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Objectives: The aim of this study was to investigate the psychometric properties of the Greek version of the Pediatric Quality of Life Inventory(TM) 4.0 (PedsQL(TM) 4.0) as a population health outcome measure.Methods: After cultural linguistic validation, a cross-sectional study with the participation of 645 children (8-12 years old) and their primary caregivers was conducted in a nation-wide representative school-based sample to evaluate the psychometric properties of the measure.Results: All PedsQL 4.0 scales showed satisfactory reliability, with Cronbach's alpha exceeding 0.70--except in self-reported Physical Functioning (alpha = 0.65). Test-retest stability intraclass correlation coefficients (ICCs) were above 0.60 in all subscales. No floor effects were detected in either the self-report or parent proxy versions. Ceiling effects ranged from 2.2% (self-report Total Score) to 31.1% (parent-report Social Functioning). Poor to moderate agreement between self report and proxy report was observed, especially for the younger age groups of children. Impact of gender, health status, and family affluence status were detected, as hypothesised from previous bibliography, with girls reporting lower health-related quality of life (HRQOL) than boys on the Emotional Functioning subscale, healthy children scoring significantly higher on all scales than those with chronic illnesses, and lower socioeconomic groups scoring significantly lower than higher socioeconomic groups. Factor analysis showed mainly comparable results with the original version.Conclusions: Present results support the reliability and validity of the PedsQL 4.0 Greek version. The instrument could be a valuable tool in HRQOL measurement in school health care settings and population-based studies in Greek-speaking children, though it should be stressed that when possible, the child should be considered the first informant of his/her HRQOL. [ABSTRACT FROM AUTHOR]

Varicella is a common viral disease affecting almost the entire birth cohort. Although usually self-limiting, some cases of varicella can be serious, with 2 to 6% of cases attending a general practice resulting in complications. The hospitalisation rate for varicella in Europe ranges from 1.3 to 4.5 per 100,000 population/year and up to 10.1% of hospitalised patients report permanent or possible permanent sequelae (for example, scarring or ataxia). However, in many countries the epidemiology of varicella remains largely unknown or incomplete. In countries where routine childhood vaccination against varicella has been implemented, it has had a positive effect on disease prevention and control. Furthermore, mathematical models indicate that this intervention strategy may provide economic benefits for the individual and society. Despite this evidence and recommendations for varicella vaccination by official bodies such as the World Health Organization, and scientific experts in the field, the majority of European countries (with the exception of Germany and Greece) have delayed decisions on implementation of routine childhood varicella vaccination, choosing instead to vaccinate high-risk groups or not to vaccinate at all. In this paper, members of the Working Against Varicella in Europe group consider the practicalities of introducing routine childhood varicella vaccination in Europe, discussing the benefits and challenges of different vaccination options (vaccination vs. no vaccination, routine vaccination of infants vs. vaccination of susceptible adolescents or adults, two doses vs. one dose of varicella vaccine, monovalent varicella vaccines vs. tetravalent measles, mumps, rubella and varicella vaccines, as well as the optimal interval between two doses of measles, mumps, rubella and varicella vaccines). Assessment of the epidemiology of varicella in Europe and evidence for the effectiveness of varicella vaccination provides support for routine childhood programmes in Europe. Although European countries are faced with challenges or uncertainties that may have delayed implementation of a childhood vaccination programme, many of these concerns remain hypothetical and with new opportunities offered by combined measles, mumps, rubella and varicella vaccines, reassessment may be timely. [ABSTRACT FROM AUTHOR]

Background: Upper Respiratory Infections (URIs) are common in children. The cause is usually viral, but parents' attitude often contributes to inappropriate antibiotic prescribing, promoting antibiotic resistance. The objective is to describe the process of developing a questionnaire to assess parents' Knowledge, Attitude and Practices (KAP) concerning the role of antibiotics when children suffer from URIs, as well as to evaluate the response rates, the completeness and the reliability (Cronbach) of the questionnaires. Finally, to note any limitations of the study.Methods: Literature review, along with pre-testing yielded a questionnaire designed to assess the parents' KAP-level. A postal survey was set, in a national sample of 200 schools stratified by geographical region. The participants consist of a multistage geographical cluster sample of 8000 parents. The influence of demographic characteristics (i.e. sex, age, education) was analyzed. Cronbach index test and factor analysis were used to assess the reliability of the questionnaire.Results: The response rate of the parents was 69%. Islands presented the lowest response rate while in Northern Greece the response rate was the highest. Sixty-eight point nine percent of the sample returned questionnaires fully completed, while 91.5% completed 95% of the questions. Three questions out of 70 were answered in a very low rate which was associated mostly with immigrant respondents. The section describing parents' attitude toward antibiotic use was not completed as much as the sections of knowledge or practices. The questions were factor analyzed and 10 out of the 21 extracted factors were finally evaluated, reducing the number of independent variables to 46. The reliability of the questionnaire was 0.55. However, only items that increased the Cronbach when added were eventually included in the final scales raising the internal consistency to 0.68. Limitations of the study, such as the vocabulary and form of the questionnaire and the idiocycrancy of the respondents, emerged during the analysis.Conclusion: The response rate and the completeness of the questionnaires were higher than expected, probably attributed to the involvement of the teachers. The study findings were satisfactory regarding the development of a reliable instrument capable to measure parents' KAP characteristics. [ABSTRACT FROM AUTHOR]

