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Background: Climate change significantly influences the distribution and severity of tropical diseases. Rising temperatures, changing precipitation patterns, and extreme weather events are transforming the habitats of vectors like mosquitoes and ticks, promoting their proliferation and geographic spread. These changes have facilitated the resurgence of diseases such as malaria, dengue, and chikungunya fever in previously unaffected areas, including parts of Europe and Italy., Objective and Methods: This review aims to explore the relationship between climate change and the spread of vector-borne and tropical parasitic diseases across Europe, with a particular focus on Italy. Recent studies are analyzed to identify emerging trends in disease transmission influenced by shifting climates. Genome-based monitoring and predictive models incorporating climatic and ecological data are highlighted as methods to enhance disease surveillance and preparedness., Results: The analysis reveals a clear link between climate change and altered disease patterns. The proliferation of vectors into new territories is associated with increased incidence of diseases. Genome-based tools demonstrate their utility in tracking the evolution of pathogens, particularly regarding changes in virulence, drug resistance, and adaptability to new climates. Predictive models have proven effective in anticipating outbreaks and supporting timely public health interventions., Conclusions: To mitigate the risks posed by climate-induced changes in disease dynamics, continuous monitoring and international collaboration are essential. Strengthening health systems' resilience through mitigation and adaptation strategies is crucial for preventing future epidemics. These insights contribute to the development of sustainable long-term policies for managing tropical diseases in the context of climate change, ensuring timely responses to public health emergencies.

The Ohrid trout, Salmo letnica , is an endemic species of Lake Ohrid, one of Europe's oldest lakes, located on the Albania-North Macedonia border. This species exhibits distinct morphotypes- Salmo letnica typicus , Salmo letnica aestivalis , Salmo letnica balcanicus , and Salmo letnica lumi -that differ in morphology and spawning behaviour. However, the extent of their genetic differentiation remains unclear. This study aimed to investigate the genetic variability and population structure of Salmo letnica morphotypes using the mitochondrial Control Region as molecular marker. We obtained 127 sequences from Salmo letnica morphotypes and compared them with sequences from other species within the genus Salmo . Phylogenetic and clustering analyses revealed no significant genetic structuring among the four morphotypes, suggesting an ecological differentiation not (yet) fixed at mitochondrial level. Additionally, our findings suggest that the modern Salmo letnica population likely originated in Lake Ohrid from Salmo farioides founders through evolutionary differentiation, potentially driven by environmental changes. Future studies incorporating a larger number of samples from both Salmo letnica and Salmo farioides are essential to fully understand the evolutionary and ecological dynamics of Salmo letnica morphotypes.

Following the increased mass mortality of Pinna nobilis populations in the Mediterranean, reliable protocols for the transport, maintenance, and controlled reproduction of this highly endangered species were drawn up within the European Life Pinna project. To test these protocols, the large Pinnidae Atrina fragilis , which shares similar habits to P. nobilis , has been used. In December 2022, a transport trial of nine specimens of A. fragilis from Trieste (NE Italy) to Camogli (NW Italy) was carried out. Two positioning (vertical and horizontal) of the specimens were tested inside the transport box. In the laboratory, after acclimatization, the specimens were placed inside three tanks and fed three times a week with a mix of live microalgae and artificial feed. The transport and maintenance protocols tested on A. fragilis were then applied to 11 P. nobilis collected in the Venice lagoon (NE Italy) and transported to the laboratory in June 2023. Due to the possible infection with Haplosporidium pinnae , considered one of the main etiological agents of mass mortality, P. nobilis individuals were evaluated through molecular analyses during their stay in the tank. Furthermore, these specimens were used as breeders: They spontaneously released already fertilized eggs, as a consequence of transport stress. Rapid larval development stopped at the early veliger stage, and the larvae were fed three times a week with a mixture of microalgae. After the reproduction period, the four specimens that survived 6 months in the laboratory, and constantly tested negative for H. pinnae , were transplanted to the Capo Mortola Marine Protected Area (Liguria, Italy) and monitored monthly., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

We adopted a morphometric approach to provide statistical support for the description of two different morphotypes (I, reproductive, II, non-reproductive) firstly observed in Procambarus clarkii specimens caught in a population from Sardinia Island (western Mediterranean). The morphometric study was preceded by molecular taxonomic identification using the mitochondrial Cytochrome C Oxidase subunit I (COI) gene. The presence or absence of the pathogen Aphanomyces astaci , responsible for the plague, was also investigated using the ribosomal Internal Transcribed Spacer (ITS) marker. The estimation of the size at onset of maturity (SOM) was further performed in males. Finally, the population structure was examined. Our results confirmed the entirety of the individuals as P. clarkii , and the absence of the pathogen A. astaci . Morphological analysis revealed a significant correlation between chela and carapace lengths, while intra- and inter-sexual dimorphism in the chela length confirmed the occurrence of the two morphotypes. The SOM in males was established between 35.0 and 37.1 mm carapace length. Finally, the size-population structure showed a Gaussian distribution. The recognition of the two distinct morphotypes in the crayfish could be useful as an additional tool not only to identify the reproductive period of this invasive crustacean but also to enrich the guidelines for the correct taxonomic identification of the species.

Human papillomavirus (HPV) is a widespread viral pathogen, responsible for a significant burden of cervical and other cancers worldwide. Over the past decades, the development and widespread adoption of prophylactic HPV vaccines have dramatically reduced the incidence of HPV-related diseases. However, despite the efficacy of these vaccines, global immunization efforts still face several obstacles, including low vaccination coverage in low- and middle-income countries, vaccine hesitancy, and disparities in access to healthcare. This review aims to provide a comprehensive overview of the current state of HPV vaccines, including their mechanisms of action, safety profiles, and real-world efficacy. We will explore the impact of HPV vaccines on cancer prevention, examine the challenges related to vaccine distribution and uptake, and assess the role of public health policies in improving global vaccination rates. Additionally, the review will highlight the latest advancements in therapeutic HPV vaccines, ongoing research into next-generation vaccines, and the potential of HPV vaccination strategies in the context of personalized medicine. By examining these factors, we aim to provide insights into the future directions of HPV vaccination and its role in global public health.

