Isolated single coronary artery (RII-B type) presenting as an inferior wall myocardial infarction: A rare clinical entity

AbstractIsolated single coronary artery without other congenital cardiac anomalies is very rare among the different variations of anomalous coronary patterns. The prognosis in patients with single coronary varies according to the anatomic distribution and associated coronary atherosclerosis. If the left main coronary artery travels between the aorta and pulmonary arteries, it may be a cause of sudden cardiac death. We present multimodality images of a single coronary artery, in which the whole coronary system originated by a single trunk from the right sinus of Valsalva with inter-arterial course of left main coronary artery. This rare type of single coronary artery was classified as RII-B type according to Lipton's scheme of classification. A significant flow-limiting lesions were found in the right coronary artery that was successfully treated with percutaneous coronary intervention

Electromyography and muscle biopsy in paediatric neuromuscular disorders – Evaluation of current practice and literature review

The conduct and interpretation of electromyography in children is considered difficult and therefore often avoided. We assessed the diagnostic accuracy of the paediatric electromyography protocol used in our tertiary reference centre and compared it to muscle biopsy results and clinical diagnosis. Electromyography was performed in unsedated children with suspected neuromuscular diseases between January 2010 and September 2017 and was analysed quantitatively. Muscle pathology was classified into seven groups based on existing histopathology reports. The clinical diagnosis, including myopathic, neurogenic and non-neuromuscular categories was used as the gold standard. 171 children between the age of 12 days to 17.4 years were included in the analysis. 41 children (24%) were under the age of 2 years at the time of electromyography. 98 (57%) children were diagnosed with a myopathic disorder, 18 (11%) with a neurogenic disease and 55 (32%) as not having a primary neuromuscular disorder. In detecting myopathic disease, electromyography performed as well as muscle biopsy (sensitivity 87.8% for electromyography vs. 84.5% for muscle biopsy; specificity 75.7% vs. 86.4%). This also applied to children under the age of 2 years (sensitivity 81.8% vs. 86.4%). Quantitative analysis of a limited electromyography protocol performed in unsedated children is a very valuable diagnostic tool

First presentation of LPIN1 acute rhabdomyolysis in adolescence and adulthood

LPIN1 mutations are a known common cause of autosomal recessive, recurrent and life-threatening acute rhabdomyolysis of childhood-onset. The first episode of rhabdomyolysis usually happens in nearly all cases before the age of 5 and death is observed in 1/3 of patients. Here we present two cases of acute rhabdomyolysis with a milder phenotype caused by LPIN1 mutation presenting in adolescence (11 years old) and adulthood (40 years old) after Parvovirus infection and metabolic stress, respectively. In our opinion, the mutation types, epigenetic factors, the environment exposition to triggers or the existence of proteins with a similar structure of LPIN1, may have a role in modulating the onset of rhabdomyolysis. LPIN1 should be included on a panel of genes analysed in the investigation of adult individuals with rhabdomyolysis. Metabolic and viral stressors should be included in the list of possible rhabdomyolysis precipitant

Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis

Correction to Martin et al. available at: Genes & Development 30 (19): 2158 (http://genesdev.cshlp.org/content/31/9/953.full.pdf+html).Compaction of chromosomes is essential for accurate segregation of the genome duringmitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here,we report that biallelic mutations inNCAPD2,NCAPH, orNCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.This work was supported by funding from the Medical Research Council, the Lister Institute for Preventative Medicine, and the European Research Council (ERC; 281847 to A.P.J.); a Biotechnology and Biological Sciences Research Council grant (BB/ K017632/1 to P.V); a Sir Henry Dale Fellowship (grant 102560/ Z/13/Z to A.J.W.); Medical Research Scotland (to L.S.B.); the Potentials Foundation (to C.A.W.); and the Indian Council of Medical Research (BMS 54/2/2013 to S.R.P). The Deciphering Developmental Disorders Study presents independent research commissioned by the Health Innovation Challenge Fund (grant no. HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant no. WT098051). The views expressed here are those of the authors and not necessarily those of the Wellcome Trust or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83) granted by the Cambridge South Research Ethics Committee, and GEN/ 284/12 granted by the Republic of Ireland. We acknowledge the support of the National Institute for Health Research through the Comprehensive Clinical Research Network

Ubiquitous Molecular Outflows in z > 4 Massive, Dusty Galaxies II. Momentum-Driven Winds Powered by Star Formation in the Early Universe

