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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

DAU 6215, a novel 5-HT3 receptor antagonist, improves performance in the aged rat in the Morris water maze task.

The effects of the new 5-HT3 receptor antagonist, DAU 6215, on aged rats' cognition were assessed in the Morris water maze task. Task performance of aged animals that received acutely the dose of 10 micrograms/kg IP was not different than that of their aged controls treated with the vehicle. Conversely, a repeated IP administration of 10 micrograms/kg DAU 6215 for 3 weeks significantly improved task performance of the aged animals as compared to that displayed by the old rats treated with the vehicle.

Synthesis and biological evaluation of new antimuscarinic compounds with amidine basic centers. A useful bioisosteric replacement of classical cationic heads.

Amidines (guanidine, formamidine, and acetamidine) were introduced as substitutes for the cationic heads present in atropine, scopolamine, and corresponding quaternary derivatives. Amidine systems are intermediate in structure between tertiary amines and quaternary compounds, at least as regards ionization and electronic properties, but differ from the latter in shape (planar not tetrahedral). They have additional binding opportunities on account of their hydrogen-bond-forming capacity. The effect of the introduction of these cationic heads on the affinity for different muscarinic acetyl choline receptor (m-AcChR) subtypes was investigated in vitro, in binding displacement studies, and in functional tests on isolated organs. All new compounds (3a,b-5a,b) showed high affinity for the m-AcChR considered, comparable or slightly inferior to that of the parent drugs (1a-e). The new amidine derivatives proved effective as spasmolytic agents, with little tendency to cause central effects. However, no separation was achieved of spasmolytic and other untoward effects, like inhibition of salivation. Thus, amidine moieties are effective bioisosteric substitutes for conventional cationic heads present in antimuscarinic agents. Their unusual physical-chemical properties make them useful tools when modulation of pharmacokinetic or pharmacodynamic effects is required.

Effect of antipsychotic drugs and selective dopaminergic antagonists on dopamine-induced facilitatory activity in prelimbic cortical pyramidal neurons. An in vitro study.

Intracellular recordings were obtained from 119 pyramidal neurons localized in prelimbic cortex, five in the dorsal cingulate cortex, one in the infralimbic cortex, one in the border of prelimbic and cingulate cortex and two in the border of prelimbic and infralimbic cortex. The passive membrane properties of these pyramidal neurons (i.e. resting membrane potential, input membrane resistance, shape of the tetrodotoxin-sensitive action potentials, spike frequency adaptation with a prominent postspike afterhyperpolarization, tetrodotoxin-sensitive inward rectification in the depolarizing direction and the absence of bursting) suggested that they resembled regular spiking or intrinsically bursting pyramidal neurons. Bath application of dopamine (EC50 of 1.8 microM) produced a reversible facilitatory effect on all 119 pyramidal neurons localized in the middle layer of the prelimbic cortex. No consistent change in membrane potential was detected during the application of dopamine. No effect of dopamine was noted on the nine pyramidal neurons that were not localized in the prelimbic cortex. The facilitatory effect of dopamine in prelimbic cortex was concentration dependently antagonized by haloperidol, risperidone, quetiapine, clozapine and by the selective D4 dopaminergic receptor antagonist L-745,870, but not by the selective D2/D3 dopaminergic receptor antagonist (-)-sulpiride. (+)-SCH 23390, which is a selective D1/D5 dopamine receptor antagonist, produced, similarly to dopamine, a facilitatory effect per se, and an additive effect when co-administered with dopamine. These results provide evidence that dopamine has a facilitatory effect specifically on pyramidal neurons localized in the middle layer of prelimbic cortex. Antipsychotic drugs and L-745,870 block this effect of dopamine.

Pharmacological characterization of AMPA-induced biting behaviour in mice.

The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. It is well established that excitatory amino acids, aspartate and glutamate, are involved in the spinal transmission of nociceptive information and in the development of hyperalgesia. In the present study, intrathecal (i.t.) administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), a structural analog of L-glutamate, produced a dose-dependent behavioural syndrome characterized by caudally directed biting in mice. We demonstrated that peripheral pre-administration of the AMPA receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX, 10-100 mg/kg s.c.) and 1-(4-aminophenyl)-3-methylcarbamoyl-4-methyl-3,4-dihydro-7, 8-methylene-dioxy-5H-2,3-benzo-diazepine-HCl (GYKI 53655, 3-10 mg/kg s.c.), and also of the NMDA receptor antagonist 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine maleate (MK 801, 0.3-1 mg/kg s.c.) reversed this effect. These findings suggest that the hyperalgesia induced by the i.t. injection of AMPA in mice involves the activation of both NMDA and non-NMDA excitatory amino acid receptor sites.

Effect of flibanserin (BIMT 17), fluoxetine, 8-OH-DPAT and buspirone on serotonin synthesis in rat brain.