The family Paramyxoviridae includes a number of negative RNA viruses known for their wide host range and significant zoonotic potential. In recent years, there has been a surge in the identification of emerging zoonotic paramyxoviruses, particularly those hosted by bat species, which serve as key reservoirs. Among these, the genera Henipavirus and Pararubulavirus are of particular concern. Henipaviruses, including the highly pathogenic Hendra and Nipah viruses, have caused severe outbreaks with high mortality rates in both humans and animals. In contrast, zoonotic pararubulaviruses such as the Menangle virus typically induce mild symptoms or remain asymptomatic in human hosts. This review summarizes current knowledge on the evolution, ecology, and epidemiology of emerging zoonotic paramyxoviruses, focusing on recently discovered viruses and their potential to cause future epidemics. We explore the molecular mechanisms underlying host-switching events, viral replication strategies, and immune evasion tactics that facilitate interspecies transmission. In addition, we discuss ecological factors influencing virus emergence, including changes in bat populations and habitats and the role of wildlife-human interfaces. We also examine the public health impact of these emerging viruses, underlining the importance of enhanced surveillance, developing improved diagnostic tools, and implementing proactive strategies to prevent potential outbreaks. By providing a comprehensive overview of recent advances and gaps in knowledge, this review aims to inform future research directions and public health policies related to zoonotic paramyxoviruses.

From 1 January 2022 to 31 May 2024, the World Health Organization (WHO) reported 97,745 laboratory-confirmed Mpox cases, including 203 deaths, across 116 countries. Despite a 2.3% decrease in new cases in May 2024 compared to April 2024, significant regional variations persist. The African Region reported the highest proportion of new cases, while other regions experienced mixed trends. Phylogenomic analyses of the Mpox virus Clade IIb lineage B.1 reveal stable genetic variability with minimal diversification. The Bayesian Skyline Plot indicates a generally stable viral population size with a modest peak in late 2023, followed by a decline. In general, the data indicate that the MPXV outbreak is primarily localized within a few consistent geographic clusters. The virus's evolution is relatively slow, as indicated by its stable genetic variability, and Clade IIb lineage B.1 does not currently show signs of rapid genetic changes or population growth. The current low level of genetic diversity should not lead to complacency. Ongoing genomic surveillance is essential for effective outbreak management and understanding. This monitoring is crucial for identifying any shifts in the virus's behavior or transmission, allowing for prompt public health responses and adjustments. In addition, continued vigilance is necessary to detect any new variants that might influence the outbreak's trajectory.

The Atlantic blue crab, Callinectes sapidus , is acknowledged as one of the worst invasive alien species in the Mediterranean, impacting biodiversity and human activities. Native to the western Atlantic, it has expanded to European coastal waters since the early 1900s. Despite its ecological and commercial importance, genetic research on this species is limited. Here we show a comprehensive investigation of the genetic variation and evolutionary history in Callinectes sapidus using 667 mitochondrial COI gene sequences. Our dataset encompasses 36 newly generated sequences from previously understudied Mediterranean sites and 631 from worldwide locations obtained from the GenBank public database. Our findings reveal two distinct, but closely related, genetic groups within the species' distribution range, suggesting the occurrence of a potential species complex. Furthermore, in the Mediterranean, low levels of genetic variability were observed except for substantial haplotypic differentiation in Turkish samples. This study depicts the global genetic diversity and evolutionary patterns of Callinectes sapidus , offering new insights into the taxonomic status of the species.

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host-pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host-pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage.

Objective: Vitamin D deficiency is a common public health issue worldwide. The purpose of this study was to investigate the vitamin D status and its potential determinants in children residing in Sardinia (40°N), Italy., Methods: Children were enrolled over a 12-month period. Serum 25(OH)D was measured by an immunochemiluminescence assay. A questionnaire was used to gather information on other variables, including passive smoke exposure., Results: A total of 182 children (males: 51.7%; median age: 9 years) were included. Mean±standard deviation serum 25(OH)D was 25.2±8.3 ng/mL for the whole group. The majority (n=123, 67.6%) had vitamin D sufficient values >20 ng/mL, while 32.4% (n=59) had vitamin D insufficient/deficient values (≤20 ng/mL). Among the variables investigated, passive smoke exposure was significantly associated with insufficient 25(OH)D levels (p<0.0001)., Conclusion: Our results confirm that hypovitaminosis D is common in Italian children. Furthermore, passive smoke exposure was identified as a significant risk factor for hypovitaminosis D., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Background: In children, asthma and sleep-disordered breathing (SDB) may affect quality of life (QoL), and SDB may complicate asthma management., Objective: To evaluate the prevalence of SDB, its association with asthma control, and risk factors associated with SDB in a cohort of asthmatic children. The effects of asthma control and SDB on QoL were also investigated., Methods: We consecutively recruited asthmatic children referred to our Pulmonology Service from December 1, 2022 to May 31, 2023. Data on anthropometrics, respiratory function, and allergies were collected. The prevalence of SDB was assessed by the Pediatric Sleep Questionnaire (PSQ). Asthma control status was assessed by the Childhood Asthma Control Test (C-ACT), while QoL was evaluated by the Pediatric Quality of Life Inventory (PedsQL) questionnaire. Factors associated with SDB were analyzed., Results: A total of 78 asthmatic children aged 5-12 years were included. SDB was found in 37.2% of them, with a higher prevalence in children with uncontrolled versus well-controlled asthma (60.1% vs. 27.3%; p-value = 0.005). The C-ACT score was significantly lower in SDB-positive versus SDB-negative group, and uncontrolled asthma (C-ACT ≤19) was associated with a 4.15-fold increased risk of SDB. The PedsQL score was significantly lower in asthmatic children with than without SDB and was associated with lower SDB risk. SDB increased the risk of uncontrolled asthma in children, and asthmatic children with SDB had lower QoL., Conclusion: In asthmatic children, SDB affects both asthma control and QoL. Children with uncontrolled asthma should be referred for polysomnography to identify a possible underlying SDB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The COVID-19 pandemic underscored the critical importance of vaccination to global health security and highlighted the potential of digital health solutions to improve immunization strategies. This article explores integrating digital health technologies with immunization programs to improve coverage, monitoring, and public health outcomes. It examines the current landscape of digital tools used in immunization initiatives, such as mobile health apps, electronic health records, and data analytics platforms. Case studies from different regions demonstrate the effectiveness of these technologies in addressing challenges such as vaccine hesitancy, logistics, and real-time monitoring of vaccine distribution and adverse events. The paper also examines ethical considerations, data privacy issues, and the need for a robust digital infrastructure to support these innovations. By analyzing the successes and limitations of digital health interventions in immunization campaigns during and after the COVID-19 pandemic, we provide recommendations for future integration strategies to ensure resilient and responsive immunization systems. This research aims to guide policymakers, health professionals, and technologists in leveraging digital health to strengthen immunization efforts and prepare for future public health emergencies.

