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Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Several studies found in the literature apply Computational Fluid Dynamics (CFD) for the swirling flow in cyclones, such as Costa et al. (2013) who studied solid-solid interactions, and Sgrott Jr. et al. (2013) that investigated a technique for cyclones’ project optimization. The main characteristic of this flow is the anisotropic behavior of the turbulence due to the highly swirling gas flow. In this sense, a turbulence model with capability to predict the swirling flow, such as the Reynolds Stress Model (RSM), must be applied. This model has been used in numerous studies of cyclones and the results showed that the model is well suited to predict the pressure drop and the axial velocity component of the flow. However, for the tangential velocity component the results were not satisfactory for quantitative validation. Based on a comparison of numerical and experimental results, and knowing the importance of the axial and the tangential velocities for the efficiency of collection in cyclones and for the pressure drop, the latter which is related to energy costs; the main objective of this study is to present a sensibility study of the Reynolds Stress Model parameters for swirling flow in cyclones. To perform this study, a CFD commercial code was used to simulate cases based on a 2n-3 factorial design. In this design, seven parameters of the RSM-SSG model (C1, C1*, C2, C3, C3*, C4 and C5) were varied 5% above and below their standard values in order to analyze the effect of each parameter in the pressure drop and in the axial and tangential velocity profiles in cyclones for the gas phase flow. The results showed that the parameters C1 and C1* have more influence in the pressure drop and the parameters C3 and C3* have more influence in the axial and tangential velocity peaks.

Purpose: New drugs are needed for the therapy of anaplastic thyroid cancer (ATC). This study aims to investigate doxorubizen (a dual-action structural hybrid (chimera) of doxorubicin (Dox) and DNA methylating drug temozolomide), in comparison with Dox, and alone or in combination with lenvatinib in ATC 8305C cells, and in primary human ATC cell cultures (pATC)., Methods: We have investigated doxorubizen, Dox, and lenvatinib on 5 different pATC and in continuous 8305C cell line in vitro, evaluating their effect on cells proliferation by WST-1, apoptosis (Hoechst ad Annexin V assays) and migration (Chemicon QCM™ 96-well Migration Assay)., Results: The results have demonstrated: (1) a significant antiproliferative and proapoptotic effect of doxorubizen in 8305C and in pATC; (2) a significant antiproliferative and proapoptotic effect of Dox in pATC, and in 8305C; (3) the antineoplastic effect of lenvatinib in 8305C and in pATC; (4) a stronger antiproliferative and proapoptotic effect of doxorubizen than that of Dox, or lenvatinib; (5) that doxorubizen induced an inhibition of migration in pATC stronger than that of Dox, or lenvatinib; (6) that doxorubizen is able to synergize in vitro with lenvatinib increasing the antiproliferative effect, while doxorubizen alone is the primary factor that promotes the proapoptotic impact., Conclusion: We have first shown that doxorubizen has a potent antineoplastic effect in vitro in 8305C and in 5 different pATC, and that can synergize with lenvatinib. These results open the way to a future evaluation of the antineoplastic effect of doxorubizen in ATC patients., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Informed consent: Informed consent was obtained from all subjects involved in the study. Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee for Clinical trials of Pisa University Hospital (date of approval 18 November 2012)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pharmaceuticals like ibuprofen (IBU) entering marine environments are of great concern due to their increasing consumption and impact on wildlife. No information on IBU toxicity to seagrasses is yet available. Seagrasses form key habitats and are threatened worldwide by multiple stressors. Here, the responses of the seagrass Cymodocea nodosa to a short-term exposure (12 days) to environmentally realistic IBU concentrations (0.25-2.5-25 µg L -1 ), both at organism (plant growth) and sub-organism level (oxidative status, photosynthetic efficiency, and specialized metabolites production), were assessed in mesocosm. Chemical analyses to detect the presence of IBU and its metabolites in seawater and plants were also performed. IBU did not affect plant growth but caused physiological alterations which varied in severity depending on its concentration. Concentrations of 0.25 and 2.5 µg L -1 resulted in oxidative stress, but an increased antioxidant enzyme activity enabled plants to tolerate stress. A concentration of 25 µg L -1 caused greater oxidative stress, reduced antioxidant enzyme activity and specialized metabolites production, and impaired photosynthetic machinery functioning (particularly PSII). IBU was detected in seawater but not in plants suggesting no bioaccumulation. These findings indicate that C. nodosa could not withstand high IBU stress, and this could reduce its resilience to additional environmental stressors., 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 Elsevier B.V. All rights reserved.)

Importance: A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes., Objective: To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units., Design, Setting, and Participants: This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy. Follow-up examinations included neurodevelopmental, growth, and respiratory outcomes of these children at cPNA 2 years. Participants included spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 hours of life. Data were analyzed from April 2023 to January 2024., Intervention: Infants were randomly assigned (1:1) to IN-REC-SUR-E or IN-SUR-E and then followed up., Main Outcomes and Measures: The primary outcome was the occurrence of death after discharge or major disability at cPNA 2 years. Secondary outcomes were neurodevelopmental outcomes (major disability, cerebral palsy, cognitive impairment, visual deficit, or auditory deficit), anthropometric measurements (weight, length, and head circumference), and recurrent respiratory infections and hospitalizations because of respiratory causes at 2y cPNA., Results: A total of 137 extremely preterm infants (median [IQR] gestational age, 26.5 [25.3-27.5] weeks and 75 [54.7%] female), initially enrolled in the original RCT, were followed up at cPNA 2 years, including 64 infants in the IN-SUR-E group and 73 infants in the IN-REC-SUR-E group. There were no significant differences in the occurrence of death after discharge or major disability at cPNA 2 years (IN-SUR-E: 13 children [20.3%] vs IN-REC-SUR-E: 10 children [13.7%]; P = .36). There were no significant differences in incidence of disability, cerebral palsy, or cognitive impairment in the IN-REC-SUR-E group compared with the IN-SUR-E group. There were no significant differences in anthropometric measurements (weight, length, and head circumference) between groups. There were no significant differences in the incidence of recurrent respiratory infections or in hospitalizations because of respiratory causes between groups., Conclusions and Relevance: In this RCT of lung recruitment before surfactant vs standard care there were no significant differences between the 2 groups in death, neurodevelopmental outcomes, anthropometric measurements, or recurrent respiratory infections at the 2-year follow-up. These findings can aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.

Introduction: Oncogenic tyrosine kinases (TK) are enzymes that play a key role in cell growth and proliferation and their mutations can lead to uncontrolled cell growth and development of aggressive cancer. This knowledge has led to the development of new classes of drugs, Tyrosine kinase inhibitors (TKI). They target oncogenic kinases who are associated with advanced radioactive iodine (RAI) refractory TC, which is not able to uptake RAI anymore and/or still grows between consecutive treatments with Iodine 131 (I131)., Areas Covered: Since Lenvatinib and Sorafenib approval, several other molecular inhibitors have been studied and then introduced for the treatment of aggressive and refractory thyroid cancer (TC), and, although the development of adverse effects or tumor resistance mechanisms, more and more compounds are still under investigation. The literature search was executed in PubMed and ClinicalTrials.gov to identify relevant articles and clinical trials published until December 2023., Expert Opinion: In the context of clinical trials, driven by the presence of specific molecular mutations or even in the absence of both conditions, systemic therapy TKIs are valuable weapons to be used in patients affected by aggressive forms of TC, waiting for further expansion of the treatment landscape with more efficacious and safer drugs.

