Defective Biomechanics and Pharmacological Rescue of Human Cardiomyocytes with Filamin C Truncations.

Actin-binding filamin C (FLNC) is expressed in cardiomyocytes, where it localizes to Z-discs, sarcolemma, and intercalated discs. Although FLNC truncation variants (FLNCtv) are an established cause of arrhythmias and heart failure, changes in biomechanical properties of cardiomyocytes are mostly unknown. Thus, we investigated the mechanical properties of human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) carrying FLNCtv. CRISPR/Cas9 genome-edited homozygous FLNCKO-/- hiPSC-CMs and heterozygous knock-out FLNCKO+/- hiPSC-CMs were analyzed and compared to wild-type FLNC (FLNCWT) hiPSC-CMs. Atomic force microscopy (AFM) was used to perform micro-indentation to evaluate passive and dynamic mechanical properties. A qualitative analysis of the beating traces showed gene dosage-dependent-manner "irregular" peak profiles in FLNCKO+/- and FLNCKO-/- hiPSC-CMs. Two Young's moduli were calculated: E1, reflecting the compression of the plasma membrane and actin cortex, and E2, including the whole cell with a cytoskeleton and nucleus. Both E1 and E2 showed decreased stiffness in mutant FLNCKO+/- and FLNCKO-/- iPSC-CMs compared to that in FLNCWT. The cell adhesion force and work of adhesion were assessed using the retraction curve of the SCFS. Mutant FLNC iPSC-CMs showed gene dosage-dependent decreases in the work of adhesion and adhesion forces from the heterozygous FLNCKO+/- to the FLNCKO-/- model compared to FLNCWT, suggesting damaged cytoskeleton and membrane structures. Finally, we investigated the effect of crenolanib on the mechanical properties of hiPSC-CMs. Crenolanib is an inhibitor of the Platelet-Derived Growth Factor Receptor α (PDGFRA) pathway which is upregulated in FLNCtv hiPSC-CMs. Crenolanib was able to partially rescue the stiffness of FLNCKO-/- hiPSC-CMs compared to control, supporting its potential therapeutic role.

Cardiogenic shock diagnosis and management in general intensive care: a nationwide survey.

BACKGROUND: The epidemiology of cardiogenic shock has evolved over the years: in the last decades an increasing prevalence of cardiogenic shock related to acute decompensated heart failure was observed. Therefore, treatment bundles should be updated according to the underlying pathophysiology. No data exist regarding the diagnostic/therapeutic strategies in general intensive care units. METHODS: A 27-questions survey was spread through the GiViTi (Italian Group for the Evaluation of Interventions in Intensive Care Medicine). The results were then divided according to level of hospitals (1st-2nd versus 3rd). RESULTS: Sixty-nine general intensive care units replied to the survey. The shock team is present in 13% of institutions; Society for Cardiovascular Angiography and Interventions shock classification is applied only in 18.8%. 94.2% routinely uses a cardiac output monitoring device (pulmonary artery catheter more frequently in 3rd level centers). The first-line adrenergic drug are vasopressors in 27.5%, inotrope in 21.7% or their combination in 50.7%; 79.7% applies fluid challenge. The first vasopressor of choice is norepinephrine (95.7%) (maximum dosage tolerated higher than 0.5 mcg/kg/min in 29%); the first line inotrope is dobutamine (52.2%), followed by epinephrine in 36.2%. The most frequently used mechanical circulatory supports are intra-aortic balloon pump (71%), Impella (34.8%) and VA-ECMO (33.3%); VA-ECMO is the first line strategy in refractory cardiogenic shock (60.8%). CONCLUSIONS: According to this survey, there is no standardized approach to cardiogenic shock amongst Italian general intensive care units. The application of shock severity stratification and the treatment bundles may play a key role in improving the outcome.

Social media analysis of Twitter tweets related to ASD in 2019-2020, with particular attention to COVID-19: topic modelling and sentiment analysis.