Background: To assess hearing outcomes at 24 months of age in infants with mild congenital cytomegalovirus (cCMV) infection, depending on whether they have received antiviral treatment or not., Methods: A retrospective study within the European Registry of Children with cCMV was performed. Included children had cCMV diagnosed in utero/in the first 21 days of life, with normal physical examination, alanine aminotransferase <80 U/L and platelets >100,000 cs/mm3 and absence of hearing loss (HL) at birth. Cranial ultrasound (cUS) and/or cranial magnetic resonance imaging was normal or with minor findings (isolated lenticulostriate vasculopathy and/or germinolysis/caudothalamic or subependymal cysts, and/or focal/multifocal white matter involvement). The main outcome was the presence of HL at 24 months of age., Results: One hundred ninety-six patients met inclusion criteria. A total of 34.7% received antiviral treatment with valganciclovir/ganciclovir. Children treated had lower gestational age, birth weight and head circumference, and maternal primary infection was less frequent. Among treated children, 21.3% presented minor findings in cUS versus 6.3% in nontreatment group (P = 0.003). Nine patients (4.6%) developed HL at 24 months. Among children with HL, 20% presented minor findings in cUS versus 11.3% in non-HL group (P = NS). HL rate was similar in treated and nontreated groups (4.6% vs. 6.3%; P = 0.6)., Conclusions: One-third of the children were treated with antivirals and infants with minor neuroimaging findings at birth were more likely to receive antiviral. There were no differences in the prevalence of HL at 2 years of age between treated and not-treated children. Minor neuroimaging findings were not clearly associated with an increased risk of delayed onset HL., Competing Interests: D.B.-G. has received fees from MSD as a speaker in educational activities. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/objectives: Vaccination of pregnant and postpartum women for pertussis, influenza and COVID-19 not only protects themselves but also offspring. Despite the benefits of this approach, vaccination uptake remains suboptimal in pregnancy. Where the opportunity to be vaccinated in pregnancy is missed, the offer of vaccination in the post-partum period may be an alternative strategy. The aim of this systematic review is to assess the impact of interventions to increase vaccination uptake in the postpartum period on vaccination uptake., Methods: A literature search was performed in MEDLINE, including interventional studies promoting vaccination uptake in postpartum women published between 2009 and 2024. The search was conducted according to PRISMA guidelines and registered with PROSPERO., Results: We finally included 16 studies in the review, and the primary outcome was vaccination uptake in the postpartum period. The most significant factors for increasing uptake were recommendation from healthcare providers, type of interventions used, and delivery of vaccines in the maternity wards or the community., Conclusions: In conclusion, maternal vaccination rates in the postpartum period may increase with targeted education by healthcare professionals and positive reinforcement. The interventions described in these studies could be applied in the healthcare systems worldwide.

Background: Leptin is known for its metabolic, immunomodulatory and neuroendocrine properties, but the full spectrum of molecules downstream of leptin and relevant underlying mechanisms remain to be fully clarified. Our objective was to identify proteins and pathways influenced by leptin through untargeted proteomics in two clinical trials involving leptin administration in lean individuals., Methods: We performed untargeted liquid chromatography-tandem mass spectrometry serum proteomics across two studies a) Short-term randomized controlled crossover study of lean male and female humans undergoing a 72-h fast with concurrent administration of either placebo or high-dose leptin; b) Long-term (36-week) randomized controlled trial of leptin replacement therapy in human females with acquired relative energy deficiency and hypoleptinemia. We explored longitudinal proteomic changes and run adjusted mixed models followed by post-hoc tests. We further attempted to identify ontological pathways modulated during each experimental condition and/or comparison, through integrated qualitative pathway and enrichment analyses. We also explored dynamic longitudinal relationships between the circulating proteome with clinical and hormonal outcomes., Results: 289 and 357 unique proteins were identified per each respective study. Short-term leptin administration during fasting markedly upregulated several proinflammatory molecules, notably C-reactive protein (CRP) and cluster of differentiation (CD) 14, and downregulated lecithin cholesterol acyltransferase and several immunoglobulin variable chains, in contrast with placebo, which produced minimal changes. Quantitative pathway enrichment further indicated an upregulation of the acute phase response and downregulation of immunoglobulin- and B cell-mediated immunity by leptin. These changes were independent of participants' biological sex. In the long term study, leptin likewise robustly and persistently upregulated proteins of the acute phase response, and downregulated immunoglobulin-mediated immunity. Leptin also significantly and differentially affected a wide array of proteins related to immune function, defense response, coagulation, and inflammation compared with placebo. These changes were more notable at the 24-week visit, coinciding with the highest measured levels of serum leptin. We further identified distinct co-regulated clusters of proteins and clinical features during leptin administration indicating robust longitudinal correlations between the regulation of immunoglobulins, immune-related molecules, serpins (including cortisol and thyroxine-binding globulins), lipid transport molecules and growth factors, in contrast with placebo, which did not produce similar associations., Conclusions: These high-throughput longitudinal results provide unique functional insights into leptin physiology, and pave the way for affinity-based proteomic analyses measuring several thousands of molecules, that will confirm these data and may fully delineate underlying mechanisms., Competing Interests: Declaration of competing interest V. P. reports honorarium for lectures by MSD, Pfizer, and Takeda, support of research by GSK, and travel support by Pfizer. None of the above is related to the work reported herein. C.S.M. reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer-Ingellheim, has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, reports educational activity meals through his institution or national conferences from Esperion, Merck, Boehringer Ingelheim and travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. None of the above is related to the work reported herein. The other authors have nothing to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although gut dysbiosis is associated with cow's milk allergy (CMA), causality remains uncertain. This study aimed to identify specific bacterial signatures that influence the development and outcome of the disease. We also investigated the effect of hypoallergenic formula (HF) consumption on the gut microbiome of milk-allergic children. 16S rRNA amplicon sequencing was applied to characterize the gut microbiome of 32 milk-allergic children aged 5-12 years and 36 age-matched healthy controls. We showed that the gut microbiome of children with CMA differed significantly from that of healthy children, regardless of whether they consumed cow's milk. Compared to that of healthy cow's milk consumers, it was depleted in Bifidobacterium , Coprococcus catus , Monoglobus , and Lachnospiraceae GCA-900066575, while being enriched in Oscillibacter valericigenes , Negativibacillus massiliensis , and three genera of the Ruminococcaceae family. Of these, only the Ruminococcaceae taxa were also enriched in healthy children not consuming cow's milk. Furthermore, the gut microbiome of children who developed tolerance and had received an HF was similar to that of healthy children, whereas that of children who had not received an HF was significantly different. Our results demonstrate that specific gut microbiome signatures are associated with CMA, which differ from those of dietary milk elimination. Moreover, HF consumption affects the gut microbiome of children who develop tolerance.

Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55-13.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection.

