471 research outputs found
A comparative case-study of school-LEA-NGO interactions across different socio-economic strata in Israel
This study examines the interaction between non-governmental organization (NGO), the Local Education Authority (LEA), and public schools in communities of different socioeconomic backgrounds in Israel. We characterize how schools serving more and less affluent communities create, cultivate, and preserve interactions with NGOs; how NGOs form, and sustain interactions with schools serving communities of different socioeconomic backgrounds; and how this process is maintained through LEA regulation. We show how school–NGO–LEA interaction is largely shaped by the affluence of respective schools’ communities within given educational settings. Analysis of interviews conducted with different stakeholders exposed two main themes: (1) the differing capabilities of various actors in this interaction to express agency; (2) the power relations between involved parties, whereby NGO and LEA impose a global agenda on local schools (particularly those serving less affluent communities) – occasionally in contrast to the needs as perceived by schools’ leaders. Our conclusions offer some insights into the nature and possible consequences of the interaction between third sector organizations and schools serving communities of diverse socioeconomic backgrounds
The role of FDG-PET/CT imaging in early detection of extra-cardiac complications of infective endocarditis
AbstractThe exact incidence of extra-cardiac complications (ECC) in patients with infective endocarditis (IE) is unknown but presumed to be high. These patients, although mostly asymptomatic, may require a more aggressive therapeutic approach. 18fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) is used for the diagnosis of infections, but its role in the early diagnosis of IE complications is still unclear. This study aimed to evaluate the role of FDG-PET/CT in the early diagnosis of ECC in IE and its implications for medical management. We prospectively studied 40 consecutive patients with a confirmed diagnosis of IE (according to the modified Duke criteria) who underwent a whole body FDG-PET/CT study within 14 days from diagnosis. The FDG-PET/CT demonstrated ECC in 17 (42.5%) patients, while 8 (38.1%) of them were asymptomatic. The most frequent embolic sites were musculoskeletal and splenic. Owing to the FDG-PET/CT findings, treatment planning was modified in 14 (35%) patients. This included antibiotic treatment prolongation (27.5%), referral to surgical procedures (15%) and, most substantially, prevention of unnecessary device extraction (17.7%). According to our experiences, FDG-PET/CT imaging was useful in the detection of embolic and metastatic infections in IE. This clinical information had a significant diagnostic and therapeutic impact in managing IE disease
Criteria for determining the need for surgical treatment of tricuspid regurgitation during mitral valve replacement
<p>Abstract</p> <p>Background</p> <p>Tricuspid regurgitation (TR) is common in patients with mitral valve disease; however, there are no straightforward, rapidly determinably criteria available for deciding whether TR repair should be performed during mitral valve replacement. The aim of our retrospective study was to identify a simple and fast criterion for determining whether TR repair should be performed in patients undergoing mitral valve replacement.</p> <p>Methods</p> <p>We reviewed the records of patients who underwent mitral valve replacement with or without (control) TR repair (DeVega or Kay procedure) from January 2005 to December 2008. Preoperative and 2-year postoperative echocardiographic measurements included right ventricular and atrial diameter, interventricular septum size, TR severity, ejection fraction, and pulmonary artery pressure.</p> <p>Results</p> <p>A total of 89 patients were included (control, n = 50; DeVega, n = 27; Kay, n = 12). Demographic and clinical characteristics were similar between groups. Cardiac variables were similar between the DeVega and Kay groups. Right atrium and ventricular diameter and ejection fraction were significantly decreased postoperatively both in the control and operation (DeVega + Kay) group (<it>P </it>< 0.05). Pulmonary artery pressure was significantly decreased postoperatively in-operation groups (<it>P </it>< 0.05). Our findings indicate that surgical intervention for TR should be considered during mitral valve replacement if any of the following preoperative criteria are met: right atrial transverse diameter > 57 mm; right ventricular end-diastolic diameter > 55 mm; pulmonary artery pressure > 58 mmHg.</p> <p>Conclusions</p> <p>Our findings suggest echocardiography may be used as a rapid and simple means of determining which patients require TR repair during mitral valve replacement.</p
747-1 Progression of Aortic Regurgitation Assessed by Doppler Echocardiography in 127 Patients: Degree of Regurgitation
To assess the progression of chronic aortic regurgitation (AR), 127 patients 169 men; 59±21 yr) with AR (59 mild, 8 mild-to-moderate, 41 moderate, 4 moderate-to-severe, 15 severe) who had ≥6 months of follow-up (6–47 months) by color Doppler and 2-D echo were studied. The degree of AR was established at entry and follow-up studies using an algorithm (semi-quantitative) that takes into account several Doppler criteria (jet area and jet height ratios, jet length, pressure half-time, reversal of flow in descending aorta) and the jet height/LV outflow tract (LVOT) height ratio (quantitative). LV volume (Simpson) and LV mass (Devereux) were calculated. A significant increase in jet/LVOT height ratio was observed in the whole population (30±17 vs. 35±20%; p<0.00001) and in the subsets of patients with mild (18±7 vs. 22.3±9%; p<0.01), moderate (40±14 vs. 44±16%; p<0.01) and severe (54±19 vs. 65±15%; p<0.05) AR. An increase in the degree of AR (semi-quantitative) during the follow-up was observed in 38 (30%) of patients: 25% with mild, 37% with mild-to-moderate, 44% with moderate and 50% with moderate-to-severe AR (p<0.006). Patients were further divided according to the rank order in the rate of progression of jet/LVOT height ratio into “progressives” (n=18; rate>5.64%/yr) and “non-progressives” (n=109). Patients with “progressive” AR had a faster rate of progression of LV end-diastolic volume, LV end-systolic volume and LV mass than “non-progressives” (p<0.025).ConclusionsAR is a progressive disease even in patients with mild insufficiency. The progression in the degree of AR is more frequent in patients with more severe disease. The rate of progression of regurgitation appears to playa role in LV overload in patients with AR