Introduction: This is an observational and retrospective study, in which we have analyzed data from patients affected by gastric diseases (p) who have been treated with liquid L-T4 (L-LT4;84 p), or tablet L-T4 (T-LT4;120 p), for the replacement therapy of hypothyroidism. The aim of the study is to compare the stability of TSH [normal range, 0.3-3.5 μIU/ml] in these patients., Methods: All p assumed L-T4 30 minutes before breakfast. The types of gastric disease were: a) T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). 66% p in T-LT4 group were chronically treated with proton pump inhibitors (PPI), against 51% in L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the 2 groups (p>0.05). The mean L-T4 dosage in T-LT4 group at the basal evaluation was 1.22+/-0.27 μg/kg/die, in the L-LT4 group 1.36+/-0.22 μg/kg/die (p>0.05)., Results: At the basal evaluation the prevalence of patients with a TSH>3.5 μIU/mL in T-LT4 group was 36%, in L-LT4 group 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the p were re-evaluated in an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of p with a TSH>3.5 μIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of p with a TSH>3.5 μIU/mL in T-LT4 group was 26%, in L-LT4 group 13% (p>0.05). At the third re-evaluation, the prevalence of p with TSH<3.5 μIU/mL in T-LT4 group was 19%, in L-LT4 group 9% (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH>3.5 μIU/mL in T-LT4 group was 18%, in L-LT4 group 5% (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit., Discussion: These data suggest that the liquid L-T4 formulation therapy can result in a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up., 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. The reviewer EB declared a shared affiliation with the author AA to the handling editor at the time of review. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Fallahi, Ragusa, Patrizio, Mazzi, Botrini, Elia, Balestri, Barozzi, Rugani, Palmisano, Cosenza, Varricchi, Ulisse, Benvenga, Ferrari and Antonelli.)

Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and represents <2% of thyroid carcinomas. A therapeutic target for ATC is represented by anaplastic lymphoma kinase (ALK) rearrangements, involved in tumor growth. Crizotinib is an oral small-molecule tyrosine kinase inhibitor of the ALK, MET, and ROS1 kinases, approved in ALK-positive non-small cell lung cancer. Until now, the effect of crizotinib in "primary human ATC cells" (pATCs) with transforming striatin (STRN)-ALK fusion has not been reported in the literature. In this study, we aimed to obtain pATCs with STRN-ALK in vitro and evaluate the in vitro antineoplastic action of crizotinib. Thyroid surgical samples were obtained from 12 ATC patients and 6 controls (who had undergone parathyroidectomy). A total of 10/12 pATC cultures were obtained, 2 of which with transforming STRN-ALK fusion (17%). Crizotinib inhibited proliferation, migration, and invasion and increased apoptosis in 3/10 pATC cultures (2 of which with/1 without STRN-ALK), particularly in those with STRN-ALK. Moreover, crizotinib significantly inhibited the proliferation of AF cells (a continuous cell line obtained from primary ATC cells). In conclusion, the antineoplastic activity of crizotinib has been shown in human pATCs (with STRN-ALK) in preclinical studies in vitro, opening the way to future clinical evaluation in these patients.

Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health issue of social and economic relevance. Both hyperthyroidism and hypothyroidism are very common in the adult population, and both disorders may contribute to the onset and progression of CVD. After a brief description of the role of thyroid hormones (THs) on the physiology of the cardiovascular system and the potential mechanism that links THs alterations with changes in cardiac function, blood pressure, endothelial function, and lipid levels, we review updated data about the clinical impact of overt hypothyroidism (OH) and subclinical hypothyroidism (SCH) on CV risk, CVD, and mortality. Furthermore, we summarize the current evidence for treating SCH with levothyroxine (L-T4). Several guidelines of distinguished endocrine societies recommend treatment for SCH with TSH higher than 10 mIU/L, where the benefit of L-T4 therapy is more evident for younger people, but still controversial in those aged over 65 years. Based on current knowledge, more research efforts are needed to better address the clinical management of CV risk and CVD in the elderly affected by SCH., 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 © 2024 Patrizio, Ferrari, Elia, Ragusa, Balestri, Botrini, Rugani, Mazzi, Antonelli, Fallahi and Benvenga.)

In hypothyroid patients needing large doses of levothyroxine (L-T4) (>1.7-2 μg/kg/day) to reach euthyroidism, lactose intolerance (LI) needs to be excluded, owing to the high prevalence in the population. If LI is present, a lactose-free diet decreases the rate of L-T4 malabsorption. However, an increased requirement of L-T4 is described in patients with LI, which can be beneficially treated using lactose-free L-T4 formulation. The lactose-free liquid L-T4 formulation is able to circumvent LI malabsorption leading to the normalization of thyroid-stimulating hormone (TSH) in patients with subclinical hypothyroidism and long-term stable TSH levels., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ferrari, Patrizio, Mazzi, Ragusa, Botrini, Elia, Balestri, Barozzi, Rugani, Bracchitta, Stoppini, Frenzilli, Baldini, Virili, Benvenga, Fallahi and Antonelli.)

