inv(7)(p15q34) - t(7;7)(p15;q34)

Review on inv(7)(p15q34) - t(7;7)(p15;q34), with data on clinics, and the genes involved

Beyond Site-Specific Criteria: Conservation of Migratory Birds and Their Habitats from a Network Perspective

Many populations of birds depend on networks of sites to survive. Sufficient connectivity that allows movement between the sites throughout the year is a critical requirement. We found that existing international frameworks and policies for identifying sites important for bird conservation focus more at the level of the individual site than on the site network and its connectivity. Only 21% of site criteria acknowledge the importance of movement networks for birds, and such network criteria were mostly (67%) qualitative. We suggest a three-step quantitative approach for informing conservation about the connectivity of bird movements (especially when migrating) from a network perspective, by reviewing current scientific knowledge. The first step is to construct a bird movement network by identifying sites frequently used by birds as ‘nodes’, and then define ‘edges’ from the probability of non-stop flight between each pair of nodes. The second step is to quantify network connectivity, i.e., the extent to which the site network facilitates bird movements. The last step is to assess the importance of each site from its contribution to network connectivity. This approach can serve as a tool for comprehensive and dynamic monitoring of the robustness of site networks during global change

Beyond Site-Specific Criteria: Conservation of Migratory Birds and Their Habitats from a Network Perspective

Many populations of birds depend on networks of sites to survive. Sufficient connectivity that allows movement between the sites throughout the year is a critical requirement. We found that existing international frameworks and policies for identifying sites important for bird conservation focus more at the level of the individual site than on the site network and its connectivity. Only 21% of site criteria acknowledge the importance of movement networks for birds, and such network criteria were mostly (67%) qualitative. We suggest a three-step quantitative approach for informing conservation about the connectivity of bird movements (especially when migrating) from a network perspective, by reviewing current scientific knowledge. The first step is to construct a bird movement network by identifying sites frequently used by birds as ‘nodes’, and then define ‘edges’ from the probability of non-stop flight between each pair of nodes. The second step is to quantify network connectivity, i.e., the extent to which the site network facilitates bird movements. The last step is to assess the importance of each site from its contribution to network connectivity. This approach can serve as a tool for comprehensive and dynamic monitoring of the robustness of site networks during global change

Intra aortic balloon pumping in myocardial infarction and unstable angina

From 1972 to 1979 intra aortic balloon pumping (IABP) was attempted in 181 patients; catheter insertion failed in 13 (8%). More complications occurred with prolonged treatment but all three lethal complications (2%) were related to catheter insertion. Seventy-six patients had clinical cardiogenic shock after myocardial infarction (CSMI). Haemodynamically, 23 were classified as preshock: 15 (66%) could be weaned, 12 (53%) survived over 3 months; whereas only 27/51 patients (51%) haemodynamically classified as shock could be weaned and 21 (40%) survived over 3 months. Of forty-two patients with refractory angina at rest, 41 had prompt relief of pain after IABP, and subsequently underwent coronary artery bypasss grafting (CABG). Perioperative infarction rate was 8% (4/41), perioperative mortality was 7% (3/41). Total infarction rate was 11% (5/42), and total mortality 7% (3/41). Pain relief was prompt in 14/17 patients (82%) with refractory angina after infarction. Pain persisted in three patients: all three sustained an infarction, one died. Two patients were excluded from surgery. Twelve patients underwent CABG; none died, none developed MI. In eight patients persistence of pain suggested a slowly evolving MI, IABP abolished pain in seven. Conclusion: IABP has demonstrated its efficacy both in pump failure and in refractory ischaemia. However, its use is not without risks

Right to left shunt, with severe hypoxemia, at the atrial level in a patient with hemodynamically important right ventricular infarction

This report describes a patient with a massive right ventricular infarction, complicated by severe hypoxemia. Contrast echocardiography demonstrated a right to left shunt through a previously asymptomatic atrial septal defect. This phenomenon should be considered as a possible cause of hypoxemia in the presence of right ventricular infarction

Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure

Background: Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF)-specific circulating miRNAs and well-known heart failure biomarkers.Methods: Associations between 16 biomarkers predictive for 180 day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48 hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis.Results: No significant correlations were found at hospital admission. However, after 48 hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n = 21); miR-16-5p was correlated to C-reactive protein (R = -0.66, p-value = 0.0027), miR-106a-5p to creatinine (R = -0.68, p-value = 0.002), miR-223-3p to growth differentiation factor 15 (R = -0.69, p-value = 0.0015), miR-652-3p to soluble ST-2 (R = -0.77, p-value &lt;0.001), miR-199a-3p to procalcitonin (R = -0.72, p-value &lt;0.001) and galectin-3 (R = -0.73, p-value &lt;0.001) and miR-18a-5p to procalcitonin (R = -0.68, p-value = 0.002). MiRNA target prediction and pathway analysis identified several pathways related to cardiac diseases, which could be linked to some of the miRNA-biomarker correlations.Conclusions: The majority of correlations between circulating AHF-specific miRNAs were related to biomarkers predictive for a worse clinical outcome in a subgroup of worsening heart failure patients at 48 hours of hospitalization. The selective findings suggest a time-dependent effect of circulating miRNAs and highlight the susceptibility to individual patient characteristics influencing potential relations between miRNAs and biomarkers. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.</p

Forskolin-induced Organoid Swelling is Associated with Long-term CF Disease Progression

RATIONALE: Cystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids (PDO) with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC). METHODS: We retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed effect models and multivariable logistic regression to estimate the association of FIS with long-term FEV1pp decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC. RESULTS: FIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95%CI: 0.11%-0.54%; p=0.004) per 1000-points change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR: 0.18, 95%CI: 0.07-0.46, p<0.001), CF-related liver disease (adjusted OR: 0.18, 95%CI: 0.06-0.54, p=0.002) and diabetes (adjusted OR: 0.34, 95%CI: 0.12-0.97, p=0.044). These associations were absent for SCC. CONCLUSION: This study exemplifies the prognostic value of a PDO-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences

MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene

Double minutes (dmin)-circular, extra-chromosomal amplifications of specific acentric DNA fragments-are relatively frequent in malignant disorders, particularly in solid tumors. In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), dmin are observed in approximately 1% of the cases. Most of them consist of an amplified segment from chromosome band 8q24, always including the MYC gene. Besides this information, little is known about their internal structure. We have characterized in detail the genomic organization of 32 AML and two MDS cases with MYC-containing dmin. The minimally amplified region was shown to be 4.26 Mb in size, harboring five known genes, with the proximal and the distal amplicon breakpoints clustering in two regions of approximately 500 and 600 kb, respectively. Interestingly, in 23 (68%) of the studied cases, the amplified region was deleted in one of the chromosome 8 homologs at 8q24, suggesting excision of a DNA segment from the original chromosomal location according to the 'episome model'. In one case, sequencing of both the dmin and del(8q) junctions was achieved and provided definitive evidence in favor of the episome model for the formation of dmin. Expression status of the TRIB1 and MYC genes, encompassed by the minimally amplified region, was assessed by northern blot analysis. The TRIB1 gene was found over-expressed in only a subset of the AML/MDS cases, whereas MYC, contrary to expectations, was always silent. The present study, therefore, strongly suggests that MYC is not the target gene of the 8q24 amplifications

Genetic insights into resting heart rate and its role in cardiovascular disease

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.</p