ZnO Nanostructured Thin Films via Supersonic Plasma Jet Deposition

Zinc Oxide nanostructured thin films were grown by a novel plasma assisted vapour deposition method, which aims to combine the versatility of deposition processes that are mediated by plasma with the capability to control particles diffusion and nucleation. For this purpose, the proposed approach spatially separates into two different vacuum chambers the creation of zinc oxide from a metalorganic precursor from the actual film growth, thanks to the extraction of a supersonic jet of plasma seeded by the precursor fragments. The characterization of the reactor in different plasma conditions has been carried out by means of optical emission spectroscopy (OES). ZnO films with different degrees of purity, thickness uniformity, as well as different morphologies can be obtained varying the deposition parameters. The samples profiles have been collected in order to evaluate deposition rates and films uniformity. The as-prepared as well as annealed thin films were characterized by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) to evaluate their chemical composition and purity. According to Raman analyses, the annealed samples are high-purity wurtzite-type crystalline zinc oxide films. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) confirm a surface morphology characterized by columnar structures

Risk factors for long-stay in an Italian acute psychiatric ward: a 7-year retrospective analysis

Background: In West during the last decades, the phenomenon of "bed blockers" has been more frequently investigated, probably because of increasing economic constraints in the management of public health. According to most authors, the lack of rehabilitation facilities, organizational problems within the hospital, the long wait for medical consultations and diagnostic procedures would be the main causes of "delayed discharge". Early studies were carried out in long-term care, rehabilitation and post-acute geriatric wards. In Psychiatry, the few studies on this topic highlighted a wide range of causes, including both patient conditions and organizational health system problems. In Italy, the problem of psychiatric delayed discharges has become more pressing after the 180 Law, which established the closure of all psychiatric hospitals and implemented psychiatric wards inside General Hospitals to admit only 15 acute patients for a very short period. Purposes: To highlight the phenomenon of long-stay in an acute psychiatric ward and to relate it to demographic, clinical and organizational variables. Methods: The survey was conducted in the 15-bed public psychiatric ward of Modena (Italy). All admissions were retrospectively collected from the database of the Department from 1 January 2005 to 31 December 2011 (3981 hospitalizations with an average stay of 12.49 days). Demographic data, clinical variables, inpatient care problems, discharge programs were statistically related to the duration of admissions (survival analysis: log-rank test, Kaplan-Meier curves). The 3981 hospitalizations were divided into two groups according to the 90° percentile of duration: < 27 days (n=3575) and ≥ 27 days (n=406) and the variables of the two groups were compared (multiple logistic regression). Secondary analysis was conducted on the subgroup of the longest hospitalizations further divided into two groups according to the 90° (from 27 days to < 36 days) and 95° percentile (≥36 days), in order to find out variables related (survival analysis: log-rank test; multiple logistic regression test). Results: The longest hospitalizations (≥27 days) represent 11% of all admissions during the observation period. When all variables are compared to the duration of hospitalizations, most of them are statistically significantly related to the length of hospitalizations, but, when statistical analysis was focused on the comparison between the two groups of the longest hospitalizations, a smaller number of variables (“gender”, “age”, “rehabilitative programs”, “extra-psychiatric clinical activities”, “pharmacotherapy” and “aggressiveness of patient”) were identified by survival analysis as statistically significant correlates of long-stay (log-rank test), whereas only “female gender” and aggressiveness pf patient” were the variables statistically significantly related to the length of hospitalizations evidenced by multivariate logistic regression analysis. Conclusions: Our results suggest that a wide range of factors may be responsible for the delayed discharges in psychiatry as most previous studies have already shown. However, only few factors were related to the longest duration of hospitalization and, among these, aggressiveness was the only one statistically significant correlate to long-stay in all statistic tests. This data confirms the clinical observation that aggressive behaviour can be sufficient by itself to explain the difficulty of discharging

Practical Guidance for the Use of Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia

