Episodic ataxia and severe infantile phenotype in spinocerebellar ataxia type 14: expansion of the phenotype and novel mutations

Journal of Neurology - Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurological disorder characterized by slowly progressive cerebellar ataxia. SCA14 is caused by mutations in...     

Clinical features and cognitive sequelae in COVID-19: a retrospective study on N=152 patients

Neurological Sciences - The novel human coronavirus (SARS-CoV-2) shows neurotropism and systemically affects the central nervous system (CNS). Cognitive deficits have been indeed reported as both...     

Episodic long-term memory in post-infectious SARS-CoV-2 patients

Neurological Sciences - Episodic long-term memory (LTM) difficulties/deficits are frequent in COVID-19-recovered patients and negatively impact on prognosis and outcome. However, little is known...     

Posterior reversible encephalopathy syndrome after kidney transplantation in pediatric recipients: Two cases

PRES is a neuro‐clinical and radiological syndrome that can result as a consequence of several different conditions including hypertension, fluid overload, and immunosuppressive treatment. Herein, we report two children who received kidney and combined liver–kidney transplantation as treatment for renal hypodysplasia associated with bilateral vesico‐ureteral reflux and methylmalonic acidemia, respectively. Early after surgery (seven and 10 days), both patients presented with hypertension and seizures. The patients' immunosuppressive regimen included steroid and calcineurin inhibitors (tacrolimus and cyclosporine, respectively) and basiliximab and one with anti‐IL2 receptor. In both cases, the imaging strongly supported the diagnosis of PRES. In details, the CT scan showed hypodensities in the posterior areas of the brain, and brain MRI demonstrated parieto‐occipital alterations indicative of vasogenic edema. Treatment with calcineurin inhibitors was temporally discontinued and restarted at lower dosage; arterial hypertension was treated with Ca‐channel blockers. Both children fully recovered without any neurological sequels. In conclusion, in children undergoing solid organ transplantation, who develop neurological symptoms PRES, should be carefully considered in the differential diagnosis and once the diagnosis is ruled in, we recommend strict arterial blood pressure control and adjustment or withholding of calcineurin inhibitor therapy should be considered based upon blood levels.     

Mutagenic and DNA repair activity in traffic policemen: a case-crossover study

Background

Emissions from vehicles are composed of heterogeneous mixtures of hazardous substances; several pollutants such as Polycyclic Aromatic Hydrocarbons (PAHs) are amongst the most dangerous substances detected in urban monitoring. A cohort of traffic policemen usually occupationally exposed to PAHs present in the urban environment were examined in order to assess the mutagenicity and DNA capacity repair.

Methods

Seventy-two urban traffic policemen working in Catania’s metropolitan area were enrolled in the study. Two spot urine samples were collected from each subject during the whole working cycle as follows: sample 1 (S1), pre-shift on day 1; sample 2 (S2) post-shift on day 6. 1-hydroxypyrene (1-OHP) was measured to serve as an indirect exposure indicator. Urinary mutagenic activity was assessed through the plate incorporation pre-incubation technique with S9, using YG1024 Salmonella typhimurium strain over-sensitive to PAH metabolite. Concentrations of urinary 8-oxodG were measured using liquid chromatography tandem mass spectrometry.

Results

As regards the exposure to PAHs, results highlighted a statistically significant difference (p?<?0.001) between pre-shift on day 1 and post-shift on day 6 levels. Mutagenic activity was detected in 38 (66%) workers on S1 and in 47 (81%) on S2. Also 8-oxodG analysis showed a statistically significant difference between S1 and S2 sampling.

Conclusions

This study demonstrated that occupational exposure to pollutants from traffic emission, assessed via 1-OHP measurements in urine, may lead to DNA repair and mutagenic activity, in line with other studies.

     

Nanoparticulate vaccine inhibits tumor growth via improved T cell recruitment into melanoma and huHER2 breast cancer

Nanoparticulate vaccines are promising tools to overcome cancer immune evasion. However, a deeper understanding on nanoparticle–immune cell interactions and treatments regime is required for optimal efficacy. We provide a comprehensive study of treatment schedules and mode of antigen-association to nanovaccines on the modulation of T cell immunity in vivo, under steady-state and tumor-bearing mice. The coordinated delivery of antigen and two adjuvants (Monophosphoryl lipid A, oligodeoxynucleotide cytosine-phosphate-guanine motifs (CpG)) by nanoparticles was crucial for dendritic cell activation. A single vaccination dictated a 3-fold increase on cytotoxic memory-T cells and raised antigen-specific immune responses against B16.M05 melanoma. It generated at least a 5-fold increase on IFN-γ cytokine production, and presented over 50% higher lymphocyte count in the tumor microenvironment, compared to the control. The number of lymphocytes at the tumor site doubled with triple immunization. This lymphocyte infiltration pattern was confirmed in mammary huHER2 carcinoma, with significant tumor reduction.     

