Anatomic Thoracoscopic Repair of Esophageal Atresia

Background: The thoracoscopic approach to repair esophageal atresia (EA) with tracheoesophageal fistula (TEF) provides excellent view, allowing the most skillful surgeons to spare the azygos vein by performing the esophageal anastomosis over (on the right side) the azygos vein. Seeking the most anatomic repair, we started to perform the esophageal anastomosis underneath (on the left side) the azygos vein: anatomic thoracoscopic repair of esophageal atresia (ATREA). We aim to compare results of ATREA with the classic thoracoscopic repair. Methods: During the last 4 years, in our center, all infants with EA with distal TEF were operated by thoracoscopy sparing the azygos vein. According to the surgical technique, two groups were created: Group A-treated with ATREA and Group B-treated with classic thoracoscopic repair over (on the right side) the azygos vein. We retrospectively collected data regarding features of the newborn (gestational age, gender, karyotype changes, associated anomalies, birth weight), surgery (operative technique, operative time, and surgical complications), hospitalization (duration of mechanical ventilation, thoracic drainage, time for the first feeding, time of admission, and early complications) and follow-up [tracheomalacia, gastroesophageal reflux disease (GERD), anastomotic stricture, recurrence of fistula]. results: Group A had seven newborns and Group B had four newborns. There were no statistically significant differences between both groups concerning the evaluated variables on surgery, hospitalization, and follow-up. Nevertheless, in Group A, there was an infant with a right aortic arch where ATREA was particularly useful as it avoided that the azygos vein and the aortic arch were left compressed in between the esophagus and trachea. Postoperatively, one patient of Group B had a major anastomotic leak with empyema requiring surgical re-intervention. During follow-up, anastomotic stricture requiring esophageal dilation occurred with similar rates in both groups. In Group B, one patient had severe and symptomatic tracheomalacia requiring aortopexy and severe GERD requiring fundoplication. No patients developed recurrent fistula. conclusion: The ATREA is feasible in the great majority of patients with EA with TEF without compromising long-term results and might be particularly useful for those infants with malformations of the cardiac venous return vessels and/or major aortic malformations.projects NORTE-01-0246-FEDER-000012, NORTE-01-0145-FEDER-000013, and NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)info:eu-repo/semantics/publishedVersio

Surface water microbial community response to the biocide 2-2-dibromo-3-nitrilopropionamide used in unconventional oil and gas extraction.

Production of unconventional oil and gas continues to rise, but the effects of high-density hydraulic fracturing (HF) activity near aquatic ecosystems are not fully understood. A commonly used biocide in HF, 2,2-dibromo-3-nitrilopropionamide (DBNPA), was studied in microcosms of HF-impacted vs. HF-unimpacted surface water streams to (1) compare the microbial community response, (2) investigate DBNPA degradation products based on past HF exposure, and (3) compare the microbial community response differences and similarities between the HF biocides DBNPA and glutaraldehyde. The microbial community responded to DBNPA differently in HF-impacted vs. HF-unimpacted microcosms in terms of 16S rRNA gene copies quantified, alpha and beta diversity, and differential abundance analyses of microbial community composition through time. The difference in microbial community changes affected degradation dynamics. HF-impacted microbial communities were more sensitive to DBNPA, causing the biocide and byproducts of the degradation to persist for longer than in HF-unimpacted microcosms. Seventeen DBNPA byproducts were detected, many of them not widely known as DBNPA byproducts. Many of the believed to be uncharacterized brominated byproducts detected may pose environmental and health impacts. Similar taxa were able to tolerate glutaraldehyde and DBNPA, however DBNPA was not as effective for microbial control as indicated by a smaller overall decrease of 16S rRNA gene copies/mL after exposure to the biocide and a more diverse set of taxa was able to tolerate it. These findings suggest that past HF activity in streams can affect the microbial community response to environmental perturbation such as the biocide DBNPA

Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis

Objective To quantify the prevalence of incidental findings on magnetic resonance imaging (MRI) of the brain