Background: Social media contains an overabundance of health information relating to people living with different type of diseases. Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with lifelong impacts and reported trends have revealed a considerable increase in prevalence and incidence. Research had shown that the ASD community provides significant support to its members through Twitter, providing information about their values and perceptions through their use of words and emotional stance. Our purpose was to analyze all the messages posted on Twitter platform regarding ASD and analyze the topics covered within the tweets, to understand the attitude of the various people interested in the topic. In particular, we focused on the discussion of ASD and COVID-19. Methods: The data collection process was based on the search for tweets through hashtags and keywords. After bots screening, the NMF (Non-Negative Matrix Factorization) method was used for topic modeling because it produces more coherent topics compared to other solutions. Sentiment scores were calculated using AFiNN for each tweet to represent its negative to positive emotion. Results: From the 2.458.929 tweets produced in 2020, 691.582 users were extracted (188 bots which generated 59.104 tweets), while from the 2.393.236 total tweets from 2019, the number of identified users was 684.032 (230 bots which generated 50.057 tweets). The total number of COVID-ASD tweets is only a small part of the total dataset. Often, the negative sentiment identified in the sentiment analysis referred to anger towards COVID-19 and its management, while the positive sentiment reflected the necessity to provide constant support to people with ASD. Conclusions: Social media contributes to a great discussion on topics related to autism, especially with regards to focus on family, community, and therapies. The COVID-19 pandemic increased the use of social media, especially during the lockdown period. It is important to help develop and distribute appropriate, evidence-based ASD-related information.

Subcellular elements responsive to the biomechanical activity of triple-negative breast cancer-derived small extracellular vesicles.

Triple-negative breast cancer (TNBC) stands out for its aggressive, fast spread, and highly metastatic behavior and for being unresponsive to the classical hormonal therapy. It is considered a disease with a poor prognosis and limited treatment options. Among the mechanisms that contribute to TNBC spreading, attention has been recently paid to small extracellular vesicles (sEVs), nano-sized vesicles that by transferring bioactive molecules to recipient cells play a crucial role in the intercellular communication among cancer, healthy cells, and tumor microenvironment. In particular, TNBC-derived sEVs have been shown to alter proliferation, metastasis, drug resistance, and biomechanical properties of target cells. To shed light on the molecular mechanisms involved in sEVs mediation of cell biomechanics, we investigated the effects of sEVs on the main subcellular players, i.e., cell membrane, cytoskeleton, and nuclear chromatin organization. Our results unveiled that TNBC-derived sEVs are able to promote the formation and elongation of cellular protrusions, soften the cell body, and induce chromatin decondensation in recipient cells. In particular, our data suggest that chromatin decondensation is the main cause of the global cell softening. The present study added new details and unveiled a novel mechanism of activity of the TNBC-derived sEVs, providing information for the efficient translation of sEVs to cancer theranostics.

Atomic force spectroscopy-based essay to evaluate oocyte postovulatory aging.

Postovulatory aging is a process occurring in the mature (MII) oocyte leading the unfertilized ones to apoptosis. The optimal time window of fertility for different mammalian species after oocytes maturation depends on its timeliness: the higher the time elapsed from the accomplishment of the MII stage, the lower are the chances of fertilization and of development of a viable embryo. In the in vitro fertilization, the selection of competent oocytes for intracytoplasmic sperm injection (ICSI) is mostly made by the visual inspection of the MII oocyte morphology, which does not allow to determine the oocyte postovulatory age. On the other hand, more specific tests usually involve some kind of staining, thus compromising the viability of the oocyte for reproductive purposes. Hence, the need of a noninvasive analysis of oocyte aging to improve the success rate of in vitro fertilization procedures. Here, we exploit atomic force microscopy to examine the evolution of the mechanical properties of mouse oocytes during in vitro postovulatory aging. Three hours before the occurrence of any visual morphological feature related to degradation, we observe a sudden change of the mechanical parameters: the elastic modulus doubles its initial value, while the viscosity decreases significantly. These mechanical variations are temporally correlated with the release of the cortical granules, investigated by fluorescence microscopy. Interestingly, the oocyte mechanics correlates as well with the yield of embryo formation, evaluated up to the blastocyst formation stage. These results demonstrate that minimally invasive mechanical measurements are very sensitive to the aging of the oocyte and can be used as a label-free method to detect the age of the postovulatory oocytes.

