Hand-carried ultrasound performed at bedside in cardiology inpatient setting – a comparative study with comprehensive echocardiography

BACKGROUND: Hand-carried ultrasound (HCU) devices have been demonstrated to improve the diagnosis of cardiac diseases over physical examination, and have the potential to broaden the versatility in ultrasound application. The role of these devices in the assessment of hospitalized patients is not completely established. In this study we sought to perform a direct comparison between bedside evaluation using HCU and comprehensive echocardiography (CE), in cardiology inpatient setting. METHODS: We studied 44 consecutive patients (mean age 54 ± 18 years, 25 men) who underwent bedside echocardiography using HCU and CE. HCU was performed by a cardiologist with level-2 training in the performance and interpretation of echocardiography, using two-dimensional imaging, color Doppler, and simple calliper measurements. CE was performed by an experienced echocardiographer (level-3 training) and considered as the gold standard. RESULTS: There were no significant differences in cardiac chamber dimensions and left ventricular ejection fraction determined by the two techniques. The agreement between HCU and CE for the detection of segmental wall motion abnormalities was 83% (Kappa = 0.58). There was good agreement for detecting significant mitral valve regurgitation (Kappa = 0.85), aortic regurgitation (kappa = 0.89), and tricuspid regurgitation (Kappa = 0.74). A complete evaluation of patients with stenotic and prosthetic dysfunctional valves, as well as pulmonary hypertension, was not possible using HCU due to its technical limitations in determining hemodynamic parameters. CONCLUSION: Bedside evaluation using HCU is helpful for assessing cardiac chamber dimensions, left ventricular global and segmental function, and significant valvular regurgitation. However, it has limitations regarding hemodynamic assessment, an important issue in the cardiology inpatient setting

Selection of Conditions for Cellulase and Xylanase Extraction from Switchgrass Colonized by Acidothermus cellulolyticus

Solid-state fermentation has been widely used for enzyme production. However, secreted enzymes often bind to the solid substrate preventing their detection and recovery. A series of screening studies was performed to examine the role of extraction buffer composition including NaCl, ethylene glycol, sodium acetate buffer, and Tween 80, on xylanase and cellulase recovery from switchgrass. Our results indicated that the selection of an extraction buffer is highly dependent on the nature and source of the enzyme being extracted. While a buffer containing 50 mM sodium acetate at pH 5 was found to have a positive effect on the recovery of commercial fungal-derived cellulase and xylanase amended to switchgrass, the same buffer had a significant negative effect on enzyme extraction from solid fermentation samples colonized by the bacterium Acidothermus cellulolyticus. Xylanase activity was more affected by components in the extraction buffers compared to cellulase. This study demonstrated that extraction followed by diafiltration is important for assessing enzyme recovery from solid fermentation samples. Reduction in activity due to compounds present in the switchgrass extracts is reversible when the compounds are removed via diafiltration

Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado-Joseph disease

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease currently with no treatment. We describe a novel mouse model of MJD which expresses mutant human ataxin-3 at near endogenous levels and manifests MJD-like motor symptoms that appear gradually and progress over time. CMVMJD135 mice show ataxin-3 intranuclear inclusions in the CNS and neurodegenerative changes in key disease regions, such as the pontine and dentate nuclei. Hsp90 inhibition has shown promising outcomes in some neurodegenerative diseases, but nothing is known about its effects in MJD. Chronic treatment of CMVMJD mice with Hsp90 inhibitor 17-DMAG resulted in a delay in the progression of their motor coordination deficits and, at 22 and 24 weeks of age, was able to rescue the uncoordination phenotype to wild-type levels; in parallel, a reduction in neuropathology was observed in treated animals. We observed limited induction of heat-shock proteins with treatment, but found evidence that 17-DMAG may be acting through autophagy, as LC3-II (both at mRNA and protein levels) and beclin-1 were induced in the brain of treated animals. This resulted in decreased levels of the mutant ataxin-3 and reduced intranuclear aggregation of this protein. Our data validate this novel mouse model as a relevant tool for the study of MJD pathogenesis and for pre-clinical studies, and show that Hsp90 inhibition is a promising therapeutic strategy for MJD.We would like to thank to Dr. Henry Paulson for providing the anti-ataxin-3 serum, Dr. Monica Sousa for the pCMV vector and to Eng. Lucilia Goreti Pinto, Lu s Martins, Miguel Carneiro and Celina Barros for technical assistance. This work was supported by Fundacao para a Ciencia e Tecnologia through the projects FEDER/FCT, POCI/SAU-MMO/60412/2004 and PTDC/SAU-GMG/64076/2006. This work was supported by Fundacao para a Ciencia e Tecnologia through fellowships SFRH/BPD/91562/2012 to A.S-F., SFRH/BD/78388/2011 to S. D-S., SFRH/BD/51059/2010 to A.N-C., and SFRH/BPD/79469/2011 to A.T-C.

