Systemic sclerosis associated myopathy: how to treat.

Purpose Of Review: Systemic sclerosis (SSc) and myositis are two different entities that may coexist as an overlap syndrome. Immunological biomarkers such as anti-PM/Scl or anti-Ku reinforce the syndrome. This review is focused on the treatment of different and characteristic manifestations of this syndrome.

Clinico-pathological phenotypes of systemic sclerosis-associated myopathy: analysis of a large multicentre cohort.

Objective: The objective of this study was to analyse the clinico-serological and histological phenotypes of patients with SSc with associated myopathy.

Methods: From November 2002 to September 2020, 52 patients with SSc underwent a muscle biopsy for suspected myopathy. We established two subgroups according to the histological findings based on the presence of isolated fibrosis or fibrosis together with significant inflammation.

DLG4-related synaptopathy: a new rare brain disorder.

Purpose: Postsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants.

Methods: The clinical and genetic information were collected through GeneMatcher collaboration.

Statin use and myopathy. Not always guilty.

Objectives: Statins are the cornerstone of the treatment and prevention of cardiovascular disease but have been associated with muscular side effects, among others. If patients are not properly evaluated, statin discontinuation may take place, leaving patients' symptoms unresolved and precluding an effective cardiovascular treatment. The present study aims to describe the clinical characteristics, the diagnostic process and the final diagnosis of selected patients with suspected statin-induced myopathy, with quite different alternative diagnoses.

Sporadic inclusion body myositis: Diagnostic value of p62 immunostaining.

Background And Objectives: Sporadic inclusion body myositis (sIBM) diagnosis is frequently delayed or confused with another class of disorders, and misdiagnosis is common. Sometimes, we have problems diagnosing an sIBM in the early stages or predicting when a PM is going to become an sIBM. In this sense, we believe that p62 immunostaining could help clinicians.

RNA-binding proteins regulate cell respiration and coenzyme Q biosynthesis by post-transcriptional regulation of COQ7.

Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain carrying electrons from complexes I and II to complex III and it is an intrinsic component of the respirasome. CoQ concentration is highly regulated in cells in order to adapt the metabolism of the cell to challenges of nutrient availability and stress stimuli. At least 10 proteins have been shown to be required for CoQ biosynthesis in a multi-peptide complex and COQ7 is a central regulatory factor of this pathway.

Novel Therapeutic Targets and Drug Candidates for Modifying Disease Progression in Adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is the most frequent inherited monogenic demyelinating disease. It is often lethal and currently lacks a satisfactory therapy. The disease is caused by loss of function of the ABCD1 gene, a peroxisomal ATP-binding cassette transporter, resulting in the accumulation of very-long-chain fatty acids (VLCFA) in organs and plasma.

Forms of Circulating Luteinizing Hormone Human Chorionic Gonadotropin Receptor for the Prediction of Early and Late Preeclampsia in the First Trimester of Pregnancy.

Objective: To explore the value of circulating luteinizing human chorionic gonadotropin receptor (LHCGR) forms for the prediction of preeclampsia (PE) in the first trimester of pregnancy.

Methods: Case-control study, based on a cohort of 5,759 pregnancies, including 20 early PE, 20 late PE, and 300 controls. We recorded/measured maternal characteristics, mean arterial pressure (MAP), uterine artery (UtA) Doppler, placental growth factor (PlGF), soluble Fms-like tyrosine kinase-1 (sFtl-1), and LHCGR forms (hCG-LHCGR and soluble LHCGR), and their independent predictive values were analyzed by logistic regression.

Monocyte-mediated regulation of genes by the amyloid and prion peptides in SH-SY5Y neuroblastoma cells.

Alzheimer's disease as well as prion-related encephalopathies are neurodegenerative disorders of the central nervous system, which cause mental deterioration and progressive dementia. Both pathologies appear to be primarily associated with the pathological accumulation and deposit of β-amyloid or prion peptides in the brain, and it has been even suggested that neurotoxicity induced by these peptides would be associated to essentially similar pathogenic mechanisms, in particular to those that follow the activation of microglial cells. To probe whether the neurotoxic effects induced by the β-amyloid and prion peptides are actually mediated by similar glial-associated mechanisms, we have examined the differential expression of genes in SH-SY5Y neuroblastoma cells incubated with conditioned media from β-amyloid or prion-stimulated THP-1 monocytic cells.

Laser confocal microscopy analysis of human interphase nuclei by three-dimensional FISH reveals dynamic perinucleolar clustering of telomeres.

Nuclear functions are strongly dependent on the three-dimensional organization of the interphase nucleus. Given the importance of telomeres in the behaviour and stability of chromosomes, we have investigated the architecture of the human nucleus from the telomere perspective by 3D-FISH and laser confocal microscopy. We observed a randomly scattered telomere distribution in all confocal sections of the interphase nuclear volume with various levels of telomere clustering in different cell types.

Brain injury in glutaric aciduria type I: the value of functional techniques in magnetic resonance imaging.

Background: Acute striatal necrosis is a devastating consequence of encephalopathic crisis in patients with glutaric aciduria type I (GA-I), but the mechanisms underlying brain injury are not completely understood.

Objective: To approach pathophysiological aspects of brain injury in GA-I by means of functional techniques in magnetic resonance imaging (MRI).

Patients And Methods: Four patients during an acute encephalopathic crisis and three asymptomatic siblings with GA-I underwent single-voxel hydrogen magnetic resonance spectroscopy (MRS) and brain MRI including gradient echo T1-weighted, FLAIR, T2-weighted and diffusion-weighted imaging.

Long-term evolution of eight Spanish patients with CDG type Ia: typical and atypical manifestations.

Congenital disorder of glycosylation Ia (CDG-Ia) is a metabolic disease with a broad spectrum of clinical signs, including recently described mild phenotypes. Our aim was to describe the clinical presentation and follow-up of eight CDG-Ia patients highlighting atypical features and aspects of evolution of the disease. CDG diagnosis was confirmed by enzymatic analysis of phosphomannomutase (PMM2) and molecular studies of the PMM2 gene.

Vanishing white matter disease associated with progressive macrocephaly.

Vanishing white matter disease (VWM) is one of the most frequent inherited childhood leukoencephalopathies. Five genes have been implicated in this disease ( EIF2B1-5), which encode the five subunits of translation initiation factor eIF2B. The disease has an autosomal recessive mode of inheritance.

Reference ranges for uterine artery mean pulsatility index at 11-41 weeks of gestation.

Objectives: To construct gestational age (GA)-based reference ranges for the uterine artery (UtA) mean pulsatility index (PI) at 11-41 weeks of pregnancy.

Methods: A prospective cross-sectional observational study was carried out of 20 consecutive singleton pregnancies for each completed gestational week at 11-41 weeks. UtAs were examined by color and pulsed Doppler imaging, and the mean PI, as well as the presence or absence of a bilateral protodiastolic notch, were recorded.

A novel two-domain architecture within the amino acid kinase enzyme family revealed by the crystal structure of Escherichia coli glutamate 5-kinase.

Glutamate 5-kinase (G5K) makes the highly unstable product glutamyl 5-phosphate (G5P) in the initial, controlling step of proline/ornithine synthesis, being feedback-inhibited by proline or ornithine, and causing, when defective, clinical hyperammonaemia. We determined two crystal structures of G5K from Escherichia coli, at 2.9 A and 2.