composition, determining proteolysis, which induce the formation of aroma precursor metabolites. The chemical-physical interactions of volatile molecules with various constituents of the matrix affect the retention of aroma compounds. Here, the effect on volatile molecule profiles and on protein networks formation after mTG treatment in sourdoughs obtained with four GF flours belonging to cereals, pseudo-cereals and legumes (rice, corn, amaranth and lentil) was investigated. Sourdough was prepared with a two-step fermentation using Lactobacillus sanfrancisciensis (LSCE1) and Candida milleri (PFL44), then mTG was added after 21 h of fermentation at increasing levels. The results showed that mTG had the capacity to modify GF flour proteins and improve protein networks formation, involving mainly the prolamin protein fraction. This is particularly relevant for the production of GF backed goods generally lacking of technological, structural and sensorial features compared with products obtained with wheat flour sourdough fermentation. Interestingly, mTG treatment of sourdough affected also the volatile composition and indeed possibly the final organoleptic properties of the products.
Subject(s)
Bacterial Proteins/chemistry , Candida/enzymology , Diet, Gluten-Free , Flour , Food Technology/methods , Fungal Proteins/chemistry , Lactobacillus/enzymology , Transglutaminases/chemistryABSTRACT
BACKGROUND: The aim of this work was to study the physico-chemical and microbiological parameters of 10 Italian fermented sausages, produced industrially, in order to highlight the differences in relation to their size. The sausages were classified as small, medium and large and the data concerning every feature considered were analysed with some statistical explorative tools: ANOVA, principal component analysis (PCA) and linear discriminant analysis (LDA). RESULTS: Significant differences in relation to the sausage size were found regarding microbial populations (in particular, enterobacteria and staphylococci). The pH was higher in the small sausages, and consequently the presence of lactate and acetate was higher in the bigger one. Also the biogenic amine content (particularly tyramine, cadaverine and putrescine) was influenced by the size. CONCLUSIONS: In spite of the extreme variability of the sausage types at the end of ripening, this work showed that it was possible to find a strict relationship between sausages diameter and some essential physico-chemical parameters. Thus, the cross-sectional size of the product is an essential parameter, which can drive the biochemical processes during ripening, not only by affecting the kinetics of water losses, but also by influencing the microbiota enzymatic activity. © 2015 Society of Chemical Industry.
Subject(s)
Food Analysis , Food Microbiology , Meat Products/analysis , Meat Products/microbiology , Fermentation , Italy , Principal Component AnalysisABSTRACT
Outbreaks of food-borne disease associated with the consumption of fresh and minimally processed fruits and vegetables have increased dramatically over the last few years. Traditional chemical sanitizers are unable to completely eradicate or kill the microorganisms on fresh produce. These conditions have stimulated research to alternative methods for increasing food safety. The use of protective cultures, particularly lactic acid bacteria (LAB), has been proposed for minimally processed products. However, the application of bioprotective cultures has been limited at the industrial level. From this perspective, the main aims of this study were to select LAB from minimally processed fruits and vegetables to be used as biocontrol agents and then to evaluate the effects of the selected strains, alone or in combination with natural antimicrobials (2-(E)-hexenal/hexanal, 2-(E)-hexenal/citral for apples and thyme for lamb's lettuce), on the shelf-life and safety characteristics of minimally processed apples and lamb's lettuce. The results indicated that applying the Lactobacillus plantarum strains CIT3 and V7B3 to apples and lettuce, respectively, increased both the safety and shelf-life. Moreover, combining the selected strains with natural antimicrobials produced a further increase in the shelf-life of these products without detrimental effects on the organoleptic qualities.
