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Background: The premature-born adult population is set to grow significantly, and prematurity has emerged as an important cardiovascular risk factor. We aimed to comprehensively assess cardiac mechanics and function in a cohort of ex-preterm preschoolers. Methods: Ex-preterm children (<30 weeks of gestation), aged 2 to 5 years, underwent transthoracic 2D, speckle-tracking, and 4D echocardiography. The findings were compared with 19 full-term children. Results: Our cohort of 38 children with prematurity history showed a normal morpho-functional echocardiographic assessment. However, compared to controls, the indexed 3D end-diastolic volumes of ventricular chambers were reduced (left ventricle 58.7 ± 11.2 vs. 67.2 ± 8.5 mL/m 2 ; right ventricle 50.3 ± 10.4 vs. 57.7 ± 11 mL/m 2 ; p = 0.02). Left ventricle global and longitudinal systolic function were worse in terms of fraction shortening (32.9% ± 6.8 vs. 36.5% ± 5.4; p = 0.05), ejection fraction (59.2% ± 4.3 vs. 62.3% ± 3.7; p = 0.003), and global longitudinal strain (-23.6% ± 2.4 vs. -25.5% ± 1.7; p = 0.003). Finally, we found a reduced left atrial strain (47.4% ± 9.7 vs. 54.9% ± 6.8; p = 0.004). Conclusions: Preschool-aged ex-preterm children exhibited smaller ventricles and subclinical impairment of left ventricle systolic and diastolic function compared to term children. Long-term follow-up is warranted to track the evolution of these findings.

Few studies have evaluated the effect of bovine lactoferrin (bLf) on reducing respiratory infections in preschool children. This randomized controlled trial evaluated the effect of bLf in preschool children with recurrent respiratory infections. Participants were randomly assigned bLf (n = 25) or control ( n = 25). Outcomes included respiratory infection episodes (RIEs), symptom duration, school absence and medication. Fifty children aged 4.2 ± 0.1 years were included. During the active 4-month phase, median number of RIEs was reduced by 50% in the bLf group [1-episode, interquartile range (IQR): 0-2] vs. control (2, IQR: 1-3; p = 0.02). The proportion of participants with >3 RIEs was significantly lower in bLf ( n = 1, 4%) vs. control ( n = 7, 28%) with 80% lower odds of upper RIEs in the bLf arm (odds ratio: 0.20, 95% CI:0.06-0.74, p = 0.015). The duration of symptoms (3 vs. 6, p = 0.009) and days absent from school (3 vs. 6, p = 0.15) were lower in the active arm. Over the 2-month follow-up, no significant differences were observed between groups for infection episodes, symptom duration or school absence. However, bLf-treated children received significantly less corticosteroids over the entire 6-month study period (32% vs. 60%; p = 0.047). bLf supplementation significantly reduced the frequency and duration of RIEs in children with decreased corticosteroid use.

Background: Premature newborns represent a vulnerable population, at high risk of acquiring nosocomial infections during neonatal intensive care unit (NICU) admission. Multidrug-resistant organisms represent the greatest concern due to their intrinsic virulence and the limited therapeutic options. Resistant Enterobacterales are a growing threat for critically ill neonates, with increasing numbers of NICU outbreaks caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales being described. This study reports the early detection and successful control of an outbreak caused by ESBL-producing Klebsiella pneumoniae (ESBL-KP) in an Italian NICU in February 2021., Results: A total of 13 newborns tested positive for ESBL-KP between 2-9 February 2021, of whom four (31%) had a bloodstream infection. Two were critically ill, extremely premature newborns who died because of multiple comorbidities, and two were cured after treatment with meropenem. All other patients survived and were either discharged home or moved to other hospitals/wards in good clinical condition. ESBL-KP ST45 was found in all isolates by multilocus sequence typing (MLST) analysis. An outbreak control plan was set, including surveillance cultures for all neonates, NICU environments, and medical devices, along with the extended use of contact precautions and cohorting. In addition, the infection control plan was carried out through reinforcement and enhancement measures to guarantee maximal compliance. The outbreak was successfully controlled in seven days, given that no further cases were identified after 9 February. The source of the ESBL-KP outbreak was not identified through environmental sampling., Conclusions: Thanks to multidisciplinary management, a threatening outbreak of ESBL-KP in a NICU was controlled in few days. The prompt recognition of the event onset and the adoption of infection control interventions helped contain the bacteria spread on the ward.