Galactic outflows of molecular gas are a common occurrence in galaxies and may represent a mechanism by which galaxies self-regulate their growth, redistributing gas that could otherwise have formed stars. We previously presented the first survey of molecular outflows at z > 4 towards a sample of massive, dusty galaxies. Here we characterize the physical properties of the molecular outflows discovered in our survey. Using low-redshift outflows as a training set, we find agreement at the factor-of-two level between several outflow rate estimates. We find molecular outflow rates 150-800Msun/yr and infer mass loading factors just below unity. Among the high-redshift sources, the molecular mass loading factor shows no strong correlations with any other measured quantity. The outflow energetics are consistent with expectations for momentum-driven winds with star formation as the driving source, with no need for energy-conserving phases. There is no evidence for AGN activity in our sample, and while we cannot rule out deeply-buried AGN, their presence is not required to explain the outflow energetics, in contrast to nearby obscured galaxies with fast outflows. The fraction of the outflowing gas that will escape into the circumgalactic medium (CGM), though highly uncertain, may be as high as 50%. This nevertheless constitutes only a small fraction of the total cool CGM mass based on a comparison to z~2-3 quasar absorption line studies, but could represent >~10% of the CGM metal mass. Our survey offers the first statistical characterization of molecular outflow properties in the very early universe.Comment: ApJ accepted. 25 pages, 16 figures. Data and tables from Papers I and II available at https://github.com/spt-smg/publicdat

Ubiquitous Molecular Outflows in z > 4 Massive, Dusty Galaxies I. Sample Overview and Clumpy Structure in Molecular Outflows on 500pc Scales

Massive galaxy-scale outflows of gas are one of the most commonly-invoked mechanisms to regulate the growth and evolution of galaxies throughout the universe. While the gas in outflows spans a large range of temperatures and densities, the cold molecular phase is of particular interest because molecular outflows may be capable of suppressing star formation in galaxies by removing the star-forming gas. We have conducted the first survey of molecular outflows at z > 4, targeting 11 strongly-lensed dusty, star-forming galaxies (DSFGs) with high-resolution Atacama Large Millimeter Array (ALMA) observations of OH 119um absorption as an outflow tracer. In this first paper, we give an overview of the survey, focusing on the detection rate and structure of molecular outflows. We find unambiguous evidence for outflows in 8/11 (73%) galaxies, more than tripling the number known at z > 4. This implies that molecular winds in z > 4 DSFGs must have both a near-unity occurrence rate and large opening angles to be detectable in absorption. Lensing reconstructions reveal that 500pc-scale clumpy structures in the outflows are common. The individual clumps are not directly resolved, but from optical depth arguments we expect that future observations will require 50-200pc spatial resolution to do so. We do not detect high-velocity [CII] wings in any of the sources with clear OH outflows, indicating that [CII] is not a reliable tracer of molecular outflows. Our results represent a first step toward characterizing molecular outflows at z > 4 at the population level, demonstrating that large-scale outflows are ubiquitous among early massive, dusty galaxies.Comment: ApJ accepted. 28 pages, 12 figures + appendix. Data and tables from Papers I and II available at https://github.com/spt-smg/publicdat

Chaotic and Clumpy Galaxy Formation in an Extremely Massive Reionization-era Halo

© 2022. The Author(s). Published by the American Astronomical Society. Original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. https://creativecommons.org/licenses/by/4.0/Abstract: The SPT 0311–58 system at z = 6.900 is an extremely massive structure within the reionization epoch and offers a chance to understand the formation of galaxies at an extreme peak in the primordial density field. We present 70 mas Atacama Large Millimeter/submillimeter Array observations of the dust continuum and [C ii] 158 μm emission in the central pair of galaxies and reach physical resolutions of ∼100–350 pc, among the most detailed views of any reionization-era system to date. The observations resolve the source into at least a dozen kiloparsec-size clumps. The global kinematics and high turbulent velocity dispersion within the galaxies present a striking contrast to recent claims of dynamically cold thin-disk kinematics in some dusty galaxies just 800 Myr later at z ∼ 4. We speculate that both gravitational interactions and fragmentation from massive parent disks have likely played a role in the overall dynamics and formation of clumps in the system. Each clump individually is comparable in mass to other 6 < z < 8 galaxies identified in rest-UV/optical deep field surveys, but with star formation rates elevated by a factor of ~3-5. Internally, the clumps themselves bear close resemblance to greatly scaled-up versions of virialized cloud-scale structures identified in low-redshift galaxies. Our observations are qualitatively similar to the chaotic and clumpy assembly within massive halos seen in simulations of high-redshift galaxies.Peer reviewe

