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961.
Background
The aims of this study were to investigate the safety of combined intravenous, oral and topical tranexamic acid (TXA) in primary total knee replacement. We assessed dose-related efficacy on hemoglobin level, transfusion, length of stay and thromboembolic complications. In addition, TXA safety in patients with previous history of thromboembolism > 12 months ago was monitored specifically.Methods
From January 2013 until January 2016, 922 patients were included who received TXA after primary total knee replacement. Patients without TXA administration or with thromboembolic events < 12 months ago were excluded. TXA dosage groups were divided into ≤ 10 mg/kg, > 10–25 mg/kg and > 25–50 mg/kg.Results
Between the three TXA groups no significant difference was found in thromboembolic complications (deep venous thrombosis (DVT) and pulmonary embolism (PE)), wound leakage and transfusion rate. For patients with DVT or PE in their history > 12 months ago specifically, no more complications were noted in higher-TXA-dosage groups compared to the low-dosage group. Length of stay was shorter in the highest-TXA-dosage group compared with lower-dosage groups (median two vs three days). With high TXA dose a smaller difference between pre- and postoperative Hb was found: the > 25–50 mg/kg TXA group had a 0.419 mmol/l smaller decrease in postoperative hemoglobin compared to the lowest-dosage group (P < 0.05).Conclusion
Combined intravenous, oral and topical TXA is effective in knee replacement and can safely be given to patients with a thromboembolic history > 12 months ago. High dosage (> 25–50 mg/kg) TXA resulted in the smallest decrease in postoperative hemoglobin. 相似文献962.
Validation and application of a novel integrated genetic screening method to a cohort of 1,112 men with idiopathic azoospermia or severe oligozoospermia
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Manon S. Oud Liliana Ramos Moira K. O'Bryan Robert I. McLachlan Özlem Okutman Stephane Viville Petra F. de Vries Dominique F.C.M. Smeets Dorien Lugtenberg Jayne Y. Hehir‐Kwa Christian Gilissen Maartje van de Vorst Lisenka E.L.M. Vissers Alexander Hoischen Aukje M. Meijerink Kathrin Fleischer Joris A. Veltman Michiel J. Noordam 《Human mutation》2017,38(11):1592-1605
Microdeletions of the Y chromosome (YCMs), Klinefelter syndrome (47,XXY), and CFTR mutations are known genetic causes of severe male infertility, but the majority of cases remain idiopathic. Here, we describe a novel method using single molecule Molecular Inversion Probes (smMIPs), to screen infertile men for mutations and copy number variations affecting known disease genes. We designed a set of 4,525 smMIPs targeting the coding regions of causal (n = 6) and candidate (n = 101) male infertility genes. After extensive validation, we screened 1,112 idiopathic infertile men with non‐obstructive azoospermia or severe oligozoospermia. In addition to five chromosome YCMs and six other sex chromosomal anomalies, we identified five patients with rare recessive mutations in CFTR as well as a patient with a rare heterozygous frameshift mutation in SYCP3 that may be of clinical relevance. This results in a genetic diagnosis in 11–17 patients (1%–1.5%), a yield that may increase significantly when more genes are confidently linked to male infertility. In conclusion, we developed a flexible and scalable method to reliably detect genetic causes of male infertility. The assay consolidates the detection of different types of genetic variation while increasing the diagnostic yield and detection precision at the same or lower price compared with currently used methods. 相似文献
963.
Erythropoietin (Epo) is a glycoprotein hormone that promotes the production of red blood cells. Recombinant human Epo (rhEpo) is illicitly used to improve performance in endurance sports. Doping in sports is discouraged by the screening of athletes for rhEpo. Both direct tests (indicating the presence of exogeneous Epo isoforms) and indirect tests (indicating hematological changes induced by exogenous Epo administration) can be used for Epo detection. At present, the test adopted by the World Anti Doping Agency is based on a combination of isoelectric focusing and double immunoblotting, and distinguishes between endogenous and rhEpo. However, the adopted monoclonal anti-Epo antibodies are not monospecific. Therefore, the test can occasionally lead to the false-positive detection of rhEpo (epoetin-beta) in post-exercise, protein-rich urine, or in case of contamination of the sample with microorganisms. An improved preanalytical care may counteract a lot of these problems. Adaptation of the criteria may be helpful to further refine direct Epo testing. Indirect tests have the disadvantage that they require blood instead of urine samples, but they can be applied to detect a broader range of performance improving techniques which are illicitly used in sports. 相似文献
964.
965.