Glucose impairment is common in preterm infants but the impact of early neonatal hyperglycemia on long term neurodevelopment is still highly controversial. This review reports current evidence of the effect of hyperglycemia on neurodevelopmental outcome. It was conducted according to the PRISMA guidelines. We searched MEDLINE via PubMed; EMBASE via Ovid; the Cochrane Central Register of Controlled Trials; the Cochrane Library; ClinicalTrials.gov; and the World Health Organization's International Trials Registry and Platform. We included studies that investigated the association between hyperglycemia, defined as at least one episode of glycemia ≥8 mmol/L, and neurodevelopment outcome evaluated either through the Griffiths Mental Developmental Scales (GMDS) or the Bayley Scales of Infant Development (BSID) for the first 5 years of life, and the Wechsler Intelligence Scale for Children (WISC) and the Movement Assessment Battery for Children (MABC) for the following age category. We selected six studies, comprising 2226 infants in total and which included 1059 (48%) infants for whom neurodevelopment assessment was available. We found an association between hyperglycemia and neurological delay in the first two years of life, especially for motor functions; this result was confirmed in later childhood. The quality of evidence was poor; therefore, the negative influence of neonatal hyperglycemia on the neurological development of preterm infants must be investigated in further studies.

Anthracnose is a severe disease caused by Colletotrichum spp. on several crop species. Fungal infections can occur both in the field and at the post-harvest stage causing severe lesions on fruits and economic losses. Physical treatments and synthetic fungicides have traditionally been the preferred means to control anthracnose adverse effects; however, the urgent need to decrease the use of toxic chemicals led to the investigation of innovative and sustainable protection techniques. Evidence for the efficacy of biological agents and vegetal derivates has been reported; however, their introduction into actual crop protection strategies requires the solutions of several critical issues. Biotechnology-based approaches have also been explored, revealing the opportunity to develop innovative and safe methods for anthracnose management through genome editing and RNA interference technologies. Nevertheless, besides the number of advantages related to their use, e.g., the putative absence of adverse effects due to their high specificity, a number of aspects remain to be clarified to enable their introduction into Integrated Pest Management (IPM) protocols against Colletotrichum spp. disease.

Antenatal factors play a role in NEC pathogenesis. This study aimed to investigate the predictive value of fetal ductus venosus doppler (DV) for NEC in fetal growth restriction fetuses (FGRF) and to assess the predictive accuracy of IG21 and Fenton curves in NEC development. Data from FGRF, postnatal findings, and Doppler characteristics were collected between 2010 and 2020 at a single center. Patients were then divided into two groups (i.e., with and without NEC). Bivariate and multivariate analyses were performed. We identified 24 cases and 30 controls. Absent or reversed end-diastolic flow (AREDF) and increased resistance in the DV were more impaired in cases (p < 0.05). Although the median birthweight was not different, the Fenton z-score was lower in NEC (p < 0.05). Fetal cardiopulmonary resuscitation, synchronized intermittent mandatory ventilation, neonatal respiratory distress, persistent patent ductus arteriosus (PDA), and inotropic support were more frequent in the NEC group. Furthermore, NEC patients had lower white blood cells (WBC) (p < 0.05). The predictive model for NEC (model 4), including Fenton z-score, WBC, PDA, and DV had an AUC of 84%. Fetal Doppler findings proved effective in predicting NEC in FGR. The Fenton z-score was the most predictive factor considering the fetal growth assessment showing high sensitivity.

Background: While it has been described that adults can develop long-lasting deterioration in pulmonary function (PF) after coronavirus disease 19 (COVID-19), regardless of disease severity, data on the long-term pneumological impact of SARS-CoV-2 infection in children are lacking., Methods: Performing a single-center, prospective, observational study on children aged 6-18 years with a previous diagnosis of asymptomatic/mild COVID-19, we evaluated the long-term impact of mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children., Results: A total of 61 subjects underwent spirometry after a mean time of 10 ± 4 months from asymptomatic or mild infection. None of the children reported any respiratory symptoms, needed any inhaled therapy, or had abnormal lung function., Conclusions: In our study, we observed that children and adolescents did not develop chronic respiratory symptoms and did not present lung function impairment after asymptomatic or mild SARS-CoV-2 infection.