Septin 9 isoforms promote tumorigenesis in mammary epithelial cells by increasing migration and ECM degradation through metalloproteinase secretion at focal adhesions
© 2019, The Author(s), under exclusive licence to Springer Nature Limited. The cytoskeletal interacting protein Septin 9 (SEPT9), a member of the septin gene family, has been proposed to have oncogenic functions. It is a known hot spot of retroviral tagging insertion and a fusion partner of both de novo and therapy-induced mixed lineage leukemia (MLL). Of all septins, SEPT9 holds the strongest link to cancer, especially breast cancer. Murine models of breast cancer frequently exhibit SEPT9 amplification in the form of double minute chromosomes, and about 20% of human breast cancer display genomic amplification and protein over expression at the SEPT9 locus. Yet, a clear mechanism by which SEPT9 elicits tumor-promoting functions is lacking. To obtain unbiased insights on molecular signatures of SEPT9 upregulation in breast tumors, we overexpressed several of its isoforms in breast cancer cell lines. Global transcriptomic profiling supports a role of SEPT9 in invasion. Functional studies reveal that SEPT9 upregulation is sufficient to increase degradation of the extracellular matrix, while SEPT9 downregulation inhibits this process. The degradation pattern is peripheral and associated with focal adhesions (FAs), where it is coupled with increased expression of matrix metalloproteinases (MMPs). SEPT9 overexpression induces MMP upregulation in human tumors and in culture models and promotes MMP3 secretion to the media at FAs. Downregulation of SEPT9 or chemical inhibition of septin filament assembly impairs recruitment of MMP3 to FAs. Our results indicate that SEPT9 promotes upregulation and both trafficking and secretion of MMPs near FAs, thus enhancing migration and invasion of breast cancer cells
Stepwise conversion of the Cys6[4Fe–3S] to a Cys4[4Fe–4S] cluster and its impact on the oxygen tolerance of [NiFe]-hydrogenase
The membrane-bound [NiFe]-hydrogenase of Cupriavidus necator is a rare example of a truly O2-tolerant hydrogenase. It catalyzes the oxidation of H2 into 2e− and 2H+ in the presence of high O2 concentrations. This characteristic trait is intimately linked to the unique Cys6[4Fe–3S] cluster located in the proximal position to the catalytic center and coordinated by six cysteine residues. Two of these cysteines play an essential role in redox-dependent cluster plasticity, which bestows the cofactor with the capacity to mediate two redox transitions at physiological potentials. Here, we investigated the individual roles of the two additional cysteines by replacing them individually as well as simultaneously with glycine. The crystal structures of the corresponding MBH variants revealed the presence of Cys5[4Fe–4S] or Cys4[4Fe–4S] clusters of different architecture. The protein X-ray crystallography results were correlated with accompanying biochemical, spectroscopic and electrochemical data. The exchanges resulted in a diminished O2 tolerance of all MBH variants, which was attributed to the fact that the modified proximal clusters mediated only one redox transition. The previously proposed O2 protection mechanism that detoxifies O2 to H2O using four protons and four electrons supplied by the cofactor infrastructure, is extended by our results, which suggest efficient shutdown of enzyme function by formation of a hydroxy ligand in the active site that protects the enzyme from O2 binding under electron-deficient conditions
Effect of cyclic, low dose pyrimethamine treatment in patients with Late Onset Tay Sachs: an open label, extended pilot study
Serum 25-hydroxyvitamin D is not related to cardiac natriuretic peptide in nulliparous and lactating women
Bilateral polymicrogyria associated with dystonia: A new neurogenetic syndrome?
The clinical presentation of bilateral perisylvian polymicrogyria (PMG) is highly variable, including oromotor dysfunction, epilepsy, intellectual disability, and pyramidal signs. Extrapyramidal features are extremely rare. We present four apparently unrelated patients with a unique association of PMG with dystonia. The clinical, genetic, and radiologic features are described and possible mechanisms of dystonia are discussed. All patients were female and two were born to consanguineous families. All presented with early childhood onset dystonia. Other neurologic symptoms and signs classically seen in bilateral perisylvian PMG were observed, including oromotor dysfunction and speech abnormalities ranging from dysarthria to anarthria (4/4), pyramidal signs (3/4), hypotonia (3/4), postnatal microcephaly (1/4), and seizures (1/4). Neuroimaging showed a unique pattern of bilateral PMG with an infolded cortex originating primarily from the perisylvian region in three out of four patients. Whole exome sequencing was performed in two out of four patients and did not reveal pathogenic variants in known genes for cortical malformations or movement disorders. The dystonia seen in our patients is not described in bilateral PMG and suggests an underlying mechanism of impaired connectivity within the motor network or compromised cortical inhibition. The association of bilateral PMG with dystonia in our patients may represent a new neurogenetic disorder
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