Clinical profile and outcome of cardiomyopathies in infants and children seen at a tertiary centre.

INTRODUCTION: Due to their rare prevalence and marked heterogeneity, pediatric cardiomyopathies (CMPs) are little known and scarcely reported. We report the etiology, clinical profile and outcome of a consecutive cohort of children diagnosed with CMP and followed at Meyer Children's Hospital over a decade. PATIENTS AND METHODS: We retrospectively reviewed patients consecutively referred from May 2008 to May 2019 for pediatric onset CMP (<18 years). Heart disease caused by arrhythmic disorders, toxic agents, rheumatic conditions and maternal disease were excluded. RESULTS: We enrolled 110 patients (65 males), diagnosed at a median age of 27 [4-134] months; 35% had an infant onset (<1 year of age). A positive family history was more often associated with childhood-onset (38.8%). Hypertrophic cardiomyopathy (HCM; 48 patients) was the most frequent phenotype, followed by dilated cardiomyopathy (DCM; 35 patients). While metabolic and idiopathic etiologies were preponderant in infants, metabolic and sarcomeric diseases were most frequent in the childhood-onset group. Major adverse cardiac events (MACE) occurred in 31.8% of patients, including hospitalization for acute heart failure in 25.5% of patients, most commonly due to DCM. Overall, the most severe outcomes were documented in patients with metabolic diseases. CONCLUSIONS: In a consecutive cohort of pediatric patients with CMP, those with infantile onset and with a metabolic etiology had the worst prognosis. Overall, MACE occurred in 41% of the entire population, most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. Systematic NGS genetic testing was critical for etiological diagnosis and management.

Validation Checklist for Massive Vaccination Centers.

Abstract: Starting from the minimum requirements indicated by Lombardy Region, a validation checklist has been developed by experts in design, healthcare layout planning, hygiene and public health, planning and compliance, in order to provide managers of COVID-19 massive vaccination centers with a useful and easy-to-use tool to ensure quality, safety and efficiency of the different activities performed.

Chest radiography predictor of COVID-19 adverse outcomes. A lesson learnt from the first wave.

AIM: To assess the role of a severity score based on chest radiography (CXR) in predicting the risk of adverse outcomes in coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Of the patients who presented to L. Sacco Hospital (Milan, Italy) between 21 February and 31 March 2020, patients with a laboratory confirmation of COVID-19 who also underwent a CXR were included in the study. To quantify the extent of lung involvement, each CXR image was given a score (Milan score), ranging from 0 to 24, depending on the presence of reticular pattern and/or ground-glass opacities and/or extensive consolidations in each of the 12 areas in which the lungs were divided. The score was calculated by an expert radiologist, blinded to laboratory tests. The ability of the Milan score to predict hospital admission and mortality, after adjusting for some variables (age; gender; comorbidities; time between symptoms onset and admission), using univariate and multivariate statistical analysis was investigated retrospectively. RESULTS: Among the 554 patients, 115 of which (21%) had a negative CXR, the in-hospital mortality was 16% (90/554). At univariate analysis, age, gender, and comorbidities were significant predictors of mortality and hospital admission. At multivariate analysis, adjusting for age and gender, the Milan score was an independent predictor of mortality and hospitalisation. In particular, patients with a Milan score ≥ 9 had a mortality risk five-times higher than those with a lower score. Other independent predictors of mortality were gender and age. CONCLUSIONS: The CXR Milan score was an independent predictive factor of both in-hospital mortality and hospital admission.

Reversible metamorphosis from Fe3O4 to FeO of epitaxial iron oxide films grown on the Fe-p(1 × 1)O surface.

The reduction and oxidation of epitaxial Fe3O4 films grown by reactive deposition on a Fe-p(1 × 1)O surface have been investigated by means of Auger electron spectroscopy (AES), low energy electron diffraction (LEED) and scanning tunneling microcopy (STM). The as-grown iron oxide samples display a square LEED pattern with a lattice constant compatible with a p(1 × 1) bulk terminated Fe3O4(001) surface. STM topographic images of Fe3O4 are characterized by atomically flat terraces separated by highly oriented steps running along the (010) and (100) crystallographic directions of the substrate. Upon annealing at 800 K in an ultra-high vacuum, AES reveals that magnetite transforms to FeO. The sample exposes the (001) surface of the rock salt structure, with a lattice parameter close to that of bulk wüstite. The Fe3O4 phase can be recovered by oxidation at 10-6 mbar of molecular oxygen.

Educational Challenges in Healthcare Design: Training Multidisciplinary Professionals for Future Hospitals and Healthcare.