Aim: Vaccinations have reduced illnesses and mortality rates globally, yet negative attitudes and uncertainty about them hinder their acceptability and efficacy. The study aims to document Greek parents' immunization perceptions and risk factors., Methods: Spanning 2014-2017, 447 parents (68% mothers) who participated in the Greek Health Examination Survey EMENO (National Survey of Morbidity and Risk Factors) completed an interview-delivered questionnaire. Attitudes were categorized into three groups: absolutely positive, positive, and negative. Absolutely positive attitudes included positive responses to all five statements in favor of vaccination and negative responses to the two statements against vaccination. Negative attitudes included positive responses to either one or both statements against vaccination and negative responses to all five statements in favor of vaccination.. All other participants were categorized as having a positive attitude. Skepticism towards vaccinations was classified into skeptical and non-skeptical groups based on responses to five statements implying uncertainty or skepticism. Participants were considered skeptical if they provided positive responses to at least three of these statements, and non-skeptical if they had none or up to two positive responses. The statistical analysis accounted for the study design whereas inverse probability weighting was used to adjust for non-response and multiple imputations were employed to impute missing values. The components of parental attitude and vaccine skepticism were identified using weighted multinomial logistic regression and logistic regression, respectively., Results: In total, 16.6% were classified as having absolutely positive attitudes towards vaccinations whereas 42.1% were skeptical of vaccines. Of all participants, 96.0% agreed that vaccinations are essential for their child's well-being and adhere to scientific recommendations. However, concerns were also mentioned, with 26.2% worrying about potential adverse effects, and 21.6% believing it is better to acquire immunity through illness rather than vaccination. Positive participants, compared to absolutely positive ones, were more likely to be of Greek origin (adjusted relative rate ratio (aRRR): 3.35; 95% CI: 1.53-7.30) and living in semi-urban areas (aRRR: 4.84; 95% CI: 1.77-13.29). Negative participants, in contrast, were more likely to have higher education (aRRR: 2.98; 95% CI: 1.05-8.44) but also to live in semi-urban areas (aRRR: 6.43; 95% CI: 1.69-24.56). Furthermore, parents of Greek origin had significantly higher odds of being skeptical towards vaccination (adjusted Odds Ratio (aOR): 2.86; 95% CI: 1.36-5.98), while married or cohabiting parents had lower odds of being skeptical compared to single parents (aOR: 0.60; 95% CI: 0.35-1.06)., Conclusions: While parents in this study recognize the importance of childhood immunizations, there is a widespread presence of negative attitudes and skepticism that can have a detrimental impact on vaccination rates., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Bioethics & Deontology Committee of the Medical School of National and Kapodistrian University of Athens issued approval 2564-12/11/2014. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The EMENO survey was implemented under the Operational Program “Education and Lifelong Learning” and was co-funded by the European Union (European Social Fund) and national resources (grant number: MIS 376659). Additional funding was obtained from the Hellenic Diabetes Association to measure glycated hemoglobin (grant number: Κ.Ε. 12008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Financial relationships: Giota Touloumi declare(s) a grant from European Union, National Resources Grants, Hellenic Diabetes Association, Gilead Sciences Europe, UCL, ECDC, University of Bristol, Harvard University, and National Funds. GT has received EU and National Resources Grants as well as a grant from the Hellenic Diabetes Association, all paid to her institution, to support this study and grants unrelated to this study and paid to her institution from Gilead Sciences Europe, UCL, ECDC, EU, University of Bristol, Harvard University, and National Funds. The rest of 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. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kotsia et al.)

The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. This study aims to evaluate SARS-CoV-2 seroprevalence in children during the different variants' subperiods. A prospective multicenter seroprevalence study was conducted in 7 University public hospitals in Greece from November 2021 to August 2022 (3 subperiods: November 2021-February 2022, March 2022-May 2022, June 2022-August 2022). Children from different age groups, admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 were enrolled. Neutralizing antibodies (Nabs), anti-Spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 IgG in serum were evaluated. A total of 2127 children (males:57,2%; median age:4,8years) were enrolled. Anti-N IgG seropositivity increased from 17,8% in the first sub-period to 40,7% in the second sub-period and then decreased in the third sub-period (36,7%). Anti-S IgG seropositivity appeared to have an increasing trend over the study period, starting from 34,8% and reaching 80,7%. Children aged 1-4 years old have significantly higher anti-N IgG titers compared to children aged 0-1 years old (p < 0,001). Infants have significantly lower anti-S IgG titers compared to all other age groups (p < 0,001). Immunocompromised children and infants have the lowest seropositivity for NAbs.Conclusions During the Omicron period, seropositivity significantly increased, as a result of higher transmissibility. Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1-4 years old present higher antibody titers, suggesting that this age group may mount a higher antibody response. Continuous surveillance seroprevalence studies are needed in children, in order to identify the true extent of SARS-CoV-2 and guide the planning of adequate public health measures., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Congenital cytomegalovirus (cCMV) infection carries a significant burden with a 0.64% global prevalence and a 17-20% chance of serious long-term effects in children. Since the last guidelines, our understanding, particularly regarding primary maternal infections, has improved. A cCMV guidelines group was convened under the patronage of the European Society of Clinical Virology in April 2023 to refine these insights. The quality and validity of selected studies were assessed for potential biases and the GRADE framework was employed to evaluate quality of evidence across key domains. The resulting recommendations address managing cCMV, spanning prevention to postnatal care. Emphasizing early and accurate maternal diagnosis through serological tests enhances risk management and prevention strategies, including using valaciclovir to prevent vertical transmission. The guidelines also strive to refine personalized postnatal care based on risk assessments, ensuring targeted interventions for affected families., Competing Interests: MLV reports receiving support for attending meetings by BioMérieux and Altona outside the submitted work. MLV reports payment made to her institution for presentation/lecture by Diasorin, Abbott Molecular and Roche Diagnostic outside the submitted work. DBG received Grant from the Spanish Ministry of Science and Innovation. ISCIII and Fondos FEDER (EU) outside the submitted work and received Honoraria for lectures from the Medscape, outside the submitted work. JF received honoraria for poster presentation by Abbott GmbH, outside the submitted work. CJ received consulting fees from Moderna, outside the submitted work; Participated on a Data Safety Monitoring Board or Advisory Board of Moderna, outside the submitted work; Is Co-director of the European Congenital CMV Initiative; Her institution received payment for clinical trials by Moderna, outside the submitted work. HL participated on advisory board for the Study of Zidovudine in children with Aicadri-Goutiere Syndrome, outside the submitted work and she is Trustee of European Society For Paediatric Infectious Diseases (ESPID). VP institution received honoraria for lectures from MSD and Pfizer, outside the submitted work and received support for attending a meeting (ESPID 2023) from Pfizer. PV is president and board-member of the European Congenital CMV Initiative. AV is participating in the Advisory Council European Society of Virology. The rest author of the authors declare no conflict of interest., (© 2024 The Author(s).)