Seagrass wrack plays multiple ecological roles in coastal habitats but is often removed from beaches and used for economical processing, neglecting its potential role in sustaining dune plant establishment under changing climate scenarios. Rainwater shortage is a major stress for seedlings and reduced precipitations are expected in some coastal areas. We investigated in mesocosm how wrack influenced seedling performance of Cakile maritima, Thinopyrum junceum, and Calamagrostis arenaria under current and reduced precipitation. We also assessed wrack water holding capacity and leachate chemical/physical properties. Wrack stimulated seedling growth while reduced precipitation decreased root development. Wrack mitigated the effects of reduced precipitation on T. junceum and C. arenaria biomass. Wrack retained water up to five-fold its weight, increased water pH, conductivity, and nutrient content. Wrack promotes dune colonization by vegetation even under rainwater shortage. Thus, the maintenance of this natural resource on beaches is critical for improving dune resilience against climate changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ultraviolet filters (UVFs) added to sunscreens (SS) are emerging contaminants in marine environments due to their adverse effects on organisms and ecosystems. UVFs have also been detected in beach-dune systems, but their influence on resident organisms has not been explored yet. Native plants are fundamental components of coastal dunes, and these ecologically/economically important systems are currently among the most threatened globally. Thus, understanding whether UVFs may act as threats to dune plants is crucial. This field study evaluated and compared the effects of titanium dioxide nanoparticles (nTiO 2 ), one of the inorganic UVFs most commonly added to sunscreens, and those of a commercial sunscreen product containing it (SS-nTiO 2 ) on the performance of adult dune plants of a native (Thinopyrum junceum) and a non-native invasive species (Carpobrotus sp. pl.) and their competitive interactions at environmentally realistic concentrations. The effects of nTiO 2 , SS-nTiO 2 and of a sunscreen product containing just organic UVFs (SS-OF) on early life stages of T. junceum were also examined. Ti bulk content in sand and plants at the study site ranged from 970 to 1069 mg kg -1 and from 2 to 7.9 mg kg -1 , respectively. Thinopyrum junceum adult plants periodically exposed during the summer season to seawater contaminated by SS-nTiO 2 produced less biomass than un-exposed plants and nTiO 2 exposed plants. nTiO 2 and SS-nTiO 2 reduced the capacity of T. junceum to control the spread of Carpobrotus. Both SS-nTiO 2 and SS-OF reduced seedling emergence in T. junceum whereas nTiO 2 did not. These results demonstrated that the periodical exposures of native dune plants to sunscreens could reduce their establishment success and growth and favor invasive plant spread potentially resulting in community structure changes. They also emphasize the need to assess the phytotoxicity not only of single UVFs but especially that of complete sunscreen products to design more eco-friendly formulations in the future., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare., Methods: This is a retrospective, single-center observational study conducted over 16 years (2001-2017). The data were collected from the clinical records of patients who underwent total thyroidectomy at the Endocrine Unit-Department of Medicine of the University Hospital of Pisa, Italy., Results: Over 690 analyzed cases, 650 (94.2%) were exclusive DTC, 19 exclusive MTC (2.75%) and 5 PTC/MTC (0.7%). No case of mixed medullary/follicular TC or hereditary MTC (familial MTC/multiple endocrine neoplasia type 2) was found. Among the five PTC/MTC cases, there was a male prevalence (M:F = 3:2), and all PTC components were at stage I, whereas 40% of MTC were at stage I and III and 20% of MTC were at stage II; microPTC (mPTC) was prevalent (80%) and also microMTCs were frequent (40%); 60% of MTC patients recovered, while 40% of patients developed metastatic disease. The search for germline mutations of the RET gene resulted in being negative in all cases., Conclusions: The incidence of PTC/MTC has been increasing over the past 30 years. The etiology of PTC/MTC forms is still unknown, and although this simultaneous occurrence could be only a coincidence, we cannot exclude the hypothesis of a shared genetic origin.

Background: Sepsis is the third leading cause of neonatal death in low and middle-income countries, accounting for one third of all deaths in Ethiopia. A concerning issue is the increasing number of multidrug-resistant microorganisms facilitated by suboptimal antibiotic stewardship. The study aims to identify clusters of newborns switching antibiotic lines for sepsis in a neonatal intensive care unit (NICU) in Ethiopia, and to explore their potential association with sepsis outcomes., Methods: A retrospective cohort study was conducted including all newborns discharged with a diagnosis of probable neonatal sepsis from the St. Luke Catholic Hospital NICU between April and July 2021. The antibiotic management protocol included two lines according to WHO guidelines and a third line based on internal hospital guidelines. In the cluster analysis, the Gower distance was estimated based on the antibiotics employed in the different lines and the duration of each line. Mortality and respiratory distress (RD) were the response variables., Results: In the study period, 456 newborns were admitted to the NICU and 196 (42.8%) had probable neonatal sepsis. Four antibiotic management clusters were identified. Cluster 1 (n = 145, 74.4%) had no antibiotic switches, using only the first line. Cluster 2 (n = 26, 13.3%) had one switch from the first to the second line. Cluster 4 (n = 9, 4.6%) had two switches: from first to second and then to third line. In cluster 3 (n = 15, 7.7%), newborns were switched from ceftriaxone/cloxacillin as second line to off-protocol antibiotics. There were no differences in sex, age, weight on admission or crude mortality between clusters. Cluster 3 included a higher frequency of infants who did not breathe at birth (53.3%, p = 0.011) and that necessitated bag ventilation (46.7%, p = 0.039) compared to the other clusters., Conclusions: The first antibiotic line failed in one out of four newborns with probable sepsis while third-generation cephalosporins were insufficient in one in ten patients. Cluster analysis can provide valuable insights into antibiotic treatment patterns and their potential implications. This approach may support antibiotic stewardship and aid in contrasting antimicrobial resistance in limited resource settings., (© 2023. The Author(s).)

Introduction: The impact of COVID-19 pandemic represents a serious challenge for 'frail' patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic., Patients and Method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines., Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients ( death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p < 0.0001)., Conclusions: An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A careful monitoring of response to COVID-19 vaccines together with adequate preventive/therapeutical strategies are highly recommendable in the near course of pandemic in this frail patients' population., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Alessandro Antonelli reports financial support was provided by Italian 10.13039/100009647Ministry of Health, Ricerca Finalizzata (RF-2021-12374986) Destinatario istituzionale: Regione Toscana. Unità Operative:U.O.1: Azienda Ospedaliero-Universitaria Pisana; U.O.2: Azienda Ospedaliero-Universitaria Aldo Moro Bari; U.O.3: Azienda Ospedaliero-Universitaria Modena, CUP Master: D55E22000670001., (© 2023 Published by Elsevier B.V.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological culprit of COronaVIrus Disease 19 (COVID-19), can enter the cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which has been found in several tissues including in endocrine organs, such as the ovaries, testes, pancreas, and thyroid. Several thyroid disorders have been associated with SARS-CoV-2 infection [subacute thyroiditis (SAT), thyrotoxicosis, and non-thyroidal illness syndrome (NTIS)] and, in part, they are believed to be secondary to the local virus replication within the gland cells. However, as documented for other viruses, SARS-CoV-2 seems to interfere with several aspects of the immune system, inducing the synthesis of autoantibodies and triggering latent or new onset autoimmune disease (AID), including autoimmune thyroid disease (AITD), such as Hashimoto Thyroiditis (HT) and Graves' disease (GD). Several mechanisms have been hypothesized to explain this induction of autoimmunity by SARS-CoV-2 infection: the immune system hyper-stimulation, the molecular mimicry between the self-antigens of the host and the virus, neutrophils extracellular traps, and finally, the virus induced transcriptional changes in the immune genes; nonetheless, more evidence is needed especially from large, long-term cohort studies involving COVID-19 patients, to establish or reject this pathogenetic relationship.

In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with duplication of the maxillary arch; (2) supernumerary mouth laterally placed with rudimentary segments; (3) single mouth with replication of the mandibular segments; and (4) true facial duplication, namely diprosopus. We describe a newborn born with wide-spaced eyes, a very broad nose, and two separate mouths. Workup revealed the absence of the corpus callosum and the presence of a brain midline lipoma, wide sutures, and a Chiari I malformation with cerebellar herniation. We conducted a systematic review of the literature and compared all the cases described as diprosopus. In 96% of these, the central nervous system is affected, with anencephaly being the most commonly associated abnormality. Other associated anomalies include cardiac malformations (86%), cleft palate (63%), diaphragmatic hernia (13%), and disorder of sex development (DSD) (13%). Although the facial features are those that first strike the eye, the almost obligate presence of cerebral malformations suggests a disruptive event in the cephalic pole of the forming embryo. No major monogenic contribution has been recognized today for this type of malformation.