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

Strain engineering and one-dimensional organization of metal-insulator domains in single-crystal VO2 beams

Spatial phase inhomogeneity at the nano- to microscale is widely observed in strongly-correlated electron materials. The underlying mechanism and possibility of artificially controlling the phase inhomogeneity are still open questions of critical importance for both the phase transition physics and device applications. Lattice strain has been shown to cause the coexistence of metallic and insulating phases in the Mott insulator VO2. By continuously tuning strain over a wide range in single-crystal VO2 micro- and nanobeams, here we demonstrate the nucleation and manipulation of one-dimensionally ordered metal-insulator domain arrays along the beams. Mott transition is achieved in these beams at room temperature by active control of strain. The ability to engineer phase inhomogeneity with strain lends insight into correlated electron materials in general, and opens opportunities for designing and controlling the phase inhomogeneity of correlated electron materials for micro- and nanoscale device applications.Comment: 14 pages, 4 figures, with supplementary informatio

Variation in 5-hydroxymethylcytosine across human cortex and cerebellum

Background: The most widely utilized approaches for quantifying DNA methylation involve the treatment of genomic DNA with sodium bisulfite; however, this method cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Previous studies have shown that 5hmC is enriched in the brain, although little is known about its genomic distribution and how it differs between anatomical regions and individuals. In this study, we combine oxidative bisulfite (oxBS) treatment with the Illumina Infinium 450K BeadArray to quantify genome-wide patterns of 5hmC in two distinct anatomical regions of the brain from multiple individuals. Results: We identify 37,145 and 65,563 sites passing our threshold for detectable 5hmC in the prefrontal cortex and cerebellum respectively, with 23,445 loci common across both brain regions. Distinct patterns of 5hmC are identified in each brain region, with notable differences in the genomic location of the most hydroxymethylated loci between these brain regions. Tissue-specific patterns of 5hmC are subsequently confirmed in an independent set of prefrontal cortex and cerebellum samples. Conclusions: This study represents the first systematic analysis of 5hmC in the human brain, identifying tissue-specific hydroxymethylated positions and genomic regions characterized by inter-individual variation in DNA hydroxymethylation. This study demonstrates the utility of combining oxBS-treatment with the Illumina 450k methylation array to systematically quantify 5hmC across the genome and the potential utility of this approach for epigenomic studies of brain disorders

Decoherence in Crystals of Quantum Molecular Magnets

Decoherence in Nature has become one of the most pressing problems in physics. Many applications, including quantum information processing, depend on understanding it; and fundamental theories going beyond quantum mechanics have been suggested [1-3], where the breakdown of quantum theory appears as an 'intrinsic decoherence', mimicking environmental decoherence [4]. Such theories cannot be tested until we have a handle on ordinary environmental decoherence processes. Here we show that the theory for insulating electronic spin systems can make accurate predictions for environmental decoherence in molecular-based quantum magnets [5]. Experimental understanding of decoherence in molecular magnets has been limited by short decoherence times, which make coherent spin manipulation extremely difficult [6-9]. Here we reduce the decoherence by applying a strong magnetic field. The theory predicts the contributions to the decoherence from phonons, nuclear spins, and intermolecular dipolar interactions, for a single crystal of the Fe8 molecular magnet. In experiments we find that the decoherence time varies strongly as a function of temperature and magnetic field. The theoretical predictions are fully verified experimentally - there are no other visible decoherence sources. Our investigation suggests that the decoherence time is ultimately limited by nuclear spins, and can be extended up to about 500 microseconds, by optimizing the temperature, magnetic field, and nuclear isotopic concentrations.Comment: Submitted version including 11 pages, 3 figures and online supporting materials. Appeared on Nature Advance Online Publication (AOP) on July 20th, 2011. (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10314.html

TXNIP Regulates Peripheral Glucose Metabolism in Humans

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure. METHODS AND FINDINGS: We combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated to total body measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the gene product is also a regulator of glucose uptake. TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. CONCLUSIONS: TXNIP regulates both insulin-dependent and insulin-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic β-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM

Cervical spondylosis with spinal cord encroachment: should preventive surgery be recommended?