Subject(s)
Bacteria/growth & development , Food Microbiology , Food Safety , Lactobacillus/physiology , Lactuca/microbiology , Malus/microbiology , Acyclic Monoterpenes , Anti-Infective Agents/pharmacology , Antibiosis , Escherichia coli/growth & development , Hexobarbital/pharmacology , Lactic Acid , Lactobacillus/growth & development , Lactobacillus/isolation & purification , Lacticaseibacillus casei/growth & development , Lacticaseibacillus casei/isolation & purification , Lacticaseibacillus casei/physiology , Lactobacillus plantarum/isolation & purification , Lactobacillus plantarum/physiology , Listeria monocytogenes/growth & development , Monoterpenes/pharmacology , Salmonella enteritidis/growth & development , Thymus PlantABSTRACT
BACKGROUND: Salama da sugo is a fermented sausage from the Ferrara tradition (Italy, Emilia-Romagna region), subjected to a long ripening period (4-6 months) and characterised by a high content of wine and spices in the mixture. It can be consumed after cooking and it is served with its sugo, i.e. the liquid extracted by cooking process. The aim of this work was to set up a method for the sensory profile of Salama da sugo as a request for Protected Geographical Indication (PGI) has been made to the European Commission. RESULTS: A system of sample preparation that provides for the precooking in an autoclave and cooking in boiling water was set up. A specific sheet for sensory evaluation of Salama da sugo has been created and reports 23 descriptors identified during the lexicon development. The differences in sensory profile of four samples were evaluated and principal component analysis highlighted the more discriminant parameters, i.e. odour intensity, wine odour, spicy aroma, fat/lean connection, sweet, bitter, juiciness, chewiness and pricking. CONCLUSIONS: The proposed method allows the standardisation of sensory profiling of Salama da sugo, and is also to verify compliance with the specification PGI.
Subject(s)
Diet , Food Inspection/methods , Meat Products/analysis , Animals , Chemical Phenomena , Cooking , Diet/ethnology , Discriminant Analysis , European Union , Fermentation , Food Labeling , Humans , Italy , Meat Products/microbiology , Meat Products/standards , Mechanical Phenomena , Odorants , Principal Component Analysis , Records , Sensation , Spices/analysis , Sus scrofa , Taste , Urinary Bladder/chemistry , Wine/analysisABSTRACT
Children with severe neurological impairment (SNI) frequently present feeding problems requiring a close monitoring of their nutritional status. In addition to constant clinical monitoring of body composition and nutritional indexes in these patients, frequent reports of dietary intake and weight gain variations are useful to ensure proper nutritional management. Furthermore, non-oral feeding is often needed to avoid malnutrition or aspiration pneumonia, constantly necessitating medical assistance. Despite their necessity for frequent hospital accesses, these patients' disabilities represent an important obstacle to accessing care, generating anxiety and concern in children and their families. Telemedicine has proven to be a promising instrument for improving pediatric patients' healthcare in several fields. By breaking down geographical and temporal barriers, telehealth may represent a valuable tool to implement in clinical practice, in order to improve patients' outcomes and quality of life. The aim of this narrative review is to provide an overview of the main nutritional issues in children with SNI, the potential implications of telemedicine in their management and the available evidence regarding the effects and benefits of telehealth.
ABSTRACT
Neurodegenerative disorders are a group of diseases characterized by progressive degeneration of the nervous system, leading to a gradual loss of previously acquired motor, sensory and/or cognitive functions. Leukodystrophies are amongst the most frequent childhood-onset neurodegenerative diseases and primarily affect the white matter of the brain, often resulting in neuro-motor disability. Notably, gastrointestinal (GI) symptoms and complications, such as gastroesophageal reflux disease (GERD) and dysphagia, significantly impact patients' quality of life, highlighting the need for comprehensive management strategies. Gut dysbiosis, characterized by microbial imbalance, has been implicated in various GI disorders and neurodegenerative diseases. This narrative review explores the intricate relationship between GI symptoms, Gut Microbiota (GM), and neurodegeneration. Emerging evidence underscores the profound influence of GM on neurological functions via the microbiota gut-brain axis. Animal models have demonstrated alterations in GM composition associated with neuroinflammation and neurodegeneration. Our single-centre experience reveals a high prevalence of GI symptoms in leukodystrophy population, emphasizing the importance of gastroenterological assessment and nutritional intervention in affected children. The bidirectional relationship between GI disorders and neurodegeneration suggests a potential role of gut dysbiosis in disease progression. Prospective studies investigating the GM in leukodystrophies are essential to understand the role of gut-brain axis dysfunction in disease progression and identify novel therapeutic targets. In conclusion, elucidating the interplay between GI disorders, GM, and neurodegeneration holds promise for precision treatments aimed at improving patient outcomes and quality of life.