The presence of plastic litter in coastal environments like beach-dune systems has been well documented, and recent studies have shown that this pollutant can influence sand properties as well as dune vegetation. However, the effects of plastics on rhizosphere bacterial communities of dune plants have largely been neglected. This is an ecologically relevant issue since these communities may play an important role in improving plant growth and resilience of dune systems. Here, we explored the impact of plastic litter made of either non-biodegradable polymers (NBP) or biodegradable/compostable polymers (BP) on the structure and composition of rhizosphere bacterial communities associated with two widespread species along coastal European dunes, Thinopyrum junceum and Sporobolus pumilus, by using a one-year field experiment combined with metabarcoding techniques. Both plastics did not affect neither the survival nor the biomass of T. junceum plants, but they significantly increased alpha-diversity of rhizosphere bacterial communities. They also changed rhizosphere composition by increasing the abundance of the phyla Acidobacteria, Chlamydiae, and Nitrospirae, and of the family Pirellulaceae, and reducing the abundance of the family Rhizobiaceae. NBP reduced drastically the survival of S. pumilus while BP increased its root biomass compared to controls. BP also increased the abundance of the phylum Patescibacteria of the rhizosphere bacterial communities. Our findings provide the first evidence that NBP and BP can change rhizosphere bacterial communities associated with dune plants and highlight the importance of investigating how these changes can affect the resilience of coastal dunes to climate change., 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 © 2023 Elsevier B.V. All rights reserved.)

Breast cancer (BC), the most commonly diagnosed malignancy, frequently metastasizes to the bone, lungs, brain and liver at advanced stages, whereas the thyroid gland represents a rare target site for secondary disease. We examined the most recent literature about thyroid metastasis (TM) from BC after we encountered a peculiar case of a 71-year-old woman who developed sudden dysphagia, severe hypothyroidism and hypoparathyroidism due to TM 18 years after the diagnosis of her primary cancer. Based on published data, the prevalence of TM in BC ranges from 3% to 34%, with a median onset time of 48.2 months, although longer time intervals are not infrequent. TM negatively impacts the prognosis of these patients, however thyroid surgery can limit the local disease burden. Therefore, we suggest that clinicians involved in the follow-up care of BC patients should consider a differential diagnosis of secondary thyroid malignancy when incidental lesions are diagnosed during radiological evaluations or local symptoms affect the cervical region, even many years after the diagnosis of the primary cancer.

Introduction: Thyroid eye disease (TED) is an autoimmune disease characterized by inflammation of orbital and extraocular muscles. It induces proptosis and diplopia, leading to a worsening of quality of life (QoL) because of its impact on physical appearance, and visual function. The natural history involves an 'active TED,' which is an autoimmune inflammatory response targeting orbital soft tissues, and 'inactive TED,' where there is tissue expansion remodeling. To date, glucocorticoids represent the main medical therapy, even if often ineffective and associated with side effects., Areas Covered: In TED, the autoimmune process leads to production of TSH-R and IGF-1 R autoantibodies. This induces inflammatory changes in the orbital tissue, and activation of fibroblasts with accumulation of glycosaminoglycans, leading to consequent proptosis, and diplopia. In two previous randomized, double-masked, placebo-controlled, parallel-group, multicenter trials, teprotumumab has been shown to be effective in improving proptosis, inflammation, diplopia, and QoL. More recently, it has been shown that teprotumumab is also effective in chronic-inactive TED. Teprotumumab was approved by the FDA on 21 January 2020 for the treatment of TED., Expert Opinion: For the above-mentioned reasons teprotumumab represents a potential first line therapy for TED that could replace the use of steroids in the next future.

Pollution associated to marine plastic litter is raising increasing concerns due to its potential harmful effects on human health, biota, and coastal ecosystems. However, limited information is available on the degradation behavior of plastics, especially biodegradable ones, in dune habitats. Moreover, the effects of plastics on dune plant growth and ability to withstand environmental stresses and invasion by non-native plants have been largely neglected. This is a particularly relevant issue since biological invasions are major threats to dune ecosystems. In this 18-month study, we examined the degradation behavior of two plastic bags, non-biodegradable (NBP) or biodegradable/compostable (BP), in the dune environment by visual observations and analytical techniques. Concomitantly, we investigated the individual and combined effects of bag type and sand burial (no burial vs. partial burial) on the performance of a native dune plant (Thinopyrum junceum) and an invasive plant (Carpobrotus sp.) and on their interaction. NBP did not show relevant degradation signs over the experimental period as expected. BP exhibited gradual surface modifications and changes in chemical functionality and were almost disintegrated after 18 months. Bags and burial reduced independently T. junceum survival and growth, and most plants died within 8 months of plastic exposure. Bags and burial did not affect Carpobrotus survival. However, burial decreased Carpobrotus growth while NBP increased it. Both plastics increased Carpobrotus competitive ability, and no T. junceum plants survived to co-occurrent Carpobrotus, BP, and burial. These findings indicate that removing all littered plastics from beach-dune systems not only is critical to reduce plastic pollution but also to prevent further spread of invasive species in coastal dunes., 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.)

Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) have a worse prognosis with respect to well differentiated TC, and the loss of the capability of up-taking 131 I is one of the main features characterizing aggressive TC. The knowledge of the genomic landscape of TC can help clinicians to discover the responsible alterations underlying more advance diseases and to address more tailored therapy. In fact, to date, the antiangiogenic multi-targeted kinase inhibitor (aaMKIs) sorafenib, lenvatinib, and cabozantinib, have been approved for the therapy of aggressive radioiodine (RAI)-resistant papillary TC (PTC) or follicular TC (FTC). Several other compounds, including immunotherapies, have been introduced and, in part, approved for the treatment of TC harboring specific mutations. For example, selpercatinib and pralsetinib inhibit mutant RET in medullary thyroid cancer but they can also block the RET fusion proteins-mediated signaling found in PTC. Entrectinib and larotrectinib, can be used in patients with progressive RAI-resistant TC harboring TRK fusion proteins. In addition FDA authorized the association of dabrafenib (BRAF V600E inhibitor) and trametinib (MEK inhibitor) for the treatment of BRAF V600E -mutated ATC. These drugs not only can limit the cancer spread, but in some circumstance they are able to induce the re-differentiation of aggressive tumors, which can be again submitted to new attempts of RAI therapy. In this review we explore the current knowledge on the genetic landscape of TC and its implication on the development of new precise therapeutic strategies., 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 © 2022 Elia, Patrizio, Ragusa, Paparo, Mazzi, Balestri, Botrini, Rugani, Benvenga, Materazzi, Spinelli, Antonelli, Fallahi and Ferrari.)