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory condition that may occur following SARS-CoV-2 infection. This retrospective, descriptive study of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) in 12 tertiary care centers from 3/11/2020 to 12/31/2021. Demographics, clinical and laboratory characteristics, treatment and outcomes are described. Among 145 patients (95 males, median age 8.2 years) included, 123 met the WHO criteria for MIS-C, while 112 (77%) had serological evidence of SARS-CoV-2 infection. Fever was present in 99%, gastrointestinal symptoms in 77%, mucocutaneous involvement in 68% and respiratory symptoms in 28%. Fifty-five patients (38%) developed myocarditis, 29 (20%) pericarditis and 19 (13%) coronary aneurysms. Among the above cases 11/55 (20%), 1/29 (3.4%) and 5/19 (26.3%), respectively, cardiac complications had not fully resolved at discharge. Underlying comorbidities were reported in 18%. Median CRP value was 155 mg/l, ferritin 535 ng/ml, PCT 1.6 ng/ml and WBC 14.2 × 10 9 /mm 3 . Most patients had elevated troponin (41.3%) and/or NT-pro-BNP (49.6%). Intravenous immunoglobulin plus corticosteroids were used in 117/145 (80.6%), monotherapy with IVIG alone in 13/145 (8.9%) and with corticosteroids alone in 2/145 (1.3%). Anti-IL1 treatment was added in 15 patients (10.3%). Thirty-three patients (23%) were admitted to the PICU, 14% developed shock and 1 required ECMO. Mortality rate was 0.68%. The incidence of MIS-C was estimated at 0.69/1000 SARS-CoV-2 infections. Patients who presented with shock had higher levels of NT-pro-BNP compared to those who did not (p < 0.001). Acute kidney injury and/or myocarditis were associated with higher risk of developing shock., Conclusion: MIS-C is a novel, infrequent but serious disease entity. Cardiac manifestations included myocarditis and pericarditis, which resolved in most patients before discharge. Timely initiation of immunomodulatory therapy was shown to be effective. NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. Further research is required to elucidate the pathogenesis, risk factors and optimal management, and long-term outcomes of this clinical entity., What Is Known: • MIS-C is an infrequent but serious disease entity. • Patients with MIS-C present with multi-organ dysfunction, primarily involving the gastrointestinal and cardiovascular systems., What Is New: • NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. • Acute kidney injury and/or myocarditis were associated with higher risk of developing shock., (© 2024. The Author(s).)

Constructed wetlands (CWs) have been extensively used in Cr(VI) removal and have proven their ability to achieve high removal efficiencies. Although, numerous studies have been published in the past years presenting experimental results of CWs treating wastewater with Cr(VI) concentrations, a mathematical modeling describing the processes for Cr(VI) removal in CWs is lacking. In this work a mathematical model was developed, able to accurately describe the main mechanisms and reactions (i.e. biological reduction, plant biomass uptake-sorption) which are responsible for Cr(VI) removal in a wetland system. The model was calibrated and validated using data from a previously reported experimental study of horizontal subsurface CWs. Mathematical simulation indicates that in an unplanted wetland Cr(VI) was mainly removed through the diffusion/reduction process inside biofilm, attached on the porous media, while in the planted unit Cr(VI) was mainly removed through the sorption process to the root system of the plants. The developed model's simulations showed high correlation between predicted and experimental data, indicating that the proposed model can be used to design and predict full scale constructed wetland process for Cr(VI) removal., 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. Published by Elsevier B.V.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Objective: Maternal COVID-19 infection during pregnancy has been associated with adverse neonatal outcomes, such as prematurity and neonatal morbidity. Those adverse events are mainly attributed to maternal factors, rather than to the neonatal infection itself. Our aim is to add our experience and present the neonatal outcome of neonates born to mothers with perinatal SARS-CoV-2 infection., Methods: This is a prospective case-control study with data from two Academic Tertiary Referral Hospitals in Greece. Electronic records of all births from SARS-CoV-2 positive mothers between March 2020 and April 2021 were analyzed. Demographic data, the severity of maternal COVID-19 disease, gestational age (GA), mode of delivery, birth weight (BW), need for resuscitation and/or supplemental oxygen and duration of hospitalization were recorded. A comparison with 2:1 matched neonates according to sex, GA, and BW born to SARS-CoV-2 negative mothers during the same period was performed. Chi-square and Mann-Whitney U test were used for categorical and non-categorical variables respectively., Results: A total of eighty-one neonates were born to SARS-CoV-2 positive mothers during this period. Forty-three percent of pregnant mothers were asymptomatic. Median GA and median BW were 38 weeks (Interquantile range (IQR): 36-39 weeks) and 2940 gr (IQR: 2560-3340 gr) respectively. Prematurity was observed in 24.7% of the cases. Only 2 (2.4%) neonates were PCR positive after delivery. SARS-CoV-2 positive women were more likely to undergo Cesarean section. APGAR score at 5 min and the need for resuscitation did not differ between the two groups. In comparison with the control group, neonates born to SARS-CoV-2 positive mothers presented with gastrointestinal symptoms (53.6% vs 5.1%, p -value= <.001) and hospitalization was longer, mostly due to maternal factors., Conclusion: In our study neonatal positivity was limited and no vertical transmission was noted. Neonatal outcomes were comparable to the control group. However, the presence of gastrointestinal symptoms in neonates born to PCR-positive women compared to controls needs further investigation.

Introduction: Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide causing severe morbidity in newborns, infants, and children. Despite the clinical importance of congenital CMV (cCMV) infection, studies conducted so far indicate that there is limited awareness in the medical community in the field. The aim of this study was to assess Greek medical students' knowledge on cCMV infection., Methods: We performed a questionnaire-based nationwide cross-sectional study. A convenience sample of medical students from seven medical schools was enrolled., Results: Of the 562 respondents, 54,8% considered themselves undereducated on cCMV infection. However, almost half of the participants could correctly recognize some basic principles of cCMV infection including ways of transmission, diagnosis and treatment, while there were aspects of cCMV infection with knowledge deficit. The year of study had a positive impact on the level of knowledge with students of higher years of study being of more sufficient education on the specific topic., Conclusion: Overall, our study indicates a discrepancy between self-reported awareness and the level of knowledge among medical students in Greece. Further educational opportunities about cCMV should be offered, particularly in areas of the curriculum involving the care of women and children. Establishing medical students' solid background on the disease burden and educating them about preventative strategies for at-risk populations, should be the main pillars of such efforts in order to promote confidence in managing these cases in their future professional careers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Benou, Hatzidaki, Kalaintzi, Grivea, Baltogianni, Giapros, Thomaidou, Sarafidis, Tsichla, Sinopidis, Papachatzi, Karatza, Lagadinou, Dassios, Dimitriou, Papaevangelou and Gkentzi.)