BACKGROUND: Healthcare environments are one of the most complex and demanding fields of work. Scientific, technological and research developments along with new discoveries within health promotion and prevention strategies are increasingly requiring a multidisciplinary and interdisciplinary approach. Therefore, it is likely that the current professions will need to be significantly adapted to accommodate new and more specialized roles. OBJECTIVES: To present an overview of the current educational and training courses of the emerging professions, such as hospital planner, physician-engineer, doctor-architect, nurse-architect or engineer, we review the present global training courses (BSc, MSc, specialization and PhD courses) related to healthcare design focusing on the fields of Medicine and Nursing, Architecture and Engineering sciences. RESULTS: The paper analyses the literature review and website analysis about active teaching programs and courses. Several academic institutions offer BSc, MSc and PhD degree programs in Healthcare Design, Environmental and Building Hygiene, and Public Health. In addition, there are several professional postgraduate courses, either in classroom, hybrid-based or online. CONCLUSIONS: A considerable number of international training experiences addresses the topic of training multidisciplinary professionals. Further in-depth investigations are needed to examine the content, teaching format and impact of the courses, student outcomes and professional careers, fields of interest and the degree of collaborations with other institutions.

Evidence Based Hospital Design. A literature review of the recent publications about the EBD impact of built environment on hospital occupants' and organizational outcomes.

INTRODUCTION: Healthcare facilities are complex infrastructures where different features from technological, social, clinical and architectural field interact. In modern healthcare systems there is a growing attention to the need of quality in terms of process and outcome, while the structural (physical) aspects are not often considered. Since the Nineties the theory of the Evidence Based Design (EBD) states that there is significant relationship between built environment and health related outcome. OBJECTIVE: Aim of this paper is to investigate, in the recent scientific literature, which are the most important occupants' and organizational outcomes influenced by EBD hospital built environment qualities. METHODOLOGY: A Literature Review based on Scopus and PubMed databases has been run in order to understand the existing situation in terms of hospital quality evaluation from the physical and architectural point of view and to highlight the current trends. The results of the different reviews, empirical studies and post Occupancy Evaluations have been analyzed according to Ulrich's EBD conceptual framework. RESULTS: 35 peer reviewed papers from the last 2 years were included. The methodologies adopted are very different and data are mainly collected through structured interviews or observations and elaborated with qualitative (33%), quantitative (26%) or mixed (41%) methodologies. The topic is mostly investigated in USA, Australia, Canada, UK and in the Scandinavian region; few contributions come also from Italy. Built environment variables that affect user's or organizational outcomes are mainly the Visual Environment (29%), the Audio Environment (20%) and the Patient Room Design (20%). DISCUSSION AND CONCLUSION: The most recurrent outcomes found to be affected by the built environmental qualities are staff job satisfaction (n=11), patients' stress reduction (n=9), patients' satisfaction (n=6) and patients' fall reduction (n=6). Organizational outcomes are mentioned only two times. Although EBD is an old theory, the topic is both contemporary and relevant. Due to the diversity of the contributions and the limitations of the research, a deep comparison is challenging. Further investigation is necessary to deepen each of the variables identified.

Assessment of climate change effects on mountain ecosystems through a cross-site analysis in the Alps and Apennines.

Mountain ecosystems are sensitive and reliable indicators of climate change. Long-term studies may be extremely useful in assessing the responses of high-elevation ecosystems to climate change and other anthropogenic drivers from a broad ecological perspective. Mountain research sites within the LTER (Long-Term Ecological Research) network are representative of various types of ecosystems and span a wide bioclimatic and elevational range. Here, we present a synthesis and a review of the main results from ecological studies in mountain ecosystems at 20 LTER sites in Italy, Switzerland and Austria covering in most cases more than two decades of observations. We analyzed a set of key climate parameters, such as temperature and snow cover duration, in relation to vascular plant species composition, plant traits, abundance patterns, pedoclimate, nutrient dynamics in soils and water, phenology and composition of freshwater biota. The overall results highlight the rapid response of mountain ecosystems to climate change, with site-specific characteristics and rates. As temperatures increased, vegetation cover in alpine and subalpine summits increased as well. Years with limited snow cover duration caused an increase in soil temperature and microbial biomass during the growing season. Effects on freshwater ecosystems were also observed, in terms of increases in solutes, decreases in nitrates and changes in plankton phenology and benthos communities. This work highlights the importance of comparing and integrating long-term ecological data collected in different ecosystems for a more comprehensive overview of the ecological effects of climate change. Nevertheless, there is a need for (i) adopting co-located monitoring site networks to improve our ability to obtain sound results from cross-site analysis, (ii) carrying out further studies, in particular short-term analyses with fine spatial and temporal resolutions to improve our understanding of responses to extreme events, and (iii) increasing comparability and standardizing protocols across networks to distinguish local patterns from global patterns.

