Bach1, among the genes encoded on chromosome 21, is a transcription repressor, which binds to antioxidant response elements of DNA thus inhibiting the transcription of specific genes involved in the ...cell stress response including heme oxygenase-1 (HO-1). HO-1 and its partner, biliverdin reductase-A (BVR-A), are upregulated in response to oxidative stress in order to protect cells against further damage. Since oxidative stress is an early event in Down syndrome (DS) and might contribute to the development of multiple deleterious DS phenotypes, including Alzheimer's disease (AD) pathology, we investigated the status of the Bach1/HO-1/BVR-A axis in DS and its possible implications for the development of AD. In the present study, we showed increased total Bach1 protein levels in the brain of all DS cases coupled with reduced induction of brain HO-1. Furthermore, increased oxidative stress could, on one hand, overcome the inhibitory effects of Bach1 and, on the other hand, promote BVR-A impairment. Our data show that the development of AD in DS subjects is characterized by (i) increased Bach1 total and poly-ubiquitination; (ii) increased HO-1 protein levels; and (iii) increased nitration of BVR-A followed by reduced activity. To corroborate our findings, we analyzed Bach1, HO-1, and BVR-A status in the Ts65Dn mouse model at 3 (young) and 15 (old) months of age. The above data support the hypothesis that the dysregulation of HO-1/BVR-A system contributes to the early increase of oxidative stress in DS and provide potential mechanistic paths involved in the neurodegenerative process and AD development.
In children affected by malignancies and/or who received hematopoietic stem cell transplantation (HSCT), acute kidney injury (AKI) may occur causing a high mortality rate, despite the implementation ...of renal replacement therapy (RRT). We performed a nationwide, multicenter, retrospective, observational cohort study including consecutive patients between January 2010 and December 2019. One hundred and fourteen episodes of AKI requiring RRT coming from nine different Italian centers were included. The overall mortality rate was 61.4%. At the 3-month follow-up, the mortality rate was 47.4%. The mortality rate was higher in transplanted patients than those receiving chemotherapy. In particular, HSCT (p = 0.048) and invasive mechanical ventilation (p = 0.040) were significantly associated with death at three months after the end of dialysis in the multivariate analysis. Pediatric patients affected by malignancies complicated by AKI requiring RRT have a high mortality. The main factors associated to death are respiratory failure and having received HSCT.
In the setting of solitary pulmonary nodules (SPNs), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (
F-FDG-PET/CT) is considered a useful non-invasive diagnostic ...tool though false positive (FP) and false negative (FN) results affects accuracy due to different conditions, such as inflammatory diseases or low-uptake neoplasms. Aim of this study is to evaluate overall diagnostic performance of
F-FDG-PET/CT for malignant pulmonary nodules.
A computerized research, including published articles from 2012 and 2017, was carried out.
F-FDG-PET/CT overall sensitivity (Se), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), diagnostic index and odds ratio were pooled. No selection-bias were found according to asymmetry test.
A total of twelve studies were included in the meta-analysis. The pooled Se, Spe, PLR, NLR, PPV, NPV and accuracy index (AI) with relative 95% confidence intervals (CI) were 0.819 (95% CI: 0.794-0.843), 0.624 (95% CI: 0.582-0.665), 2.190 (95% CI: 1.950-2.440), 0.290 (95% CI: 0.250-0.330), 0.802 (95% CI: 0.783-0.819), 0.652 (95% CI: 0.618-0.684) and 0.649 (95% CI: 0.625-0.673), respectively. The diagnostic odds ratio (DOR) was 7.049 with a relative 95% CI between 5.550 and 8.944.
The results suggest
F-FDG-PET/CT has good diagnostic accuracy in SPNs evaluation; but, it should not be considered as a discriminatory test rather than a method to be included in a clinical and diagnostic pathway.
Acute peripheral trauma is a controversial risk factor for idiopathic dystonia.
We retrospectively analyzed data from the Italian Dystonia Registry regarding the occurrence of acute peripheral trauma ...severe enough to require medical attention in 1382 patients with adult-onset idiopathic dystonia and 200 patients with acquired adult-onset dystonia.
Patients with idiopathic and acquired dystonia showed a similar burden of peripheral trauma in terms of the number of patients who experienced trauma (115/1382 vs. 12/200, p = 0.3) and the overall number of injuries (145 for the 1382 idiopathic patients and 14 for the 200 patients with secondary dystonia, p = 0.2). Most traumas occurred before the onset of idiopathic or secondary dystonia but only a minority of such injuries (14 in the idiopathic group, 2 in the acquired group, p = 0.6) affected the same body part as that affected by dystonia. In the idiopathic group, the elapsed time between trauma and dystonia onset was 8.1 ± 9.2 years; only six of the 145 traumas (4.1%) experienced by 5/1382 idiopathic patients (0.36%) occurred one year or less before dystonia onset; in the acquired dystonia group, the two patients experienced prior trauma to the dystonic body part 5 and 6 years before dystonia development.