ABSTRACT
BACKGROUND: The diverse manifestations of Long-COVID have become increasingly important due to their significant impact on patients' lives. Telemedicine has emerged as an important tool for post COVID-19 follow-up. This study is part of a large cohort study involving COVID-positive patients monitored by the COD19 telemedicine platform operations center. We recontacted patients who were initially monitored from February 2020 to May 2020 to assess the presence of Long-COVID symptoms at a 2-year follow-up. METHODS: We conducted interviews to evaluate Long-COVID symptoms at the 2-year mark and investigated whether patients had contracted a second COVID-19 infection between the 1-year and 2-year follow-ups, and recorded their vaccination status. RESULTS: Out of 165 patients, 139 (84%) reported symptoms at the 1-year follow-up, while only 101 (61%) reported symptoms at the 2-year follow-up. Among patients with Long-COVID symptoms at the 2-year follow-up, the majority (80, 49%) had experienced Long-COVID at the 1-year follow-up, received the SARS-CoV-2 vaccine, and had not experienced a second infection between the two follow-ups. Both having Long-COVID at the 1-year follow-up and contracting a second infection were significant risk factors for presenting with Long-COVID at the 2-year follow-up. CONCLUSIONS: To the best of our knowledge, this study stands out as one of the few that includes a 2-year follow-up on Long-COVID symptoms using telemedicine. Telemedicine has proven to be an effective and innovative tool for long-term patient monitoring, early diagnosis, and treatment. Telemedicine represents a significant future challenge for healthcare.
Subject(s)
COVID-19 , SARS-CoV-2 , Telemedicine , Humans , COVID-19/epidemiology , COVID-19/virology , COVID-19/diagnosis , Female , Male , Middle Aged , SARS-CoV-2/isolation & purification , Aged , Adult , Follow-Up Studies , Cohort Studies , Post-Acute COVID-19 Syndrome , COVID-19 VaccinesABSTRACT
Advancements in food science technology have allowed the development of new products for the therapeutic management of inherited metabolic diseases such as phenylketonuria (PKU). Glycomacropeptide (GMP), a peptide derived from casein, is naturally low in phenylalanine (Phe) and, thus, adequate for protein substitutes (PSs) for the management of PKU in children. This review aims primarily to analyse the differences in the nutritional composition of GMP-based protein substitutes in different formulations (ready to drink, powdered, and bars), and secondarily to assess the quality of these products, comparing their nutritional composition with that of standard amino acid (L-AA) mixtures. Thirty-five GMP-based PSs produced by six different companies were included in this review: twenty-one powdered PSs, eight ready to drink, and six bars. The analysis revealed great heterogeneity not only among the different formulations (powdered, ready to drink, and bars) but also within the same group, in terms of energy content and nutritional composition. GMP-based PSs were shown to have higher contents of sugars and saturated fatty acids compared to L-AA PSs, especially in ready-to-drink formulations and bars. The latter also provided the highest amounts of energy among the GMP-based products. This finding may be related to a higher risk of developing overweight and obesity. The greater palatability of these GMP-based PSs, combined with improved nutritional quality, could not only improve adherence to diet therapy but also reduce the incidence of obesity-related comorbidities in PKU.
Subject(s)
Caseins , Peptide Fragments , Phenylketonurias , Child , Humans , Italy , ObesityABSTRACT
Companilactobacillus alimentarius is a facultatively heterofermentative lactic acid bacterium (LAB) that is a significant constituent within the microbiota of various traditional fermented foods exerting several functions in fermentative or ripening processes. This species has been isolated from Spanish fermented sausages, where its frequency of isolation was comparable to those of Latilactobacillus sakei and Latilactobacillus curvatus. Despite to its presence in several niches, ecological information on this species is still scarce and only few publications report information about its safety features (i.e. antibiotic resistance). Since studies on C. alimentarius concern the analysis of a few individual traits regarding this species, a more extensive work on a larger number of isolates from the same matrix have been performed to allow a clearer interpretation of their phenotypic and technological characteristics. Specifically, 14 strains of C. alimentarius isolated from Mediterranean spontaneously fermented sausages, have been screened for their safety and technological characteristics (such as antibiotic resistance, biogenic amine production, inhibiting potential, growth at different temperatures and NaCl concentrations) and with phenotype microarrays with the aim to elucidate their potential role and contribution to sausage fermentation and ripening. In general, a wide variability was observed in relation to the parameters considered. Several of the tested strains were able to produce histamine, tyramine and putrescine while the antibiotic resistance greatly varied according to the strains, with the exception of vancomycin. In addition, C. alimentarius strains showed a relevant potential to grow in conditions of salt and temperature mimicking those found in fermented foods. In particular, the growth at 10 °C and in the presence of salt can explain the presence of C. alimentarius in sausages and its adaptation to fermented meat environment in which low temperature can be applied during ripening. The differentiation of the phenotypic profile reflected the environmental conditions that influenced the isolation source, including those derived by the raw materials. Given the species frequent association with spontaneous fermentations or the ripening microbiota of various products, despite not being intentionally used as starter cultures, the data presented in this study contribute to a deeper comprehension of their role, both advantageous and detrimental, in numerous significant fermented foods.