Numerical Verification of an Analytical Model for Phase Noise in MEMS Oscillators.

A new analytical formulation for phase noise in MEMS oscillators was recently presented encompassing the role of essential nonlinearities in the electrical and mechanical domains. In this paper, we validate the effectiveness of the proposed analytical formulation with respect to the unified theory developed by Demir et al. describing phase noise in oscillators. In particular, it is shown that, over a range of the second-order mechanical nonlinear stiffness of the MEMS resonator, both models exhibit an excellent match in the phase diffusion coefficient calculation for a square-wave MEMS oscillator.

Electron spectroscopy investigation of the oxidation of ultra-thin films of Ni and Cr on Fe(0 0 1).

We investigated the room temperature oxidation of ultra-thin Ni and Cr films grown on Fe(0 0 1). In particular, we characterized the degree of crystallinity and the stoichiometry of the oxide layers and addressed the chemical stability of the interface with the highly reactive Fe substrate by means of low-energy electron diffraction and x-ray and UV photoemission spectroscopy. In the Ni case we detected, upon oxidation, the formation of a Fe(3)O(4) layer covering the Ni oxide, due to the diffusion of Fe cations towards the surface. At high temperature and in ultra-high vacuum conditions, the Ni oxide dissolved and the Fe oxide layer was reduced to FeO. In the Cr case, we observed the formation of a thin Cr(2)O(3) oxide layer, showing a diffraction pattern compatible with a defective γ-Cr(2)O(3) phase. A thicker Cr oxide layer could be produced by oxidizing the sample at 300 °C, at the expense of the incorporation of trace amounts of Fe cations.

Enhanced atom mobility on the surface of a metastable film.

A remarkable enhancement of atomic diffusion is highlighted by scanning tunneling microscopy performed on ultrathin metastable body-centered tetragonal Co films grown on Fe(001). The films follow a nearly perfect layer-by-layer growth mode with a saturation island density strongly dependent on the layer on which the nucleation occurs, indicating a lowering of the diffusion barrier. Density functional theory calculations reveal that this phenomenon is driven by the increasing capability of the film to accommodate large deformations as the thickness approaches the limit at which a structural transition occurs. These results disclose the possibility of tuning surface diffusion dynamics and controlling cluster nucleation and self-organization.

Direct observation of spin-resolved full and empty electron states in ferromagnetic surfaces.

We present a versatile apparatus for the study of ferromagnetic surfaces, which combines spin-polarized photoemission and inverse photoemission spectroscopies. Samples can be grown by molecular beam epitaxy and analyzed in situ. Spin-resolved photoemission spectroscopy analysis is done with a hemispherical electron analyzer coupled to a 25 kV-Mott detector. Inverse photoemission spectroscopy experiments are performed with GaAs crystals as spin-polarized electron sources and a UV bandpass photon detector. As an example, measurements on the oxygen passivated Fe(100)-p(1×1)O surface are presented.

X-ray photoemission spectroscopy investigation of the interaction between 4-mercaptopyridine and the anatase TiO2 surface.

In polymer-metal oxide hybrid solar cells, an extremely careful engineering of the interface is required to ensure good device performances. Recently, very promising results have been obtained by functionalizing titanium dioxide (TiO2) by means of 4-mercaptopyridine (4-MPy) molecules, showing the beneficial effect of these molecules on the interface morphology. This study investigates the nature of the interaction of 4-MPy molecules with the TiO2 surface by means of X-ray photoemission spectroscopy. In order to mimic the device processing conditions, our analysis is carried out on molecules adsorbed from solution on a nanocrystalline surface. According to our analysis, 4-MPy molecules (C5H5NS) are likely bound with the oxide through the nitrogen atom. The bonding precedes either via a covalent interaction with Lewis surface sites, or via hydrogen mediation, possibly in the form of hydrogen bonds. Interestingly, in the latter case, we also observe strong changes in the spectroscopic features attributed to the thiol group.

Severe Neonatal Metabolic Decompensation in Methylmalonic Acidemia Caused by CblD Defect.