To assess the exposure of beachgoers to viruses, a study on seawater, sand, and beach-stranded material was carried out, searching for human viruses, fecal indicator organisms, and total fungi. Moreover, for the first time, the genome persistence and infectivity of two model viruses was studied in laboratory-spiked sand and seawater samples during a one-week experiment. Viral genome was detected in 13.6 % of the environmental samples, but it was not infectious (Human Adenovirus - HAdV, and enterovirus). Norovirus and SARS-CoV-2 were not detected. The most contaminated samples were from sand and close to riverine discharges. In lab-scale experiments, the infectivity of HAdV5 decreased by ~1.5-Log 10 in a week, the one of Human Coronavirus-229E disappeared in <3 h in sand. The genome of both viruses persisted throughout the experiment. Our results confirm viral contamination of the beach and suggest HAdV as an index pathogen for beach monitoring and quantitative risk assessment., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Since the beginning of the pandemic, numerous risk factors have been associated with SARS-CoV-2 infection and COVID-19 outcomes, such as older age, male sex, and the presence of comorbidities, such as hypertension, obesity, and diabetes. Preliminary data also suggest epidemiological association between SARS-CoV-2 infection and systemic autoimmune disease. For this reason, we investigated if patients affected by autoimmune thyroid disorders (AITD) are at risk of developing SARS-CoV-2 infection or COVID-19 disease. From April to September 2020, we have conducted a telephone survey that included 515 consecutive unselected patients with known thyroid disorders, of which 350 were affected by AITD. All 11 definitive diagnosis of COVID-19 (def-sympt-COVID-19) belonged to the AITD group, while the rest 14 cases highly suspected for COVID-19 (suspect-sympt-COVID-19) were equally detected in both group (7 in AITD and 7 in not-AITD). The overall prevalence of symptomatic COVID-19 (def-sympt-COVID-19 + suspect-sympt-COVID-19), recorded in the 350 AITD population was statistically significant higher compared to that reported in the Italian and Tuscan general population at the same time period of the present survey (18/350 = 5.14% vs 516/100000 = 0.51% [p < 0.001; OR = 10.45, 95% CI 6.45-16.92] and vs 394/100000 = 0.39% [p < 0.001; OR = 13.70, 95% CI 8.44-22.25], respectively). Therefore, our results suggest a higher prevalence of SARS-CoV-2 infection and COVID-19 disease in patients with AITD., 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 B.V. All rights reserved.)

Aim: Identifying the severity of neonatal respiratory distress (RD) is essential, so that resources can be appropriately allocated. We assessed the ability of nurses to grade neonatal RD in a low-resource setting before and after they were trained to use a dedicated scoring tool., Methods: The study was conducted in the Special Care Unit of St Luke Wolisso Hospital, Ethiopia. Ten nurses reviewed nine local video recordings and graded neonatal RD without a standardised method, which was current practice, and then after they were trained to use the Silverman and Andersen score. The data were analysed using the McNemar test and Cohen's kappa., Results: Training increased the identification of mild RD from 63% to 93% (p = 0.008) and moderate RD from 40% to 73% (p = 0.03). Severe RD was 93% before and 90% after training (p = 0.99). Overall, the agreement improved from kappa 0.59 to 0.84, mainly by reducing the overestimation of milder degrees of RD., Conclusion: Being trained on how to use the Silverman and Andersen score improved the ability of nurses to identify mild and moderate neonatal RD. This improvement has the potential to optimise the use of equipment, staff and time., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Microplastics (MPs) and nanoplastics (NPs) are ubiquitous in natural habitats and the risks their presence poses to marine environments and organisms are of increasing concern. There is evidence that seagrass meadows are particularly prone to accumulate plastic debris, including polystyrene particles, but the impacts of this pollutant on seagrass performance are currently unknown. This is a relevant knowledge gap as seagrasses provide multiple ecosystem services and are declining globally due to anthropogenic impact and climate-change-related stressors. Here, we explored the potential effects of a 12 day-exposure of seagrasses to one concentration (68 μg/L) of polystyrene MPs and NPs on the growth, oxidative status, and photosynthetic efficiency of plants using the foundation species Cymodocea nodosa as a model. Among plant organs, adventitious roots were particularly affected by MPs and NPs showing complete degeneration. The number of leaves per shoot was lower in MPs- and NPs-treated plants compared to control plants, and leaf loss exceeded new leaf production in MPs-treated plants. MPs also reduced photochemical efficiency and increased pigment content compared to control plants. Shoots of NPs-treated plants showed a greater oxidative damage and phenol content than those of control plants and MPs-treated plants. Biochemical data about oxidative stress markers were consistent with histochemical results. The effects of MPs on C. nodosa could be related to their adhesion to plant surface while those of NPs to entering tissues. Our study provides the first experimental evidence of the potential harmful effects of MPs/NPs on seagrass development. It also suggests that the exposure of seagrasses to MPs/NPs in natural environments could have negative consequences on the functioning of seagrass ecosystems. This stresses the importance of implementing cleaning programs to remove all plastics already present in marine habitats as well as of undertaking specific actions to prevent the introduction of these pollutants within seagrass meadows., 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 B.V. All rights reserved.)

Plants play a fundamental role in maintaining coastal dunes but also accumulate littered microplastics (MPs). Migration tests suggest that naturally weathered MPs can leach out a broader range of potentially phytotoxic chemicals than virgin MPs. Thus, assessing MPs effects on plants using beached-collected particles rather than virgin ones is critically important. Here, the effects on plants of leachates from two pools of beach-collected and virgin MPs, high-density polyethylene (HDPE) and polypropylene (PP), and their mixture, were explored combining toxicity tests and chemical analyses. Phytotoxicity of MP leachates at different dilutions was evaluated under standard laboratory conditions using test species and under environmentally realistic conditions using the dune species Thinopyrum junceum. Leachates from beached PP and HDPE adversely affected all species, and the extent of these effects varied according to polymer type, concentration, and species. Virgin MPs had weaker effects than beached ones. Several potentially phytotoxic oxidized compounds were detected in water by GC/MS analysis, and their amount estimated. Results indicate that the molecular species leaching from beached MPs - at ppm concentration levels for the individual chemical species - can inhibit plant growth, and the effects of leachates from mixtures of degraded MPs can differ from those from individual polymers, highlighting the need for further investigation of MPs consequences for coastal ecosystems., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Myoinositol (Myo) is an isoform of inositol, a cyclic polyol with 6 hydroxyl groups. Myo is mainly derived from dietary intake while its endogenous production is generated from glucose by enzymatic reactions. Moreover, Myo is also synthesized de novo by catabolism of phosphatidylinositol (PI), phosphoinositides (PIP), and inositol phosphates (IP). Myo has a determinant role in thyroid function and autoimmune diseases as it regulates iodine organification and thyroid hormone biosynthesis by the formation of hydrogen peroxide (H 2 O 2 ) in thyrocytes. Depletion of Myo that is involved in the thyroid stimulating hormone (TSH) signaling pathway, may cause the development of thyroid diseases such as hypothyroidism. TSH levels significantly decreased in patients with subclinical hypothyroidism, with or without autoimmune thyroiditis, after treatment with Myo plus Selenium (Myo+Se). In addition to TSH, antithyroid autoantibodies are reduced. This review summarizes the role of Myo in the thyroidal physiology and its role in the management of some thyroid diseases., 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 © 2022 Paparo, Ferrari, Patrizio, Elia, Ragusa, Botrini, Balestri, Guarneri, Benvenga, Antonelli and Fallahi.)