Our data suggest that the contribution of peripheral acute trauma to idiopathic dystonia is negligible, if anything, and likely involves only a small subset of patients.
•Acute peripheral trauma is a controversial risk factor for idiopathic dystonia.•The role of trauma in idiopathic dystonia has relevant implications.•The contribution of peripheral acute trauma to idiopathic dystonia is negligible.
Abstract
$$\mathrm{NdNi}_5$$
NdNi
5
is an intermetallic compound with a bulk Curie temperature (
$$T_{\mathrm{Curie}}$$
T
Curie
) of 6–13 K. While existing studies have focused on
$$\mathrm{NdNi}_5$$
...NdNi
5
crystals, amorphous thin-films of
$$\mathrm{NdNi}_5$$
NdNi
5
are potentially important since they would be magnetically soft without magnetocrystalline anisotropy, meaning that small external magnetic fields could reverse the direction of their magnetization. Here, we report
$$\mathrm{NdNi}_5$$
NdNi
5
thin-films with a thickness in the 5–200 nm range, deposited by DC magnetron sputtering onto Si(100). Films are amorphous with a weak temperature-dependent resistivity with values ranging between 150 and 300
$$\upmu \Omega$$
μ
Ω
cm. By means of noise spectroscopy, by analyzing the time-dependence of fluctuation-induced voltages, it is found that at low temperatures the resistance fluctuations are due to the Kondo effect. Volume magnetometry indicates
$$T_{\mathrm{Curie}} = 70$$
T
Curie
=
70
K with a magnetic coercive field of 30 mT at 5 K for a 125-nm-thick film. The results are promising for the development of Ferromagnet(F)/Superconductor(S)/Ferromagnet(F) pseudo spin-valve devices based on amorphous
$$\mathrm{NdNi}_5$$
NdNi
5
thin films.
We describe the incidence and characteristics of infections in children with severe congenital neutropenia (SCN), autoimmune neutropenia (AN) and idiopathic neutropenia (IN). Data extracted from the ...Italian Neutropenia Registry on 73 patients with 108 episodes of infections were collected from 2000 to 2009. All SCN patients with SCN and one third of AN and IN experienced at least 1 infectious episode, equating to 5.7 infections/patient in SCN and approximately 0.6 in AN and IN. The rate of infections before diagnosis of neutropenia was 6.35/1000 patient-days at risk in SCN, 0.48 in AN and 0.71 in IN (P < 0.001) and significantly decreased after diagnosis. Skin and subcutaneous abscesses and cellulitis were the most frequent types of infection encountered, followed by pneumonia. Infections are an important clinical issue in the management of neutropenic patients, even in those considered at lower risk.
Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven ...approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to "a priori" classifications and clinical overlapping.
Data were obtained by the Italian Registry of Functional Motor Disorders. Patients identified with multiple or "combined" FMDs by standardized clinical assessments were selected to be analyzed. Non-hierarchical cluster analysis was performed based on FMDs phenomenology. Multivariate analysis was then performed after adjustment for principal confounding variables.
From a study population of
= 410 subjects with FMDs, we selected
= 188 subjects women: 133 (70.7%); age: 47.9 ± 14.4 years; disease duration: 6.4 ± 7.7 years presenting combined FMDs to be analyzed. Based on motor phenotype, two independent clusters were identified: Cluster C1 (
= 82; 43.6%) and Cluster C2 (
= 106; 56.4%). Cluster C1 was characterized by functional tremor plus parkinsonism as the main clinical phenotype. Cluster C2 mainly included subjects with functional weakness. Cluster C1 included older subjects suffering from anxiety who were more treated with botulinum toxin and antiepileptics. Cluster C2 included younger subjects referring to different associated symptoms, such as pain, headache, and visual disturbances, who were more treated with antidepressants.
Using a data-driven approach of clinical data from the Italian registry, we differentiated clinical subtypes among combined FMDs to be validated by prospective studies.
The Palazzolo Formation calcarenite, commonly known as “Pietra di Noto”, has been widely used in the late Baroque monuments of the Val di Noto area. In this work, two different lithofacies have been ...identified through a minero-petrographic and physical–mechanical characterisation of the Noto stone samples. These latter have been taken out from three quarries, two of which are located near to Noto Antica (Porcari and Leone), and one next to Palazzolo Acreide (Camelio). Samples from Camelio have a white-cream colour and a higher sparry cement abundance than those from the Porcari and Leone quarries, which display a yellowish colour, a minor resistance and a more heterogeneous texture due to the presence of bioturbation (trace of fossils). The greater compactness of samples from Camelio compared to the other two is related to their higher ultrasonic velocities, better mechanical properties and reduced capability to absorb water by capillarity and total immersion which are related to the textural features. The existence of two lithofacies better explains the heterogeneity of degradation forms (chiefly consisting of differential degradation, alveolization, detachment and chromatic alteration) that can be observed on the monuments built in these stone materials. The main causes of deterioration have been related to bioturbation, as well as to the occurrence of expandable clay minerals (smectite) and to salt crystallization. The presence of bioturbation also affects the mechanical characteristics of these stones.
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