The Role of Cytoskeleton Revealed by Quartz Crystal Microbalance and Digital Holographic Microscopy.

The connection between cytoskeleton alterations and diseases is well known and has stimulated research on cell mechanics, aiming to develop reliable biomarkers. In this study, we present results on rheological, adhesion, and morphological properties of primary rat cardiac fibroblasts, the cytoskeleton of which was altered by treatment with cytochalasin D (Cyt-D) and nocodazole (Noc), respectively. We used two complementary techniques: quartz crystal microbalance (QCM) and digital holographic microscopy (DHM). Qualitative data on cell viscoelasticity and adhesion changes at the cell-substrate near-interface layer were obtained with QCM, while DHM allowed the measurement of morphological changes due to the cytoskeletal alterations. A rapid effect of Cyt-D was observed, leading to a reduction in cell viscosity, loss of adhesion, and cell rounding, often followed by detachment from the surface. Noc treatment, instead, induced slower but continuous variations in the rheological behavior for four hours of treatment. The higher vibrational energy dissipation reflected the cell's ability to maintain a stable attachment to the substrate, while a cytoskeletal rearrangement occurs. In fact, along with the complete disaggregation of microtubules at prolonged drug exposure, a compensatory effect of actin polymerization emerged, with increased stress fiber formation.

Microfabricated cantilevers for parallelized cell-cell adhesion measurements.

Single-cell adhesion measured with atomic force microscopy (AFM) offers outstanding time and force resolution and allows the investigation of many important phenomena with unmatched precision. However, this technique suffers from serious practical limitations that hinder its effective application to a broader set of situations. Here we propose a different strategy based on the fabrication of large cantilevers and on the culture of the cells directly on them. Cantilevers are fabricated by standard micromachining, with an active area of 300 × 300 µm. A wedged structure is created so that the cantilever surface lies parallel to the substrate when mounted on an AFM system, so that the adhesion measurement probes the whole surface area at the same time. Thanks to the large area, cells can be seeded and grown on the cantilevers the day before the experiment, and let recover to optimal condition for the experiment. We used Human Embryonic Kidney cells, HEK 293A, to demonstrate the measurement of adhesion forces of up to 100 cells in parallel, and obtain a straightforward measurement of the average single cell adhesion energy. Our approach can improve significantly the cell-cell and cell-substrate adhesion statistics, reduce the experiment time and allow the investigation of the adhesion properties of cells that do not grow well in solution or on low adherent substrates, or that develop their characteristic features only after several hours or days of culture on a solid and adherent substrate.

Ten Years (2011-2021) of the Italian Lombardy ADHD Register for the Diagnosis and Treatment of Children and Adolescents with ADHD.

BACKGROUND: The purpose of this article is to update the diagnostic assessment, therapeutic approach, and 12-18 month follow-up of patients added to the Italian Lombardy Attention Deficit Hyperactivity Disorder (ADHD) Register. METHODS: Medical records of patients added to the Registry from 2011 to 2021 were analysed. RESULTS: 4091 of 5934 patients met the criteria for a diagnosis of ADHD, and 20.3% of them presented a familiarity with the disorder. A total of 2879 children (70.4%) had at least one comorbidity disorder, in prevalence a learning disorder (39%). Nearly all (95.9%) received at least one psychological prescription, 17.9% of them almost one pharmacological treatment, and 15.6% a combination of both. Values of ≥5 of the Clinical Global Impression-Severity scale (CGI-S) are more commonly presented by patients with a pharmacological prescription than with a psychological treatment (p < 0.0001). A significant improvement was reported in half of the patients followed after 1 year, with Clinical Global Impression-Improvement scale (CGI-I) ≤ 3. In all, 233 of 4091 are 18-year-old patients. CONCLUSIONS: A ten-year systematic monitoring of models of care was a fruitful shared and collaborative initiative in order to promote significant improvement in clinical practice, providing effective and continuous quality of care. The unique experience reported here should spread.