Multiple sclerosis in patients with hereditary spastic paraplegia: a case report and systematic review

Neurological Sciences - An increasing number of cases of comorbid hereditary spastic paraplegia (HSP) and multiple sclerosis (MS) have been described. We report a patient with the SPG3A form of HSP...     

Marek's disease viruses circulating in commercial poultry in Italy in the years 2015–2018 are closely related by their meq gene phylogeny

Marek's disease (MD) is a lymphoproliferative disease important to the poultry industry worldwide; it is caused by Gallid alphaherpesvirus 2 (GaHV‐2). The virulence of GaHV‐2 isolates has shifted over the years from mild to virulent, very virulent and very virulent +. Nowadays the disease is controlled by vaccination, but field strains of increased virulence are emerging worldwide. Economic losses due to MD are mostly associated with its acute form, characterized by visceral lymphomas. The present study aimed to molecularly classify a group of 13 GaHV‐2 strains detected in vaccinated Italian commercial chicken flocks during acute MD outbreaks, and to scrutinize the ability of predicting GaHV‐2 virulence, according to the meq gene sequence. The full‐length meq genes were amplified, and the obtained amino acid (aa) sequences were analysed, focusing mainly on the number of stretches of four proline molecules (PPPP) within the transactivation domain. Phylogenetic analysis was carried out with the Maximum Likelihood method using the obtained aa sequences, and the sequences of Italian strains detected in backyard flocks and of selected strains retrieved from GenBank. All the analysed strains showed 100% sequence identity in the meq gene, which encodes a Meq protein of 339 aa. The Meq protein includes four PPPP motifs in the transactivation domain and an interruption of a PPPP motif due to a proline‐to‐serine substitution at position 218. These features are typically encountered in highly virulent isolates. Phylogenetic analysis revealed that the analysed strains belonged to a cluster that includes high‐virulence GaHV‐2 strains detected in Italian backyard flocks and a hypervirulent Polish strain. Our results support the hypothesis that the virulence of field isolates can be suggested by meq aa sequence analysis.     

Exercise Performance of Chronic Heart Failure Patients in the Early Period of Support by an Axial‐Flow Left Ventricular Assist Device as Destination Therapy

Axial‐flow left ventricular assist devices (LVADs) are increasingly used as destination therapy in end‐stage chronic heart failure (CHF), as they improve survival and quality of life. Their effect on exercise tolerance in the early phase after implantation is still unclear. The aim of this study was to evaluate the effect of LVADs on the exercise capacity of a group of CHF patients within 2 months after initiation of circulatory support. Cardiopulmonary exercise test data were collected for 26 consecutive LVAD‐implanted CHF patients within 2 months of initiation of assistance; the reference group consisted of 30 CHF patients not supported by LVAD who were evaluated after an episode of acute heart failure. Both LVAD and reference groups showed poor physical performance; LVAD patients achieved lower workload (LVAD: 36.3 ± 9.0 W, reference: 56.6 ± 18.2 W, P < 0.001) but reached a similar peak oxygen uptake (peak VO₂; LVAD: 12.5 ± 3.0 mL/kg/min, reference: 13.6 ± 2.9 mL/kg/min, P = ns) and similar percentages of predicted peak VO₂ (LVAD: 48.8 ± 13.9%, reference: 54.2 ± 15.3%, P = ns). While the values of the O₂ uptake efficiency slope were 12% poorer in LVAD patients than in reference patients (1124.2 ± 226.3 vs. 1280.2 ± 391.1; P = ns), the kinetics of VO₂ recovery after exercise were slightly better in LVAD patients (LVAD: 212.5 ± 62.5, reference: 261.1 ± 80.2 sec, P < 0.05). In the first 2 months after initiation of circulatory support, axial‐flow LVAD patients are able to sustain a low‐intensity workload; though some cardiopulmonary exercise test parameters suggest persistence of a marked physical deconditioning, their cardiorespiratory performance is similar to that of less compromised CHF patients, possibly due to positive hemodynamic effects beginning to be produced by the assist device.