Introduction: The low-density lipoprotein receptor-related protein 5 (LRP5) and its inhibitor sclerostin, are key components of bone metabolism and potential contributors to type 2 diabetes mellitus susceptibility. This study aims at evaluating the expression of placental LRP5 and sclerostin in pregnancies with gestational diabetes mellitus (GDM) and investigate possible associations with umbilical sclerostin concentrations and clinical outcomes in mothers and their neonates., Methods: Twenty-six GDM-mothers and 34 non-GDM mothers of Caucasian origin and their neonates admitted in a gynecology and obstetrics department of a university hospital were included in this study. Demographic data and maternal fasting glucose concentrations (24-28 weeks of gestation) were retrieved from the patients' medical records. Placental LRP5 was determined by immunohistochemistry (IHC) and Western blotting analysis; placental sclerostin was determined by IHC. Umbilical serum sclerostin concentrations were measured by ELISA., Results: Placental sclerostin IHC intensity values were positively correlated with LRP5 values as detected either by IHC (r = 0.529; P < .001) or Western blotting (r = 0.398; P = .008), with pregestational maternal body mass index values (r = 0.299; P = .043) and with maternal fasting glucose concentrations (r = 0.475; P = .009). Placental sclerostin and LRP5 were significantly greater in GDM compared with non-GDM placentas (histo-score: 65.08 ± 17.09 vs 11.45 ± 2.33, P < .001; 145.53 ± 43.74 vs 202.88 ± 58.65, P < .001; respectively)., Discussion: Sclerostin and LRP5 were detected in human placentas. The overexpression of placental sclerostin and LRP5 values in GDM compared with non-GDM pregnancies, as well as the positive association of placental sclerostin values with pregestational maternal body mass index and maternal fasting glucose concentrations may indicate the development of an adaptive mechanism in face of maternal hyperglycemia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We performed an international survey regarding management of infants with congenital cytomegalovirus (cCMV) born at less than 32 weeks gestation or with birth weight under 1500 g. Replies from 51 level 3 neonatal intensive care units across 13 countries demonstrated striking discrepancies in screening practices, testing for cCMV, further investigations of confirmed cases, indications for initiation, and duration of treatment., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The development of early-onset cow's milk protein allergy and atopic dermatitis during the first months of life is multifactorial, including both genetic and nutritional aspects. This study aims to assess the impact of different feeding patterns on the incidence of cow's milk protein allergy, atopic dermatitis, and growth among infants with a family history of allergy. A total of 551 high-risk infants were randomly recruited from 3 European countries in three feeding regimens: exclusive breastfeeding, partially hydrolyzed formula, or standard formula with intact protein either exclusively or supplementary to breastfeeding. During the first 6 months of intervention, amongst infants with a family history of atopic dermatitis, 6.5% of partially hydrolyzed formula-fed infants and 22.7% of exclusively breastfed infants ( p = 0.007) presented with atopic dermatitis respectively. Growth as assessed by weight increase did not differ between the aforementioned groups. Although cow's milk protein allergy was not related to the different milk feeding regimens in the whole cohort, when adjusting for high breast milk intake, the respective incident was significantly lower in the infants consuming partially hydrolyzed formula ( p < 0.001). This data indicates that a specific partially hydrolyzed formula could serve as a more appropriate complement to breast milk compared to a standard intact protein formula in high-risk infants, to reduce the incidence of atopic dermatitis.

In this nationwide retrospective study, a substantial decline in the incidence of multisystem inflammatory syndrome in children over 3 successive pandemic waves characterized by different severe acute respiratory syndrome coronavirus 2 variants was documented-from 3.4 of 1000 to 1.1 of 1000 and finally to 0.25 of 1000 confirmed severe acute respiratory syndrome coronavirus 2 positive cases (P < 0.0001), respectively, whereas clinical findings and severity did not significantly vary., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ., Competing Interests: Conflict of interest: S.A. Papiris reports grants, personal fees and nonfinancial support from La Roche Hoffman and Boehringer Ingelheim, and other support from Savara, outside the submitted work. Conflict of interest: F. Bonella reports grants and personal fees from Savara Pharma outside the submitted work. Conflict of interest: R. Borie has received consulting fees from Boehringer Ingelheim, Roche and Sanofi, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim and Roche, outside the submitted work; support for attending meetings and/or travel received from Boehringer Ingelheim, Roche and Chiesi outside the submitted work; and participation on a data safety monitoring or advisory board for Savara, outside the submitted work. Conflict of interest: M. Molina-Molina reports personal fees and grants from Esteve-Teijin, Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: E. Jouneau reports personal fees and other support from Actelion, AIRB, AstraZeneca, Bellerophon Therapeutics, Biogen, BMS, Boehringer Ingelheim, Chiesi, FibroGen, Galecto Biotech, Genzyme, Gilead, GlaxoSmithKline, LVL, Mundipharma, Novartis, Pharm-Olam, Pfizer, Pliant Therapeutics, F. Hoffmann-La Roche, Ltd, Sanofi and Savara-Serendex, outside the submitted work. Conflict of interest: C. McCarthy is a scientific advisory board member of Savara Inc. unrelated to this work and has not received any payment from Savara Inc. for any work to date. Conflict of interest: E. Bendstrup reports grants and personal fees from Boehringer Ingelheim and Hofmann la Roche, and personal fees from Galapagos, outside the submitted work. Conflict of interest: M. Griese has received grants or contracts from Boehringer Ingelheim, outside the submitted work; has participated on a data safety or advisory board for Boehringer Ingelheim, outside the submitted work; and is the Head of chILD-EU, outside the submitted work. Conflict of interest: E.D. Manali reports personal fees and nonfinancial support from La Roche Hoffman; grants, personal fees and nonfinancial support from Boehringer Ingelheim; and other support from Savara, all outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Offspring exposed in foetal life to gestational diabetes mellitus (GDM) are at increased risk for future metabolic diseases., Objective: To explore the prognostic role of abdominal aorta intima-media thickness (aIMT) in neonates exposed to GDM as a possible biomarker for later atherogenesis and its possible correlation with thioredoxin- interacting protein (TXNIP), a protein involved in oxidative stress., Methods: In this prospective, observational study, mother-infant pairs were studied in 2 groups (57 patients with GDM and 51 controls without GDM). TXNIP levels were measured in the placenta, as well as in the umbilical and neonatal blood. The data were correlated with aIMT in neonates., Results: aIMT was increased in GDM offspring (patients: median [range]=0.39 mm [0.31-0.46] vs controls: median=0.28 mm [0.23-0.33]; p=0.001) and remained significant after adjusting for possible confounders (e.g., triglycerides, blood pressure, vitamin D, birth weight and gender; β coefficient=0.131 p=0.049). TXNIP levels were increased in trophoblasts (p=0.001) and syncytiotrophoblasts (p=0.001) and were decreased in endothelial cells (p=0.022) in GDM offspring vs controls. Moreover, TXNIP levels in trophoblasts positively correlated with aIMT (r=0.369; p=0.001). TXNIP levels in umbilical/ neonatal blood were not associated with GDM., Conclusion: Increased aIMT was demonstrated in the offspring of mothers with GDM. Non-invasive measurement of aIMT could be used as a biomarker to identify children at increased risk for atherogenesis later in life. This information may encourage early preventive measures. TXNIP may be associated with GDM and/or aIMT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