Subject(s)
Latilactobacillus sakei , Meat Products , Lactobacillus , Fermentation , Biogenic Amines , Meat Products/microbiologyABSTRACT
Pulmonologists may be involved in managing pulmonary diseases in children with complex clinical pictures without a diagnosis. Moreover, they are routinely involved in the multidisciplinary care of children with rare diseases, at baseline and during follow-up, for lung function monitoring. Lysosomal storage diseases (LSDs) are a group of genetic diseases characterised by a specific lysosomal enzyme deficiency. Despite varying pathogen and organ involvement, they are linked by the pathological accumulation of exceeding substrates, leading to cellular toxicity and subsequent organ damage. Less severe forms of LSDs can manifest during childhood or later in life, sometimes being underdiagnosed. Respiratory impairment may stem from different pathogenetic mechanisms, depending on substrate storage in bones, with skeletal deformity and restrictive pattern, in bronchi, with obstructive pattern, in lung interstitium, with altered alveolar gas exchange, and in muscles, with hypotonia. This narrative review aims to outline different pulmonary clinical findings and a diagnostic approach based on key elements for differential diagnosis in some treatable LSDs like Gaucher disease, Acid Sphingomyelinase deficiency, Pompe disease and Mucopolysaccharidosis. Alongside their respiratory clinical aspects, which might overlap, we will describe radiological findings, lung functional patterns and associated symptoms to guide pediatric pulmonologists in differential diagnosis. The second part of the paper will address follow-up and management specifics. Recent evidence suggests that new therapeutic strategies play a substantial role in preventing lung involvement in early-treated patients and enhancing lung function and radiological signs in others. Timely diagnosis, driven by clinical suspicion and diagnostic workup, can help in treating LSDs effectively.
ABSTRACT
Olipudase alfa is indicated for the non-central nervous system manifestations of Acid sphingomyelinase deficiency (ASMD). Anaphylaxis is a very rare and life-threatening adverse reaction described for this drug. Here, we report the case of a 2-year-old boy affected by chronic neurovisceral ASMD who experienced signs of hypersensitivity reactions to olipudase alfa since the administered dose of 1 mg/kg during dose escalation and a proper anaphylactic reaction during the second administration of the target therapeutic dose of 3 mg/kg. The treatment was stopped for 15 weeks and then a 7-step desensitization protocol with the infused dose of 0.03 mg/kg was applied. Subsequent gradual dose escalation was resumed, successfully reaching the dose of 0.3 mg/kg. Moreover, biochemical, and radiological disease indexes, which were increased during treatment discontinuation, have gradually improved since the restart of treatment. However, at the second administration of the dose of 0.6 mg/kg, the patient experienced another adverse drug reaction with facial urticarial rash and bronchospasm, requiring the administration of adrenaline, methylprednisolone, and inhaled salbutamol. This case report highlights the need to customize the olipudase alfa desensitization protocol according to individual tolerance and raises the issue of achieving the established therapeutic target in the most sensitive children. Synopsis: We report a case of anaphylaxis to olipudase alfa in a child affected by chronic neurovisceral Acid sphingomyelinase deficiency (ASMD) and describe a 7-step desensitization procedure. This procedure, with the total administered dose of 0.03 mg/kg, followed by gradual dose escalation, allowed to reach the dose of 0.3 mg/kg without adverse reactions; however, at the second administration of the dose of 0.6 mg/kg our patient presented another adverse reaction suggesting the need of a different desensitization strategy.
