Alternative splicing expands the clinical spectrum of NDUFS6-related mitochondrial disorders.

Purpose: We describe 3 families with Charcot-Marie-Tooth neuropathy (CMT), harboring a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant previously linked to fatal Leigh syndrome.

Phenotypic detection of clinical isolates of Haemophilus influenzae with altered penicillin-binding protein 3.

The aims of this study were to determine the correlation of mutations in the ftsI gene (coding for PBP3) of Haemophilus influenzae with aminopenicillin resistance and to evaluate the 2017 European Committee for Antibiotic Susceptibility Testing (EUCAST) guidelines for clinical categorization of ampicillin, amoxicillin, and amoxicillin-clavulanate for strains with mutated PBP3 conferring resistance (rPBP3). A panel of 91 H. influenzae isolates was genetically characterized by sequencing of the fstI gene.

Overproduction of Outer Membrane Protein A by Acinetobacter baumannii as a Risk Factor for Nosocomial Pneumonia, Bacteremia, and Mortality Rate Increase.

Background: Outer membrane protein A (OmpA) is a porin involved in Acinetobacter baumannii pathogenesis. However, OmpA clinical implication in hospital-acquired infections remains unknown. We aimed to determine whether OmpA overproduction was a risk factor associated with pneumonia, bacteremia, and mortality.

Genomic Evolution of Two Acinetobacter baumannii Clinical Strains from ST-2 Clones Isolated in 2000 and 2010 (ST-2_clon_2000 and ST-2_clon_2010).

Acinetobacter baumannii is a successful nosocomial pathogen due to its ability to persist in hospital environments by acquiring mobile elements such as transposons, plasmids, and phages. In this study, we compared two genomes of A. baumannii clinical strains isolated in 2000 (ST-2_clon_2000) and 2010 (ST-2_clon_2010) from GenBank project PRJNA308422.

Mapping the HLA diversity of the Iberian Peninsula.

The polymorphism of HLA genes can be used to reconstruct human peopling history. However, this huge diversity impairs successful matching in stem cell transplantation, a situation which has led to the recruitment of millions of donors worldwide. In parallel to the increase of recruitment, registries are progressively relying on information from population genetics to optimize their donor pools in terms of HLA variability.

Lewy- and Alzheimer-type pathologies in midbrain and cerebellum across the Lewy body disorders spectrum.

Aims: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are pathologically characterized by intraneuronal α-synuclein aggregates and thus labelled as Lewy body disorders (LBD). Conjoint cortical α-synuclein, tau and amyloid-β (Aβ), and striatal Aβ aggregates, have been related to dementia in LBD. Interpretation of current and emerging in vivo molecular imaging of these pathologies will need of precise knowledge of their topographic distribution.

Multimodal MRI assessment of nigro-striatal pathway in multiple system atrophy and Parkinson disease.

Background: Parkinson's disease (PD) and multiple system atrophy (MSA) are two neurodegenerative alpha-synucleinopathies characterized by severe impairment of the nigro-striatal pathway. Based on T1-, T2*-, and diffusion-weighted magnetic resonance imaging (MRI), macro-structural and micro-structural abnormalities in these diseases can be detected.

Objective: This study was undertaken to compare the nigro-striatal changes that occur in patients with PD with those in patients with both variants of MSA (the parkinsonian variant, MSA-P, and the cerebellar variant, MSA-C), and to explore correlations between different MRI parameters and clinical data.

High-resolution copy number analysis of paired normal-tumor samples from diffuse large B cell lymphoma.

Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and their matched normal samples. We detected 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH).

Activated Regulatory T Cells Expressing CD4(+)CD25(high)CD45RO(+)CD62L(+) Biomarkers Could Be a Risk Factor in Liver Allograft Rejection.

Activated regulatory T cells (aTregs) are nowadays a hot topic in organ transplantation to establish their role during acute rejection (AR) episodes. The aim of this multi-center study was to monitor the frequency of aTregs within the first year after transplantation in a cohort of first-time liver transplant recipients enrolled from 2010 to 2012. aTregs frequency was analyzed by means of flow cytometry.

Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins.

Objective: To describe the response to rituximab in patients with treatment-resistant chronic inflammatory demyelinating polyneuropathy (CIDP) with antibodies against paranodal proteins and correlate the response with autoantibody titers.

Methods: Patients with CIDP and IgG4 anti-contactin-1 (CNTN1) or anti-neurofascin-155 (NF155) antibodies who were resistant to IV immunoglobulin and corticosteroids were treated with rituximab and followed prospectively. Immunocytochemistry was used to detect anti-CNTN1 and anti-NF155 antibodies and ELISA with human recombinant CNTN1 and NF155 proteins was used to determine antibody titers.

Role of Amylase-α2A Autoantibodies in the Diagnosis of Autoimmune Pancreatitis.

Objectives: Several serological markers have been reported in autoimmune pancreatitis (AIP) patients. However, only serum IgG4 (sIgG4) is available in clinical practice for AIP diagnosis. Antiamylase α antibodies (AMY-α Abs) have been proposed to diagnose AIP.