School closures were enforced as measures to restrain the COVID-19 pandemic, based on the assumption that young children may play a key role in SARS-CoV-2 spread. This study aims to determine the prevalence of SARS-CoV-2 IgG antibodies in children and corresponding parents, in order to improve surveillance and estimate the prevalence of asymptomatic or subclinical COVID-19 cases. A prospective multicenter study was conducted between March and June 2021 in Greece. Children admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 and their parents were tested for anti-Spike SARS-CoV-2 IgG in serum. A questionnaire about clinical and demographic data was completed. The study included 823 participants: 427 children and 396 corresponding parents. The overall seroprevalence was 16.4% in parents and 13.8% in children. Among families with ≥ 1 seropositive child or parent, the combination of a seropositive parent and a corresponding seronegative child was 29.6%, a seronegative parent and a corresponding seropositive child was 24.7%, and a seropositive child with a corresponding seropositive parent was 45.7%. Age, level of education, and school or work attendance were not significantly associated with increased seropositivity. On the contrary, ethnic minority of Roma, close contact with known COVID-19 case, previous symptoms consistent with COVID-19, and mass gatherings were risk factors for seropositivity., Conclusion: The spread of SARS-CoV-2 during a period of lockdown in Greece was low in children and comparable to adults most likely due to intrafamilial transmission. Accordingly, it is unlikely that children have boosted virus transmission., What Is Known: • In the earliest months of the pandemic, it was demonstrated that children had significantly lower seroprevalence rates than the older age groups, due to the fact that children had decreased exposure to the virus, because of early public health interventions, such as school and day care closure. • Later, further studies reported that children have similar incidence rate of SARS-CoV-2 infection compared to adults in households and community settings., What Is New: • In this seroprevalence study, the spread of SARS-CoV-2 infection during a period of lockdown in Greece with the predominance of the Alpha-variant was particularly low in children and comparable to adults, most likely due to intrafamilial transmission. • These study findings will be useful for decisions regarding non-pharmaceutical interventions during the pandemic, and especially, to guide in designing and implementing appropriate containment measures for schools and social gatherings., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The Pediatric Respiratory Assessment Measure (PRAM) score is a useful tool for the assessment of asthma exacerbations in children. This study aimed to estimate the risk of hospitalization in children, assessed with the PRAM score and having mild-moderate asthma exacerbation, who were treated with salbutamol delivered via a metered-dose inhaler and spacer (MDI/S)., Methods: The study population consisted of children aged 3-16 years with mild-moderate asthma exacerbations. All children received 1mg/kg prednisolone p.o. (max 40 mg) and 4-6 puffs of salbutamol via MDI/S., Results: Fifty patients participated in the study. Admission was associated positively with the initial PRAM score (OR: 18.91, CI: 2.42-123.12, P = 0.005) and negatively with the improvement in PRAM score (OR: 0.52, CI: 0.01-0.78, P = 0.032)., Conclusion: PRAM is a reliable tool that can be used effectively to estimate the asthma exacerbation severity., Competing Interests: The authors have no conflicts of interest to declare.

The aim of the present study was to assess the psychological impact of hospitalization during the COVID-19 pandemic on parents and their offspring. We performed a nationwide cross-sectional study in Greece based on an Internet questionnaire survey. A convenience sample of parents whose offspring had been hospitalized due to COVID-19 (including multisystem inflammatory syndrome in children, MIS-C), diagnosed with COVID-19 but not hospitalized, and hospitalized for another reason during the pandemic were enrolled. Parental stress was assessed using the Perceived Stress Scale (PSS) and the Revised Impact of Event Scale (IES-R) tools, and childhood mental wellbeing with the Children’s Revised Impact of Event 13 (CRIES-13) scale. Out of 214 received responses, stress levels were significantly higher in parents whose children had been admitted for COVID-19 or MIS-C versus those not admitted or admitted for other reasons (p < 0.001, for PSS/IES-R). Parental and childhood stress levels were correlated. In the multivariable linear regression analysis, children’s hospitalization because of COVID-19 or MIS-C, younger parental age, the existence of comorbidities, and another family member’s hospitalization because of COVID-19 were independent factors for higher stress. In light of the above, stricter hospital admission criteria for COVID-19 could be implemented, and psychological support for eventually admitted families may be beneficial.

Background: Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide causing serious morbidity in newborns, infants, and children. Despite the clinical importance of congenital CMV (cCMV), studies conducted so far conclude that there is limited awareness in both the medical community and public of cCMV infection. The aim of this systematic review was to assess the knowledge and awareness of cCMV among pregnant women and healthcare providers during the last decade., Methods: A literature search was performed in PubMed and Scopus, including studies published between 2011 and 2020. Eligibility criteria included articles focusing on either pregnant women or healthcare providers and reporting data about cCMV awareness. We included cross-sectional and interventional studies. Study quality was assessed using the Study Quality Assessment Tools by National Institute of Health., Results: Overall, 23 studies fulfilled the inclusion criteria, 13 studies referred to pregnant women and 10 to healthcare providers. A total of 6521 pregnant women and 3609 healthcare providers were included. The level of awareness of pregnant women about cCMV was low to moderate. However, pregnant women showed willingness to adopt hygiene strategies following interventional-educational practices. Concurrently, awareness among healthcare providers varied depending on the specialty. Nonetheless, a great proportion admitted feeling inadequate in advising pregnant women for cCMV screening and prevention., Conclusion: The role of healthcare providers in growing awareness among pregnant women is of paramount importance. Due to the lack of an effective vaccine as yet, education of women regarding hygiene measures is currently the best strategy to prevent cCMV disease.

