The region of the dystrophin gene containing introns 45–50 is characterized by a high rate of recombination events that give rise to large deletions causing dystrophinopathy. The nucleotide sequence ...of this intronic region has recently been released in GenBank. With the aim of further understanding the mechanism favoring the occurrence of these deletions, we have characterized the distribution of introns 47 and 48 deletion endpoints in 39 dystrophinopathy patients. In 14 of these patients we were able to sequence the break junction. On these sequences we were able to identify several intronic motifs that could predispose to DNA double-strand breaks. Our results, combined with other literature data, show that unequal homologous recombination is a very poorly represented event in the dystrophin gene, whereas junction features are suggestive of a model of recombination in which DNA double-strand breaks are incorrectly repaired by a nonhomologous end-joining mechanism. The correlation among recombination rate, deletion frequency, and percentage of repetitive elements is discussed.
Transcriptional profiles of an alveolar rhabdomyosarcoma (RMS) and of a RMS cell line were reconstructed by a computational and statistical approach. Expression data of 29,963 genes in 11 adult human ...healthy tissues and in 37 tumour tissues were analysed for comparison. We identified 202 genes differentially expressed in at least one RMS sample, as compared with normal skeletal muscle. Among them, 107 resulted specifically overexpressed in RMS, but in no tumour affecting other tissues. Cluster analysis applied to expression data detected a series of genes presumably co-expressed with genes encoding known tumour markers and/or reportedly involved in genesis or development of rhabdomyosarcoma. This study succeeded in identifying a number of genes, which become candidates for in vitro study, thus facilitating discovery of novel tumour markers or targets for drug therapy.
Introduction
The standard of care for thrombotic antiphospholipid syndrome (APS) is anticoagulation with vitamin K antagonists (VKAs). Prothrombin time, and its corresponding international normalized ...ratio (INR), is the laboratory test routinely performed to assess anticoagulation. Self-management of VKA therapy using point-of-care (POC) devices seems to be an attractive option.
Purpose/objective
To evaluate the accuracy of a POC device (CoaguChek XS) in APS patients by comparing it with venous laboratory INR. Furthermore, we analyzed whether other clinical and laboratory features could interfere with the CoaguChek XS results.
Patients and methods
This is a single-center cross-sectional study with 94 APS patients from a tertiary rheumatology clinic performed from August 2014 to March 2015. The comparison between CoaguChek XS and venous laboratory INR results was evaluated using the coefficient of determination (r) followed by the Bland–Altman test. A paired t-test was also applied. A difference of up to ±0.5 INR unit between the two systems was considered clinically acceptable.
Results
The mean CoaguChek-INR was 2.94 ± 1.41 and venous laboratory INR was 2.43±0.86, with a correlation coefficient (r) of 0.95. Categorizing INR values in ranges (INR <2, INR 2–3, INR 3–4, and INR >4), we found that the INR >4 group presented a lower correlation (r = 0.64) compared to the other ranges (p < 0.05). Although both methods were highly correlated, CoaguChek XS showed higher values than the venous laboratory INR, with an increased average of 0.42 ± 0.54. Therefore, we proposed a simple linear regression model to predict the venous laboratory INR values, using results obtained from CoaguChek XS. A difference ≤0.5 INR unit between the two systems was observed in 57.4% of patients, and the aPL profile did not influence the results.
Conclusion
Although CoaguChek XS and venous laboratory INR demonstrated a good linear correlation in the group of INR ≤4, extra caution should be taken in APS patients, since a reasonable proportion of patients can present differences in INR results that are not acceptable. We do not recommend routine POC in APS patients.
Background: Peri‐implantitis is an inflammatory condition that can lead to implant loss. The aim of this descriptive retrospective study is to describe the histopathologic findings in soft tissue ...biopsies of implants with peri‐implantitis.
Methods: Thirty‐six human peri‐implantitis biopsies were analyzed using light microscopy (LM) and scanning electron microscopy (SEM). The composition of foreign materials found in the tissues was assessed using an energy dispersive x‐ray spectrometer.
Results: At the LM level, the inflammatory lesion of peri‐implantitis was in most cases a mixture of subacute and chronic inflammation dominated by plasma cells. At the SEM level, radiopaque foreign bodies were identified in 34 of the 36 biopsies. The predominant foreign bodies found were titanium and dental cement. These foreign materials were surrounded by inflammatory cells.
Conclusions: At present, the exact mechanism for introduction of these materials and their role in peri‐implantitis is unknown. Further research is warranted to determine their etiology and potential role in pathogenesis.
The advent of multidrug resistance among pathogenic bacteria has attracted great attention worldwide. As a response to this growing challenge, diverse studies have focused on the development of novel ...anti-infective therapies, including antimicrobial peptides (AMPs). The biological properties of this class of antimicrobials have been thoroughly investigated, and membranolytic activities are the most reported mechanisms by which AMPs kill bacteria. Nevertheless, an increasing number of works have pointed to a different direction, in which AMPs are seen to be capable of displaying non-lytic modes of action by internalizing bacterial cells. In this context, this review focused on the description of the in vitro and in vivo antibacterial and antibiofilm activities of non-lytic AMPs, including indolicidin, buforin II PR-39, bactenecins, apidaecin, and drosocin, also shedding light on how AMPs interact with and further translocate through bacterial membranes to act on intracellular targets, including DNA, RNA, cell wall and protein synthesis.
Postgadolinium MR imaging is crucial for brain tumor diagnosis and morphometric assessment. We compared brain tumor enhancement visualization and the "target" object morphometry obtained with the ...most commonly used 3D MR imaging technique, MPRAGE, with 2 other routinely available techniques: sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) and volumetric interpolated brain examination (VIBE).