The contribution of 7q33 copy number variations for intellectual disability

Copy number variations (CNVs) at the 7q33 cytoband are very rarely described in the literature, and almost all of the cases comprise large deletions affecting more than just the q33 segment. We report seven patients (two families with two siblings and their affected mother and one unrelated patient) with neurodevelopmental delay associated with CNVs in 7q33 alone. All the patients presented mild to moderate intellectual disability (ID), dysmorphic features, and a behavioral phenotype characterized by aggressiveness and disinhibition. One family presents a small duplication in cis affecting CALD1 and AGBL3 genes, while the other four patients carry two larger deletions encompassing EXOC4, CALD1, AGBL3, and CNOT4. This work helps to refine the phenotype and narrow the minimal critical region involved in 7q33 CNVs. Comparison with similar cases and functional studies should help us clarify the relevance of the deleted genes for ID and behavioral alterations.FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects PIC/IC/83026/2007, PIC/IC/83013/2007, and POCI-01-0145-FEDER-007038. This work has also been funded by the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)info:eu-repo/semantics/publishedVersio

Optimization of xylanase production by filamentous fungi in solid state fermentation and scale-up to horizontal tube bioreactor

Five microorganisms, namely Aspergillus niger CECT 2700, A. niger CECT 2915, A. niger CECT 2088, Aspergillus terreus CECT 2808, and Rhizopus stolonifer CECT 2344, were grown on corncob to produce cell wall polysaccharide-degrading enzymes, mainly xylanases, by solid-state fermentation (SSF). A. niger CECT 2700 produced the highest amount of xylanases of 504±7 U/g dry corncob (dcc) after 3 days of fermentation. The optimization of the culture broth (5.0 g/L NaNO3, 1.3 g/L (NH4)2SO4, 4.5 g/L KH2PO4, and 3 g/L yeast extract) and operational conditions (5 g of bed loading, using an initial substrate to moistening medium of 1:3.6 (w/v)) allowed increasing the predicted maximal xylanase activity up to 2,452.7 U/g dcc. However, different pretreatments of materials, including destarching, autoclaving, microwave, and alkaline treatments, were detrimental. Finally, the process was successfully established in a laboratory-scale horizontal tube biore- actor, achieving the highest xylanase activity (2,926 U/g dcc) at a flow rate of 0.2 L/min. The result showed an overall 5.8-fold increase in xylanase activity after optimization of culture media, operational conditions, and scale-up.We are grateful to the Spanish Ministry of Science and Innovation for the financial support of this work (project CTQ2011-28967), which has partial financial support from the FEDER funds of the European Union; to the Leonardo da Vinci Programme for founding the stay of Felisbela Oliveira in Vigo University; to MAEC-AECID (Spanish Government) for the financial support for Perez-Bibbins, B. and to Spanish Ministry of Education, Culture and Sports for Perez-Rodriguez's FPU; and to Solla E. and Mendez J. (CACTI-University of Vigo) for their excellent technical assistance in microscopy

Left ventricular twist mechanics during incremental cycling and knee extension exercise in healthy men

Purpose: The objective of the present study was to investigate left ventricular (LV) twist mechanics in response to incremental cycling and isometric knee extension exercises. Methods: Twenty-six healthy male participants (age = 30.42 ± 6.17 years) were used to study peak twist mechanics at rest and during incremental semi-supine cycling at 30 and 60% work rate maximum (W) and during short duration (15 s contractions) isometric knee extension at 40 and 75% maximum voluntary contraction (MVC), using two-dimensional speckle tracking echocardiography. Results: Data presented as mean ± standard deviation or median (interquartile range). LV twist increased from rest to 30% W (13.21° ± 4.63° to 20.04° ± 4.76°, p  0.05), whilst twisting velocity increased (rest 89.15° ± 21.77° s to 75% MVC 124.32° ± 34.89° s, p  0.05) then increased from 40 to 75% MVC [−98.44 (43.54)° s to −138.42 (73.29)° s, p < 0.01]. Apical rotations and rotational velocities were greater than basal during all conditions and intensities (all p < 0.01). Conclusion: Cycling increased LV twist to 30% W which then remained unchanged thereafter, whereas twisting velocities showed further increases to greater intensities. A novel finding is that LV twist was unaffected by incremental knee extension, yet systolic and diastolic twisting velocities augmented with isometric exercise