Understanding the composition of human milk (HM) can provide important insights into the links between infant nutrition, health, and development. In the present work, we have longitudinally investigated the metabolome of milk from 36 women delivering preterm at different gestational ages (GA): extremely (<28 weeks GA), very (29-31 weeks GA) or moderate (32-34 weeks GA) premature. Milk samples were collected at three lactation stages: colostrum (3-6 days post-partum), transitional milk (7-15 days post-partum) and mature milk (16-26 days post-partum). Multivariate and univariate statistical data analyses were performed on the 1 H NMR metabolic profiles of specimens in relation to the degree of prematurity and lactation stage. We observed a high impact of both the mother's phenotype and lactation time on HM metabolome composition. Furthermore, statistically significant differences, although weak, were observed in terms of GA when comparing extremely and moderately preterm milk. Overall, our study provides new insights into preterm HM metabolome composition that may help to optimize feeding of preterm newborns, and thus improve the postnatal growth and later health outcomes of these fragile patients.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections (LRTIs) in infants worldwide. The global direct medical cost associated with RSV LRTIs reaches billions of dollars, with the highest burden in low-middle-income countries. Many efforts have been devoted to improving its prevention and management, including both non-pharmaceutical and pharmaceutical strategies, often with limited routine use in high-income countries due to high costs. During the ongoing COVID-19 pandemic, a dramatic decrease in RSV infections (up to 70-90%) has been reported around the globe, directly related to the implementation of containment measures (face masks, hand hygiene, and social distancing). Primary prevention has demonstrated the highest cost effectiveness ratio in reducing the burden of a respiratory infection such as RSV, never reached before. Thus, we emphasize the importance of non-pharmaceutical preventive hygiene measures that should be implemented and maintained even after the COVID-19 outbreak.

The current SARS-CoV-2 disease (COVID-19) pandemic is a sudden major stressor superimposed on pre-existing high distress in parents of infants admitted to the neonatal intensive care unit (NICU). This study aimed to investigate the psychological wellbeing of NICU parents during the COVID-19 pandemic. Forty-four parents of 25 inpatients of the Padua University Hospital NICU were included from June 2020 to February 2021. At 7-14 days postpartum parents completed the Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI), Parental Stressor Scale: NICU (PSS:NICU) and an ad-hoc questionnaire measuring parental COVID-19 related stress. About one third of parents reported extreme/high stress and a relevant negative impact on parenthood experience. Less time (82%) and less physical contact (73%) with infants due to COVID-19 preventive measures were the most frequent negative factors. Higher COVID-19 related parental stress was positively associated with anxiety, depression, NICU parental stress, stress related to NICU environment, and parental role alterations. Depression symptoms, stress related to infant condition and parental role alterations were higher in mothers. The pandemic affected parental emotional and relational wellbeing directly through additional stress due to COVID-19 concerns and indirectly through the impact of restrictions on the experience of becoming parents.

Plant pathogenic fungi are the largest group of disease-causing agents on crop plants and represent a persistent and significant threat to agriculture worldwide. Conventional approaches based on the use of pesticides raise social concern for the impact on the environment and human health and alternative control methods are urgently needed. The rapid improvement and extensive implementation of RNA interference (RNAi) technology for various model and non-model organisms has provided the initial framework to adapt this post-transcriptional gene silencing technology for the management of fungal pathogens. Recent studies showed that the exogenous application of double-stranded RNA (dsRNA) molecules on plants targeting fungal growth and virulence-related genes provided disease attenuation of pathogens like Botrytis cinerea , Sclerotinia sclerotiorum and Fusarium graminearum in different hosts. Such results highlight that the exogenous RNAi holds great potential for RNAi-mediated plant pathogenic fungal disease control. Production of dsRNA can be possible by using either in-vitro or in-vivo synthesis. In this review, we describe exogenous RNAi involved in plant pathogenic fungi and discuss dsRNA production, formulation, and RNAi delivery methods. Potential challenges that are faced while developing a RNAi strategy for fungal pathogens, such as off-target and epigenetic effects, with their possible solutions are also discussed.