Beach litter can affect public health and economic activities worldwide forcing local authorities to expensive beach cleaning. Understanding the key mechanisms affecting the accumulation of this waste on beaches, such as sea state and proximity to entry points, is critical to plan effective management strategies. In this one-year study, we estimated the impact of storm events and waterways runoff on litter abundance and local economy using as a model a managed, peri-urban beach facing a north-western sector of the Mediterranean Sea. We also investigated the relationship between litter composition/density and beach proximity to major/closest harbors/rivers at regional scale by combining our data with those on litter density available in literature. Autumn/winter storms caused larger litter depositions than spring/summer ones in the peri-urban beach. No preferential accumulation occurred near to waterway mouths. Litter mainly consisted of plastic, and its composition in terms of micro-categories varied over seasons. In total, 367,070 items were deposited along 4.7 km of beach over one year, and the cost for the removal of this waste amounted to approximately 27,600 euros per km/year. At regional scale, beach litter density was positively correlated to the proximity of major harbors while its composition was related to the proximity to both major harbors and rivers. Results indicate that autumn/winter storms are important drivers of marine litter deposition. They also suggest that beaches in front of the convergence zone of littoral currents and close to major harbors can be particularly subjected to this kind of pollutant. To increase their effectiveness, litter mitigation/cleaning activities should be planned based on predictions of major storm events and performed at spatial scales encompassing at least coastal regional sectors., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have influenced the present work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Thyroid cancer is the most common (~90%) type of endocrine-system tumor, accounting for 70% of the deaths from endocrine cancers. In the last years, the high-throughput genomics has been able to identify pathways/molecular targets involved in survival and tumor progression. Targeted therapy and immunotherapy individually have many limitations. Regarding the first one, although it greatly reduces the size of the cancer, clinical responses are generally transient and often lead to cancer relapse after initial treatment. For the second one, although it induces longer-lasting responses in cancer patients than targeted therapy, its response rate is lower. The individual limitations of these two different types of therapies can be overcome by combining them. Here, we discuss MAPK pathway inhibitors, i.e., BRAF and MEK inhibitors, combined with checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4. Several mutations make tumors resistant to treatments. Therefore, more studies are needed to investigate the patient's individual tumor mutation burden in order to overcome the problem of resistance to therapy and to develop new combination therapies.

Six minute walk test (6MWT) is a field exercise test widely used in clinical practice, both in adults and in pediatric patients. The primary aim of the study is to evaluate the physical performance of the subjects and compare them with the predicted Italian values. The secondary aim is to verify the possible relationship between the 6MWT distance (6MWD) and the clinical variables of the sample. Italian children between 6-11 years affected by CF were recruited from 9 regional centers for CF. Short questionnaire assessments about their health state and physical activity routine was administered. Anthropometric characteristics were measured before the test and, peripheral oxygen saturation (SpO2), heart and respiratory rate were measured before and after a 6-minute walk test. The tests were performed according to the American Thoracic Society (ATS) guidelines. 6MWD was compared with the predicted distance calculated by the reference equation for healthy subjects of the same age. A total of 132 children were recruited (70 male) and completed the assessment. The mean (±SD) for 6MWD was 557.4 (±69.9), male = 551.4 (±80.0), female = 560.4 (±63.3), however the predicted distance mean was 605 m. A total of 101(76.5%) subjects practice regular physical activity. A total of 31 (23%) had a FEV1 lower than their lower limits of normal (LLN). Functional performance on the 6MWT was poorer among the CF patients than among the predicted distance estimated with Italian values. The correlation with the amount of physical activity and 6MWD has been verified.

Epiphytes colonizing adult seagrasses highly contribute to seagrass ecosystem functioning and plant growth. Yet, little information exists on epiphytic communities developing on seagrass seedlings. Moreover, for some species our knowledge about seedling performance is limited to early establishment phases, and the role of substrate type in affecting their growth is still unclear. These are considerable knowledge gaps, as seedlings play an important role in meadow expansion and recovery from disturbance. In this study, seedlings of Posidonia oceanica , a keystone species of the Mediterranean, were grown in a shallow (1.5 m deep) coastal area along the Tuscany coast (Italy). After five years of growth (July 2009), seedlings were collected and, through multivariate analysis, we examined whether the epiphytic communities of leaves (both internal and external side) and rhizomes, as well as the growth characteristics differed between rock and sand substrate. The epiphytic communities of seedlings largely reflected those found on adult shoots. Epiphyte cover was similar between the two leaf sides, and it was higher on seedlings grown on rock than on sand, with encrusting algae dominating the community. No differences in epiphyte cover and community structure on rhizomes were found between substrates. Seedling growth characteristics did not differ between substrates, apart from the number of standing leaves being higher on rock than on sand. No correlation was found among epiphyte communities and seedling growth variables (i.e., leaf area, maximum leaf length, number of leaves, total number of leaves produced, rhizome length, total biomass, and root to shoot biomass ratio). Results indicate that epiphytes successfully colonize P. oceanica seedlings, and the surrounding micro-environment (i.e., substrate type) can influence the leaf epiphytic community. This study provides new valuable insights on the biological interactions occurring in seagrass ecosystems and highlights the need for better understanding the effects of seedling epiphytes and substrate on the formation of new meadows., 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 2021 De Battisti, Balestri, Pardi, Menicagli and Lardicci.)

Most researches on the plastisphere in coastal environments deal with plastics floating in seawater. Comparatively smaller attention has been devoted to the plastisphere of plastics buried in marine sediments, and very little is known on that of plastics on coastal sand dunes. Yet, limited information is available on the impact of plastics, especially biodegradable plastics, on microbial organisms in their surroundings. Nevertheless, a large amount of plastics sink on the seabed or is deposited on beach-dune systems. We investigated the succession of plastisphere microbial community on two biodegradable composites based on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and seagrass fibres (PHBV/PO), buried in seabed and dune sediments over a 27 months period in mesocosm. PHBV is regarded as a valuable alternative to conventional plastics and PHBV/PO has recently been designed for applications in coastal habitat restoration. We also examined the degradation rate and impact of these plastics on the microbial communities of surrounding sediments. Microbial communities of the surface of PHBV and PHBV/PO in seabed and dune sand differ from those of surrounding sediments, displaying a lower richness. Plastics colonization occurs largely from bacteria present in surrounding sediments, although the contribution from the water column bacterial pool could be not negligible for plastics in the seabed. No significant differences were detected between the communities of the two plastics and no significant impact of plastics on microbial community of the surrounding sediments was detected. The exceptional long duration of this study allowed to gain information on the succession of a plastisphere community over a previously unexplored time scale. Succession appears highly dynamic in dune sand even after two years, while the community structure in seabed seems to reach stability after one year. These findings highlight the importance of performing long-term studies when trying to characterize composition and dynamics of plastisphere bacterial communities., 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 © 2020 Elsevier B.V. All rights reserved.)