[Comparing two regional health services: is it always the same italian NHS?] / Due servizi sanitari regionali a confronto: è sempre lo stesso SSN?

The Italian National Health Service (NHS) provides universal and almost free health coverage to all Italian citizens. However, since 1992 the NHS has been progressively decentralized, with a gradual transfer of health powers to the regions. This has made a radical difference in terms of health administration and service delivery. Here we focus our analysis on two of the most important and populous northern Italian regions: Lombardy and Veneto. Although they are two neighboring regions and similar in many aspects, nevertheless they are totally different as regards their regional health services. Large differences stand out above all in the number of health sector agencies and the density of acute care hospitals. This heterogeneity is mainly due to the profound local political interference, which have been deeply rooted within the NHS over the years. Finally, we analyze the main implications of this situation and try to give insights for an indispensable future (re)harmonization of the NHS.

Burnout in Intensive Care Unit Workers during the Second Wave of the COVID-19 Pandemic: A Single Center Cross-Sectional Italian Study.

The COVID-19 pandemic had a massive impact on the Italian healthcare systems, which became overwhelmed, leading to an increased risk of psychological pressure on ICU workers. The present study aimed to investigate the prevalence of distress (anxiety, depression and insomnia symptoms), burnout syndrome and resilience in healthcare workers during the COVID-19 pandemic and to detect potential factors associated with their psychological response. This cross-sectional, survey-based study enrolled 136 healthcare workers assisting COVID-19 patients in the new COVID-19 ward (Intensive Care Unit), at Milano Fiera, Lombardy. Participants completed an online survey that comprised different validated and standardized questionnaires: Maslach Burnout Inventory (MBI), Resilience Scale for adults (RSA), Hospital Anxiety and Depression scale (HADS) and Insomnia Severity Index (ISI). Socio-demographic and work characteristics were also collected. Out of 136 ICU specialists, there were 84 nurses (62%) and 52 physicians (38%). Over half (60%) met the criteria for burnout, with nearly the same percentages among nurses and physicians. Nurses reported significantly higher scores of anxiety and insomnia levels. Forty-five percent of participants reported symptoms of depression (of whom 13.9% in the clinical range) and most of the staff showed moderate to high levels (82.4%) of resilience. The COVID-19 pandemic can have a significant impact on ICU staff. Effective interventions are needed to maintain healthcare professionals' mental health and relieve burnout. Follow-up and tailored procedures should be provided to alleviate the psychological burden in the frontline staff at highest risk.

Distance learning in Italian primary and middle school children during the COVID-19 pandemic: a national survey.

BACKGROUND: School closure created difficulties for parents, who were asked to care for their children and help them with schooling, while working at home. We aimed to explore the experiences in organising school for children at home and its implications on children's psychological well-being and educational progress during the quarantine for the COVID-19 pandemic. METHODS: A nationwide online survey of mothers of primary and middle school students was conducted during the COVID-19 pandemic. Demographic data and information on distance learning organisation and children's attitudes and behavioural changes were collected. RESULTS: 2149 mothers completed the survey, with a final sample of 1601 subjects. Large differences between primary and middle school emerged: lessons were less organised and routines were more instable for the youngest, who could not pay attention for more than 20 min (28.3%) and needed breaks every 10 min (21.6%), with lower quality of learning (40.6%), increased restlessness (69.1%), and aggressiveness (33.3%). A large use of screens was reported, with an abuse in screen time in 2%. Two thirds of mothers did not approve of distance learning (72.2%) because of their role in replacing teachers (77.8%), the effort required (66%), and the great commitment required (78.3%). CONCLUSIONS: Distance learning increased educational deprivation and social inequalities, especially for the youngest children, who lost almost one year of school. The situation was even worse for children with disabilities, who were neglected by the institutions. This period should be considered as an opportunity to correct the weaknesses of our school system.