ABSTRACT
Background: Gaucher disease is a lysosomal storage disorder caused by functional glucocerebrosidase enzyme deficiency. Hepatosplenomegaly and hematological complications are found in both Gaucher disease and Acid Sphingomyelinase Deficiency, which is caused by acid sphingomyelinase dysfunction. The possible overlap in clinical presentation can cause diagnostic errors in differential diagnosis. For this reason, in patients with an initial clinical suspicion of Gaucher disease, we aimed to carry out a parallel screening of acid sphingomyelinase and glucocerebrosidase. Methods: Peripheral blood samples of 627 patients were collected, and enzymatic activity analysis was performed on both glucocerebrosidase and acid sphingomyelinase. The specific gene was studied in samples with null or reduced enzymatic activity. Specific molecular biomarkers helped to achieve the correct diagnosis. Results: In 98.7% of patients, normal values of glucocerebrosidase activity excluded Gaucher disease. In 8 of 627 patients (1.3%), the glucocerebrosidase enzymatic activity assay was below the normal range, so genetic GBA1 analysis confirmed the enzymatic defect. Three patients (0.5%) had normal glucocerebrosidase activity, so they were not affected by Gaucher disease, and showed decreased acid sphingomyelinase activity. SMPD1 gene mutations responsible for Acid Sphingomyelinase Deficiency were found. The levels of specific biomarkers found in these patients further strengthened the genetic data. Conclusions: Our results suggest that in the presence of typical signs and symptoms of Gaucher disease, Acid Sphingomyelinase Deficiency should be considered. For this reason, the presence of hepatosplenomegaly, thrombocytopenia, leukocytopenia, and anemia should alert clinicians to analyze both enzymes by a combined screening. Today, enzyme replacement therapy is available for the treatment of both pathologies; therefore, prompt diagnosis is essential for patients to start accurate treatment and to avoid diagnostic delay.
ABSTRACT
BACKGROUND: Limited evidence exists regarding the association between COVID-19 and Long COVID manifestations in children, particularly concerning variants of concern (VOCs). We aimed to characterize a cohort of pediatric patients hospitalized with confirmed acute SARS-CoV-2 and monitor them for Long COVID symptoms. Additionally, it seeks to explore any potential correlations between VOCs and clinical symptoms. METHODS: We conducted a prospective study involving children hospitalized from November 2021 to March 2023, with confirmed acute SARS-CoV-2 infection. A telephone survey was conducted at 3-6-12 months after discharge. RESULTS: We included 167 patients (77 F/90 M). Upon hospital admission, 95.5% of patients presented as symptomatic. Regarding patients for whom it was feasible to determine the SARS-CoV-2 variant (n = 51), the Delta variant was identified in 11 children (21.6%) and Omicron variant in the remaining 40 patients (78.4%: 27.5% BA.1 variant; 15% BA.2 variant; 57.5% BA.5 variant). 19 patients (16.5%) reported experiencing at least one symptom indicative of Long COVID (weight loss 31.6%, inappetence 26.3%, chronic cough 21.1%, fatigue 21.1%, and sleep disturbances, wheezing, abdominal pain and mood disorders 15.8%). In only 4 patients with Long COVID we could identified a specific SARS-CoV-2 variant (3 Omicron: 2 BA.1 and 1 BA.2; 1 Delta). CONCLUSIONS: this study underscores that long COVID is a significant concern in the pediatric population. Our data reinforce the importance of continuously monitoring the impact of long-COVID in infants, children, and adolescents. A follow-up following SARS-CoV-2 infection is therefore advisable, with symptom investigation tailored to the patient's age.
Subject(s)
COVID-19 , Child, Hospitalized , Adolescent , Infant , Humans , Child , SARS-CoV-2 , COVID-19/epidemiology , Post-Acute COVID-19 Syndrome , Prospective Studies , Italy/epidemiologyABSTRACT
BACKGROUND: This review aims to identify the current indications and gaps in the management of fat-soluble vitamins in pediatric patients with cholestasis. METHODS: A comprehensive review of the literature using PubMed, Scopus, Web of Science and Embase was performed. Two authors independently identified the most relevant studies published over the past 20 years up to February 2022, including original papers, narrative reviews, observational studies, clinical trials, systematic reviews and meta-analyses. The literature was screened, and preclinical studies about pathogenetic mechanisms were also included. Keywords searched for each fat-soluble vitamin (A, D, E and K), alone or in combination, were "cholestasis", "chronic liver disease", "biliary atresia", "malnutrition" and "nutritional needs". Studies published prior to the selected time range were searched manually and, when considered relevant, included within the list of references. RESULTS: Eight hundred twenty-six articles were initially screened. From these, 48 studies were selected. A comparison of the recommended methods of supplementation for fat-soluble vitamins was then carried out. The causes of malabsorption were explained and current methods for defining deficiency and monitoring complications were summarized. CONCLUSIONS: According to the literature, children with cholestasis are at a higher risk of fat-soluble vitamin deficiency. Although there are general recommendations, the treatment for vitamin deficiency is not uniformly validated.