Physical exercise and oxidative stress in muscular dystrophies: is there a good balance?

The effect of oxidative stress on muscle damage inducted by physical exercise is widely debated. It is generally agreed that endurance and intense exercise can increase oxidative stress and generate changes in antioxidant power inducing muscle damage; however, regular and moderate exercise can be beneficial for the health improving the antioxidant defense mechanisms in the majority of cases. Growing evidences suggest that an increased oxidative/nitrosative stress is involved in the pathogenesis of several muscular dystrophies (MDs).

Revisiting mitochondrial ocular myopathies: a study from the Italian Network.

Ocular myopathy, typically manifesting as progressive external ophthalmoplegia (PEO), is among the most common mitochondrial phenotypes. The purpose of this study is to better define the clinical phenotypes associated with ocular myopathy. This is a retrospective study on a large cohort from the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases".

Mitochondrial ANT-1 related adPEO leading to cognitive impairment: is there a link?

ANT1 is one of the nuclear genes responsible of autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA multiple deletions. The course of ANT1- related adPEO is relatively benign, symptoms being generally restricted to skeletal muscle. Here we report the case of an Italian 74 years old woman with ANT1-related adPEO and dementia.

Decreased Methylation of the Mitochondrial D-Loop Region in Late-Onset Alzheimer's Disease.

Mitochondrial impairment is a feature of neurodegeneration and many investigators have suggested that epigenetic modifications of the mitochondrial DNA (mtDNA) might be involved in late-onset Alzheimer's disease (LOAD), but evidence in humans is limited. We assessed the methylation levels of the mtDNA D-loop region in blood DNA from 133 LOAD patients and 130 controls, observing a significant 25% reduction of DNA methylation levels in the first group (2.3 versus 3.

China's dam-builders: their role in transboundary river management in South-East Asia.

This article investigates China's role as the world's largest builder of and investor in large dams, focussing on the Greater Mekong Sub-Region in South-East Asia. It addresses the role Chinese actors play in dam-building as well as the environmental, social, economic and political implications by drawing on case studies from Cambodia and Vietnam. The article finds that China's dam-building is perceived very differently in different countries of South-East Asia.

Hard ways towards adulthood: the transition phase in young people with myotonic dystrophy.

Myotonic dystrophy type 1 (DM1), also called Steinert's disease, is a genetic multisystem disorder that has raised, in the last years, high interest because of the high variable clinical spectrum and related disability. Children with myotonic dystrophy are affected by behavioural problems and intellectual disability, finally impacting on their degree of engagement in family, work and social activities. The transition phase, representing the process of moving from adolescence to adulthood, can be severely affected by growing up with a neuromuscular disorder, with significant impact on patient's and families' quality of life.

α-Synuclein Aggregates with β-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects.

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid (Aβ), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aβ or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet.

Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease.

Aims: Mitochondrial disease (MD) is a genetic disorder affecting skeletal muscles, with possible myocardial disease. The ergoreflex, sensitive to skeletal muscle work, regulates ventilatory and autonomic responses to exercise. We hypothesized the presence of an increased ergoreflex sensitivity in MD patients, its association with abnormal ventilatory and autonomic responses, and possibly with subclinical cardiac involvement.

The Methylenetetrahydrofolate Reductase C677T Polymorphism and Risk for Late-Onset Alzheimer's disease: Further Evidence in an Italian Multicenter Study.

Background: A functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, namely C677T (rs1801133), results in increased Hcy levels and has been associated with risk of late-onset Alzheimer's disease (LOAD). Many investigators reported association between rs1801133 and LOAD risk in Asian populations and in carriers of the apolipoprotein E (APOE) ɛ4 allele, but recent meta-analyses suggest a contribution also in other populations, including Caucasians and/or northern Africans.

Objective: To further address this issue, we performed a relatively large case-control study, including 581 LOAD patients and 468 matched controls of Italian origin.

Novel POLG mutations and variable clinical phenotypes in 13 Italian patients.

POLG gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial DNA (mtDNA) replication and repair. Mutations in POLG have been linked to a spectrum of clinical phenotypes, resulting in autosomal recessive or dominant mitochondrial diseases. These mutations have been associated with heterogeneous phenotypes, presenting with varying severity and at different ages of onset, ranging from the neonatal period to late adult life.

A high susceptibility to redox imbalance of the transmissible stages of Plasmodium falciparum revealed with a luciferase-based mature gametocyte assay.