Scanning Probe Microscopies: Imaging and Biomechanics in Reproductive Medicine Research.

Basic and translational research in reproductive medicine can provide new insights with the application of scanning probe microscopies, such as atomic force microscopy (AFM) and scanning near-field optical microscopy (SNOM). These microscopies, which provide images with spatial resolution well beyond the optical resolution limit, enable users to achieve detailed descriptions of cell topography, inner cellular structure organization, and arrangements of single or cluster membrane proteins. A peculiar characteristic of AFM operating in force spectroscopy mode is its inherent ability to measure the interaction forces between single proteins or cells, and to quantify the mechanical properties (i.e., elasticity, viscoelasticity, and viscosity) of cells and tissues. The knowledge of the cell ultrastructure, the macromolecule organization, the protein dynamics, the investigation of biological interaction forces, and the quantification of biomechanical features can be essential clues for identifying the molecular mechanisms that govern responses in living cells. This review highlights the main findings achieved by the use of AFM and SNOM in assisted reproductive research, such as the description of gamete morphology; the quantification of mechanical properties of gametes; the role of forces in embryo development; the significance of investigating single-molecule interaction forces; the characterization of disorders of the reproductive system; and the visualization of molecular organization. New perspectives of analysis opened up by applying these techniques and the translational impacts on reproductive medicine are discussed.

Informatics Methodology Used in the Web-Based Portal of the NASCITA Cohort Study: Development and Implementation Study.

BACKGROUND: Many diseases occurring in adults can be pinned down to early childhood and birth cohorts are the optimal means to study this connection. Birth cohorts have contributed to the understanding of many diseases and their risk factors. OBJECTIVE: To improve the knowledge of the health status of Italian children early on and how it is affected by social and health determinants, we set up a longitudinal, prospective, national-level, population-based birth cohort, the NASCITA study (NAscere e creSCere in ITAlia). The main aim of this cohort is to evaluate physical, cognitive, and psychological development; health status; and health resource use in the first 6 years of life in newborns, and potential associated factors. A web-based system was set up with the aim to host the cohort; provide ongoing information to pediatricians and to families; and facilitate accurate data input, monitoring, and analysis. This article describes the informatics methodology used to set up and maintain the NASCITA cohort with its web-based platform, and provides a general description of the data on children aged over 7 months. METHODS: Family pediatricians were contacted for participation in the cohort and enrolled newborns from April 2019 to July 2020 at their first well-child visit. Information collected included basic data that are part of those routinely collected by the family pediatricians, but also parental data, such as medical history, characteristics and lifestyle, and indoor and outdoor environment. A specific web portal for the NASCITA cohort study was developed and an electronic case report form for data input was created and tested. Interactive data charts, including growth curves, are being made available to pediatricians with their patients' data. Newsletters covering the current biomedical literature on child cohorts are periodically being put up for pediatricians, and, for parents, evidence-based information on common illnesses and problems in children. RESULTS: The entire cohort population consists of 5166 children, with 139 participating pediatricians, distributed throughout Italy. The number of children enrolled per pediatrician ranged from 1 to 100. The 5166 enrolled children represent 66.55% (5166/7763) of the children born in all of 2018 covered by the same pediatricians participating in the cohort. The number of children aged over 7 months at the time of these analyses, and for whom the most complete data were available upon initial analyses, was 4386 (2226/4381 males [50.81%] and 142/4370 twins [3.25%]). The age of the mothers at birth of the 4386 children ranged from 16 to 54 years. Most newborns' mothers (3758/4367, 86.05%) were born in Italy, followed by mothers born in Romania (101/4367, 2.31%), Albania (75/4367, 1.72%), and Morocco (60/4367, 1.37%). Concerning the newborns, 138/4386 (3.15%) were born with malformations and 352/4386 (8.03%) had a disease, most commonly neonatal respiratory distress syndrome (n=52), neonatal jaundice (n=46), and neonatal hypoglycemia (n=45). CONCLUSIONS: The NASCITA cohort is well underway and the population size will permit significant conclusions to be drawn. The key role of pediatricians in obtaining clinical data directly, along with the national-level representativity, will make the findings even more solid. In addition to promoting accurate data input, the multiple functions of the web portal, with its interactive platform, help maintain a solid relationship with the pediatricians and keep parents informed and interested in participating. TRIAL REGISTRATION: ClinicalTrials.gov NCT03894566; https://clinicaltrials.gov/ct2/show/NCT03894566.