Background/aim: Early human milk provides protection against viral infections due to its high nutritional value, abundance of maternal antibodies and the specific role of lactoferrin (Lf). Lf blocks the early interaction between SARS-CoV-2 and host cells by binding to specific cell receptors and has been proposed as a preventative and adjunct treatment for COVID-19. This preliminary report aimed to investigate concentrations of Lf in early milk of SARS-CoV-2 positive mothers versus non-infected controls., Material and Methods: In a cohort of 13 SARS-CoV-2 positive mothers and 15 controls, breast milk concentrations of Lf were determined by ELISA on day 3 postpartum. Additionally, colostrum samples of infected mothers were analyzed for SARS-CoV-2 RNA detection and anti-SARS-CoV-2 IgA and IgG determination using RT-qPCR and ELISA, respectively., Results: No differences were found in breast milk Lf concentrations between SARS-CoV-2 positive mothers and controls. In a subgroup analysis, however, symptomatic mothers ( n  = 7) presented with lower breast milk Lf concentrations, as compared to asymptomatic mothers ( p  = .041) and healthy controls ( p  = .029). All milk samples tested negative for SARS-CoV-2 RNA. Early human milk of infected mothers displayed IgA and IgG SARS-CoV-2 specific reactivity., Conclusions: Our data showed a different early breast milk Lf "profile" between COVID-19 symptomatic and asymptomatic mothers with the latter being at non-COVID levels (control group). SARS-CoV-2 RNA was not detected in any breast milk sample. Early human milk Lf levels are potentially influenced by the severity of maternal COVID-19 infection during pregnancy.

The COVID-19 pandemic has turned perinatal healthcare into a worldwide public health challenge. Although initial data did not demonstrate pregnancy as a more susceptible period to adverse outcomes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, an increasing number of reports now certify maternal illness as a high-risk condition for the development of maternal-fetal complications. Despite the rarity of SARS-CoV-2 vertical transmission, severe maternal illness might induce adverse perinatal and neonatal outcomes. Additionally, perinatal COVID-19 data may raise concerns about long-term harmful consequences to the offspring in the framework of non-communicable diseases. The World Health Organisation, as well as scientific literature, consider the protection of the maternal-fetal dyad against COVID-19 as a critical issue and, therefore, strongly promote and encourage the vaccination of pregnant and lactating women. Furthermore, the pandemic has triggered an unprecedented recession, leading to historic levels of unemployment and deprivation, while health, societal, economic and gender inequities particularly affecting low-income and middle-income countries, have increased. This mini-review provides an updated brief report on historical, clinical, psychological and socioeconomic aspects of the COVID-19 pandemic based on 10 lectures presented at the 9th Maria-Delivoria-Papadopoulos Perinatal Symposium, held virtually on 19 March 2022., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

This study comprehensively examines clinical symptoms, laboratory findings, and placental pathology in 40 cases of singleton full-term SARS-CoV-2 negative neonates. Their mothers, previously healthy, with uncomplicated pregnancies, were infected peripartum and presented COVID-19 symptoms of various severity. Neonates had predominately diarrhea, the yet unreported absent sucking reflex, elevated COVID-19 inflammatory and ischemia/asphyxia markers as serum ferritin, interleukin-6 and cardiac troponin-T, while placentas demonstrated mild vascular and/or inflammatory lesions. We hypothesize that the above placental lesions may be associated with transient perinatal hypoxia resulting in absent sucking reflex, as well as with inflammatory cytokines transfer causing diarrhea.

Background: Since child abuse and neglect (CAN) is prevalent worldwide, medical students should acquire basic knowledge, skills, and confidence in identifying and addressing CAN. Although significant educational efforts have been previously described, none has focused on using participatory methods to teach medical students CAN., Purpose: To: 1) develop a participatory educational workshop in CAN for medical students, 2) gather, train, and establish a peer-to-peer teaching group, and 3) assess the effectiveness of the workshop in gain of knowledge and improvement of self-confidence for participants., Methods: A two-hour workshop was created with role-playing, the use of mannikins and peer-to-peer teaching. A 15-item knowledge and a 9-item self-confidence questionnaire were used before, right after, and six months after each workshop., Results: Nine workshops in two academic pediatric departments with a total attendance of 300 6th year medical students were conducted. For the 69 students who completed the questionnaires at all three times, there were statistically significant gains in knowledge right after (p < .001) and six months after (p < .0001) the workshops. Similarly, self-confidence increased right after (p < .0001) and six months after (p < .001) the workshops. Self-selection bias testing indicated that these 69 students who completed all three questionnaires were representative of those who completed the pre-testing and the testing right after., Conclusions: We successfully established a peer-to-peer teaching group to conduct nine participatory workshops that improved the participants' knowledge and self-confidence in CAN. This feasible and novel active learning approach may help address inadequacies in medical curricula., (© 2022. The Author(s).)

COVID-19 pandemic has raised questions on pregnant women and newborns' management. Guidelines, issued by most international agencies and national bodies, recommend rooming-in and direct breastfeeding. In the early days of this pandemic, breastfeeding practices have been challenged by fear among both parents and healthcare workers occasionally resulting in mother-newborn separation. We herein review current breastfeeding guidelines and discuss remaining questions and challenges. As we are facing the second wave of this pandemic, more information is gathered, especially regarding possible virus transmissibility through breastfeeding, enabling more definite instructions about breastfeeding practices.

