A bumpy ride on the diagnostic bench of massive parallel sequencing, the case of the mitochondrial genome

The advent of massive parallel sequencing (MPS) has revolutionized the field of human molecular genetics, including the diagnostic study of mitochondrial (mt) DNA dysfunction. The analysis of the complete mitochondrial genome using MPS platforms is now common and will soon outrun conventional sequencing. However, the development of a robust and reliable protocol is rather challenging. A previous pilot study for the re-sequencing of human mtDNA revealed an uneven coverage, affecting predominantly part of the plus strand. In an attempt to address this problem, we undertook a comparative study of standard and modified protocols for the Ion Torrent PGM system. We could not improve strand representation by altering the recommended shearing methodology of the standard workflow or omitting the DNA polymerase amplification step from the library construction process. However, we were able to associate coverage bias of the plus strand with a specific sequence motif. Additionally, we compared coverage and variant calling across technologies. The same samples were also sequenced on a MiSeq device which showed that coverage and heteroplasmic variant calling were much improved

An Asymptomatic Case of Wolff-Parkinson-White Syndrome with Right-sided Free-wall Accessory Pathway and Left Ventricular Dysfunction

AbstractA 16-year-old girl with a known history of asymptomatic Wolff-Parkinson-White syndrome exhibited signs of left ventricular (LV) septal akinesia and LV dysfunction during routine follow-up. A 12-lead surface ECG showed pre-excitation, a predominantly negative delta wave in V1 and left axis deviation, which was consistent with the presence of a right free-wall accessory pathway. Radiofrequency ablation of the anterolateral right atrium around the local shortest atrium-to-ventricle interval created the accessory pathway block. An echocardiogram taken one month after the procedure revealed that LV septal wall motion had normalized and that LV ejection fraction had improved from 50% before the ablation to 64% after the ablation. Most previous reports of asymptomatic patients of WPW with LV septal dyskinesia and dysfunction have described right septal or posteroseptal accessory pathways. This patient reported here represents a rare case with right free-wall accessory pathway and LV dysfunction without tachycardia

Deposition of tin oxide, iridium and iridium oxide films by metal-organic chemical vapor deposition for electrochemical wastewater treatment

In this research, the specific electrodes were prepared by metal-organic chemical vapor deposition (MOCVD) in a hot-wall CVD reactor with the presence of O2 under reduced pressure. The Ir protective layer was deposited by using (Methylcyclopentadienyl) (1,5-cyclooctadiene) iridium (I), (MeCp)Ir(COD), as precursor. Tetraethyltin (TET) was used as precursor for the deposition of SnO2 active layer. The optimum condition for Ir film deposition was at 300 °C, 125 of O2/(MeCp)Ir(COD) molar ratio and 12 Torr of total pressure. While that of SnO2 active layer was at 380 °C, 1200 of O2/TET molar ratio and 15 Torr of total pressure. The prepared SnO2/Ir/Ti electrodes were tested for anodic oxidation of organic pollutant in a simple three-electrode electrochemical reactor using oxalic acid as model solution. The electrochemical experiments indicate that more than 80% of organic pollutant was removed after 2.1 Ah/L of charge has been applied. The kinetic investigation gives a two-step process for organic pollutant degradation, the kinetic was zero-order and first-order with respect to TOC of model solution for high and low TOC concentrations, respectively

DERMITE DE CONTACTO ALÉRGICA AO METILCLORO- E METILISOTIAZOLINONA NUMA CAMA DE ÁGUA?