Bromelain is a complex natural mixture of sulfhydryl-containing proteolytic enzymes that can be extracted from the stem or fruit of the pineapple. This compound is considered a safe nutraceutical, has been used to treat various health problems, and is also popular as a health-promoting dietary supplement. There is continued interest in bromelain due to its remarkable therapeutic properties. The mechanism of action of bromelain appears to extend beyond its proteolytic activity as a digestive enzyme, encompassing a range of effects (mucolytic, anti-inflammatory, anticoagulant, and antiedematous effects). Little is known about the clinical use of bromelain in pediatrics, as most of the available data come from in vitro and animal studies, as well as a few RCTs in adults. This narrative review was aimed at highlighting the main aspects of the use of bromelain in children, which still appears to be limited compared to its potential. Relevant articles were identified through searches in MEDLINE, PubMed, and EMBASE. There is no conclusive evidence to support the use of bromelain in children, but the limited literature data suggest that its addition to standard therapy may be beneficial in treating conditions such as upper respiratory tract infections, specific dental conditions, and burns. Further studies, including RCTs in pediatric settings, are needed to better elucidate the mechanism of action and properties of bromelain in various therapeutic areas.

The risk of cardiac involvement with electrophysiological abnormalities during COVID-19 infection has been reported in adults but remains poorly studied in children. Our aim was to determine the frequency of cardiac involvement and the necessity of routine cardiac evaluation in children hospitalized for COVID-19. This observational study included 127 children, with a median (IQR) age of 2 (0.83-6.0) years, who were hospitalized for COVID-19 between 1 January 2021 and 31 August 2022, 62 (48.8%) of whom were males. Each patient underwent an ECG on admission and discharge as well as a laboratory assessment. A comparison between patients with COVID-19 and healthy controls showed significantly higher HR ( p < 0.0001) and lower PR values ( p = 0.02) in the first group. No arrhythmias or other electrocardiographic abnormalities were detected during hospitalization. The median levels of troponin, NT-proBNP, ferritin, and D-dimer were significantly higher in children aged <2 years, but they fell within the normal range for their age. Our results indicate that a detectable cardiac involvement is very rare in children hospitalized for COVID-19 and not suffering from Multisystem Inflammatory Syndrome in Children (MIS-C) and suggest that routine electrocardiographic assessment is not mandatory in these patients in the absence of cardiac symptoms/signs.

Orf virus (ORFV) belongs to the genus Parapoxvirus (Poxviridae family). It is the causative agent of contagious ecthyma (CE) that is an economically detrimental disease affecting small ruminants globally. Contagious ecthyma outbreaks are usually reported in intensive breeding of sheep and goats but they have also been reported in wildlife species. Notably, ORFV can infect humans, leading to a zoonotic disease. This study aims to elucidate the global evolutionary history of ORFV genomes in sheep and goats, including the first genomes from Central America in the analyses. In comparison to the last study on ORFV whole genomes, the database now includes 11 more sheep and goat genomes, representing an increase of 42%. The analysis of such a broader database made it possible to obtain a fine molecular dating of the coalescent time for ORFV S and G genomes, further highlighting the genetic structuring between sheep and goat genomes and corroborating their emergence in the latter half of 20th century.

Introduction: The prevalence of COVID-19 is slightly lower, and its mortality is higher in beta-thalassemia patients than in the general population. We evaluated the impact of COVID-19 in terms of incidence, clinical course, management, and specific antibody response to vaccination, in a cohort of patients with beta-thalassemia major., Methods: We retrospectively enrolled all transfusion-dependent beta-thalassemia major patients attending the Thalassemia Day Care Center of the University Hospital of Sassari, Italy, from March 1, 2020, to May 31, 2021. For each patient, demographic, clinical, laboratory, instrumental, and therapy data were collected. Patients aged ≥16 years received two doses of mRNA COVID-19 vaccine. Anti-SARS-CoV-2 serum antibodies were tested before and after the first vaccine dose., Results: A total of 68 patients (median age: 36.5 years; IQR: 13-42 years) were included. Nasopharyngeal swab (NPS) for SARS-CoV-2 detection by RT-PCR was positive in 5 (7.35%) of 68 patients (4 symptomatic). No COVID-19-related complications, hospitalizations, or deaths were observed. The transfusion regimen and iron chelation therapy were not significantly changed. Prior to COVID-19 vaccination, anti-SARS-CoV-2 antibodies were tested in 61 patients, 51 negative and 10 positive; five of the latter were also positive for SARS-CoV-2 on NPS. The 46 vaccinated subjects had an antibody response, with higher levels in subjects previously infected with SARS-CoV-2., Conclusion: Our findings suggest that patients with beta-thalassemia major are not at a higher risk of contracting SARS-CoV-2 infection and developing a severe form of COVID-19 despite being considered more vulnerable than the general population., (© 2024 S. Karger AG, Basel.)

Background and Objectives : Vitamin D is synthesized in the skin upon sunlight exposure, showing variations with season and latitude. We aimed to investigate the influence of age, sex, and season on vitamin D status in a large pediatric cohort during the COVID-19 pandemic period and the corresponding pre-pandemic period. Materials and Methods : Retrospective data concerning subjects aged < 18 years were extracted anonymously from the large database of a reference laboratory hospital (Sassari, Northern Sardinia, Italy). Serum 25-hydroxyvitamin D [25(OH)D] levels measured during the pre-pandemic period (1 March 2018 to 30 September 2019) were compared with those detected during the pandemic period (1 March 2020 to 30 September 2021). Results: A total of 2317 samples from subjects aged < 18 years were included in the analysis, 1303 (47.9% females) of which were collected in the pre-pandemic period and 1014 (51.3% females) in the pandemic period. No significant differences in 25(OH)D levels were found between the two periods, whereas, in children aged < 2 years, levels were higher than those in children aged 11-16 years ( p < 0.05). Monthly levels of 25(OH)D between pre-pandemic and pandemic periods did not differ, although significant differences were detected across months ( p < 0.0001). Similarly, 25(OH)D values did not differ significantly between males and females in both periods. Marked seasonal variations were observed in males and females across all age groups. Conclusions: Serum vitamin D levels and their season-related variations were not significantly affected by the COVID-19 pandemic and associated restrictions in a large cohort of Italian children and adolescents.

Pinna nobilis , commonly known as the noble pen shell, is a marine bivalve endemic to the Mediterranean Sea. Unfortunately, due to a multifactorial disease that began affecting its populations in 2016, the species is currently facing the threat of extinction. To gain insights into the evolutionary history of P. nobilis before the mass mortality event (MME), and to obtain a comprehensive understanding of how evolutionary processes led to the adaptation of the species into the Mediterranean Sea, phylogenetic and phylogeographic analyses were carried out. The dataset analysed includes 469 sequences of COI gene fragment both from GenBank and the present study (100). The analysis performed evidenced that P. nobilis diverged about 2.5 mya, after the entrance of its ancestor into the Mediterranean Sea following the Zanclean flood (5.33 mya). Moreover, our results suggest that the starting point of colonisation was the central part of the western Mediterranean basin, with the eastern basin being populated subsequently. From a conservational viewpoint, these results provide important hints for present and future restocking plans, helping to reconstruct the pre-existing genetic variability in sites where the species became extinct.

