COVID-19–related laboratory coagulation findings

The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID-19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID-19 patients. Elevated D-dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID-19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID-19 patients but have currently no place in diagnosis or management in COVID-19 patients. For monitoring the heparin anticoagulant therapy, the anti-Xa assay is suggested, because the severe acute-phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.     

The role of working memory in the attentional control of pain

Attention is acknowledged as an important factor in the modulation of pain. A recent model proposed that an effective control of pain by attention should not only involve the disengagement of selective attention away from nociceptive stimuli, but should also guarantee that attention is maintained on the processing of pain-unrelated information without being recaptured by the nociceptive stimuli. This model predicts that executive functions are involved in the control of selective attention by preserving goal priorities throughout the achievement of cognitive activities. In the present study, we tested the role of working memory in the attentional control of nociceptive stimuli. In the control condition, participants had to discriminate the color of visually presented circles preceded by tactile distracters. In some trials (20%), tactile stimuli were replaced by novel nociceptive distracters in order to manipulate the attentional capture. In the working memory condition, participants had to respond to the visual stimulus presented one trial before, and were thus required to maintain the color of the visual stimulus in working memory during the entire inter-trial time interval. Results showed that, while novel nociceptive stimuli induced greater distraction than regular tactile stimuli in the control condition, the distractive effect was suppressed in the working memory condition. This suggests that actively rehearsing the feature of pain-unrelated and task-relevant targets successfully prevents attention from being captured by novel nociceptive distracters, independently of general task demands.     

A mutation affecting the latency-associated peptide of TGFbeta1 in Camurati-Engelmann disease enhances osteoclast formation in vitro

Camurati-Engelmann disease (CED) is a rare autosomal dominant disorder characterized by bone pain and osteosclerosis affecting the diaphysis of long bones. CED is caused by various missense mutations in the TGFB1 gene that encodes TGFbeta1, the most common of which is an arginine-cysteine amino acid change at codon 218 (R218C) in the latency-associated peptide domain of TGFbeta1. We studied osteoclast formation in vitro from peripheral blood mononuclear cells obtained from three related CED patients harboring the R218C mutation, in comparison with one family-based and several unrelated controls. Osteoclast formation was enhanced approximately 5-fold (P < 0.001) and bone resorption approximately 10-fold (P < 0.001) in CED patients, and the increase in osteoclast formation was inhibited by soluble TGFbeta type II receptor. Total serum TGFbeta1 levels were similar in affected and unaffected subjects, but concentrations of active TGFbeta1 in conditioned medium of osteoclast cultures was higher in the three CED patients than in the unaffected family member. We concluded that the R218C mutation increases TGFbeta1 bioactivity and enhances osteoclast formation in vitro. The activation of osteoclast activity noted here is consistent with clinical reports that have shown biochemical evidence of increased bone resorption as well as bone formation in CED.     

Comparative genetics in the grasses

Genetic mapping of wheat, maize, and rice and other grass species with common DNA probes has revealed remarkable conservation of gene content and gene order over the 60 million years of radiation of Poaceae. The linear organization of genes in some nine different genomes differing in basic chromosome number from 5 to 12 and nuclear DNA amount from 400 to 6,000 Mb, can be described in terms of only 25 “rice linkage blocks.” The extent to which this intergenomic colinearity is confounded at the micro level by gene duplication and micro-rearrangements is still an open question. Nevertheless, it is clear that the elucidation of the organization of the economically important grasses with larger genomes, such as maize (2n = 10, 4,500 Mb DNA), will, to a greater or lesser extent, be predicted from sequence analysis of smaller genomes such as rice, with only 400 Mb, which in turn may be greatly aided by knowledge of the entire sequence of Arabidopsis, which may be available as soon as the turn of the century. Comparative genetics will provide the key to unlock the genomic secrets of crop plants with bigger genomes than Homo sapiens.     

Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin

Skeletal muscle regeneration mainly depends on satellite cells, a population of resident muscle stem cells. However, our understanding of the molecular mechanisms underlying satellite cell activation is still largely undefined. Here, we show that Cripto, a regulator of early embryogenesis, is a novel regulator of muscle regeneration and satellite cell progression toward the myogenic lineage. Conditional inactivation of cripto in adult satellite cells compromises skeletal muscle regeneration, whereas gain of function of Cripto accelerates regeneration, leading to muscle hypertrophy. Moreover, we provide evidence that Cripto modulates myogenic cell determination and promotes proliferation by antagonizing the TGF-β ligand myostatin. Our data provide unique insights into the molecular and cellular basis of Cripto activity in skeletal muscle regeneration and raise previously undescribed implications for stem cell biology and regenerative medicine.     

The impact of executive functions on verb production in patients with Parkinson's disease

A growing number of studies suggest that language problems in Parkinson's disease (PD) are a result of executive dysfunction. To test this hypothesis we compared Dutch verb production in sentence context in a group of 28 PD patients with a control group consisting of 28 healthy participants matched for age, gender and education. All subjects were assessed on both verb production in sentence context as well as on cognitive functions relevant for sentence processing.PD patients scored lower than healthy controls on the verb production ability-scale and showed a response pattern in which performance was worse (1) in base than in derived position; (2) in present than in past tense; (3) for intransitive than in transitive verbs. For the PD group the score on the verb production ability-scale correlated significantly with set-switching and working memory. These results provide support for previous research suggesting that executive dysfunctions underlie the performance of the PD patients on verb production. It is furthermore suggested that because of failing automaticity, PD patients rely more on the cortically represented executive functions. Unfortunately, due to the disturbed intimate relation between the basal ganglia and the frontal cortex, these executive functions are also dysfunctional.