49 research outputs found

    Medical Implications of the Genetic Revolution

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    Métodos alternativos de muestreo para estimar la estructura y caracteres reproductivos de bosques

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    Aleppo pine had a large forest cover in North Africa and along the Mediterranean basin which management is not fully developed and new forest tools are required. In this research, the forest structure, epidometric characteristics and allometric relationships were studied in 79 plots covering four bioclimatic zones from natural even aged forests of Aleppo pine located between eastern Algeria to the western coastal part of Tunisia. To characterize the forest structure three sampling methods were carried out: classical inventories (recording all pine trees), and two simplified approach using one average size or five dominant pine tree per plot. Annual growth increment and cone production were only calculated for the average size tree. Furthermore, the analysis of variance showed non-significant differences recorded between bioclimatic zones in trunk or crown diameter using the two simplified approach. Moreover, a significant decrease from wetter to drier areas in total height, crown height, cone seed production was observed only for average size tree method. However, the analysis of covariance showed significant differences between both approaches in total height, trunk diameter and crown coverage which were largely influenced by the pine tree density. In future investigations, we confirmed previous research that the dominant tree is a good sampling method to examine the site fertility, whereas the average size tree constitutes a valuable approach to study the population growth and reproduction.El pino carrasco muestra una gran cobertura forestal, tanto en el norte de África como en toda la Cuenca Mediterránea, cuyo manejo no está totalmente desarrollado lo que requiere nuevas herramientas de manejo. En esta investigación, se estudiaron la estructura forestal, las características epidométricas y las relaciones alométricas de 79 parcelas distribuidas a lo largo de cuatro zonas bioclimáticas en bosques regulares de pino carrasco situados entre el este de Argelia y la costa este de Túnez. Para caracterizar la estructura forestal se aplicaron tres métodos de muestreo: inventario clásico (midiendo todos los pies) y dos propuestas más sencillas, usando un árbol medio o cinco pies dominantes por parcela. El análisis de varianza no mostraba diferencias significativas de las mediciones de diámetro de tronco y de copa realizadas entre las distintas zonas bioclimáticas usando ambos métodos. Por otra parte, se observó una disminución significativa de las zonas más húmedas a las más secas en altura toral, altura de copa y producción de semillas fue observada aplicando el método de árbol medio. Además, el análisis de covarianzas mostraba diferencias significativas, usando ambas metodologías, en los valores medios de altura total, diámetro de tronco y cobertura de copa que mostraron estar influenciados por los valores de la densidad de arbolado de cada zona. Para futuras investigaciones, confirmamos estudios previos que apuntaban que la propuesta de muestreo de árboles dominantes como un buen método de muestreo para caracterizar la calidad de sitio mientras que la de árbol medio constituye una valiosa propuesta para el estudio del crecimiento de poblaciones y sus características reproductivas

    Novel missense mutation (G314R) in a cystic fibrosis patient with hepatic failure

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    No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38583/1/10_ftp.pd

    Assessment of p.Phe508del-CFTR functional restoration in pediatric primary cystic fibrosis airway epithelial cells

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    © 2018 Sutanto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene can reduce function of the CFTR ion channel activity and impair cellular chloride secretion. The gold standard method to assess CFTR function of ion transport using the Ussing chamber requires a high number of airway epithelial cells grown at air-liquid interface, limiting the application of this method for high throughput screening of potential therapeutic compounds in primary airway epithelial cells (pAECs) featuring less common CFTR mutations. This study assessed an alternative approach, using a small scale halide assay that can be adapted for a personalized high throughput setting to analyze CFTR function of pAEC. Methods Pediatric pAECs derived from children with CF (pAEC CF ) were established and expanded as monolayer cultures, before seeding into 96-well plates for the halide assay. Cells were then transduced with an adenoviral construct containing yellow fluorescent protein (eYFP) reporter gene, alone or in combination with either wild-type CFTR (WT-CFTR) or p.Phe508-del CFTR. Four days post transduction, cells were stimulated with forskolin and genistein, and assessed for quenching of the eYFP signal following injection of iodide solution into the assay media. Results Data showed that pAEC CF can express eYFP at high efficiency following transduction with the eYFP construct. The halide assay was able to discriminate functional restoration of CFTR in pAEC CF treated with either WT-CFTR construct or the positive controls syntaxin 8 and B-cell receptor-associated protein 31 shRNAs. Significance The current study demonstrates that the halide assay can be adapted for pediatric pAEC CF to evaluate restoration of CFTR function. With the ongoing development of small molecules to modulate the folding and/or activity of various mutated CFTR proteins, this halide assay presents a small-scale personalized screening platform that could assess therapeutic potential of molecules across a broad range of CFTR mutations

    A novel treatment of cystic fibrosis acting on-target:cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR

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    We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts ‘on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment

    Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

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    Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

    Identification and rejection of pile-up jets at high pseudorapidity with the ATLAS detector