Adenotonsillectomy (AT) is the first-line treatment for pediatric obstructive sleep apnea syndrome (OSAS). Relatively few studies have evaluated the clinical and functional outcomes of AT in children with OSAS, but these studies show that surgery improves behavior and quality of life (QOL). However, residual OSAS after AT is reported in severe cases. This study aimed to retrospectively evaluate the clinical and functional outcomes of AT in a cohort of children with OSAS. We consecutively enrolled children with OSAS who underwent AT and were admitted to our clinic from 1 July 2020 to 31 December 2022. For each participant, medical history and physical examinations were performed. Before and after surgery, all patients underwent a standard polygraphic evaluation, and caregivers completed the OSA-18 questionnaire. A total of 65 children with OSAS, aged 2-9 years, were included. After AT, 64 (98.4%) children showed a reduction in AHI, with median (IQR) values decreasing from 13.4/h (8.3-18.5/h) to 2.4/h (1.8-3.1/h) ( p -value < 0.0001). Conversely, median (IQR) SpO 2 nadir increased after surgery from 89% (84-92%) to 94% (93-95%) ( p -value < 0.0001). Moreover, 27 children (18%) showed residual OSAS. The OSA-18 score decreased after AT from median (IQR) values of 84 (76-91) to values of 33 (26-44) ( p -value < 0.0001). A positive significant correlation was found between OSA-18 post-operative scores and AHI post-operative scores (rho 0.31; p -value = 0.01). Our findings indicate that, in children with OSAS, AT is associated with significant improvements in behavior, QOL, and polygraphic parameters. However, long-term post-surgical follow-up to monitor for residual OSAS is highly recommended, especially in more severe cases.

The severe acute respiratory syndrome coronavirus 2 EG.5 lineage is the latest variant under monitoring, and it is generating significant concern due to its recent upward trend in prevalence. Our aim was to gain insights into this emerging lineage and offer insights into its actual level of threat. Both genetic and structural data indicate that this novel variant presently lacks substantial evidence of having a high capacity for widespread transmission. Their viral population sizes expanded following a very mild curve and peaked several months after the earliest detected sample. Currently, neither the viral population size of EG.5 nor that of its first descendant is increasing. The genetic variability appear to be flattened, as evidenced by its relatively modest evolutionary rate (9.05 × 10 -4 subs/site/year). As has been observed with numerous prior variants, attributes that might theoretically provide advantages seem to stem from genetic drift, enabling the virus to continually adjust to its host, albeit without a clear association with enhanced dangerousness. These findings further underscore the necessity for ongoing genome-based monitoring, ensuring preparedness and a well-documented understanding of the unfolding situation., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

The XBB.1.16 SARS-CoV-2 variant, also known as Arcturus , is a recent descendant lineage of the recombinant XBB (nicknamed Gryphon ). Compared to its direct progenitor, XBB.1, XBB.1.16 carries additional spike mutations in key antigenic sites, potentially conferring an ability to evade the immune response compared to other circulating lineages. In this context, we conducted a comprehensive genome-based survey to gain a detailed understanding of the evolution and potential dangers of the XBB.1.16 variant, which became dominant in late June. Genetic data indicates that the XBB.1.16 variant exhibits an evolutionary background with limited diversification, unlike dangerous lineages known for rapid changes. The evolutionary rate of XBB.1.16, which amounts to 3.95 × 10 -4 subs/site/year, is slightly slower than that of its direct progenitors, XBB and XBB.1.5, which have been circulating for several months. A Bayesian Skyline Plot reconstruction suggests that the peak of genetic variability was reached in early May 2023, and currently, it is in a plateau phase with a viral population size similar to the levels observed in early March. Structural analyses indicate that, overall, the XBB.1.16 variant does not possess structural characteristics markedly different from those of the parent lineages, and the theoretical affinity for ACE2 does not seem to change among the compared variants. In conclusion, the genetic and structural analyses of SARS-CoV-2 XBB.1.16 do not provide evidence of its exceptional danger or high expansion capability. Detected differences with previous lineages are probably due to genetic drift, which allows the virus constant adaptability to the host, but they are not necessarily connected to a greater danger. Nevertheless, continuous genome-based monitoring is essential for a better understanding of its descendants and other lineages.

Recombination events are very common and represent one of the primary drivers of RNA virus evolution. The XBF SARS-CoV-2 lineage is one of the most recently generated recombinants during the COVID-19 pandemic. It is a recombinant of BA.5.2.3 and BA.2.75.3, both descendants of lineages that caused many concerns (BA.5 and BA.2.75, respectively). Here, we performed a genomic survey focused on comparing the recombinant XBF with its parental lineages to provide a comprehensive assessment of the evolutionary potential, epidemiological trajectory, and potential risks. Genetic analyses indicated that although XBF initially showed the typical expansion depicted by a steep curve, causing several concerns, currently there is no indication of significant expansion potential or a contagion rate surpassing that of other currently active or previously prevalent lineages. BSP indicated that the peak has been reached around 19 October 2022 and then the genetic variability suffered slight oscillations until early 5 March 2023 when the population size reduced for the last time starting its last plateau that is still lasting. Structural analyses confirmed its reduced potential, also indicating that properties of NTDs and RBDs of XBF and its parental lineages present no significant difference. Of course, cautionary measures must still be taken and genome-based monitoring remains the best tool for detecting any important changes in viral genome composition.

The SARS-CoV-2 BF.7 variant represents one of the most recent subvariant under monitoring. At the beginning of the 2023 it caused several concerns especially in Asia because of a resurge in COVID-19 cases. Here we perform a genome-based integrative approach on SARS-CoV-2 BF.7 to shed light on this emerging lineage and produce some consideration on its real dangerousness. Both genetic and structural data suggest that this new variant currently does not show evidence of an high expansion capability. It is very common in Asia, but it appears less virulent than other Omicron variants as proved by its relatively low evolutionary rate (5.62 × 10 -4 subs/sites/years). The last plateau has been reached around December 14, 2022 and then the genetic variability, and thus the viral population size, no longer increased. As already seen for several previous variants, the features that may be theoretically related to advantages are due to genetic drift that allows to the virus a constant adaptability to the host, but is not strictly connected to a fitness advantage. These results have further pointed that the genome-based monitoring must continue uninterruptedly to be prepared and well documented on the real situation., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Since the beginning of the pandemic, the generation of new variants periodically recurs. The XBB.1.5 SARS-CoV-2 variant is one of the most recent. This research was aimed at verifying the potential hazard of this new subvariant. To achieve this objective, we performed a genome-based integrative approach, integrating results from genetic variability/phylodynamics with structural and immunoinformatic analyses to obtain as comprehensive a viewpoint as possible. The Bayesian Skyline Plot (BSP) shows that the viral population size reached the plateau phase on 24 November 2022, and the number of lineages peaked at the same time. The evolutionary rate is relatively low, amounting to 6.9 × 10 -4 subs/sites/years. The NTD domain is identical for XBB.1 and XBB.1.5 whereas their RBDs only differ for the mutations at position 486, where the Phe (in the original Wuhan) is replaced by a Ser in XBB and XBB.1, and by a Pro in XBB.1.5. The variant XBB.1.5 seems to spread more slowly than sub-variants that have caused concerns in 2022. The multidisciplinary molecular in-depth analyses on XBB.1.5 performed here does not provide evidence for a particularly high risk of viral expansion. Results indicate that XBB.1.5 does not possess features to become a new, global, public health threat. As of now, in its current molecular make-up, XBB.1.5 does not represent the most dangerous variant.

