Characterization of a novel dioxomolybdenum complex by cyclic voltammetry

Metalloenzymes that carry a pterin-based molybdenum cofactor in their center catalyze numerous reactions in the human body and play a crucial role in its metabolism. Specifically, these enzymes promote redox reactions and oxygen transport in the body. Their absence may cause many problems leading to disability or even death in early childhood. Therefore, model compounds need to be synthesized and analyzed to investigate the reactivity, redox potential, and geometry of these cofactors. This study focused on electrode processes and determined the redox potentials of the new bis-(4-mercapto-5-(p-tolyl)-3H-1,2-dithiole-3-thione)-dioxomolybdenum complex by cyclic voltammetry. The 4-mercapto-5-(p-tolyl)-3H-1,2-dithiole-3-thione ligand underwent irreversible oxidation and reduction at thiol and thione functional groups. The new dioxomolybdenum complex showed a quasi-reversible two-stage electrode process

The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations.

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations)

Neuromuscular disease genetics in under-represented populations: increasing data diversity

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses ‘solved’ or ‘possibly solved’ ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% ‘solved’ and ∼13% ‘possibly solved’ outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Akut karinla basvu?ran geri?atri?k hastalarda cerrahi? tedavi? ve sonuçlari

The aim of this study was to evaluate the factors affecting the outcome of geriatric patients presenting with acute abdomen. Eighty patients who underwent surgery with the diagnosis of acute abdomen were analysed retrospectively. The effects of age, sex, American Society of Anaesthesiology (ASA) class, preexisting disease, admission time after the onset of the symptoms, followup interval before the operation on morbidity, mortality and length of hospital stay were evaluated. Male/female ratio was 1.3, mean age was 72.4. Main causes were biliary system disease (38.8%), intestinal obstruction (31.3%), peptic ulcer perforation (12.5%) and acute appendicitis (8.7%). Median ASA class was 3 and 76.3% of the patients had at least one preexisting disease. ASA class was significantly effective on mortality and complication rate. Shock at the admission, malignity, male sex, mechanical ventilation and transfusion were the factors that have statistically significant effect on mortality. 58.8% of the patients had complications. Complications were significantly related to mortality, prolonged intensive care unit (ICU) stay and hospital stay. Male sex, ASA class, malign diseases, peptic ulcer perforation, colonic obstruction, shock, mechanical ventilation and blood transfusion were the factors affecting mortality in the elderly. Preexisting diseases other than malignity, period between the onset of symptoms and admission, follow-up time and operation time did not influence mortality. Complications and ASA classification were associated with a prolonged ICU and hospital stay

Withdrawal syndrome and hypomagnesaemia and in a newborn exposed to valproic acid and carbamazepine during pregnancy [Gebelikte annenin karbamezepin ve valproik asit kullanimina bağli hipomagnesemi ve çekilme sendromu]

The usage of drugs during pregnancy affect the fetus and the newborn. In this report, we present findings from a newborn baby, whose mother was epileptic, and was under the treatment of valproic acid and carbamazepine during pregnancy. We have found symptoms of withdrawal syndrome, hyponatremia and feeding problem, which was most probably related to exposure to the mentioned drugs. We have also diagnosed hypomagnesaemia and atrial septal defect 4 milimeters in diameter. There are already many reports about the side effects of valproic acid and carbamazepine usage during pregnancy. To the best of our knowledge, hypomagnesaemia has not yet been reported as a side effect. We think that hypomagnesaemia is also related to the usage of antiepileptics. © 2016 by Turkish Pediatric Association