Microdeletions of ELP4 Are Associated with Language Impairment,Autism Spectrum Disorder,and Mental Retardation
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Laura Addis Joo Wook Ahn Richard Dobson Abhishek Dixit Caroline M Ogilvie Dalila Pinto Andrea K Vaags Hilary Coon Pauline Chaste Scott Wilson Jeremy R Parr Joris Andrieux Bruno Lenne Zeynep Tumer Vincenzo Leuzzi Kristina Aubell Hannele Koillinen Sarah Curran Christian R Marshall Stephen W Scherer Lisa J Strug David A Collier Deb K Pal 《Human mutation》2015,36(9):842-850
Copy‐number variations (CNVs) are important in the aetiology of neurodevelopmental disorders and show broad phenotypic manifestations. We compared the presence of small CNVs disrupting the ELP4‐PAX6 locus in 4,092 UK individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridization, with WTCCC controls (n = 4,783). The phenotypic analysis was then extended using the DECIPHER database. We followed up association using an autism patient cohort (n = 3,143) compared with six additional control groups (n = 6,469). In the clinical discovery series, we identified eight cases with ELP4 deletions, and one with a partial duplication of ELP4 and PAX6. These cases were referred for neurological phenotypes including language impairment, developmental delay, autism, and epilepsy. Six further cases with a primary diagnosis of autism spectrum disorder (ASD) and similar secondary phenotypes were identified with ELP4 deletions, as well as another six (out of nine) with neurodevelopmental phenotypes from DECIPHER. CNVs at ELP4 were only present in 1/11,252 controls. We found a significant excess of CNVs in discovery cases compared with controls, P = 7.5 × 10?3, as well as for autism, P = 2.7 × 10?3. Our results suggest that ELP4 deletions are highly likely to be pathogenic, predisposing to a range of neurodevelopmental phenotypes from ASD to language impairment and epilepsy. 相似文献
966.
Involvement of interstitial telomeric sequences in two new cases of mosaicism for autosomal structural rearrangements
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967.
The diagnostic value of next generation sequencing in familial nonsyndromic congenital heart defects
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968.
Genotypic and phenotypic variation in six patients with solitary median maxillary central incisor syndrome
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969.
970.
Clarissa Campbell Francois Marchildon Anthony J. Michaels Naofumi Takemoto Joris van der Veeken Michail Schizas Yuri Pritykin Christina S. Leslie Andrew M. Intlekofer Paul Cohen Alexander Y. Rudensky 《Proceedings of the National Academy of Sciences of the United States of America》2020,117(52):33446
Reduced nutrient intake is a widely conserved manifestation of sickness behavior with poorly characterized effects on adaptive immune responses. During infectious challenges, naive T cells encountering their cognate antigen become activated and differentiate into highly proliferative effector T cells. Despite their evident metabolic shift upon activation, it remains unclear how effector T cells respond to changes in nutrient availability in vivo. Here, we show that spontaneous or imposed feeding reduction during infection decreases the numbers of splenic lymphocytes. Effector T cells showed cell-intrinsic responses dependent on the nuclear receptor Farnesoid X Receptor (FXR). Deletion of FXR in T cells prevented starvation-induced loss of lymphocytes and increased effector T cell fitness in nutrient-limiting conditions, but imparted greater weight loss to the host. FXR deficiency increased the contribution of glutamine and fatty acids toward respiration and enhanced cell survival under low-glucose conditions. Provision of glucose during anorexia of infection rescued effector T cells, suggesting that this sugar is a limiting nutrient for activated lymphocytes and that alternative fuel usage may affect cell survival in starved animals. Altogether, we identified a mechanism by which the host scales immune responses according to food intake, featuring FXR as a T cell-intrinsic sensor.Acute infection is often accompanied by physiological and behavioral alterations including changes in body temperature, anhedonia, and anorexia. Reduced feeding is a widely conserved manifestation of sickness behavior that affects host fitness in a context-dependent manner (1–3). While the effects of infection-induced anorexia on tissue function are well documented (2–5), its impact on immune responses remains poorly characterized. Despite enhancing bacterial clearance early during infection (6), starvation can reduce host resistance to subsequent challenges (7), suggesting that nutrient deprivation may limit adaptive immune responses.During an infectious challenge, adaptive lymphocytes quickly exit quiescence and undergo vigorous proliferation, with populations of antigen-specific cells expanding over 20,000-fold numerically (8). To support their heightened metabolic demands, activated lymphocytes greatly increase their glycolytic capacity and the ability to acquire nutrients from the environment (9). Although the connection between cell-intrinsic metabolism and the effector function of lymphocytes has been extensively investigated, the responses of immune cells to changes in the metabolic state of the host, particularly in the context of anorexia of infection, are not fully understood.We hypothesized that animals scale their immune responses according to nutrient availability and that lymphocytes display cell-intrinsic responses to the metabolic state of the host. We report that decreased feeding during infection causes a reduction in lymphocyte numbers that can be restored by provision of glucose. We further show that the nuclear receptor Farnesoid X Receptor (FXR), which regulates hepatic responses to fasting and refeeding (10, 11), is up-regulated upon T cell activation and plays a cell-intrinsic role in mediating starvation-induced loss of lymphocytes and in their fuel utilization. Impairing FXR-dependent T cell contraction in response to diminished nutrient availability resulted in greater weight loss and lower glycemia, indicating that the ability to scale the immune compartment according to food availability may affect organismal energy homeostasis during infection. Our results suggest that induction of FXR expression in activated T cells renders the effector T cell compartment sensitive to changes in host metabolism and that specific fuel utilization programs may support lymphocyte survival under nutrient-limiting conditions. 相似文献