Noonan syndrome (NS) is an autosomal dominant disorder characterized by clinical and genetic heterogeneity. It belongs to a wider group of pathologies, known as Rasopathies, due to the implication of genes encoding components of the Ras/MAPK signalling pathway. Recording the genetic alterations across populations helps assessing specific features to specific genes which is essential for better disease's recognition, prognosis and monitoring. Herein, we report the clinical and molecular data of a Greek cohort comprising of 86 NS or NS-like patients admitted at a single tertiary Centre in Athens, Greece. The analysis was performed using Sanger and next-generation sequencing, comprising 14 different genes. The mutational rates of the confirmed NS-associated genes in the Greek NS population are as follows: PTPN11 32.5%; RIT1 5.8%; SOS1 4.7%; BRAF 1.2%; CBL 1.2%; KRAS 1.2%; MAP2K1 1.2%; RAF1 1.2%; SHOC2 1.2%, corresponding to 50% of positivity in total NS population. The genotype-phenotype analysis showed statistically significant differences in craniofacial dysmorphisms (p = 0.005) and pulmonary valve stenosis (PS) (p < 0.001) frequencies between patients harbouring a pathogenic variant and patients without pathogenic variant in any of the tested genes. Patients with at least a pathogenic variant had 6.71 times greater odds to develop PS compared to pathogenic variant-negative patients (OR = 6.71, 95%; CI = (2.61, 17.27)). PTPN11 positive patients showed higher frequency of epicanthal folds (p = 0.004), ptosis (p = 0.001) and coarseness (p = 0.001) and lower frequency of neurological findings (p = 0.006), compared to patients carrying pathogenic variants in other genes., Conclusion: Craniofacial dysmorphism and PS prevail among pathogenic variant positive compared to pathogenic variant negative NS and NS-like patients while neurological defects are less common in PTPN11-affected NS patients compared to patients harbouring pathogenic variants in other genes. The significant prevalence of the Ras/MAPK pathogenic variants (17.4%), other than PTPN11, in Greek NS patients, highlights the necessity of a wider spectrum of molecular diagnosis., What Is Known: • Noonan syndrome (NS) has been associated with pathogenic variants in molecules-components of the Ras/MAPK pathway. • Clinical and genetic description of NS patients worldwide helps establishing personalized monitoring., What Is New: • NS and NS-like mutational rate in Greece reaches 50% with pathogenic variants identified mostly in PTPN11 (32.5%), RIT1 (6%) and SOS1 (4.7%) genes. • The risk for pulmonary stenosis increases 6.71-fold in NS patients with a pathogenic variant compared to patients without genetic alterations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Early identification of COVID-19 cases has been vital for reducing transmission and enabling treatment. In Greece, in autumn 2021 when Delta was the predominant circulating variant, unvaccinated citizens had to be tested before attending activities, and self-testing was required twice a week for students (5−17 years). Here, we describe the time of diagnosis by age group and possible exposure to assess testing strategies (September to November 2021). Information on the presence of symptoms at the time of diagnosis was available for 69,298 cases; 24,855 (36%) were asymptomatic or tested the same day as onset (early diagnosis), 21,310 (31%) reported testing one day after, and 23,133 (33%) did so two or more days after the onset of symptoms. The median lag was 2 days (1−14). Early diagnosis significantly differed among age groups (p-value < 0.001) and was higher among children. For every one-year increase of age, the odds of an early diagnosis were reduced by 1%. Cases exposed during training activities or in settings such as accommodation centers and hospitals were more frequently diagnosed early. The percentage of persons having a positive self-test before a rapid test/PCR diagnosis ranged from 7% in the age group of 60 years and above to 86% in the age group of 5−17 years. The provision of self-tests in schools and increased testing in closed settings led to an earlier diagnosis and probably to a decreased transmission of the virus in the period during which Delta was the predominant variant in Greece. However, more effort is needed for early diagnosis of adults in the community, especially after the onset of symptoms.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus., Methods: We measured spike-specific immunoglobulin G (anti-S IgG) and immunoglobulin A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in 2 academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity., Results: The study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P), and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation. VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (P < .0001), whereas INF mothers had higher BM:serum anti-S IgA ratios compared to VAX mothers (P = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (P < .0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, P = .013), but not infection., Conclusions: BNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S immunoglobulin, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM immunoglobulin production. Next-generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit., Competing Interests: Potential conflicts of interest . V. P. participated in a lecture on coronavirus disease 2019 vaccination in children (with honorarium made to their university), and also participated in the National Greek Advisory Committee for Immunization Practices. C. P. was a steering committee member for clinical trials MN42988 and MN42989 by La Roche Ltd. A. A. received an National Institute of Allergy and Infectious Diseases (NIAID) Development of Sample Sparing Assays (DSSA) for Monitoring Immune Responses Infrastructure & Opportunity Fund (IOF) Award grant for Comprehensive Analysis of the Neonatal Immune System via High-Throughout Proteomics; and honorarium for an invited review article on neonatal vaccination. All other authors report no potential conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: As Greece is a country which has introduced the 13-valent pneumococcal conjugate vaccine (PCV13) both in the infant and in the adult immunization programs, the aim of the study was to investigate age-specific and serotype-specific trends of pneumococcal meningitis over an 11-year period (2010-2020)., Materials and Methods: Data are reported from pneumococcal meningitis cases [notified to the National Public Health Organization (NPHO)], with clinical samples and bacterial isolates sent for pneumococcal identification and serotyping at the National Meningitis Reference Laboratory (NMRL). Pneumococcal identification was performed directly on clinical samples or bacterial isolates by multiplex PCR (mPCR) assay, while serotyping was carried out by application of the Capsular Sequence Typing (CST) method with the combination of single tube PCR assays., Results: A total of 427 pneumococcal meningitis cases were notified to the NPHO between 2010 and 2020. Among those, 405 (94.8%) were microbiologically confirmed, while samples from 273 patients were sent to the NMRL for identification and/or further typing. The annual notification rate peaked at 0.47/100,000 in 2016 and since then has been decreasing. The incidence was highest in infants and in older adults. Pneumococcal serotypes were identified in 260/273 (95.2%) cases, where clinical samples were sent to the NMRL. The most prevalent serotypes (≥5%) were 3, 19A, 23B, 15B/C, 11A/D, 23A, 22F. During the study period there has been a decrease of PCV13 serotypes combined with an increase of non-PCV13 serotypes (p = 0.0045)., Conclusions: This is the first study to report serotypes for pneumococcal meningitis across all ages in the post-PCV13 era in Greece. There is a need to enhance surveillance, by close monitoring of the emerging serotypes and the impact of vaccination programs. Higher-valency PCVs may help to improve the coverage of pneumococcal disease., 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 © 2022 Elsevier Ltd. All rights reserved.)