<p>Abstract</p> <p>Background</p> <p>It has been stated that individuals who have spondylotic encroachment on the cervical spinal cord without myelopathy are at increased risk of spinal cord injury if they experience minor trauma. Preventive decompression surgery has been recommended for these individuals. The purpose of this paper is to provide the non-surgical spine specialist with information upon which to base advice to patients. The evidence behind claims of increased risk is investigated as well as the evidence regarding the risk of decompression surgery.</p> <p>Methods</p> <p>A literature search was conducted on the risk of spinal cord injury in individuals with asymptomatic cord encroachment and the risk and benefit of preventive decompression surgery.</p> <p>Results</p> <p>Three studies on the risk of spinal cord injury in this population met the inclusion criteria. All reported increased risk. However, none were prospective cohort studies or case-control studies, so the designs did not allow firm conclusions to be drawn. A number of studies and reviews of the risks and benefits of decompression surgery in patients with cervical myelopathy were found, but no studies were found that addressed surgery in asymptomatic individuals thought to be at risk. The complications of decompression surgery range from transient hoarseness to spinal cord injury, with rates ranging from 0.3% to 60%.</p> <p>Conclusion</p> <p>There is insufficient evidence that individuals with spondylotic spinal cord encroachment are at increased risk of spinal cord injury from minor trauma. Prospective cohort or case-control studies are needed to assess this risk. There is no evidence that prophylactic decompression surgery is helpful in this patient population. Decompression surgery appears to be helpful in patients with cervical myelopathy, but the significant risks may outweigh the unknown benefit in asymptomatic individuals. Thus, broad recommendations for decompression surgery in suspected at-risk individuals cannot be made. Recommendations to individual patients must consider possible unique circumstances.</p

A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R

BACKGROUND: Autism is a pervasive developmental disorder characterized by a triad of deficits: qualitative impairments in social interactions, communication deficits, and repetitive and stereotyped patterns of behavior. Although autism is etiologically heterogeneous, family and twin studies have established a definite genetic basis. The inheritance of idiopathic autism is presumed to be complex, with many genes involved; environmental factors are also possibly contributory. The analysis of chromosome abnormalities associated with autism contributes greatly to the identification of autism candidate genes. CASE PRESENTATION: We describe a child with autistic disorder and an interstitial deletion on chromosome 4q. This child first presented at 12 months of age with developmental delay and minor dysmorphic features. At 4 years of age a diagnosis of Pervasive Developmental Disorder was made. At 11 years of age he met diagnostic criteria for autism. Cytogenetic studies revealed a chromosome 4q deletion. The karyotype was 46, XY del 4 (q31.3-q33). Here we report the clinical phenotype of the child and the molecular characterization of the deletion using molecular cytogenetic techniques and analysis of polymorphic markers. These studies revealed a 19 megabase deletion spanning 4q32 to 4q34. Analysis of existing polymorphic markers and new markers developed in this study revealed that the deletion arose on a paternally derived chromosome. To date 33 genes of known or inferred function are deleted as a consequence of the deletion. Among these are the AMPA 2 gene that encodes the glutamate receptor GluR2 sub-unit, GLRA3 and GLRB genes that encode glycine receptor subunits and neuropeptide Y receptor genes NPY1R and NPY5R. CONCLUSIONS: The deletion in this autistic subject serves to highlight specific autism candidate genes. He is hemizygous for AMPA 2, GLRA3, GLRB, NPY1R and NPY5R. GluR2 is the major determinant of AMPA receptor structure. Glutamate receptors maintain structural and functional plasticity of synapses. Neuropeptide Y and its receptors NPY1R and NPY5R play a role in hippocampal learning and memory. Glycine receptors are expressed in very early cortical development. Molecular cytogenetic studies and DNA sequence analysis in other patients with autism will be necessary to confirm that these genes are involved in autism