Schizophrenia is a severe mental illness causing a high degree of disability. First-and second-generation antipsychotics (FGAs and SGAs) represent key resources for its acute and long-term management. Since a poor adherence to oral treatments may negatively impact the course of the disorder, long-acting injectable antipsychotics (LAIs) are often used to reduce clinical relapses. Notwithstanding their potential beneficial features, LAIs use in clinical practice remains somewhat hampered by the limited amount of relevant systematic information. This review thus aims at providing a clinical, practical guidance for the use of LAIs in the treatment of schizophrenia. We synthetized main information on indications, dosage, and administration of LAIs approved by the US Food and Drug Administration (FDA) and/or in EU countries, as well as evidence from the most recent systematic reviews and meta-analyses. Currently available information, though heterogeneous, shows that LAIs can prevent relapses and rehospitalizations, improving clinical outcomes and favouring sustained remission among people with schizophrenia. The use of SGA LAIs is supported by more robust evidence than FGA LAIs. Along with their positive impact on the prevention of treatment discontinuation, some LAIs might also enhance individual global functioning and quality of life, without additional adverse events or health-care costs, as compared with oral antipsychotics. Although which LAIs can be considered a first-choice option, as well as their superiority over oral antipsychotics, remain unclear issues, this review offers a comprehensive overview of information available on the use of LAIs for people with schizophrenia, providing clinicians with practical guidance in terms of efficacy and acceptability of single agents. Literature gaps and future research needs are also described

Effectiveness of combination of Mini-and Microsatellite loci to sub-type Mycobacterium avium subsp. paratuberculosis Italian type C isolates

<p>Abstract</p> <p>Background</p> <p><it>Mycobacterium avium </it>subsp. <it>paratuberculosis </it>(Map) is the etiological agent of paratuberculosis. The aim of our study was to combine Mini-and Microsatellite loci analysis in order to explore the effectiveness of this sub-typing method in a group of Map isolates. For this purpose, 84 Italian Type C Map isolates, each from a different cattle herd, were submitted to MIRU-Variable-Number Tandem-Repeats (VNTRs) typing and Short Sequence repeats (SSRs) sequencing. Moreover, the method was used to analyse the variability inside 10 herds (from three to 50 isolates per herd).</p> <p>Results</p> <p>The molecular sub-typing, carried out using three SSR and 10 MIRU-VNTR loci, differentiated the 84 isolates into 33 clusters, reaching a Simpson's Discriminatory Index (SID) value of 0.952 (0.933 to 0.972, 95% confidence intervals). Among all considered loci, six (SSR2, MIRU2, SSR1, SSR8, VNTR3527 and VNTR1067) showed relevant allelic variability. Thirty-eight% of the isolates were clustered into four genotypes, differing from each other for the SSR2 locus. The other isolates, characterised by differences in two or more loci, were spread among the rest of the clusters. The intra-herd analysis revealed more than one genotype in most herds with a similar distribution of clusters.</p> <p>Conclusions</p> <p>Our results revealed the advantage of using both Mini-and Microsatellite approaches for successfully discriminating among Map Type C isolates from the same geographic area, host species and herd. These data suggest that the combination of loci here proposed could be a useful molecular tool for regional epidemiological studies.</p

SerpinA1 levels in amyotrophic lateral sclerosis patients: An exploratory study

Background: SerpinA1, a serine protease inhibitor, is involved in the modulation of microglial-mediated inflammation in neurodegenerative diseases. We explored SerpinA1 levels in cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients to understand its potential role in the pathogenesis of the disease. Methods: SerpinA1, neurofilament light (NfL) and heavy (NfH) chain, and chitinase-3-like protein-1 (CHI3L1) were determined in CSF and serum of ALS patients (n = 110) and healthy controls (n = 10) (automated next-generation ELISA), and correlated with clinical parameters, after identifying three classes of progressors (fast, intermediate, slow). Biomarker levels were analyzed for diagnostic power and association with progression and survival. Results: SerpinA1serum was significantly decreased in ALS (median: 1032 μg/mL) compared with controls (1343 μg/mL) (p = 0.02). SerpinA1CSF was elevated only in fast progressors (8.6 μg/mL) compared with slow (4.43 μg/mL, p = 0.01) and intermediate (4.42 μg/mL, p = 0.03) progressors. Moreover, SerpinA1CSF correlated with neurofilament and CHI3L1 levels in CSF. Contrarily to SerpinA1CSF , neurofilament and CHI3L1 concentrations in CSF correlated with measures of disease progression in ALS, while SerpinA1serum mildly related with time to generalization (rho = 0.20, p = 0.04). In multivariate analysis, the ratio between serum and CSF SerpinA1 (SerpinA1 ratio) and NfHCSF were independently associated with survival. Conclusions: Higher SerpinA1CSF levels are found in fast progressors, suggesting SerpinA1 is a component of the neuroinflammatory mechanisms acting upon fast-progressing forms of ALS. Both neurofilaments or CHI3L1CSF levels outperformed SerpinA1 at predicting disease progression rate in our cohort, and so the prognostic value of SerpinA1 alone as a measure remains inconclusive

Clinical trajectories of individuals with severe mental illness continuing and discontinuing long-acting antipsychotics: a one-year mirror-image analysis from the STAR Network Depot study

