Metabolic characterization and transcriptional profiling of polyphenols in Cannabis sativa L. inflorescences with different chemical phenotypes.

MAIN CONCLUSION: After the most comprehensive analysis of the phenolic composition in Cannabis reported to date, a total of 211 compounds were identified, phenolic profiles were able to discriminate cannabis varieties and a complex regulatory network for phenolics accumulation in Cannabis chemovars was highlighted. Female inflorescences of Cannabis sativa L. are plenty of secondary metabolites, of which flavonoids and phenolic acids have been investigated by far less than phytocannabinoids and terpenoids. Understanding the biochemical composition in phenylpropanoids of Cannabis inflorescences, the molecular basis of flavonoid synthesis and how their content can be modulated by specific transcription factors will shed light on the variability of this trait in the germplasm, allowing the identification of biologically active metabolites that can be of interest to diverse industries. In this work, an untargeted metabolomic approach via UHPLC-HRMS was adopted to investigate the composition and variability of phenylpropanoids in thirteen Cannabis genotypes differentiated for their profile in phytocannabinoids, highlighting that phenolic profiles can discriminate varieties, with characteristic, unique genotype-related patterns. Moreover, the transcription profile of candidate phenolics regulatory MYB and bHLH transcription factors, analyzed by RT-qPCR, appeared strongly genotype-related, and specific patterns were found to be correlated between biochemical and transcriptional levels. Results highlight a complex regulatory network for phenolic accumulation in Cannabis chemovars that will need further insights from the functional side.

Disrupted Seasonality of Respiratory Viruses: Retrospective Analysis of Pediatric Hospitalizations in Italy from 2019 to 2023.

This multicenter study in Italian hospitals highlights the epidemiologic disruptions in the circulation of the 5 main respiratory viruses from 2019 to 2023. Our data reveal a resurgence of respiratory syncytial virus and influenza during the 2022-2023 winter season, with an earlier peak in cases for both viruses, emphasizing the importance of timely monitoring.

A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce.

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta-analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta-analysis was performed using random-effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower-middle, 12 in upper-middle, and only two in high-income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta-analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta-analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high-income countries.

A systematic review and meta-analysis of nutritional and dietary interventions in randomized controlled trials for skin symptoms in children with atopic dermatitis and without food allergy: An EAACI task force report.

This systematic review and meta-analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo-controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta-analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta-analysis of SCORAD outcomes was conducted using random-effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta-analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well-designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies.

Eu- or hypoglycemic ketosis and ketoacidosis in children: a review.

The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of ß-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and ß-hydroxybutyrate.

Definition and assessment of fever-related discomfort in pediatric literature: a systematic review.

Guidelines advocate that the symptomatic management of fever should prioritize alleviating the child's discomfort. We investigated the definition and assessment of discomfort in febrile children within the scientific pediatric literature. A systematic review was conducted in accordance with PRISMA 2020 guidelines and preregistered on the Prospero database (CRD42023471590). Databases including PubMed, Embase, and Cochrane were searched. Studies addressing discomfort in febrile children were eligible. Out of 794 initially identified articles, 27 original studies and seven guidelines specifically used the term 'discomfort'. Only 14 original articles provided a definition of discomfort, revealing substantial heterogeneity and no clear-cut definition. Discomfort was often assessed subjectively, predominantly through parent or self-report, and only two studies used a scoring system for assessment. The definitions varied widely, with terms such as crying, irritability, shivering and chills, pain and distress, goosebumps commonly used and evaluation of observable modifications such as facial modifications. Overall, no consensus on a single, standardized definition was available. CONCLUSIONS: This systematic review shows the absence of a standardized definition and assessment of discomfort in febrile children. The findings of the present analysis might be the basis for building a consensus and developing a new tool to evaluate discomfort. WHAT IS KNOWN: • Discomfort is currently considered the main criterion to guide antipyretic administration in children with fever. • Despite this clear-cut recommendation, it has been questioned whether a commonly accepted understanding and assessment of this condition exists. WHAT IS NEW: • This systematic review identifies a significant heterogeneity in definitions and assessment of discomfort in children with fever. • Both subjective parameters and observable modifications in physiological parameters should be included in a new and shared characterization of discomfort.

Effects of vitamin D supplementation in obese and overweight children and adolescents: A systematic review and meta-analysis.