Background and Objective: Gastroesophageal reflux (GER) is a common condition in infants. Usually, it resolves spontaneously in 95% of cases within 12-14 months of age, but gastroesophageal reflux disease (GERD) may develop in some children. Most authors do not recommend pharmacological treatment of GER, while the management of GERD is debated. The aim of this narrative review is to analyze and summarize the available literature on the clinical use of gastric antisecretory drugs in pediatric patients with GERD., Methods: References were identified through MEDLINE, PubMed, and EMBASE search engines. Only articles in English were considered. The following keywords were used: "gastric antisecretory drugs", "H2RA", "PPI", "ranitidine", "GERD", "infant", "child"., Key Content and Findings: Increasing evidence of poor efficacy and potential risks of proton pump inhibitors (PPIs) is emerging in neonates and infants. Histamine-2 receptor antagonists (H2RAs), including ranitidine, have been used successfully in older children, although less effective than PPIs at relieving symptoms and healing GERD. However, in April 2020, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) requested manufacturers of ranitidine to remove all ranitidine products from the market due to the risk of carcinogenicity. Pediatric studies comparing effectiveness and safety of different acid-suppressing treatments for GERD are generally inconclusive., Conclusions: A proper differential diagnosis between GER and GERD is crucial to avoid the overuse of acid-suppressing medications in children. Further research should be directed towards the development of novel antisecretory drugs, with proven efficacy and good safety profile, for treating pediatric GERD, particularly in newborns and infants., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-22-401/coif). RA serves as an unpaid editorial board member of Translational Pediatrics from March 2022 to February 2024. The other authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

The prevalence of hypovitaminosis D is increasing worldwide. Vitamin D deficiency is supposed to play a role in sleep disturbances, but the complex relationships between hypovitaminosis D and pediatric obstructive sleep apnea syndrome (OSAS) are still incompletely understood. This study was aimed to retrospectively investigate the vitamin D status and significant clinical, laboratory, and instrumental variables in a cohort of pediatric patients with OSAS and to assess the possible relationship between serum vitamin D levels and OSAS severity. We consecutively enrolled all children aged 2-14 years admitted to our Pediatric Clinic from 1 July 2018 to 30 November 2020 for sleep-disordered breathing. Each patient underwent standard overnight in-hospital polygraphic evaluation, measurement of serum 25-hydroxyvitamin D (25(OH)D) levels, and clinical and laboratory investigation. A total of 127 children with OSAS were included. The 25(OH)D levels and BMI of OSAS patients were compared with those of an age-matched control group: the serum 25(OH)D levels were significantly lower in OSAS patients than in controls (22.4 vs. 25.5 ng/mL; p -value = 0.009), whereas no differences in the BMI percentile were found between the two groups. The mean value of 25(OH)D was not significantly lower (20.9 ng/mL) in the severe OSAS group compared with the mild (23.0 ng/mL) and moderate (23.3 ng/mL) OSAS groups ( p -value = 0.28). Our findings indicate a relationship between vitamin D status and OSAS in children and suggest that severe cases of OSAS have lower vitamin D levels. Future, more extensive prospective studies are needed to confirm such preliminary findings.

Biological invasions are a major threat to the conservation of biodiversity, as invasive species affect native biota through competition, predation, pathogen introduction, habitat alteration, and hybridisation. The present study focuses on a southern pike population, Esox cisalpinus (Teleostei: Esocidae), that has been introduced outside the species' native range. Using microsatellite markers, this study's objective was to gather baseline genetic information and assess the presence of hybrids between this species and E. lucius in the introduced population. The resulting estimates of genetic diversity and effective population size are comparable to those observed in the species' native range. Although different methods yield contrasting and uncertain evidence regarding introgressive hybridization, the presence of late-generation hybrids cannot be completely ruled out. Large numbers of breeders as well as multiple introductions of genetically divergent cohorts and introgressive hybridisation may explain the high genetic diversity of this recently introduced southern pike population. The present study issues a warning that the conservation of southern pike' introgressive hybridisation between northern and southern pike might be underestimated. The genetic information gathered herein may unravel the origin, number of introduction events, and evolutionary trajectory of the introduced population. This information may help us understand the evolution of introgressive hybridisation in the southern pike's native areas.

Antisecretory drugs are frequently used in the treatment of pediatric gastrointestinal disorders. This study was aimed to assess the prescribing patterns and the safety of ranitidine and proton pump inhibitors (PPIs) in a cohort of Italian pediatric patients. Children aged >1 month to <16 years that were admitted to our Pediatric Clinic between 2016 and 2018 were enrolled in this retrospective observational study. All data were obtained from medical records and a parent telephone questionnaire. The exclusion criteria included the use of antisecretory therapy at hospital admission, failure to collect the relevant clinical data, and failure to administer the questionnaire. This study included 461 subjects, who were divided into four age groups: <2 years, 2−5 years, 6−11 years, and ≥12 years. Ranitidine was prescribed in 396 (85.9%) patients, mainly for the acute treatment of gastrointestinal symptoms, and a PPI was given to 65 (14.1%) children to treat gastroesophageal reflux disease, gastritis/ulcer, or for gastroprotection. During the study period, the percentage of patients treated with ranitidine progressively increased, except in the 2−5-year age group. We observed eighty-seven adverse drug reactions (ADRs), 61 of which occurred in the ranitidine group and 26 in the PPI group. The most common ADR was constipation (n = 35), which occurred more frequently in children treated with PPIs and in the 6−11-year age group. Ranitidine was the most used antisecretory drug in all the age groups, especially for acute treatment. Conversely, PPIs were the drugs of choice for prolonged treatments. Further research should be focused on developing an effective and safer alternative to ranitidine.

