Complications and carcinogenic effects of mustard gas - A systematic review and meta-analysis in Iran

Background: Catastrophic effects of mustard gas as a chemical warfare agent have always been a major problem for those exposed to this agent. In this meta-analysis it was tried to evaluate carcinogenesis, ocular, cutaneous and respiratory complications of mustard gas exposure among Iranians who had been exposed to this agent during the Iran-Iraq war. Materials and Methods: In this meta-analysis, the required data were collected using keywords "mustard gas", "sulfur mustard", "cancer", "neoplasm", "respiratory complications", "ocular complications", "lung disease", "chronic complication", "eye", "skin", "cutaneous complication", "carcinogenesis" and their combination with keywords "Iran", "Iranian", "prevalence", "mortality" and their Farsi equivalent terms from the databases of SID, Iranmedex, Magiran, Pubmed, Science Direct, Google Search engine, Gray Literature and Reference of References. To determine the prevalence of each complication and perform meta-analysis, CMA: 2 (Comprehensive Meta-Analysis) software with a randomized model was used. Results: Of the 542 articles found, 7 national articles, consistent with the aims of this study were selected. Metaanalysis of seven papers revealed that cancer risk, especially cancer of the respiratory system was elevated, so that the relative risk (RR) of cancer role of mustard gas was inconsistent from 2/1 to 4 in this survey. Also prevalence of delayed skin disorders due to sulfur mustard was 94.6, pulmonary complications 94.5 and ocular complications 89.9. The incidence of various cancers in victims exposed to mustard gas was 1.7 worldwide where the rate was 2.2 in Iranian victims of the Iraq-Iran war. Conclusions: Based on present study the prevalence of delayed mustard gas related cutaneous, pulmonary and ocular complications is above 90 and risk of carcinogenesis is higher in comparison to worldwide statistics. This may suggest need for long-term and persistent follow-up and rehabilitation procedures es for populations exposed to this agent

Genera of phytopathogenic fungi: GOPHY 3

This paper represents the third contribution in the Genera of Phytopathogenic Fungi (GOPHY) series. The series provides morphological descriptions, information about the pathology, distribution, hosts and disease symptoms for the treated genera, as well as primary and secondary DNA barcodes for the currently accepted species included in these. This third paper in the GOPHY series treats 21 genera of phytopathogenic fungi and their relatives including: Allophoma, Alternaria, Brunneosphaerella, Elsinoe, Exserohilum, Neosetophoma, Neostagonospora, Nothophoma, Parastagonospora, Phaeosphaeriopsis, Pleiocarpon, Pyrenophora, Ramichloridium, Seifertia, Seiridium, Septoriella, Setophoma, Stagonosporopsis, Stemphylium, Tubakia and Zasmidium. This study includes three new genera, 42 new species, 23 new combinations, four new names, and three typifications of older names

Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele

An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy

The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose >7000 years ago. A wide age-range of patients (6–83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 ± 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses