The anti-cyclic citrullinated peptide response in tuberculosis patients is not citrulline-dependent and sensitive to treatment

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Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1

Disruptions in axonal transport have been implicated in a wide range of neurodegenerative diseases. Cramping 1 (Cra1/+) and Legs at odd angles (Loa/+) mice, with hypomorphic mutations in the dynein heavy chain 1 gene, which encodes the ATPase of the retrograde motor protein dynein, were originally reported to exhibit late onset motor neuron disease. Subsequent, conflicting reports suggested that sensory neuron disease without motor neuron loss underlies the phenotypes of Cra1/+ and Loa/+ mice. Here, we present behavioral and anatomical analyses of Cra1/+ mice. We demonstrate that Cra1/+ mice exhibit early onset, stable behavioral deficits, including abnormal hindlimb posturing and decreased grip strength. These deficits do not progress through 24 months of age. No significant loss of primary motor neurons or dorsal root ganglia sensory neurons was observed at ages where the mice exhibited clear symptomatology. Instead, there is a decrease in complexity of neuromuscular junctions. These results indicate that disruption of dynein function in Cra1/+ mice results in abnormal morphology of neuromuscular junctions. The time course of behavioral deficits, as well as the nature of the morphological defects in neuromuscular junctions, suggests that disruption of dynein function in Cra1/+ mice causes a developmental defect in synapse assembly or stabilization

A genome-wide genetic map of NB-LRR disease resistance loci in potato

Like all plants, potato has evolved a surveillance system consisting of a large array of genes encoding for immune receptors that confer resistance to pathogens and pests. The majority of these so-called resistance or R proteins belong to the super-family that harbour a nucleotide binding and a leucine-rich-repeat domain (NB-LRR). Here, sequence information of the conserved NB domain was used to investigate the genome-wide genetic distribution of the NB-LRR resistance gene loci in potato. We analysed the sequences of 288 unique BAC clones selected using filter hybridisation screening of a BAC library of the diploid potato clone RH89-039-16 (S. tuberosum ssp. tuberosum) and a physical map of this BAC library. This resulted in the identification of 738 partial and full-length NB-LRR sequences. Based on homology of these sequences with known resistance genes, 280 and 448 sequences were classified as TIR-NB-LRR (TNL) and CC-NB-LRR (CNL) sequences, respectively. Genetic mapping revealed the presence of 15 TNL and 32 CNL loci. Thirty-six are novel, while three TNL loci and eight CNL loci are syntenic with previously identified functional resistance genes. The genetic map was complemented with 68 universal CAPS markers and 82 disease resistance trait loci described in literature, providing an excellent template for genetic studies and applied research in potato

Mostly concurrent compaction for mark-sweep GC

A memory manager that does not move objects may suffer from memory fragmentation. Compaction is an efficient, and sometimes inevitable, mechanism for reducing fragmentation. A Mark-Sweep garbage collector must occasionally execute a compaction, usually while the application is suspended. Compaction during pause time can have detrimental effects for interactive applications that require guarantees for maximal pause time. This work presents a method for reducing the pause time created by compaction at a negligible throughput hit. The solution is most suitable when added to a Mark-Sweep garbage collector. Compaction normally consists of two major activities: the moving of objects and the update of all the objects ’ references to the new locations. We present a method for executing the reference updates concurrently, thus eliminating a substantial portion of the pause time hit. To reduce the time for moving objects in each compaction, we use the existing technique of incremental compaction, but select the optimal area to compact. Selecting the area is done after executing the mark and sweep phases, and is based on their results. We implemented our compaction on top of the IBM J9 JVM V2.2, and present measurements of its effect on pause time, throughput, and mutator utilization. We show that our compaction is indeed an efficient fragmentation reduction tool, and that it improves the performance of a few of the benchmarks we used, with very little increase in the pause time (typically far below the cost of the mark phase)

Early Detection of Pulmonary Embolism in a General Patient Population Immediately Upon Hospital Admission Using Machine Learning to Identify New, Unidentified Risk Factors: Model Development Study

BackgroundUnder- or late identification of pulmonary embolism (PE)—a thrombosis of 1 or more pulmonary arteries that seriously threatens patients’ lives—is a major challenge confronting modern medicine. ObjectiveWe aimed to establish accurate and informative machine learning (ML) models to identify patients at high risk for PE as they are admitted to the hospital, before their initial clinical checkup, by using only the information in their medical records. MethodsWe collected demographics, comorbidities, and medications data for 2568 patients with PE and 52,598 control patients. We focused on data available prior to emergency department admission, as these are the most universally accessible data. We trained an ML random forest algorithm to detect PE at the earliest possible time during a patient’s hospitalization—at the time of his or her admission. We developed and applied 2 ML-based methods specifically to address the data imbalance between PE and non-PE patients, which causes misdiagnosis of PE. ResultsThe resulting models predicted PE based on age, sex, BMI, past clinical PE events, chronic lung disease, past thrombotic events, and usage of anticoagulants, obtaining an 80% geometric mean value for the PE and non-PE classification accuracies. Although on hospital admission only 4% (1942/46,639) of the patients had a diagnosis of PE, we identified 2 clustering schemes comprising subgroups with more than 61% (705/1120 in clustering scheme 1; 427/701 and 340/549 in clustering scheme 2) positive patients for PE. One subgroup in the first clustering scheme included 36% (705/1942) of all patients with PE who were characterized by a definite past PE diagnosis, a 6-fold higher prevalence of deep vein thrombosis, and a 3-fold higher prevalence of pneumonia, compared with patients of the other subgroups in this scheme. In the second clustering scheme, 2 subgroups (1 of only men and 1 of only women) included patients who all had a past PE diagnosis and a relatively high prevalence of pneumonia, and a third subgroup included only those patients with a past diagnosis of pneumonia. ConclusionsThis study established an ML tool for early diagnosis of PE almost immediately upon hospital admission. Despite the highly imbalanced scenario undermining accurate PE prediction and using information available only from the patient’s medical history, our models were both accurate and informative, enabling the identification of patients already at high risk for PE upon hospital admission, even before the initial clinical checkup was performed. The fact that we did not restrict our patients to those at high risk for PE according to previously published scales (eg, Wells or revised Genova scores) enabled us to accurately assess the application of ML on raw medical data and identify new, previously unidentified risk factors for PE, such as previous pulmonary disease, in general populations