Background: Extracorporeal membrane oxygenation (ECMO) implantation for neonates with severe cardiorespiratory life-threatening conditions is highly effective. However, since ECMO is a high-risk and complex therapy, this treatment is usually performed in centers with proven expertise., Methods: A retrospective review of neonates, from January 2014 to January 2020, presenting with life-threatening conditions and treated by means of Hub and Spoke (HandS) ECMO in peripheral (spoke) hospitals. Data were retrieved from our internal ECMO registry. Protocols and checklists were revised and shared with all spoke hospitals located in North-Eastern Italy., Results: Eleven neonates receiving maximal respiratory and cardiovascular support at a spoke hospital underwent HandS ECMO management. All but three patients were affected by life-threatening meconium aspiration syndrome (MAS). The median ECMO support duration and hospitalization were four (range 2-32) and 30 days (range 8-50), respectively. All but two patients (with congenital diaphragmatic hernia), were weaned off ECMO and discharged home. At a mean follow up of 33.7 ± 29.2 months, all survivors were alive and well, without medications, and normal somatic growth. All but one had normal neuropsychological development., Conclusion: HandS ECMO model for neonates with life-threatening conditions is effective and successful. A specialized multidisciplinary team and close cooperation between Hub and Spoke centers are essential for success.

Since February 2020, Italy has been faced with the dramatic spread of novel Coronavirus SARS-CoV-2. This impetuous pandemic infection forced many hospitals to reorganize their healthcare systems. Predicting a rapid spread of the SARS-CoV-2 virus within our region, the Department for Women's and Children's Health promptly decided (i) to revise the distribution of the clinical areas in order to create both designated COVID-19 and COVID-19-free areas with their own access, (ii) to reinforce infection prevention control (IPC) measures for all healthcare workers and administrative staff and (iii) to adopt the new "double-gate approach": a phone call pre-triage and nasopharyngeal swab for SARS-CoV-2 detection before the admission of all patients and caregivers. Between 21 February 2020 till 04 May 2020, only seven physicians, two nurses and two of the administrative staff resulted positive, all during the first week of March. No other cases of intra-department infection were documented among the healthcare workers since all the preventive procedures described above were implemented. It is predicted that similar situations can happen again in the future, and thus, it is necessary to be more prepared to deal with them than we were at the beginning of this COVID-19 pandemic.

Bronchopulmonary dysplasia (BPD) is the most common respiratory disorder among infants born extremely preterm. The pathogenesis of BPD involves multiple prenatal and postnatal mechanisms affecting the development of a very immature lung. Their combined effects alter the lung's morphogenesis, disrupt capillary gas exchange in the alveoli, and lead to the pathological and clinical features of BPD. The disorder is ultimately the result of an aberrant repair response to antenatal and postnatal injuries to the developing lungs. Neonatology has made huge advances in dealing with conditions related to prematurity, but efforts to prevent and treat BPD have so far been only partially effective. Seeing that BPD appears to have a role in the early origin of chronic obstructive pulmonary disease, its prevention is pivotal also in long-term respiratory outcome of these patients. There is currently some evidence to support the use of antenatal glucocorticoids, surfactant therapy, protective noninvasive ventilation, targeted saturations, early caffeine treatment, vitamin A, and fluid restriction, but none of the existing strategies have had any significant impact in reducing the burden of BPD. New areas of research are raising novel therapeutic prospects, however. For instance, early topical (intratracheal or nebulized) steroids seem promising: they might help to limit BPD development without the side effects of systemic steroids. Evidence in favor of stem cell therapy has emerged from several preclinical trials, and from a couple of studies in humans. Mesenchymal stromal/stem cells (MSCs) have revealed a reparatory capability, preventing the progression of BPD in animal models. Administering MSC-conditioned media containing extracellular vesicles (EVs) have also demonstrated a preventive action, without the potential risks associated with unwanted engraftment or the adverse effects of administering cells. In this paper, we explore these emerging treatments and take a look at the revolutionary changes in BPD and neonatology on the horizon.

Background: In the context of the so-called unified airway theory, chronic rhinosinusitis (CRS) and asthma may coexist. The inflammation underlying these conditions can be studied through the aid of biomarkers. Main body: We described the main biological mediators that have been studied in pediatric CRS and asthma, and, according to the available literature, we reported their potential role in the diagnosis and management of these conditions. As for CRS, we discussed the studies that investigated nasal nitric oxide (nNO), pendrin, and periostin. As for asthma, we discussed the role of fractional exhaled nitric oxide (feNO), the role of periostin, and that of biological mediators measured in exhaled breath condensate (EBC) and exhaled air (volatile organic compounds, VOCs)., Conclusion: Among non-invasive biomarkers, nNO seems the most informative in CRS and feNO in asthma. Other biological mediators seem promising, but further studies are needed before they can be applied in clinical practice.