Background: Neonatal hypoxic-ischemic encephalopathy is still a significant cause of neonatal death and neurodevelopmental disabilities, such as cerebral palsy, mental delay, and epilepsy. After the introduction of therapeutic hypothermia, the prognosis of hypoxic-ischemic encephalopathy has improved, with reduction of death and disabilities. However, few studies evaluated whether hypothermia affects rate and severity of postneonatal epilepsy. We evaluated rates, characteristics and prognostic markers of postneonatal epilepsy in infants with moderate to severe hypoxic-ischemic encephalopathy treated or not with therapeutic hypothermia., Methods: We analyzed clinical data, EEG recordings, cerebral Magnetic Resonance Imaging (MRI) and outcome in 23 cooled and 26 non-cooled asphyxiated neonates (≥36 weeks' gestation), admitted from 2004 to 2012., Results: Among 49 neonates 11 (22%) had postneonatal epilepsy, of which 9 (18%) were non-cooled and 2 (4%) were cooled (P=0.05). Six of 11 infants (55%) had West syndrome, 4 (36%) had focal epilepsy and 1 (9%) had Lennox-Gastaut Syndrome. At multiple logistic regression analysis MRI pattern significantly correlated with postneonatal epilepsy (OR 0.19, 95% CI 0.04-0.88, P=0.03). Extensive lesions in basal ganglia and thalami plus cortical and white matter were associated with postneonatal epilepsy., Conclusions: Only perinatal asphyxia with extensive lesions in basal ganglia and thalami plus cortical and white matter lesion conveys a high risk for early and severe postneonatal epilepsy. Moreover, therapeutic hypothermia is associated with a decrease of the risk of developing postneonatal epilepsy.

Plastics are found in marine environments worldwide, and their effects on macrophytes (seagrasses and macroalgae) colonizing sandy bottoms are still poorly known. Seagrass meadows are valuable but declining ecosystems due to local and global-change related stressors, including sediment disturbance and introduced macroalgae. Understanding whether plastics pose a further threat to seagrasses is critically important. In two simultaneous additive experiments performed in an aquaculture tank, we examined the individual and combined effects of macroplastics (non-biodegradable high-density polyethylene and biodegradable starch-based) and sedimentation (no and repeated sedimentation) on the performance (in terms of biomass and architectural variables) of a native Mediterranean seagrass (Cymodocea nodosa) and an introduced macroalga (Caulerpa cylindracea), and on the intensity of their interactions. Macroplastics were still present in sediments after 18 months. Cymodocea nodosa produced a greater biomass and longer horizontal rhizome internodes forming clones with more spaced shoots probably to escape from plastics. Plastics prevented C. nodosa to react to sedimentation by increasing vertical rhizome growth. Under C. cylindracea invasion, C. nodosa allocated more biomass to roots, particularly to fine roots. In the presence of C. nodosa, C. cylindracea performance was reduced. High-density polyethylene (HDPE) plastic and sedimentation shifted species interactions from competitive to neutral. These results suggest that both HDPE and biodegradable starch-based macroplastics, if deposited on marine bottoms, could make seagrasses vulnerable to sedimentation and reduce plant cover within meadows. HDPE plastic and sedimentation could contribute to the decline of seagrass habitats by facilitating the spread of non-native macroalgae within meadows. Overall, the study highlights the urgent need to implement more effective post-marketing management actions to prevent a further entering of plastics in natural environments in the future, as well as to establish to conservation measures specifically tailored to protect seagrass habitats from plastic pollution., 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 © 2020 Elsevier B.V. All rights reserved.)

Background: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E])., Methods: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766., Findings: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111)., Interpretation: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy., Funding: None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Large amounts of non-biodegradable plastics are currently deposited on beach-dune systems, and biodegradable plastics could enter these already declining habitats in coming years. Yet, the impacts of plastics on vegetative recruitment, a plant strategy playing a key role in dune stabilization, are unknown. Whether these pollutants interact with increased atmospheric nitrogen (N) deposition, a major global driver of plant biodiversity loss, in affecting plant communities of such nutrient-poor habitats, and how plant-plant interactions mediate their effects need to be explored. In a one-year field experiments, we examined individual and combined effects of plastic (non-biodegradable, biodegradable), N deposition (ambient, elevated) and biotic condition (no interaction, interaction with a conspecific or with a hetero-specific) on the colonization success and growth of vegetative propagules of dune plants. Thinopyrum junceum and Sporobolus pumilus were chosen as models because they co-occur along Mediterranean dunes and differ in ecological role (dune- vs. non dune-building) and photosynthetic pathway (C3 vs. C4). For both species, survival probability was reduced by non-biodegradable plastic and elevated N by up to 100%. Thinopyrum junceum survival was also reduced by S. pumilus presence. Elevated N and biodegradable plastic reduced T. junceum shoot biomass when grown alone and with a conspecific, respectively; these factors in combination mitigated their negative individual effects on root biomass. Biodegradable plastic increased S. pumilus shoot and root biomass, and in combination with elevated N caused a greater biomass investment in belowground (root plus rhizome) than aboveground organs. Non-biodegradable plastic may be a further threat to dune habitats by reducing plant colonization. Biodegradable plastic and increased N deposition could favour the generalist S. pumilus and hinder the dune-building T. junceum. These findings highlight the urgency of implementing measures for preventing plastic deposition on beaches and reducing N input., 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 © 2020 Elsevier Ltd. All rights reserved.)