Due to the lipophilic nature of vitamin D, overweight and obese patients have an increased risk of inadequate circulating 25-hydroxy-vitamin D (25(OH)D) concentrations. Vitamin D deficiency has in turn several consequences especially among children and adolescents. Therefore, a few supplementation strategies of vitamin D for pediatric subjects with an excessive body weight have been proposed, but their efficacy remains controversial. The aim of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplementation in overweight and obese children and adolescents. Three databases (PubMed, Embase and Web of Science) were searched to collect trials on the effect of vitamin D supplementation in the pediatric overweight or obese population. Twenty-three studies were included in the systematic review. Results on modification of metabolic or cardiovascular outcomes were controversial. On the other hand, the meta-analysis showed a mean difference by 1.6 ng/ml in subjects supplemented with vitamin D as compared to placebo. In conclusion, vitamin D supplementation slightly increases 25(OH)D levels in pediatric subjects with overweight and obesity. However, the effects on metabolic and cardiovascular outcomes remain controversial. New efforts should be devoted to promoting effective interventions to improve the health of children and adolescents with overweight and obesity.

Childhood fever and medical students: A multicentre, educational intervention.

AIM: Misconceptions and non-evidence-based practices toward childhood fever are reported worldwide. Medical students might be ideal candidates to introduce long-lasting changes in clinical practice. However, no study has gauged the effectiveness of an educational intervention to improve fever management in this population. We conducted an educational, interventional study on childhood fever among final-year medical students. METHODS: We conducted a prospective, multicentre interventional study employing a pre/post-test design. Participants from three Italian Universities filled in a questionnaire just before the intervention (T0), immediately after (T1) and 6 months later (T2) in 2022. The intervention was a two-hour lecture focused on the pathophysiology of fever, recommendations for its treatment and risks associated with improper management. RESULTS: 188 final-year medical students (median age of 26 years, 67% females) were enrolled. Relevant improvements in the criterion for treating fever and conceptions about the beneficial effects of fever were observed at T1 and T2. Similar data were found for the reduction of physical methods advice to decrease body temperature and concerns for brain damage from fever. CONCLUSION: This study shows for the first time that an educational intervention is effective in changing students' conceptions and attitudes toward fever both in the short and medium term.

Comparative genomics of geographically distant Fusarium fujikuroi isolates revealed two distinct pathotypes correlating with secondary metabolite profiles.

Fusarium fujikuroi causes bakanae ("foolish seedling") disease of rice which is characterized by hyper-elongation of seedlings resulting from production of gibberellic acids (GAs) by the fungus. This plant pathogen is also known for production of harmful mycotoxins, such as fusarins, fusaric acid, apicidin F and beauvericin. Recently, we generated the first de novo genome sequence of F. fujikuroi strain IMI 58289 combined with extensive transcriptional, epigenetic, proteomic and chemical product analyses. GA production was shown to provide a selective advantage during infection of the preferred host plant rice. Here, we provide genome sequences of eight additional F. fujikuroi isolates from distant geographic regions. The isolates differ in the size of chromosomes, most likely due to variability of subtelomeric regions, the type of asexual spores (microconidia and/or macroconidia), and the number and expression of secondary metabolite gene clusters. Whilst most of the isolates caused the typical bakanae symptoms, one isolate, B14, caused stunting and early withering of infected seedlings. In contrast to the other isolates, B14 produced no GAs but high amounts of fumonisins during infection on rice. Furthermore, it differed from the other isolates by the presence of three additional polyketide synthase (PKS) genes (PKS40, PKS43, PKS51) and the absence of the F. fujikuroi-specific apicidin F (NRPS31) gene cluster. Analysis of additional field isolates confirmed the strong correlation between the pathotype (bakanae or stunting/withering), and the ability to produce either GAs or fumonisins. Deletion of the fumonisin and fusaric acid-specific PKS genes in B14 reduced the stunting/withering symptoms, whereas deletion of the PKS51 gene resulted in elevated symptom development. Phylogenetic analyses revealed two subclades of F. fujikuroi strains according to their pathotype and secondary metabolite profiles.

The Role of Breastfeeding in Acute Respiratory Infections in Infancy.

BACKGROUND: Acute respiratory infections (ARIs) affect the respiratory tract, are often caused by viruses such as respiratory syncytial virus and rhinovirus, and present symptoms such as coughing, fever, respiratory distress, and breathing difficulty. The global adherence to exclusive breastfeeding (BF) for the first 6 months of life has reached 44%, supported by the World Health Organization and United Nations International Children's Emergency Fund efforts. BF provides vital nutrients and contributes to infant immune system development, protecting against infections. The role of BF in preventing and reducing complications of ARIs in infants is gaining attention, prompting a review of current data and future research needs. This review aims to summarize the evidence on the role of BF in reducing the risk and severity of ARIs in infants, elucidate the adaptations in breast milk composition during infections, and identify relevant research needs. METHODS AND RESULTS: Human milk (HM) is rich in immunoglobulins, antimicrobial peptides, and immunomodulatory factors that protect against various pathogens, including respiratory viruses. Several studies have demonstrated that BF is associated with a significant reduction in hospitalization, oxygen requirements, and mortality in infants with ARIs. The effectiveness of BF varies according to the specific respiratory virus, and a longer duration of exclusive BF appears to enhance its protective effect. It is documented that the composition of HM adjusts dynamically in response to infections, fortifying the infant's immune defenses. Specific immunological components of HM, including leukocytes and immunoglobulins, increase in response to infection in the infant, contributing to the enhancement of the immune defense in infants. Immune-boosting microRNAs enhance immune transfer to the infants and promote early gut maturation, and the HM microbiome along with other factors modifies the infant's gut microbiome and immune system. CONCLUSIONS: BF defends infants from respiratory infections, and the investigation of the microRNAs in HM offers new insights into its antiviral properties. The promotion of BF, especially in vulnerable communities, is of paramount importance in alleviating the global burden of ARIs in infancy.

