Longitudinal proteomics of leptin treatment in humans with acute and chronic energy deficiency-induced hypoleptinemia reveal novel, mainly immune-related, pleiotropic effects.

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.

Specific Gut Microbiome Signatures in Children with Cow's Milk Allergy.

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.

Cytomegalovirus-Specific Hyperimmune Immunoglobulin Administration for Secondary Prevention after First-Trimester Maternal Primary Infection: A 13-Year Single-Center Cohort Study.

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.

Corrigendum to "Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI)" [The Lancet Regional Health - Europe 40 (2024) 100892].

[This corrects the article DOI: 10.1016/j.lanepe.2024.100892.].

Attributable Mortality for Pediatric and Neonatal Central Line-Associated Bloodstream Infections in Greece.

Central line-associated bloodstream infections (CLABSIs) are the most frequent pediatric hospital-acquired infections and significantly impact outcomes. The aim of this study was to estimate the attributable mortality for CLABSIs in pediatric and neonatal patients in Greece. A retrospective matched-cohort study was performed, in two tertiary pediatric hospitals. Inpatients with a central line in neonatal and pediatric intensive care units (NICUs and PICUs), hematology/oncology units, and a bone marrow transplantation unit between June 2012 and June 2015 were eligible. Patients with confirmed CLABSI were enrolled on the day of the event and were matched (1:1) to non-CLABSI patients by hospital, hospitalization unit, and length of stay prior to study enrollment (188 children enrolled, 94 CLABSIs). Attributable mortality was estimated. During the study period, 22 patients with CLABSI and nine non-CLABSI patients died (23.4 vs. 9.6%, respectively, p = 0.011), leading to an attributable mortality of 13.8% (95% confidence interval [CI] = 3.4-24.3%). Children in PICUs were more likely to die, presenting an attributable mortality of 20.2% (95% CI = - 1.4-41.8%), without reaching, however, statistical significance. After multiple logistic regression, patients with CLABSI were four times more likely to die (odds ratio [OR] = 4.29, 95% CI = 1.28-14.36, p = 0.018). Survival analysis showed no difference in time to death after study enrollment between patients with CLABSI and non-CLABSI patients (log-rank p = 0.137, overall median survival time = 7.8 months). Greek pediatric mortality rates are increased by the CLABSI occurrence, highlighting the importance of infection prevention strategies.

Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI).

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.

SARS-CoV-2 seroprevalence among children in Greece during Omicron variant period.

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.

WHAT IS KNOWN: • Seroprevalence surveys among children may be extremely useful, in order to properly monitor the immunity, either natural or acquired, through the quantification of IgG antibodies and to plan further immunization policies. • There are variations in the seroprevalence of COVID-19 between the different periods, according to the vaccination rates, the type of circulating variant and the transmissibility of the virus. • The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. WHAT IS NEW: • In this large multicenter seroepidemiological study, SARS-CoV-2 seroprevalence rate in children is higher during the Omicron period in comparison to the previous pandemic waves, due to the high transmissibility of the virus and the increased rates of reinfection. • Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1­4 years old present higher antibody titers, indicating that the children of this age group mount a higher antibody response. • This study provides essential information about immunity and the level of protection in the pediatric population, as neutralizing antibodies were evaluated, in addition to the anti-N and anti-S IgG antibodies.

Multisystem inflammatory syndrome in children (MIS-C): A nationwide collaborative study in the Greek population.

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 × 109/mm3. 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.

Mathematical modeling of constructed wetlands for hexavalent chromium removal.

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.

Knowledge and attitudes of medical students about clinical aspects of congenital cytomegalovirus infection in newborns: A nationwide cross-sectional study in Greece.

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.

Aortic Intima-Media Thickness is Increased in Neonates of Mothers with Gestational Diabetes Mellitus: The Role of Thioredoxin-Interacting Protein as a Marker of Oxidative Stress.

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; ß 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.

The Impact of Infant Feeding Regimen on Cow's Milk Protein Allergy, Atopic Dermatitis and Growth in High-Risk Infants during the First 6 Months of Life: The Allergy Reduction Trial.

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.

Clinical outcome in newborns of perinatally COVID-19 infected women.

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.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

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.

Decreasing Incidence of the Multisystem Inflammatory Syndrome in Children Over 3 Pandemic Waves.

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.

Seroprevalence of anti-SARS-CoV-2 antibodies among children and their parents in Greece.

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.

The Psychological Impact of COVID-19 Admission on Families: Results from a Nationwide Sample in Greece.

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.

Creation and evaluation of a participatory child abuse and neglect workshop for medical students.

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.

Time Lag between COVID-19 Diagnosis and Symptoms Onset for Different Population Groups: Evidence That Self-Testing in Schools Was Associated with Timely Diagnosis among Children.

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.