We here report a case of a severe generalized allergic contact dermatitis from contact with the surface of a water bed which happened to be contaminated with the water inside that had been treated with the biocide mixture of methylchloro- and methylisothiazolinone.KEYWORDS – Dermatitis, Allergic Contact; Thiazoles.Descrevemos um caso clínico de dermite de contacto alérgica, grave e generalizada, resultante de con- tacto com a superfície de cama de água, que estava contaminada pela água do interior que tinha sido tratada pela mistura biocida de metilcloro- e metilisotiazolinona.PALAVRAS-CHAVE – Dermatite de Contacto Alérgica

Pyruvate dehydrogenase E1α deficiency in a family : Different clinical presentation in two siblings

The pyruvate dehydrogenase (PDH) complex (PDHc) is responsible for the irreversible conversion of pyruvate to acetyl-CoA. PDHc is a multienzyme complex consisting of three catalytic subunits, pyruvate decarboxylase (E1), dihydrolipoamideacetyltransferase (E2), dihydrolipoamide dehydrogenase (E3), and two regulatorysubunits, E1 kinase and phospho-E1 phosphatase. An abnormal E1asubunit, whosegene is located on the X chromosome, is the most frequent cause of PDH deÐciency. The clinical presentation of a PDH-E1adeÐciency (McKusick 312170) is variable.We have analysed a family with a mutation (36 bp insertion in exon 10) in thePDH-E1agene in which the male member had a diferent and less severe clinicalpicture than his afected sister.Facultad de Ciencias Médica

Addressing the pain-points of single-use intensified multi-product downstream and liquid processing in a dancefloor production room layout

The sales of biologics will reach over $300 billion in 2020 and the market continues to have accelerated double-digit growth under the COVID-19 burden, thus biopharmaceutical companies continue to pipeline biologics for a mounting global patient base. Nevertheless, biologics are changing and the needs of their manufacturing are changing with them. Emerging biologics (e.g., antibody–drug conjugates, viral vectors, mRNA, bi/multi-specifics) are coming with complex or lean manufacturing requirements. Additionally, the global market is searching for more affordable & sustainable biologics and biosimilars, creating an increasingly competitive space within the emerging countries who seek to manufacture locally. The BioPhorum Operations Group (BPOG), a cross-industry organization of biopharmaceutical end users and suppliers collected biopharmaceutical industry drivers stating; - 90% reduction in capital expenditure (CAPEX) and manufacturing costs in the next decade. - reduce product changeover times by 90% to improve responses to variability in demand - drive down new facility build times by 70% The question is, how does this translate to actionable and prioritized points of improvement for a biological implementer & supplier to work on? With this general need in mind, combining Design Thinking methodology and insights from single-use biological manufacturing users were gathered through an extended survey with key biopharma industry companies and institutes representing the various user groups. All interviewee responses were populated, to enable the categorization and sorting of distinct user perceptions of likes, pain-points, and benefits. The outcome of the survey was thestarting point to define what are the critical components for a sustainable technology roadmap to address the needs for the rapidly intensifying biologics manufacturing market. In the presented work will be an overview of these validated pain-points, an explanation of the corresponding technology characteristic which address the underlying user need and a journey along the downstream purification steps. The format will be interactive with feedback questions and presentation of anonymous answers from the audience. The presentation will finish with concluding remarks on how sustainable single use processing could benefit the manufacturing of biologics

Pyruvate dehydrogenase E1α deficiency in a family : Different clinical presentation in two siblings

The pyruvate dehydrogenase (PDH) complex (PDHc) is responsible for the irreversible conversion of pyruvate to acetyl-CoA. PDHc is a multienzyme complex consisting of three catalytic subunits, pyruvate decarboxylase (E1), dihydrolipoamideacetyltransferase (E2), dihydrolipoamide dehydrogenase (E3), and two regulatorysubunits, E1 kinase and phospho-E1 phosphatase. An abnormal E1asubunit, whosegene is located on the X chromosome, is the most frequent cause of PDH deÐciency. The clinical presentation of a PDH-E1adeÐciency (McKusick 312170) is variable.We have analysed a family with a mutation (36 bp insertion in exon 10) in thePDH-E1agene in which the male member had a diferent and less severe clinicalpicture than his afected sister.Facultad de Ciencias Médica