Investigation on the presence of mycotoxins in seed hemp varieties.

In recent years, the cultivation of hemp (Cannabis sativa L.) in Europe has aroused interest among farmers for the potential market opportunities of its products; its cultivation has increased from 20,450 ha in 2015 to 33,020 ha in 2022. Thanks to the great versatility of this crop, there are opportunities in the food and nutraceutical fields (gluten free), cosmetics, energy and industrial sectors. As for several crops, hemp seeds may also be contaminated by fungal pathogens compromising its quality and safety. Considering the recent interest of consumers in using hemp for food purposes, in the present work, a small survey on mycotoxin contamination was carried out during 2018-2022 in hemp seed samples cultivated in Italy for food use. The results showed a limited occurrence of the most common regulated mycotoxins (aflatoxins [AFs], fumonisins [FBs], ochratoxin A [OTA], deoxynivalenol [DON] and zearalenone), but very high levels of alternariols, reaching a maximum value of 38510, 308, 226 and 288 ug/kg for tenuazonic acid [TeA], tentoxin [TEN], alternariol [AOH] and alternariol monoether, respectively. In the same period, an investigation carried out in an experimental field showed that fungal contamination and mycotoxin occurrence were influenced by different meteorological conditions and different varieties.

Nationwide survey on the management of pediatric pharyngitis in Italian emergency units.

BACKGROUND: Acute pharyngitis is a frequent reason for primary care or emergency unit visits in children. Most available data on pharyngitis management come from primary care studies that demonstrate an underuse of microbiological tests, a tendency to over-prescribe antibiotics and a risk of antimicrobial resistance increase. However, a comprehensive understanding of acute pharyngitis management in emergency units is lacking. This study aimed to investigate the frequency of rapid antigen test use to diagnose acute pharyngitis, as well as other diagnostic approaches, the therapeutic attitude, and follow-up of children with this condition in the emergency units. METHODS: A multicentric national study was conducted in Italian emergency departments between April and June 2022. RESULTS: A total of 107 out of 131 invited units (response rate 82%), participated in the survey. The results showed that half of the units use a scoring system to diagnose pharyngitis, with the McIsaac score being the most commonly used. Most emergency units (56%) were not provided with a rapid antigen diagnostic test by their hospital, but the test was more frequently available in units visiting more than 10,000 children yearly (57% vs 33%, respectively, p = 0.02). Almost half (47%) of the units prescribe antibiotics in children with pharyngitis despite the lack of microbiologically confirmed cases of Group A ß-hemolytic streptococcus. Finally, about 25% of units prescribe amoxicillin-clavulanic acid to treat Group A ß-hemolytic streptococcus pharyngitis. CONCLUSIONS: The study sheds light on the approach to pharyngitis in emergency units, providing valuable information to improve the appropriate management of acute pharyngitis in this setting. The routinary provision of rapid antigen tests in the hospitals could enhance the diagnostic and therapeutic approach to pharyngitis.

Analysis of Sequence Variability and Transcriptional Profile of Cannabinoid synthase Genes in Cannabis sativa L. Chemotypes with a Focus on Cannabichromenic acid synthase.

Cannabis sativa L. has been long cultivated for its narcotic potential due to the accumulation of tetrahydrocannabinolic acid (THCA) in female inflorescences, but nowadays its production for fiber, seeds, edible oil and bioactive compounds has spread throughout the world. However, some hemp varieties still accumulate traces of residual THCA close to the 0.20% limit set by European Union, despite the functional gene encoding for THCA synthase (THCAS) is lacking. Even if some hypotheses have been produced, studies are often in disagreement especially on the role of the cannabichromenic acid synthase (CBCAS). In this work a set of European Cannabis genotypes, representative of all chemotypes, were investigated from a chemical and molecular point of view. Highly specific primer pairs were developed to allow an accurate distinction of different cannabinoid synthases genes. In addition to their use as markers to detect the presence of CBCAS at genomic level, they allowed the analysis of transcriptional profiles in hemp or marijuana plants. While the high level of transcription of THCAS and cannabidiolic acid synthase (CBDAS) clearly reflects the chemical phenotype of the plants, the low but stable transcriptional level of CBCAS in all genotypes suggests that these genes are active and might contribute to the final amount of cannabinoids.