Evidence on long-acting antipsychotics (LAIs) in unselected populations with severe mental illness is scant. In this mirror-image study, we compared multiple clinical outcomes 1 year before and after a first LAI prescription in adults with severe mental illness, describing clinical trajectories of LAI continuers and discontinuers. We compared LAI continuers and discontinuers through Mann–Whitney U test, Kaplan–Meier survival curves, regression for interval-censored data, and a maximum-likelihood mixed-model with individual random-effect and time as predictor. Of the 261 participants analyzed, 71.3% had schizophrenia-spectrum disorders, and 29.5% discontinued the LAI before 1 year. At baseline, LAI discontinuers had a shorter illness duration, lower attitude and adherence scores. The mirror-image analysis showed reduced hospital admissions only for LAI continuers. Over time, continuers spent less days hospitalized, but had more adverse events and more antipsychotics prescribed, with higher overall doses. In conclusion, this study shows that LAIs might be beneficial in unselected patient populations, provided that adherence is maintained. LAI continuers spent less time hospitalized, but received more antipsychotics and suffered from more cumulative adverse events over time. Therefore, the choice of initiating and maintaining a LAI should be carefully weighed on a case-by-case basis

Cabozantinib in neuroendocrine tumours: tackling drug activity and resistance mechanisms

Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures, we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through fluorescence-activated cell sorting analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the antiapoptotic myeloid cell leukemia 1 protein under CAB exposure, as a putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other tyrosine kinase inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines

The chaperone HSPB8 reduces the accumulation of truncated TDP-43 species in cells and protects against TDP-43-mediated toxicity

Aggregation of TAR-DNA-binding protein 43 (TDP-43) and of its fragments TDP-25 and TDP-35 occurs in amyotrophic lateral sclerosis (ALS). TDP-25 and TDP-35 act as seeds for TDP-43 aggregation, altering its function and exerting toxicity. Thus, inhibition of TDP-25 and TDP-35 aggregation and promotion of their degradation may protect against cellular damage. Upregulation of HSPB8 is one possible approach for this purpose, since this chaperone promotes the clearance of an ALS associated fragments of TDP-43 and is upregulated in the surviving motor neurones of transgenic ALS mice and human patients. We report that overexpression of HSPB8 in immortalized motor neurones decreased the accumulation of TDP-25 and TDP-35 and that protection against mislocalized/truncated TDP-43 was observed for HSPB8 in Drosophila melanogaster. Overexpression of HSP67Bc, the functional ortholog of human HSPB8, suppressed the eye degeneration caused by the cytoplasmic accumulation of a TDP-43 variant with a mutation in the nuclear localization signal (TDP-43-NLS). TDP-43-NLS accumulation in retinal cells was counteracted by HSP67Bc overexpression. According with this finding, downregulation of HSP67Bc increased eye degeneration, an effect that is consistent with the accumulation of high molecular weight TDP-43 species and ubiquitinated proteins. Moreover, we report a novel Drosophila model expressing TDP-35, and show that while TDP-43 and TDP-25 expression in the fly eyes causes a mild degeneration, TDP-35 expression leads to severe neurodegeneration as revealed by pupae lethality; the latter effect could be rescued by HSP67Bc overexpression. Collectively, our data demonstrate that HSPB8 upregulation mitigates TDP-43 fragment mediated toxicity, in mammalian neuronal cells and flies

Evidence of Common Isolates of Streptococcus agalactiae in Bovines and Humans in Emilia Romagna Region (Northern Italy)

Streptococcus agalactiae (group B Streptococcus, GBS) is one of the most important agents of bovine mastitis and causes remarkable direct and indirect economic losses to the livestock sector. Moreover, this species can cause severe human diseases in susceptible individuals. To investigate the zoonotic potential of S. agalactiae, 203 sympatric isolates from both humans and cattle, isolated in the same time frame (2018) and in the same geographic area (Emilia Romagna region, Northern Italy), were characterized by molecular capsular typing (MCT), pilus island typing (PI), and multi-locus sequence typing (MLST). In addition, antibiotic-resistant phenotypes were investigated. The distribution of the allelic profiles obtained by combining the three genotyping methods (MCT-PI-MLST) resulted in 64 possible genotypes, with greater genetic variability among the human compared to the bovine isolates. Although the combined methods had a high discriminatory power (&gt;96,2%), five genotypes were observed in both species (20,9% of the total isolates). Furthermore, some of these strains shared the same antibiotic resistance profiles. The finding of human and bovine isolates with common genotypes and antibiotic resistance profiles supports the hypothesis of interspecies transmission of S. agalactiae between bovines and humans