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    The rejection of forward jets originating from additional proton–proton interactions (pile-up) is crucial for a variety of physics analyses at the LHC, including Standard Model measurements and searches for physics beyond the Standard Model. The identification of such jets is challenging due to the lack of track and vertex information in the pseudorapidity range |η| &gt; 2.5. This paper presents a novel strategy for forward pile-up jet tagging that exploits jet shapes and topological jet correlations in pile-up interactions. Measurements of the per-jet tagging efficiency are presented using a data set of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of 13 TeV collected with the ATLAS detector. The fraction of pile-up jets rejected in the range 2.5 &lt; |η| &lt; 4.5 is estimated in simulated events with an average of 22 interactions per bunch-crossing. It increases with jet transverse momentum and, for jets with transverse momentum between 20 and 50 GeV, it ranges between 49% and 67% with an efficiency of 85% for selecting hard-scatter jets. A case study is performed in Higgs boson production via the vector-boson fusion process, showing that these techniques mitigate the background growth due to additional proton–proton interactions, thus enhancing the reach for such signatures

    Searches for the Z gamma decay mode of the Higgs boson and for new high-mass resonances in pp collisions at root s=13 TeV with the ATLAS detector

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    This article presents searches for the Zγ decay of the Higgs boson and for narrow high-mass resonances decaying to Zγ, exploiting Z boson decays to pairs of electrons or muons. The data analysis uses 36.1 fb−1 of pp collisions at s√=13s=13 recorded by the ATLAS detector at the CERN Large Hadron Collider. The data are found to be consistent with the expected Standard Model background. The observed (expected — assuming Standard Model pp → H → Zγ production and decay) upper limit on the production cross section times the branching ratio for pp → H → Zγ is 6.6. (5.2) times the Standard Model prediction at the 95% confidence level for a Higgs boson mass of 125.09 GeV. In addition, upper limits are set on the production cross section times the branching ratio as a function of the mass of a narrow resonance between 250 GeV and 2.4 TeV, assuming spin-0 resonances produced via gluon-gluon fusion, and spin-2 resonances produced via gluon-gluon or quark-antiquark initial states. For high-mass spin-0 resonances, the observed (expected) limits vary between 88 fb (61 fb) and 2.8 fb (2.7 fb) for the mass range from 250 GeV to 2.4 TeV at the 95% confidence level

    Metabolic syndrome among obese Qataris attending primary health care centers in Doha, 2010

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    Objectives: To determine the prevalence of metabolic syndrome among obese patients using the IDF definition and to identify factors that are associated with it. Materials and Methods: A cross-sectional randomized study was conducted at four primary care centers inside Doha, Qatar. One hundred and thirty-six Adults, ≥ 18 Qatari obese patients, were chosen by systematic random sampling. They were interviewed and screened for the presence of metabolic syndrome, which was diagnosed according to the International Diabetes Federation criteria: An abdominal circumference ≥ 94 cm in males or ≥ 80 cm in females, plus any two of the following: HDL cholesterol < 1.03 mmol / mL (< 40 mg / dL) [males] or < 1.3 mmol / mL (< 50 mg / dL) [females], Triglycerides ≥ 1.7 mmol / mL (≥150 mg / dL), Blood pressure ≥ 130 / 85 mmHg or the patient receiving antihypertensive treatment and baseline glycemia > 5.6 mmol / mL (> 100 mg / dL), or previously-diagnosed type 2 diabetes mellitus. Results: The overall prevalence of the metabolic syndrome among obese patients was 46.3%. The prevalence was higher in females (50%) than in males (42.4%). It was seen to increase with increasing body mass index class, from class 1 to class 2. The prevalence of metabolic comorbidities of abnormal waist circumference, raised blood pressure, raised fasting blood glucose, high triglycerides, and reduced high density lipoprotein was 88.2, 42.6, 32.4, 31.6, and 27.9%, respectively. Based on the logistic regression multivariable analysis, increasing age and being diabetic were the only significant associated factors that influenced the risk of having the metabolic syndrome. Conclusion: The prevalence of the metabolic syndrome was high, and the highest comorbidities were abnormal waist circumference and high blood pressure. Diabetes and increasing age were the only significant risk factors of having this syndrome

    Production of polyhydroxyalkanoate from sesame seed wastewater by sequencing batch reactor cultivation process of Haloferax mediterranei

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    Due to the high cost of bioplastic production, sesame wastewater, generated from the sesame seed hulling process, was investigated to be used as inexpensive and renewable carbon source for the production of biodegradable polyhydroxyalkanoate (PHA) by extreme Haloferax mediterranei. The sesame wastewater (SWW) was hydrolyzed using different concentrations of hydrochloric acid (0.4. 1.00 and 2.00 M) at different period of times (15, 60 and 90 min). The concentration of salt (NaCl) and nitrogen source (NH4Cl and yeast) required for H. mediterranei cells growth and the accumulation of PHA biopolymer was optimized. A maximum 0.53 g/L concentration of PHA was achieved when the SWW extract media was supplemented with 100 g/L NaCl and 6.0 g/L yeast extract. The cultivation was scaled-up using sequencing batch reactor (SBR) fermentation under non-sterile conditions. The SBR results showed that SWW needs an auxiliary carbon source to obtain high PHA production. Consequently, the system fed with SWW and glucose produced higher PHA (20.9 g/L) than the system fed with SWW
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