In male rats, the effects of the administration of the novel serotonergic agent flibanserin on the synthesis of 5-HT were evaluated in the frontal cortex (FC), hippocampus (Hip) and brainstem (Br). The selective serotonergic uptake blocker, fluoxetine, and two serotonin1A (5-HT1A) agonists, 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) and buspirone, were used as reference compounds. The synthesis of 5-HT was assessed by measuring the accumulation of 5-hydroxytryptophan (5-HTP) after blockade of aromatic amino acid decarboxylase induced by m-hydroxybenzylhydrazine (NSD-1015), at 100 mg/kg i.p., 30 min before sacrifice. Flibanserin, 8-OH-DPAT and buspirone were given 15 min before NSD-1015, while fluoxetine 120 min before NSD-1015. In our experimental conditions, a different efficacy, expressed as percentage of maximal inhibition (Max) of 5-HTP accumulation, and a different potency, expressed in terms of minimal effective dose (MED), were observed in different brain areas with tested compounds. Flibanserin (1-32 mg/kg) decreased 5-HT synthesis with preferential activity in the FC, compared to the Hip and Br, both in terms of potency (MED=2 mg/kg in FC, 16 mg/kg in Hip and Br) and efficacy (Max=65% in FC, 44% in Hip and 29% in Br). Fluoxetine (1-30 mg/kg) decreased 5-HT synthesis with preferential activity in FC than in Hip and Br, only in terms of potency (MED=3 mg/kg in FC, 10 mg/kg in Hip and Br), this result being similar to that observed for flibanserin. In contrast, it showed greater efficacy both in FC and Hip (Max about 60%), than in Br (Max=49%). On the contrary, 8-OH-DPAT (0.3-3 mg/kg) decreased 5-HT synthesis with the same potency in all brain regions (MED=3 mg/kg) and showed the greatest efficacy in FC than in Hip and Br (Max=56% in FC, 49% in Hip and 40% in Br). Furthermore, buspirone (3-30 mg/kg), while inhibiting 5-HTP accumulation in all areas with the same efficacy (Max about 30%), seemed to have higher potency in Br than in FC and Hip (MED=3 mg/kg in Br, 10 mg/kg in FC and Hip). The results in terms of regional differences are discussed.

Cholinergic control of gastric acid secretion.

In the perfused stomach preparation of the anaesthetized rat the cholinergic agonists acetylcholine (ACh) and bethanechol stimulated gastric acid secretion. Both agonists produced similar maximal acid output (70 mumols/15 min) when infused intravenously. However, bethanechol was more potent, eliciting half maximal stimulation at 1.98 mumols/kg/h, while the corresponding dose of ACh was 10.95 mumols/kg/h. Secretory responses to either agonist were antagonized in a dose related fashion by blockade of muscarinic receptors with atropine. In contrast, inhibition of nicotinic receptors with hexamethonium produced a striking potentiation of ACh stimulated secretion whilst the bethanechol elicited secretion remained unaffected. In the presence of full nicotinic receptor blockade the ACh response curve was shifted to the left sixfold, half maximal stimulation being produced at 1.79 mumols/kg/h. Cimetidine partially inhibited the secretory responses elicited by either ACh or bethanechol while blockade of adrenoceptors (alpha and beta) did not affect acid output induced by cholinergic agonists. Secretion elicited by ACh is interpreted as being the composite effect of pro-secretory action and an inhibitory mechanism due to the activation of nicotinic receptors. Hexamethonium, through nicotinic receptor blockade, inhibits the restricting mechanism and thus reveals the full stimulatory action of ACh.

Immunologic reconstitution by interleukin-2: facts and open questions.

Interleukin-2 (IL-2), one of the most potent immunoregulatory and inflammatory cytokines, is being tested in phase III clinical trials in order to demonstrate its efficacy in combination with current antiviral agents in preventing the occurrence of opportunistic infections and death in individuals infected by the human immunodeficiency virus (HIV). In the meantime, its capacity to boost the number of CD4+ T cells in peripheral blood has been confirmed by a number of individual phase I/II trials conducted in different countries by independent investigators. In the face of this remarkable result, little is known of the effects exerted by this cytokine once administered to infected individuals in terms of its impact on different immunologic functions. The recent acquisitions on the important role played by latently infected cells in in vivo infection in reinitiating HIV replication and cytopathicity once antiviral therapy is suspended or becomes suboptimal, has shed new light on the possibility of utilizing immunologic strategies, including IL-2, for eradicating the virus from latent reservoirs. Results from a clinical trial conducted at our Institute indicate a decrease in lymphocyte-associated HIV DNA after IL-2 administration, supporting this hypothesis.

Effect of DAU 6215, a novel 5-HT3 receptor antagonist, on scopolamine-induced amnesia in the rat in a spatial learning task.

The effects of different doses (1, 10, 30, and 100 micrograms/kg, IP) of a new 5-hydroxytryptamine3 (5-HT3) receptor antagonist, 3-alpha-tropanyl)1H-benzimidazolone-3-carboxamide chloride (DAU 6215), on memory and performance deficits induced by SC 0.2 mg/kg scopolamine were assessed in the Morris water maze task. No effect was observed on the performance of rats treated with DAU 6215 alone. The doses of 10 and 30 micrograms/kg DAU 6215 attenuated these scopolamine-induced behavioral deficits.