Apathy and Impulse Control Disorders: Yin & Yang of Dopamine Dependent Behaviors.

Neuropsychiatric symptoms are common non-motor symptoms in Parkinson's disease (PD). Apathy and impulse control disorders (ICD) are two opposite motivational expressions of a continuous behavioural spectrum involving hypo- and hyperdopaminergia. Both syndromes share pathological (decreased vs increased) dopamine receptor stimulation states.

Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice.

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV-seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site.

Novel clinical and diagnostic aspects of antineutrophil cytoplasmic antibodies.

Antineutrophil cytoplasmic antibodies (ANCA) are the serological hallmark of some idiopathic systemic vasculitides. Besides the investigation of ANCA-associated vasculitis (AAV) and constant effort for a standardized nomenclature and classification of the AAV, a main focus of research during the last few years has been to constantly improve the performance of enzyme immunoassays. With the latest so called third generation ELISA, this goal seemed to be fulfilled.

A Disrupted-in-Schizophrenia 1 Gene Variant is Associated with Clinical Symptomatology in Patients with First-Episode Psychosis.

Objective: DISC1 gene is one of the main candidate genes for schizophrenia since it has been associated to the illness in several populations. Moreover, variations in several DISC1 polymorphisms, and in particular Ser704Cys SNP, have been associated in schizophrenic patients to structural and functional modifications in two brain areas (pre-frontal cortex and hippocampus) that play a central role in the genesis of psychotic symptoms. This study tested the association between Ser704Cys DISC1 polymorphism and the clinical onset of psychosis.

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6.

Background: The most common spinocerebellar ataxias (SCA)--SCA1, SCA2, SCA3, and SCA6--are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset.

Methods: We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort.

White matter connections of the supplementary motor area in humans.

Introduction: The supplementary motor area (SMA) is frequently involved by brain tumours (particularly WHO grade II gliomas). Surgery in this area can be followed by the 'SMA syndrome', characterised by contralateral akinesia and mutism. Knowledge of the connections of the SMA can provide new insights on the genesis of the SMA syndrome, and a better understanding of the challenges related to operating in this region.

Serum uric acid and risk of dementia in Parkinson's disease.

Objective: Low serum uric acid (UA) levels have been associated with a worse cognitive function later in life and also with a higher risk and faster progression of Parkinson's disease (PD). Here we studied whether serum UA levels and the genetic variants related to its variability are associated with the presence of dementia in a cohort of patients with PD.

Methods: The study included 343 PD patients, which were examined for the presence of dementia according to the MDS Task Force criteria (level 1).

Subacute encephalopathy with seizures in alcoholics (SESA syndrome) revisited.

Purpose: The aim of this paper is to describe two additional cases of subacute encephalopathy with seizures in alcoholics (SESA syndrome), and to propose that this entity now should be considered as a subtype of nonconvulsive status epilepticus (NCSE).

Methods: We retrospectively analyzed the clinical characteristics, electroencephalography (EEG), neuroimaging data, and prognosis of these two further cases of SESA syndrome. In addition, we compare our findings with the cases previously described in the English literature in order to propose new diagnostic criteria.

Neurofascin IgG4 antibodies in CIDP associate with disabling tremor and poor response to IVIg.

Objective: To describe the frequency of antibodies against neurofascin in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and the associated clinical features.

Methods: Immunocytochemistry was used to identify antibodies to neurofascin 155 (NF155) and 186. Serum reactivity with paranodes and brain tissue was tested with immunohistochemistry of teased-nerve fibers and rat brain.

Evolution of Charcot-Marie-Tooth disease type 1A duplication: a 2-year clinico-electrophysiological and lower-limb muscle MRI longitudinal study.

The objective of this study was to analyze Charcot-Marie-Tooth disease type 1A (CMT1A) evolution. We conducted a 2-year longitudinal study in 14 CMT1A patients and 14 age- and sex-matched controls. In the patients, we performed neurological examination with hand-held dynamometry, electrophysiology, and lower-limb muscle MRI, both at baseline and 2 years later, while controls were examined at baseline only.

Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas.

Peripheral T cell lymphomas (PTCLs) are a heterogeneous and poorly understood group of non-Hodgkin lymphomas. Here we combined whole-exome sequencing of 12 tumor-normal DNA pairs, RNA sequencing analysis and targeted deep sequencing to identify new genetic alterations in PTCL transformation. These analyses identified highly recurrent epigenetic factor mutations in TET2, DNMT3A and IDH2 as well as a new highly prevalent RHOA mutation encoding a p.

Long-term survival after liver transplantation for alcoholic liver disease.

Currently, alcoholic cirrhosis is the second leading indication for liver transplantation in the United States and Europe. The quality of life and survival after a liver transplantation (LT) in patients with alcoholic liver disease (ALD) are similar to those in patients with other cirrhosis etiologies. The alcoholic relapse rate after a LT varies from 10%-50%, and these relapse patients are the ones who present a reduced long-term survival, mainly due to cardiovascular diseases and the onset of de novo neoplasms, including lung and upper aerodigestive tract.