CblD disorder is an autosomal recessive, rare, heterogeneous disease with variable clinical presentations, depending on the nature and location of the MMADHC gene mutations. Mutations in MMADHC lead to three distinct phenotypes: cblD-MMA, cblD-HC, and cblD-MMA/HC. To date, 18 cblD patients have been reported. Six of them were affected by cblD-MMA, but only three had a known clinical history. One of these patients presented with a metabolic decompensation at 11 months; the second one, born prematurely, was diagnosed with cblD after being treated for intracranial hemorrhage, respiratory distress syndrome, necrotizing enterocolitis, and convulsions at birth; the third one was diagnosed at 5 years of age.Here we present a case of a cblD-MMA patient who had an acute neonatal onset with severe hyperammonemia requiring hemodiafiltration. To the best of our knowledge, this is the first cblD-MMA patient who presented acutely in the newborn period. He has developed well upon treatment with B12, carnitine, and hypoproteic diet. At present time, at the age of 7, he shows normal growth and cognitive development. Thus, it is likely that the aggressive treatment of this child with hemodiafiltration might have prevented him from long-term neurological sequelae. Overall, this case shows that even severe, neonatal-onset patients may display a vitamin B12-responsive MMA. Furthermore, it suggests that an early treatment with vitamins might be beneficial for patients presenting with neonatal-onset hyperammonemia regardless of the suspected disease and before receiving the biochemical diagnosis.

Unexplained hypoglycemia during continuous nocturnal gastric drip-feeding in a patient with glycogen storage disease type ia: is it a dumping-like syndrome?

A 5 years old boy affected with Glycogen Storage Disease type Ia (GSD-Ia) with previous optimal metabolic control developed severe erratic hypoglycemic episodes during continuous nocturnal gastric drip-feeding (CNGDF) administered by nasogastric tube. The episodes of hypoglycemia were not related to pump failure or human errors or wrong position of the tube in the gastrointestinal tract. Hyperinsulinism was also considered in this patient but it was excluded mainly because hypoglycemia was only nocturnal. Moreover, hypoglycemic episodes disappeared when CNGDF was stopped and he was fed with normal meals. The fact that hypoglycemia resolved after stopping CNGDF when nocturnal meals were introduced led us to hypothesize that CNGDF rich with simple carbohydrates might have been the cause of a sort of dumping-like syndrome. Dumping syndrome (DS) develops when a large amount of carbohydrate reaches the small intestine due to rapid gastric emptying (Tack et al. 2009; Hejazi et al. 2010). We suppose that CNGDF induced a disturbance of gastric motility with a gastric accumulation of fluids at a certain time of the night followed by a rapid voiding of the stomach leading to DS.

Thalamic deep brain stimulation for treatment-refractory Tourette syndrome: two-year outcome.

BACKGROUND: Eighteen patients with severe and refractory Tourette syndrome (TS) underwent bilateral thalamic deep brain stimulation (DBS). OBJECTIVE: To assess the long-term outcome on tics, behavioral symptoms, and cognitive functions in the largest case series of thalamic DBS for TS to date. METHODS: In this prospective cohort study, 15 of the original 18 patients were evaluated before and after surgery according to a standardized protocol that included both neuropsychiatric and neuropsychological assessments. RESULTS: In addition to marked reduction in tic severity (p = 0.001), 24-month follow-up ratings showed improvement in obsessive-compulsive symptoms (p = 0.009), anxiety symptoms (p = 0.001), depressive symptoms (p = 0.001), and subjective perception of social functioning/quality of life (p = 0.002) in 15 of 18 patients. There were no substantial differences on measures of cognitive functions before and after DBS. CONCLUSIONS: At 24-month follow-up, tic severity was improved in patients with intractable Tourette syndrome (TS) who underwent bilateral thalamic deep brain stimulation. Available data from 15 of 18 patients also showed that neuropsychiatric symptoms were improved and cognitive performances were not disadvantaged. Controlled studies on larger cohorts with blinded protocols are needed to verify that this procedure is effective and safe for selected patients with TS. LEVEL OF EVIDENCE: This study provides class IV evidence that bilateral thalamic deep brain stimulation reduces global tic severity measured 24 months after implantation in patients with severe intractable Tourette syndrome.

Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation.

BACKGROUND: There have been several reports of successful deep brain stimulation (DBS) for the treatment of severe Gilles de la Tourette syndrome (GTS). METHOD: 18 cases of GTS who were resistant to at least 6 months of standard and innovative treatments, as well as to psychobehavioural techniques, underwent DBS. DBS was placed bilaterally in the centromedian-parafascicular (CM-Pfc) and ventralis oralis complex of the thalamus. Patients were evaluated after surgery, with immediate and formal assessments at least every 3 months, including "on-off" and "sham off" in the first nine patients. RESULTS: All patients responded well to DBS, although to differing degrees. The duration of follow-up assessments ranged from 3 to 18 months. The comorbid symptoms of obsessive-compulsive behaviour, obsessive-compulsive disorder, self-injurious behaviours, anxiety and premonitory sensations decreased after treatment with DBS. There were no serious permanent adverse effects. CONCLUSIONS: DBS is a useful and safe treatment for severe GTS. The results of ours and previous DBS reports suggest that the CM-Pfc and ventralis oralis complex of the thalamus may be a good DBS target for GTS.