The genus Salariopsis (Blenniidae) comprises freshwater blenny fish that inhabits Mediterranean Sea, Black Sea, and north-east Atlantic areas. Three species were formally described to date: Salariopsis fluviatilis . S. economidisi , and S. atlantica . In this study, 103 individuals were collected from different Italian regions (Sardinia, Liguria, Piedmont, Lombardy) and analyzed using the mtDNA Control Region and the ribosomal 16s gene. We aimed (i) to depict the phylogeographic patterns of S. fluviatilis in northern Italy and Sardinia and (ii) to compare the genetic structure of Italian samples with those from other Mediterranean regions. Results obtained showed the presence of a well-supported genetic structuring among Italian S. fluviatilis populations, shedding new light on the phylogeographic patterns of northern Italian populations of S. fluviatilis sensu stricto across the Ligurian Alpine ridge and the Sardinia Island-mainland dispersal patterns. Furthermore, our species delimitation analysis was consistent in supporting results of previous research about the presence of genetic differentiation among S. fluviatilis , evidencing: (i) a large group of S. fluviatilis sensu stricto that includes two sub-groups (Occidental and Oriental), (ii) one group comprising populations from the Middle East of a taxonomic entity corresponding to Salariopsis cf. fluviatilis , and (iii) one group of Iberian individuals from the Guadiana River.

Macrolides such as azithromycin are commonly prescribed antibiotics during pregnancy. The good oral bioavailability and transplacental transfer of azithromycin make this drug suitable for the treatment of sexually transmitted diseases, toxoplasmosis, and malaria. Moreover, azithromycin is useful both in the management of preterm pre-labor rupture of membranes and in the adjunctive prophylaxis for cesarean delivery. The aim of this comprehensive narrative review is to critically analyze and summarize the available literature on the main aspects of azithromycin use in pregnant women, with a special focus on adverse offspring outcomes associated with prenatal exposure to the drug. References for this review were identified through searches of MEDLINE, PubMed, and EMBASE. Fetal and neonatal outcomes following prenatal azithromycin exposure have been investigated in several studies, yielding conflicting results. Increased risks of spontaneous miscarriage, major congenital malformations, cardiovascular malformations, digestive system malformations, preterm birth, and low birth weight have been reported in some studies but not in others. Currently, there is no conclusive evidence to support that azithromycin use by pregnant women causes adverse outcomes in their offspring. Therefore, this agent should only be used during pregnancy when clinically indicated, if the benefits of treatment are expected to outweigh the potential risks., (© 2022. The Author(s).)

Monkeypox is caused by a sylvatic, double-stranded DNA zoonotic virus. Since 1 January 2022, monkeypox cases have been reported to WHO from 106 Member States across six WHO regions, and as of 2 October 2022, a total of 68,900 confirmed cases, including 25 deaths, occurred. Here, by using a whole genome approach, we perform a genetic and phylodynamic survey of the monkeypox virus Clade IIb B.1, which is the lineage causing the current multi-country outbreak. Results suggest that outbreaks seem to be isolated and localized in several epidemic clusters with geographic consistency. Currently, monkeypox appears to be a virus with a flattened genetic variability in terms of evolutionary path, with a very slow rate of growth in the population size. This scenario confirms that the monkeypox virus lacks the evolutionary advantage, given by the high level of mutation rate, which is very strong in RNA viruses. Of course, constant genome-based monitoring must be performed over time in order to detect the change in its genetic composition, if any.

Congenital Hip Dysplasia (CHD) is characterized by a hip joint dislocation between the femoral head and the acetabulum, with a multifactorial etiology. This disorder can be an isolated condition or the manifestation of a syndromic condition, and it has been estimated with higher rates than registered, with a predominance in female sex and left side; risk factors are now defined. In Italy, the incidence rate is 3-4%, with significant regional differences: higher in Lombardy and lower in Sicily. Because clinical examination alone is insufficient to diagnose CHD, it is supplemented with ultrasonography and X-ray if necessary. Surveillance, static or dynamic splints, or osteotomies are the only treatment options. The goal of this study was to evaluate our experience in terms of management and conservative treatment of all newborns from January 2018 to May 2022: female sex and left hip were major involved, risk factors were not significant in our case, but results from early diagnosis and treatments, in terms of better outcome, were interesting. After a strict 6-month follow-up period, 89.13% of the patients were classified as grade Ia or Ib according to the Graf classification system. Finally, we emphasize the importance of early universal screening and subsequent diagnosis to allow for early treatment of the disorder, at an age when conservative treatments can yield good results.

Objective: to investigate the responses to mRNA COVID-19 vaccines in a cohort of immunosuppressed patients affected by immune-mediated inflammatory diseases (IMID)., Methods: we have measured humoral and cellular immunity using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assays and specific interferon-gamma (IFN-g) release assay (IGRA) before and after the third dose of BNT162b2. The response of those on anti-CD20 (n = 18) was then compared with healthy controls (HC, n = 18) and IMID naïve to anti-CD20 drugs (n = 13)., Results: a third BNT162b2 dose is highly immunogenic in IMID patients naïve to anti-CD20, as 100% of the subjects seroconverted compared to the 55% in anti-CD20. The rate of IGRA response was of 79% in anti-CD20, 50% in IMID naïve to anti-CD20, 100% in HC. Among those who have seroconverted, IMID patients had significantly reduced anti-S-IgG and neutralization titers compared to HC, whereas no significant difference was observed when comparing anti-CD20 and HC. Furthermore, 13% of anti-CD20 and 7.7% of IMID were simultaneously negative for both neutralizing antibodies and IGRA after three doses., Conclusion: these data draw attention to the immunogenicity of COVID-19 vaccination in treated IMID, taking specific groups into consideration for vaccination program., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The COVID-19 pandemic and associated public health measures have had a profound impact on health systems worldwide. The aim of this study was to assess quantitative and qualitative changes in Pediatric Emergency Department (PED) visits in Sardinia, Italy, during the early period of the COVID-19 pandemic., Methods: We retrospectively investigated the number and characteristics of visits to two major Sardinian PEDs, in the periods January-June 2020 and January-June 2019., Results: From January to June 2020, 8399 PED visits with 1160 hospital admissions (13.8% of PED visits) were registered, compared with 15,692 PED visits (Δ = -46.5%) and 1819 hospital admissions (11.6% of PED visits) occurring from January to June 2019. Comparing January-June 2020 with January-June 2019, we found differences in the percentage of visits for age groups, and significant changes in the proportion of triage codes, with a decrease in green codes (72.1% vs 74.2%, respectively) and an increase in white codes (19.0% vs 16.5%, respectively). Moreover, in the period January-June 2020, the frequency of skin disorders and acute respiratory disease significantly decreased, while the frequency of trauma, acute surgical disease, intoxication, and neuropsychiatric disease significantly increased., Conclusions: After the beginning of the Italian lockdown, we observed a marked drop in the number of PED visits, an increase in hospital admission rate, and radical changes in the reason for visit., (© 2022. The Author(s).)