Fifty-four contrast-enhancing tumors (38 gliomas and 16 metastases) were assessed using MPRAGE, VIBE, and SPACE techniques randomly acquired after gadolinium-based contrast agent administration on a 3T scanner. Enhancement conspicuity was assessed quantitatively by calculating the contrast rate and contrast-to-noise ratio, and qualitatively, by consensus visual comparative ratings. The total enhancing tumor volume and between-sequence discrepancy in the margin delineation were assessed on the corresponding 3D target objects contoured with a computer-assisted software for neuronavigation. The Wilcoxon signed rank and Pearson χ
nonparametric tests were used to investigate between-sequence discrepancies in the contrast rate, contrast-to-noise ratio, visual conspicuity ratings, tumor volume, and margin delineation estimates. Differences were also tested for 1D (Response Evaluation Criteria in Solid Tumors) and 2D (Response Assessment in Neuro-Oncology) measurements.
Compared with MPRAGE, both SPACE and VIBE obtained higher contrast rate, contrast-to-noise ratio, and visual conspicuity ratings in both gliomas and metastases (
range, <.001-.001). The between-sequence 3D target object margin discrepancy ranged between 3% and 19.9% of lesion tumor volume. Larger tumor volumes, 1D and 2D measurements were obtained with SPACE (
range, <.01-.007).
Superior conspicuity for brain tumor enhancement can be achieved using SPACE and VIBE techniques, compared with MPRAGE. Discrepancies were also detected when assessing target object size and morphology, with SPACE providing more accurate estimates.
Within the ARVD1 (arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 1) critical region, mapped to 14q24.3, we detected an intronless gene of 4859 bp, predominantly expressed in the ...heart tissue. This gene encodes a 796-amino-acid, proline-rich protein showing polyglutamine and polyalanine tracks with variable length at the N-terminus and a C3HC4 RING finger domain at the C-terminus. CREB and AP-2 binding sites are present in the promoter region. The 5′ flanking region contains neither a TATA box nor a CAAT box, but it is high in GC content and includes several Sp1 binding sites. Protein similarity searches revealed a significant match between the C-terminus and a human hypothetical protein, whose gene is located on the chromosome 19 long arm. The predicted protein shows PEST sequences, suggesting its rapid degradation. The novel intronless gene, provisionally named C14orf4 and probably encoding a nuclear protein, was excluded from being the ARVD1 gene.
An accurate characterization of the hemodynamic behavior of ventricular assist devices (VADs) is of paramount importance for proper modeling of the heart-pump interaction and the validation of ...control strategies. This paper describes an advanced test bench, which is able to generate complex hydraulic loads, and a procedure to characterize rotary blood pump performance in a pulsatile environment. Special focus was laid on model parameter identifiability in the frequency domain and the correlation between dynamic and steady-state models. Twelve combinations of different flow/head/speed signals, which covered the clinical VAD working conditions, were generated for the pump characterization. Root mean square error (RMSE) between predicted and measured flow was used to evaluate the VAD model. The found parameters were then validated with broadband random signals. In the experiments the optimization process always successfully converged. Even in the most demanding dynamic conditions the RMSE was 7.4 ml/sec and the absolute error never exceeded 24.9 ml/sec. Validity ranges for the identified VAD model were: flow 0-180 ml/sec; head 0-120 mmHg; speed 7.5-12.5 krpm. In conclusion, a universal test bench and a characterization procedure to describe the hydrodynamic properties of rotary blood pumps were established. For a particular pump, a reliable mathematical model was identified that correctly reproduced the relationship between instantaneous VAD flow, head and impeller speed.
We present the Human Muscle Gene Map (HMGM), the first comprehensive and updated high-resolution expression map of human skeletal muscle. The 1078 entries of the map were obtained by merging data ...retrieved from UniGene with the RH mapping information on 46 novel muscle transcripts, which showed no similarity to any known sequence. In the map, distances are expressed in megabase pairs. About one-quarter of the map entries represents putative novel genes. Genes known to be specifically expressed in muscle account for <4% of the total. The genomic distribution of the map entries confirmed the previous finding that muscle genes are selectively concentrated in chromosomes 17, 19, and X. Five chromosomal regions are suspected to have a significant excess of muscle genes. Present data support the hypothesis that the biochemical and functional properties of differentiated muscle cells may result from the transcription of a very limited number of muscle-specific genes along with the activity of a large number of genes, shared with other tissues, but showing different levels of expression in muscle. The sequence data described in this paper have been submitted to the EMBL data library under accession nos. F23198-F23242.
Isthmins represent a novel family of vertebrate secreted proteins containing one copy of the thrombospondin type 1 repeat (TSR), which in mammals is shared by several proteins with diverse biological ...functions, including cell adhesion, angiogenesis, and patterning of developing nervous system. We have determined the genomic organization of human
TAIL1 (thrombospondin and AMOP containing isthmin-like 1), a novel isthmin-like gene encoding a protein that contains a TSR and a C-terminal AMOP domain (adhesion-associated domain in MUC4 and other proteins), characteristic of extracellular proteins involved in adhesion processes.
TAIL1 gene encompasses more than 24.4 kb. Analysis of the DNA sequence surrounding the putative transcriptional start region revealed a TATA-less promoter located in a CpG island. Several consensus binding sites for the transcription factors Sp1 and MZF-1 were identified in this promoter region. In humans,
TAIL1 gene is located on chromosome 14q24.3 within ARVD1 (arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 1) critical region; preliminary evidence suggests that it is expressed in several tissues, showing multiple alternative splicing.
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