Psychological distress among Italians during the 2019 coronavirus disease (COVID-19) quarantine.

BACKGROUND: Quarantine as a preventive action to reduce people's exposure to a contagious disease has substantial psychological impact. We aimed to collect information on psychologically distressing experiences of Italians living in quarantine during the COVID-19 pandemic. METHODS: From 6 to 20 April 2020 participants filled out an online questionnaire. Demographic and physical symptoms data from the prior 14 days of quarantine were collected. Psychological impact of quarantine was assessed by the COVID-19 Peritraumatic Distress Index (CPDI). RESULTS: In all, 20,158 participants completed the online survey. Of these, 11,910 (59.1%) were from Lombardy, the region with 37.7% of positive cases identified during the survey period. 30.1% of responders were male. About half (55.9%) of responders were 18-50 years old, 54.3% had a tertiary level of education, 69.5% were workers, 84.1% were living in houses with ≥3 rooms, and 13.7% were living alone. 9.7% had had contact with COVID-19 positive people. Of all responders, 9978 (48.6%) reported a psychological impact, 8897 (43.4%) of whom reported mild or moderate and 1081 (5.2%) severe psychological impact. The multivariate analysis, after adjustments, showed that an increasing CPDI score was associated with gender (female), first-second educational level, being unemployed, living in a ≤2 room house, having had new health problems during the previous 14 days, and not having been out of the house in the previous week. Concerning the type of psychological distress, 2003 responders (9.9%) reported moderate to severe depressive symptoms, 1131 (5.5%) moderate to severe anxiety symptoms, and 802 (3.9%) moderate to severe physical symptoms. A positive correlation was found between responder rate (per 10.000 residents) and positive COVID-19 cases (per 10.000 residents) by region (rs = + 0.83, p = < 0.0001), and between responder rate and region latitude (rs = + 0.91, p = < 0.0001), with a greater response rate in the north. Considering Lombardy Region responders, a negative correlation between CPDI score and distance from place of residence to the red zone (Nembro-Alzano) was found. Higher prevalence of psychological distress was found up to 25 km away from the red zone and, in particular, severe distress up to 15 km. CONCLUSIONS: Policy makers and mental health professionals should be aware of quarantine's adverse mental health consequences. Factors influencing the success of quarantine and infection control practices for both disease containment and community recovery should be identified and additional support to vulnerable persons at increased risk of adverse psychological and social consequences of quarantine should be guaranteed.

Low-Risk Planned Out-of-Hospital Births: Characteristics and Perinatal Outcomes in Different Italian Birth Settings.