Clinical spectrum, treatment and outcome of children with suspected diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable chronic disorder of the peripheral nervous system. We retrospectively studied 30 children with a suspected diagnosis of CIDP. The diagnosis of CIDP was compared against the childhood CIDP revised diagnostic criteria 2000. Of the 30 children, five did not meet the criteria and four others met the criteria but subsequently had alternative diagnosis, leaving a total of 21 children (12 male) with CIDP as the final diagnosis. Thirteen children presented with chronic symptom-onset (>8 weeks). The majority presented with gait difficulties or pain in legs (n = 16). 12 children (57%) met the neurophysiological criteria and 18/19 (94%) met the cerebrospinal fluid criteria. Nerve biopsy was suggestive in 3/9 (33%), with magnetic resonance imaging supportive in 9/20 (45%). Twenty-one children received immuno-modulatory treatment at first presentation, of which majority (n = 19, 90%) received IVIG (immunoglobulin) monotherapy with 13 (68%) showing a good response. 8 children received second line treatment with either IVIG or steroids or plasmapharesis (PE) and 4 needed other immune-modulatory agents. During a median follow-up of 3.6 years, 9 (43%) had a monophasic course and 12 (57%) had a relapsing–remitting course. At last paediatric follow up 7 (33%) were off all treatment, 9 (43%) left with no or minimal residual disability and 6 (28%) children were walking with assistance (n = 3) or were non-ambulant (n = 3). Our review highlights challenges in the diagnosis and management of paediatric CIDP. It also confirms that certain metabolic disorders may mimic CIDP

ProbFAST: Probabilistic Functional Analysis System Tool

<p>Abstract</p> <p>Background</p> <p>The post-genomic era has brought new challenges regarding the understanding of the organization and function of the human genome. Many of these challenges are centered on the meaning of differential gene regulation under distinct biological conditions and can be performed by analyzing the Multiple Differential Expression (MDE) of genes associated with normal and abnormal biological processes. Currently MDE analyses are limited to usual methods of differential expression initially designed for paired analysis.</p> <p>Results</p> <p>We proposed a web platform named ProbFAST for MDE analysis which uses Bayesian inference to identify key genes that are intuitively prioritized by means of probabilities. A simulated study revealed that our method gives a better performance when compared to other approaches and when applied to public expression data, we demonstrated its flexibility to obtain relevant genes biologically associated with normal and abnormal biological processes.</p> <p>Conclusions</p> <p>ProbFAST is a free accessible web-based application that enables MDE analysis on a global scale. It offers an efficient methodological approach for MDE analysis of a set of genes that are turned on and off related to functional information during the evolution of a tumor or tissue differentiation. ProbFAST server can be accessed at <url>http://gdm.fmrp.usp.br/probfast</url>.</p

Synpolydactyly and HOXD13 polyalanine repeat: addition of 2 alanine residues is without clinical consequences

<p>Abstract</p> <p>Background</p> <p>Type II syndactyly or synpolydactyly (SPD) is clinically very heterogeneous, and genetically three distinct SPD conditions are known and have been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated with expansion mutations in <it>HOXD13</it>, resulting in an addition of ≥ 7 alanine residues to the polyalanine repeat. It has been suggested that expansions ≤ 6 alanine residues go without medical attention, as no such expansion has ever been reported with the SPD1 phenotype.</p> <p>Methods</p> <p>We describe a large Pakistani and an Indian family with SPD. We perform detailed clinical and molecular analyses to identify the genetic basis of this malformation.</p> <p>Results</p> <p>We have identified four distinct clinical categories for the SPD1 phenotype observed in the affected subjects in both families. Next, we show that a milder foot phenotype, previously described as a separate entity, is in fact a part of the SPD1 phenotypic spectrum. Then, we demonstrate that the phenotype in both families segregates with an identical expansion mutation of 21 bp in <it>HOXD13</it>. Finally, we show that the HOXD13 polyalanine repeat is polymorphic, and the expansion of 2 alanine residues, evident in unaffected subjects of both families, is without clinical consequences.</p> <p>Conclusion</p> <p>It is the first molecular evidence supporting the hypothesis that expansion of ≤ 6 alanine residues in the HOXD13 polyalanine repeat is not associated with the SPD1 phenotype.</p