In several countries, thrombotic events after vaccination with ChAdOx1 nCoV-19 have led to heterologous messenger RNA (mRNA) boosting. We tested the antibody response to SARS-CoV-2 spike protein four weeks after heterologous priming with the ChAdOx1 (ChAd) vector vaccine followed by boosting with BNT162b2(ChAd/BNT), comparing data of homologous regimen (BNT/BNT, ChAd/ChAd) subjects positive for SARS-CoV-2 after the first dose of BNT162b2 (BNT1dose/CoV2) and convalescent COVID-19., Methods: healthy subjects naïve for SARS-CoV-2 infection were assessed for serum IgG anti-S-RBD response 21 days after priming (T1), 4 (T FULL ) and 15 (T 15W ) weeks after booster dose., Results: The median IgG anti-S-RBD levels at T FULL of Chad/BNT group were significantly higher than the BNT/BNT group and ChAd/ChAd. Those of BNT/BNT group were significantly higher than ChAd/ChAd. IgG anti-S-RBD of BNT1dose/CoV2 group were similar to BNT/BNT, ChAd/BNT and ChAd/Chad group. The levels among COVID-19 convalescents were significantly lower than ChAd/BNT, BNT/BNT, ChAd/Chad and BNT1dose/CoV2. The proportion of subjects reaching an anti-S-RBD titer >75 AU/mL, correlated with high neutralizing titer, was 94% in ChAd/BNT and BNT/BNT, 60% in BNT1dose/CoV2, 25% in ChAd/ChAd and 4.2% in convalescents. At T 15W the titer of ChAd/BNT was still significantly higher than other vaccine schedules, while the anti-S-RBD decline was reduced for ChAd/ChAd and similar for other combinations., Conclusion: Our data highlight the magnitude of IgG anti-S-RBD response in ChAd/BNT dosing, supporting the current national guidelines for heterologous boosting.

Infant botulism (IB) is defined as a potentially life-threatening neuroparalytic disorder affecting children younger than 12 months. It is caused by ingestion of food or dust contaminated by Clostridium botulinum spores, which germinate in the infant's large bowel and produce botulinum neurotoxin. Although the real impact of IB is likely underestimated worldwide, the USA has the highest number of cases. The limited reporting of IB in many countries is probably due to diagnostic difficulties and nonspecific presentation. The onset is usually heralded by constipation, followed by bulbar palsy, and then by a descending bilateral symmetric paralysis; ultimately, palsy can involve respiratory and diaphragmatic muscles, leading to respiratory failure. The treatment is based on supportive care and specific therapy with Human Botulism Immune Globulin Intravenous (BIG-IV), and should be started as early as possible. The search for new human-like antibody preparations that are both highly effective and well tolerated has led to the creation of a mixture of oligoclonal antibodies that are highly protective and can be produced in large quantities without the use of animals. Ongoing research for future treatment of IB involves the search for new molecular targets to produce a new generation of laboratory-produced antitoxins, and the development of new vaccines with safety and efficacy profiles that can be scaled up for clinical use. This narrative literature review aims to provide a readable synthesis of the best current literature on microbiological, epidemiological and clinical features of IB, and a practical guide for its treatment.

Purpose: Paracetamol is the only drug recommended to treat fever in neonates. At recommended doses, paracetamol has not been associated with liver injury in neonates, while hepatotoxicity may occur after intake of a single high dose or multiple excessive doses. The aim of this narrative review is to critically analyze and summarize the available literature on newborns and infants exposed to supratherapeutic doses of paracetamol, with special focus on their clinical features, outcome, and management., Methods: The PubMed, SCOPUS, and Google Scholar search engines were used to collect data, without time limitation. The following keywords were used: paracetamol/acetaminophen, overdose, hepatotoxicity, N-acetylcysteine, newborn, infant., Results: The literature search identified a total of 27 case reports, a number of review articles, and few other relevant publications. Neonatal poisoning from paracetamol resulted from transplacental drug transfer after maternal overdose in some published cases, while it was the consequence of medication errors in other cases. Newborns and infants who have received a single overdose and have paracetamol concentrations below the Rumack-Matthew nomogram limits are at low risk of serious hepatic damage, while those who have recently ingested more than one supratherapeutic dose of paracetamol should be managed with caution. The treatment of choice for paracetamol poisoning is N-acetylcysteine, a specific antidote which reduces paracetamol hepatotoxic effects. N-Acetylcysteine should be given according to specific regimens through weight-based dosing tables., Conclusions: Caution should be used when paracetamol is administered to the newborn. In the event of an overdose, careful patient monitoring and personalization of post-overdose procedures are recommended.

Ceftriaxone is an antibiotic agent frequently used in paediatric hospital practice for the treatment of severe bacterial infections. The use of this agent can result in cholelithiasis and/or biliary sludge, more commonly in children than in adults. This systematic review was aimed at analysing available literature concerning ceftriaxone-associated biliary pseudolithiasis in paediatric patients, with a special emphasis on the clinical aspects. A literature analysis was performed using Medline and Embase electronic databases (articles published in English up to December 2019), with the search terms and combinations as follows:'ceftriaxone', 'cholelithiasis', 'biliary sludge' 'gallstones' 'neonates' 'children' 'clinical aspects' 'management'. Several case reports, case series and prospective/retrospective studies have documented a relationship between ceftriaxone treatment and biliary pseudolithiasis in the paediatric population, even though literature data regarding neonates and infants are scarce. Ceftriaxone-associated biliary pseudolithiasis is dose-dependent and usually asymptomatic but, sometimes, it may present with abdominal pain, nausea and emesis. Abdominal ultrasonography should be performed when this complication is suspected. Generally, ceftriaxone-associated cholelithiasis resolves over a variable period of time (days to months) after cessation of therapy. Therefore, a conservative approach to this condition is advocated, but a prolonged follow-up may be necessary. A personalized assessment of factors predisposing to ceftriaxone-associated biliary pseudolithiasis before prescribing the drug can allow to minimize the risk of developing it, with significant advantages in terms of human and economic costs., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)