BACKGROUND: The present observational study aimed to describe women and delivery characteristics and early birth outcomes according to planned out-of-hospital delivery and to compare this information with comparable planned in-hospital deliveries. METHODS: 1099 healthy low-risk women who delivered out-of-hospital between 2014 to 2018, with a gestational age of 37-42 completed weeks of pregnancy, with single, vertex babies whose birth was expected to be vaginal and spontaneous were enrolled. Moreover, a case-control study was designed comparing characteristics of these births to a matched 1:5 sample. RESULTS: living in a medium city (RR 1.81, 95% CI 1.19-2.74), being multiparous (RR 1.66, CI 1.09-2.51), having the first child at ≥35 years old (RR 1.84, CI 1.02-3.33), not working (RR 1.77, CI 1.06-2.96), not being omnivorous (RR 1.80, CI 1.08-3.00), and not smoking (RR 2.53, CI 1.06-6.07) were all related to an increased chance of delivering at home compared to in a freestanding midwifery unit. The significant factors in choosing to give birth out-of-hospital instead of in-hospital were living in a large or medium city (OR 2.20; 1.75-2.77; OR 2.41; 1.93-3.02) and having a secondary or higher level of education (OR > 2 for both parents). Within the first week of delivery, 6 of 1099 mothers and 19 of 1099 neonates were hospitalized. CONCLUSIONS: out-of-hospital births in women with low-risk pregnancies is a possible option that needs to be planned, monitored, regulated, and evaluated according to healthcare control systems in order to work, as in hospitals, for the safest and most effective care to a mother and her neonate(s).

NASCITA Italian birth cohort study: a study protocol.

BACKGROUND: Young children's healthy development depends on nurturing care, which ensures health, nutrition, responsive caregiving, safety and security, and early learning. Infancy and childhood are characterized by rapid growth and development, and these two factors contribute largely to determining health status and well-being across the lifespan. Identification of modifiable risk factors and prognostic factors during the critical periods of life will contribute to the development of effective prevention and intervention strategies. The NASCITA (NAscere e creSCere in ITAlia) study was created to evaluate physical, cognitive, and psychological development, health status and health resource utilization during the first six years of life in a cohort of newborns, and to evaluate potential associated factors. METHODS: NASCITA is an ongoing, dynamic, prospective, population-based birth cohort study of an expected number of more than 5000 newborns who will be recruited in 22 national geographic clusters starting in 2019. It was designed to follow children from birth to school entry age for a wide range of determinants, disorders, and diseases. Recruitment of the newborns (and their parents) will take place during the first routine well-child visit, which takes place at the office of the pediatrician assigned to them by the local health unit of residence, and which is scheduled for all newborns born in Italy within the first 45 days of their life. Data will be web-based and collected by the family pediatricians during each of the 7 standard well-child visits scheduled for all children during their first 6 years of life. Information on every contact with the enrolled children in addition to these prescheduled visits will be also recorded. DISCUSSION: The NASCITA cohort study provides a framework in which children are followed from birth to six-years of age. NASCITA will broaden our understanding of the contribution of early-life factors to infant and child health and development. NASCITA provides opportunities to initiate new studies, also experimental ones, in parts of the cohort, and will contribute relevant information on determinants and health outcomes to policy and decision makers. Cohort details can be found on https://coortenascita.marionegri.it. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03894566. Ethics committee approval: 6 February 2019, Verbale N 59.

Waiting times for diagnosis of attention-deficit hyperactivity disorder in children and adolescents referred to Italian ADHD centers must be reduced.

BACKGROUND: To investigate timely access to and the time needed to complete the diagnostic path of children and adolescents with suspected attention deficit hyperactivity disorder (ADHD) in the 18 Italian Lombardy Region ADHD reference centers. METHODS: Data of children and adolescents enrolled in the Regional ADHD disease-oriented Registry for suspected ADHD who requested their first visit in 2013-2017 were analyzed. RESULTS: The sample comprised 2262 children and adolescents aged 5-17 years who accessed the ADHD centers for diagnostic classification and management. The median waiting time was of 177 days (range 66-375) from the request for the initial appointment to the completion of the diagnostic path, with a three - fold difference between centers. In addition to the center, the strongest significant predictors of long waiting times were age comorbidities, the severity of the disorder, and having already completed some diagnostic procedures provided by the common standard path. CONCLUSIONS: To guarantee an equal standard of care in ADHD centers for all children and adolescents there is a pressing need to reduce the times to complete the diagnostic path. It is the task of both policymakers and each center to optimize the quality of the service and of the care delivered.