Traditional revegetation techniques employed to restore seagrass meadows and coastal dunes have recently been criticized for their impact on donor populations as well as for the installation of plant anchoring structures made of non-biodegradable or not natural materials in recipient habitats. To improve the ecological sustainability of restoration practices, a novel plantable biodegradable container made of beach-cast seagrass wrack and a bio-based polymer was produced. The long-term performance of two seagrasses, Cymodocea nodosa and Zostera noltei, and two dune plants, Euphorbia paralias and Thinopyrum junceum, grown in nurseries from seeds using the bio-container or a non-biodegradable container of equal size/form made of a conventional plastic (control) was also examined. In addition, the development of bio-container-raised C. nodosa plants in the field was compared to that of plants removed from control containers at the installation and anchored with a traditional system. The bio-container degraded slowly in seawater and in sand and lost its functionality after about three years. In nurseries, all the tested species grown in bio-containers performed as well as, or better than, those raised in non-biodegradable ones. Six months after transplanting into the field, 80% of the C. nodosa nursery-raised plants installed with their bio-container have colonized the surrounding substrate while most of those planted with the traditional system was lost. These results indicate that the new bio-container may support plant growth, and it may also provide protection and anchorage to plants in the field. The use of this bio-container in combination with nursery techniques could improve the environmental sustainability of coastal restoration interventions by providing large plant stocks from seed, thus reducing the impact of collection on donor populations. This approach would also limit the introduction of extraneous materials in recipient habitats and offer an opportunity for valorizing seagrass beach-cast material., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The presence of plastic bags on coastal dunes worldwide is well documented. Plastic bags contain additives that during rainfall events can leach out from bags into sand dune and be absorbed by seeds and roots of plants. Dune plants play a fundamental role in dune system formation, yet the possible impact of bag leaching on their establishment and development has been neglected. We assessed in laboratory whether (i) not biodegradable bags (high-density polyethylene, PE) and new generation of compostable bags (Mater-bi®, MB) would influence via leaching water chemical/physical properties and (ii) leachates would affect germination and seedling growth using Thinopyrum junceum and Glaucium flavum as models. Leachates were obtained from different amounts of not-exposed and bags exposed to beach or marine conditions simulating various pollution degrees (none, low, intermediate and high pollution). All water variables were affected by leaching. The magnitude of these alterations depended on bag type and environmental exposure. Seeds of T. junceum treated with the high concentration of marine-exposed MB bag leachate germinated later than controls while those of G. flavum treated with the remaining leachates germinated earlier. For both species, leachates from the low concentration of PE and MB marine-exposed bags increased seed germinability. A short radicle was observed in T. junceum seedlings treated with not-exposed MB bag leachates. Glaucium flavum seedlings treated with beach- and marine-exposed PE bags and not-exposed MB bags leachates showed a greater below-aboveground length ratio and those grown with the low concentration of not-exposed PE bag leachate had a longer hypocotyl compared to controls. Leachates from the high concentration of PE and MB bag caused seedling anomalies in both species. These findings indicate that not biodegradable and compostable bags may interact with abiotic/biotic factors and affect via leaching germination phenology, seedling establishment and plant interactions with consequences on dune community structure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Non-biodegradable and compostable plastic bags on beaches negatively affect the development of coastal dune vegetation by drastically reducing seedling emergence and growth., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Propagule pressure is considered a major driver of plant invasion success. Great propagule pressure would enable invasive species to colonize new areas overcoming the resistance of native species. Many highly invasive aquatic macrophytes regenerate from vegetative propagules, but few studies have experimentally investigated the importance of propagule pressure and biotic resistance, and their interaction, in determining invasion success. By manipulating both recipient habitat and the input of vegetative propagules of the invasive seaweed Caulerpa cylindracea in mesocosm, we examined whether higher propagule pressure would overcome the resistance of a native congeneric (Caulerpa prolifera) and influence its performance. With the native, C. cylindracea population frond number decreased irrespectively of pressure level. High propagule pressure did not increase stolon length and single plant size decreased due to the effects of intra- and interspecific competition. Native biomass decreased with increasing C. cylindracea propagule pressure. These results indicate that higher propagule pressure may fail in enhancing C. cylindracea invasion success in habitats colonized by the native species, and they suggest that biotic resistance and propagule pressure co-regulate the invasion process. These findings emphasize the need to preserve/restore native seaweed populations and may help to design effective management actions to prevent further C. cylindracea spread.

In order to produce sustainable, bio-based and highly biodegradable materials, composites based on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and fibers of Posidonia oceanica (PO), a dominant Mediterranean seagrass, were produced by simple melt mixing and characterized in terms of thermal stability, morphology and rheological/mechanical properties. In view of their potential application in marine environments, degradation of the developed composites was evaluated under simulated and real marine environmental conditions for 1 year. Using 10 wt % of acetyl tributyl citrate (ATBC) as a plasticizer, smooth processing was achieved for up to 30 wt % of PO fibers, despite the reduction of the melt fluidity observed with increasing fiber loading. The tensile modulus slightly increased (from 2 to 2.4 GPa) while the tensile strength and the elongation decreased (from 23.6 to 21.5 MPa and from 3.2 to 1.9%, respectively) by increasing the PO fiber content from 0 to 30 wt %. Interestingly, the impact resistance of the composites increased with the increasing of the PO content: the Charpy&rsquo;s impact energy increased from 3.6 (without fiber) to 4.4 kJ/m² for the composite with 30 wt %. The results of the aerobic biodegradation under simulated marine conditions showed that the presence of PO fibers favored the physical disintegration of the composite increasing the biodegradation rate of the polymeric matrix: after 216 days, the composite with 20 wt % PO fibers showed a biodegradability of about 30% compared to 20% of the composite without fibers. Under real marine conditions, the specimens containing PO fibers showed higher weight losses and deterioration of tensile properties compared to those without fibers. Presumably, biodegradation occurred after colonization of the specimen, and the specimens with 20 wt % PO fibers showed well-developed biofilm consisting of bacteria and fungi on the surface after only 3 months of incubation in marine sediments, unlike the no-fiber specimens. Consequently, the persistence of an adequate mechanical performance for a relatively long period (1 year), due to a moderate rate of biodegradation in the marine environment, make the developed PHBV/PO composites particularly suitable for the production of relatively low-cost and biodegradable items which are usable in the sea and/or sand dunes, increasing the market opportunities for biopolymers such as PHBV and, at the same time, finding an eco-sustainable valorization for the PO fibrous residues accumulated in large quantities on Mediterranean beaches, which represents a problem for coastal municipalities.

Marine plastic litter is a global concern. Carrier bags manufactured from non-biodegradable polymers constitute a large component of this litter. Because of their adverse impact on marine life, non-biodegradable bags have recently been replaced by biodegradable ones. However, growing evidence shows that these latter are not readily degradable in marine sediments and can alter benthic assemblages. The potential impact of biodegradable bags on seagrasses inhabiting sandy bottoms, which are the most widespread and productive ecosystems of the coastal zones, has been ignored. Mesocosm experiments were conducted to assess the effect of a commercialized biodegradable bag on a common seagrass species of the Mediterranean, Cymodocea nodosa, both at the level of individual plant (clonal growth) and of plant community (plant-plant relationships), under three culture regimes (plant alone, in combination with a neighbour of the same species or of the co-existing seagrass Zostera noltei) simulating different natural conditions (bare substrate, monospecific meadows or mixed meadows). The bag behaviour in marine sediment and sediment physical/chemical variables were also examined. After six months of sediment exposure, the bag retained considerable mass (85% initial weight) and reduced sediment pore-water oxygen concentration and pH. In the presence of bag, C. nodosa root spread and vegetative recruitment increased compared to controls, both intra- and interspecific interactions shifted from neutral to competitive, and the growth form changed from guerrilla (loosely arranged group of widely spaced ramets) to phalanx form (compact structure of closed spaced ramets) but only with Z. noltei. These findings suggest that biodegradable bags altering sediment geochemistry could promote the spatial segregation of seagrass clones and influence species coexistence., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Infantile pyknocytosis (IP) is a rare, self-limited neonatal haemolytic anaemia that may require multiple blood transfusions. Only a little more than 50 cases have been reported in the medical literature, and the great majority of them concerns term infants. The etiology of IP is not well understood; most likely it results from a transient extra-corpuscular factor, whose nature is unknown, transmitted from mother to child or, alternatively, from a deficiency of an anti-oxidative agent. We report the case of two preterm twins, one of which suffered from IP and developed severe anaemia at age 2 wk, while the other was unaffected. Although no specific agent was identified as the cause of anaemia and IP, we speculate that the transmission of an agent from mother to child was unlikely, as only twin one suffered from IP. Smelly greenish diarrhoea occurred just before the presentation of IP, suggesting that the same agent led to both the diarrhoea and the oxidative injury. Because IP may remain underdiagnosed, it should be considered in cases of early unexplained severe hemolytic anemia., Competing Interests: Conflict-of-interest statement: No conflict of interest.