Interface coupling transition in a thin epitaxial antiferromagnetic film interacting with a ferromagnetic substrate.

We report experimental evidence for a transition in the interface coupling between an antiferromagnetic film and a ferromagnetic substrate. The transition is observed in a thin epitaxial NiO film grown on top of Fe(001) as the film thickness is increased. Photoemission electron microscopy excited with linearly polarized x rays shows that the NiO film is antiferromagnetic at room temperature with in-plane uniaxial magnetic anisotropy. The anisotropy axis is perpendicular to the Fe substrate magnetization when the NiO thickness is less than about 15 A, but rapidly becomes parallel to the Fe magnetization for a NiO coverage higher than 25 A.

Long-term functional outcome measures in corticosteroid-treated complex regional pain syndrome.

AIM: The aim of this paper was to assess the effects of low-dose systemic corticosteroid therapy in complex regional pain syndrome (CRPS), to measure the long-term functional outcome, and to evaluate an arbitrary scale of severity of CRPS. METHODS: An evaluation of 31 consecutive subjects diagnosed with CRPS before and after they underwent corticosteroid therapy was carried out. The clinical and functional variables considered were evaluated at baseline, halfway through therapy, at the end and after 1, 6 and 12 months after the end of treatment. A clinical severity scale of CRPS was devised. RESULTS: The comparison between baseline and post-treatment data of the principal variables resulted in all cases significant (P<0.001), as did, in most cases, the changes in variables between successive time intervals (P<0.05), supporting the long-term efficacy of treatment. The score of the clinical severity scale of CRPS showed a significant improvement in the one-year follow-up. CONCLUSION: Corticosteroid therapy in CRPS provides a short-term response to the pain with a low risk of side effects. The improvement in all the variables considered persisted at one-year follow-up. The arbitrary scale of clinical severity of CRPS should be further tested in order to propose it as an instrument for use in following the course of CRPS.

Relation between CD4 cell counts and HIV RNA levels at onset of opportunistic infections.

OBJECTIVE: To evaluate the relation between CD4 and HIV RNA levels at the onset of specific opportunistic infections (OIs) in HIV-infected patients. DESIGN AND METHODS: The OIs occurring between June 1996 and December 1998 were retrospectively reviewed, considering only the episodes of major and minor OIs in patients with simultaneously available CD4 and plasma HIV RNA determinations before clinical onset who had been untreated or on stable antiretroviral therapy (ART) for at least 2 months. RESULTS: Two hundred seventy-four episodes of different OIs were considered in 216 patients; the median CD4 count was 35 cells/mm3 (range: 0-1154 cells/mm(3)), and the median HIV RNA count was 5.1 log cp/mL (range: < 1.9-6.7 log copies/ml). The different HIV RNA levels were significantly associated with different OIs regardless of CD4 and ART (p < .0001), even when only those occurring in patients with a CD4 count of < or = 50 cells/mm(3) were considered (p = .0049). Kaposi sarcoma, esophageal candidiasis, oropharyngeal candidiasis, and Mycobacterium avium complex disease were associated with significantly above-average median HIV RNA levels, and varicella-zoster virus infection was associated with below-average levels. CONCLUSIONS: Different OIs are associated at their onset with significantly different HIV RNA levels, regardless of CD4 cell counts and ART.

Lack of interaction between flibanserin and antidepressants in inducing serotonergic syndrome in rats.

This study was aimed at evaluating the ability of flibanserin, a 5-HT1A receptor full agonist with antidepressant potential, to induce the 5-HT syndrome (flat body posture, hindlimb abduction and forepaw treading) in rats previously administered with clinically active antidepressants imipramine, fluoxetine or paroxetine. The 5-HT syndrome was observed for 50 min after intraperitoneal administration of flibanserin (0, 8 or 64 mg/kg) given 10 min after antidepressants (0 or 15 mg/kg). Flibanserin induced flat body posture and very slight hindlimb abduction only at 64 mg/kg. No dose of flibanserin elicited forepaw treading. Similar but milder symptoms were induced by antidepressants. No interaction between flibanserin and antidepressants was observed. A dose of 10 mg/kg flibanserin did not change the flat body posture induced by 8 mg/kg (+/-)-8-OH-DPAT but antagonized (+/-)-8-OH-DPAT-induced forepaw treading.