Adrenaline, also known as epinephrine, is a hormone, neurotransmitter, and medication. It is the best established drug in neonatal resuscitation, but only weak evidence supports current recommendations for its use. Furthermore, the available evidence is partly based on extrapolations from adult studies, and this introduces further uncertainty, especially when considering the unique physiological characteristics of newly born infants. The timing, dose, and route of administration of adrenaline are still debated, even though this medication has been used in neonatal resuscitation for a long time. According to the most recent Neonatal Resuscitation Guidelines from the American Heart Association, adrenaline use is indicated when the heart rate remains < 60 beats per minute despite the establishment of adequate ventilation with 100% oxygen and chest compressions. The aforementioned guidelines recommend intravenous administration (via an umbilical venous catheter) of adrenaline at a dose of 0.01-0.03 mg/kg (1:10,000 concentration). Endotracheal administration of a higher dose (0.05-0.1 mg/kg) may be considered while venous access is being obtained, even if supportive data for endotracheal adrenaline are lacking. The safety and efficacy of intraosseous administration of adrenaline remain to be investigated. This article reviews the evidence on the circulatory effects and tolerability of adrenaline in the newborn, discusses literature data on adrenaline use in neonatal cardiopulmonary resuscitation, and describes international recommendations and outcome data regarding the use of this medication during neonatal resuscitation.

Large expansions of a noncoding GGGGCC repeat in the C9orf72 gene are the main cause of amyotrophic lateral sclerosis (ALS). The GGGGCC repeat is contiguous with another GC-rich region. Recent studies reported a significantly higher frequency of insertions/deletions within the GC-rich region in patients carrying the GGGGCC expansion. A GTGGT motif comprised within the GC-rich region, which joins two 100% GC sequences, was frequently deleted, supporting the hypothesis that these deletions could make the region more prone to slippage and pathological expansion. To confirm this hypothesis, we sequenced the GC-rich region adjacent the GGGGCC repeat in ALS patients, 116 C9orf72 expansion carriers, 219 non-carriers, and 223 healthy controls, from Italian and Turkish cohorts. Deletions were significantly more frequent in C9orf72 expansion carriers (6%) compared to non-carrier ALS patients (0.46%, OR =14.00, 95% CI =1.71-306.59, p = 0.003), to controls (0%, OR =16.29, 95% CI =2.12-725.99, p = 4.86 × 10 -4 ) and to the whole cohort of non-carriers (0.2%, OR =28.51, 95% CI =3.47-618.91, p = 9.58 × 10 -5 ). Among expansion carriers, deletions with or without the GTGGT motif were equally distributed (4 vs. 3). The frequency of insertions was not statistically different between C9orf72 expansion carriers and any other group including the whole cohort of non-carriers (p = 0.439, Fisher's exact test). Our data confirmed the association between deletions within GC-rich region and the GGGGCC expansion in Italian and Turkish cases, although we did not confirm a role of the GTGGT element deletion. Further studies will be therefore necessary to assess the causal relationships between contiguous deletions of the GC-rich region and the GGGGCC expansion.

Severe hypereosinophilia (HE) in children is rare, and its etiological diagnosis is challenging. We describe a case of a 30-month-old boy, living in a rural area, who was admitted to our Clinic with a 7-day history of fever and severe hypereosinophilia. A comprehensive diagnostic workup could not identify the cause of this condition. On day 6, the rapidly increasing eosinophil count (maximum value of 56,000/mm 3 ), the risk of developing hypereosinophilic syndrome, and the patient's history prompted us to undertake an empiric treatment with albendazole. The eosinophil count progressively decreased following treatment. On day 13, clinical condition and hematological data were satisfactory, therefore the treatment was discontinued, and the patient was discharged. Three months later, anti-nematode IgG antibodies were detected in patient serum, thus establishing the etiological diagnosis. In conclusion, an empiric anthelmintic treatment seems to be justified when parasitic hypereosinophilia is strongly suspected, and other causes have been excluded., Competing Interests: Competing interests: The authors have declared that no competing interests exist.

Background: Alpha-synuclein is a constituent of Lewy bodies and mutations of its gene cause familial Parkinson's disease (PD). A previous study showed that a variant of the alpha-synuclein gene ( SNCA ), namely the 263 bp allele of Rep1 was associated with faster motor progression in PD. On the contrary, a recent report failed to detect a detrimental effect of Rep1 263 on both motor and cognitive outcomes in PD. Aim of this study was to evaluate the influence of the Rep1 variants on disease progression in PD patients., Methods: We recruited and genotyped for SNCA Rep1 426 PD patients with age at onset ≥40 years and disease duration ≥4 years. We then analyzed frequency and time of occurrence of wearing-off, dyskinesia, freezing of gait, visual hallucinations, and dementia using a multivariate Cox's proportional hazards regression model., Results: SNCA Rep1 263 carriers showed significantly increased risk of both dementia (HR = 3.03) and visual hallucinations (HR = 2.69) compared to 263 non-carriers. Risk of motor complications did not differ in the two groups., Conclusion: SNCA Rep1 263 allele is associated with a worse cognitive outcome in PD.

Hypovitaminosis D in childhood is a re-emerging public health problem in developed countries. New life style habits, current "epidemics" of obesity in children and adolescents worldwide, and other preventable risk factors may play a role in favoring the occurrence of vitamin D deficiency. In addition to skeletal consequences, hypovitaminosis D has been found to be involved in the development of serious health extra-skeletal problems in childhood, including atopy and autoimmunity. The increasing concerns about the global health impact of vitamin D deficiency make further research necessary to fill the gaps of knowledge in this field, and particularly to establish universally accepted "normal" serum 25(OH)D levels in the pediatric population, and to improve strategies for the screening, prevention and treatment of hypovitaminosis D. This review discusses the key points of hypovitaminosis D in childhood in the light of new knowledge, and highlights the limitations of current strategies to control this condition.

Background: Usually, no adverse effects are observed in breastfed infants whose mothers are treated with the anti-epileptic carbamazepine. In this article, we described unusual short-term adverse effects observed in a young infant after exposure to carbamazepine during pregnancy and lactation., Case Report: A 40-day-old female infant, born at term, was admitted to the Pediatric Clinic at University of Sassari, Italy, for recurrent regurgitations and vomiting. She was breastfed since birth and her mother was under chronic carbamazepine therapy. Gastroesophageal reflux was initially suspected; therefore, thickening of feeds and postural therapy were applied without any benefit. Subsequently, high levels of carbamazepine were detected in infant serum and in maternal breast milk. After an unsuccessful attempt to combine breastfeeding with formula feeding, the switch to exclusive formula feeding was made, with subsequent rapid resolution of symptoms and body weight increase., Discussion and Conclusions: The use of carbamazepine is considered compatible with breastfeeding, even if the potential risk of adverse reactions in breastfed infants exists. In this case, the discontinuation of breastfeeding resulted in the complete resolution of symptoms, suggesting a correlation between the observed manifestations in the infant and her exposure to maternal therapy.