ASSOCIATION OF CHOROIDAL THICKNESS WITH RHEGMATOGENOUS RETINAL DETACHMENT REPAIR

PURPOSETo compare the choroidal thickness before and after pars plana vitrectomy for rhegmatogenous retinal detachment repair. METHODSA retrospective case series of rhegmatogenous retinal detachment patients presenting between January 2015 and September 2020. Subfoveal choroidal thickness (SFCT) and anatomical success were measured in operated eyes and fellow eyes at presentation, as well as 3 months and 6 months after pars plana vitrectomy for rhegmatogenous retinal detachment repair. RESULTSA total of 93 patients (males 59%) with a mean age of 61.8 ± 15.2 years were included. Eighty-one patients were anatomically successful (Group 1) and 12 redetached (Group 2). The mean SFCT of the operated eye at presentation was 258.3 ± 82.0 µm in comparison with 257.5 ± 83.7 µm in the fellow eye (P = 0.96). Group 2 presented with thicker SFCT than Group 1 at baseline (309.2 ± 56.2 vs. 250.7 ± 82.8 µm; P = 0.01). Both groups demonstrated thinning trend throughout follow-up. At 6-month follow-up, the mean SFCT was 225.6 ± 75.5 µm (P = 0.05). Fellow-eye SFCT was stable throughout follow-up (257 ± 83.7 at baseline vs. 255 ± 80.2 µm at 6 months). CONCLUSIONEyes with rhegmatogenous retinal detachment demonstrated thinning in the SFCT after vitrectomy surgery. Eyes with recurrent retinal detachment presented with a thicker choroid at baseline. Thicker SFCT at presentation may play a role in retinal redetachment

Elevated Levels of Eotaxin-2 in Serum of Fibromyalgia Patients

FMS patients demonstrate an altered profile of chemokines relative to healthy controls (HC). Eotaxin-2 is a potent chemoattractant distributed in a variety of tissues. The aim of the study was to compare serum levels of eotaxin-2 between FMS patients and HC and to examine a potential correlation between eotaxin-2 levels and clinical parameters of FMS. Methods. 50 patients with FMS and 15 HC were recruited. Data on the severity of FMS symptoms and depression were collected. Serum levels of eotaxin-2 (ELISA) were determined in all participants. High-sensitive CRP (hs-CRP) was measured in the FMS group. Results. The FMS cohort included predominantly females (84%), mean age of 49, and mean disease duration of 6 years. FMS patients exhibited significantly higher eotaxin-2 levels (pg/ml) versus HC: 833 (±384) versus 622 (±149), p=0.04. Mean hs-CRP level among FMS patients was 4.8 ± 6 mg/l, a value not indicative of acute inflammation. No correlation was found between eotaxin-2 and hs-CRP levels. No correlation was found between eotaxin-2 and severity measures of FMS or depression. Conclusion. Eotaxin-2 does not appear to be a candidate for a disease activity biomarker in FMS. Further research is warranted into the role of this chemokine in the pathophysiology of the FMS

Elevated Levels of Eotaxin-2 in Serum of Fibromyalgia Patients

FMS patients demonstrate an altered profile of chemokines relative to healthy controls (HC). Eotaxin-2 is a potent chemoattractant distributed in a variety of tissues. The aim of the study was to compare serum levels of eotaxin-2 between FMS patients and HC and to examine a potential correlation between eotaxin-2 levels and clinical parameters of FMS. Methods. 50 patients with FMS and 15 HC were recruited. Data on the severity of FMS symptoms and depression were collected. Serum levels of eotaxin-2 (ELISA) were determined in all participants. High-sensitive CRP (hs-CRP) was measured in the FMS group. Results. The FMS cohort included predominantly females (84%), mean age of 49, and mean disease duration of 6 years. FMS patients exhibited significantly higher eotaxin-2 levels (pg/ml) versus HC: 833 (±384) versus 622 (±149), p=0.04. Mean hs-CRP level among FMS patients was 4.8 ± 6 mg/l, a value not indicative of acute inflammation. No correlation was found between eotaxin-2 and hs-CRP levels. No correlation was found between eotaxin-2 and severity measures of FMS or depression. Conclusion. Eotaxin-2 does not appear to be a candidate for a disease activity biomarker in FMS. Further research is warranted into the role of this chemokine in the pathophysiology of the FMS