The goal to prevent Plasmodium falciparum transmission from humans to mosquitoes requires the identification of targetable metabolic processes in the mature (stage V) gametocytes, the sexual stages circulating in the bloodstream. This task is complicated by the apparently low metabolism of these cells, which renders them refractory to most antimalarial inhibitors and constrains the development of specific and sensitive cell-based assays. Here, we identify and functionally characterize the regulatory regions of the P.

Magnetic susceptibility in the deep layers of the primary motor cortex in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurological disorder that entails degeneration of both upper and lower motor neurons. The primary motor cortex (M1) in patients with upper motor neuron (UMN) impairment is pronouncedly hypointense in Magnetic Resonance (MR) T2* contrast. In the present study, 3D gradient-recalled multi-echo sequences were used on a 7 Tesla MR system to acquire T2*-weighted images targeting M1 at high spatial resolution.

The italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis.

Introduction: Limb girdle muscular dystrophies (LGMDs) are characterized by high molecular heterogeneity, clinical overlap, and a paucity of specific biomarkers. Their molecular definition is fundamental for prognostic and therapeutic purposes.

Methods: We created an Italian LGMD registry that included 370 molecularly defined patients.

Mitochondrial m.3243A > G mutation and carotid artery dissection.

The common m.3243A > G mutation of the mitochondrial DNA tRNALeu (UUR) gene is a maternally inherited mutation causing a wide spectrum of neurological and multisystemic disorders, including MELAS, characterized by recurrent cerebral infarction from young age. Vascular pathology in mitochondrial diseases has been described for small vessels, while large vessels involvement in mitochondrial diseases is considered rare.

Clinical significance of prophylactic central compartment neck dissection in the treatment of clinically node-negative papillary thyroid cancer patients.

Background: Lymph nodal involvement is very common in differentiated thyroid cancer, and in addition, cervical lymph node micrometastases are observed in up to 80 % of papillary thyroid cancers. During the last decades, the role of routine central lymph node dissection (RCLD) in the treatment of papillary thyroid cancer (PTC) has been an object of research, and it is now still controversial. Nevertheless, many scientific societies and referral authors have definitely stated that even if in expert hands, RCLD is not associated to higher morbidity; it should be indicated only in selected cases.

Dysphagia in Amyotrophic Lateral Sclerosis: Relationships between disease progression and Fiberoptic Endoscopic Evaluation of Swallowing.

Objective: Our aim was to evaluate the relationship between the disease severity of Amyotrophic Lateral Sclerosis (ALS) and the following parameters of Fiberoptic Endoscopic Evaluation of Swallowing (FEES): premature spillage, post-swallowing residue and aspiration.

Methods: We studied 202 patients (95 women and 107 men) with ALS; of these, 136 had spinal and 66 had bulbar onset. They were analyzed according to the Amyotrophic Lateral Sclerosis Functioning Rating Scale (ALSFRS) and the b-ALSFRS subscale (bulbar scale).

Acute encephalopathy of the temporal lobes leading to m.3243A>G. When MELAS is not always MELAS.

MELAS syndrome (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) is a rare genetic condition whose differential diagnosis is often posed with juvenile stroke, but more rarely even with inflammatory/infectious encephalitis, causing diagnostic challenges. Here we report the case of a young man harbouring the m.3243A>G MELAS mutation presenting an acute onset mimicking the clinical and neuroimaging features of infective encephalitis.

Relationship between neuropsychological impairment and grey and white matter changes in adult-onset myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) has a wide phenotypic spectrum and potentially may affect central nervous system with mild to severe involvement. Our aim was to investigate grey matter (GM) and white matter (WM) structural alterations in a sample of adult-onset DM1 patients and to evaluate relationship with clinical and cognitive variables. Thirty DM1 patients underwent neuropsychological investigation and 3T-MRI protocol.

Mitochondrial DNA haplogroups may influence Fabry disease phenotype.

While the genetic origin of Fabry disease (FD) is well known, it is still unclear why the disease presents a wide heterogeneity of clinical presentation and progression, even within the same family. Emerging observations reveal that mitochondrial impairment and oxidative stress may be implicated in the pathogenesis of FD. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of FD, we have genotyped European mtDNA haplogroups in 77 Italian FD patients and 151 healthy controls.

Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies.

Myotonia congenita is an inherited disease that is characterized by impaired muscle relaxation after contraction caused by loss-of-function mutations in the skeletal muscle ClC-1 channel. We report a novel ClC-1 mutation, T335N, that is associated with a mild phenotype in 1 patient, located in the extracellular I-J loop. The purpose of this study was to provide a solid correlation between T335N dysfunction and clinical symptoms in the affected patient as well as to offer hints for drug development.