Comparison of a 2D iPad application and 3D body scanner to air displacement plethysmography for measurement of body fat percentage.

BACKGROUND: Novel and innovative imaging methods that rapidly estimate body fat percentage (%BF) are publicly available, yet little is known about their accuracy. The present study evaluated the test-retest reliability of a two-dimensional iPad (Apple, Inc., Cupertino, CA, USA) application (2D APP) and a three-dimensional body scanner (3D SCAN) for estimating %BF and compared both imaging methods with air displacement plethysmography (Bod Pod; Cosmed USA, Inc., Concord, CA, USA). METHODS: Seventy-nine adults (37 female, 42 male) varying widely in age [mean (SD), range] [32.9 (12.4), 18-65 years] and body mass index [25.0 (4.9), 18.2-41.8 kg m-2 ] were measured with the Bod Pod and twice with the 3D SCAN and the 2D APP in a repeated-measures design. RESULTS: Test-retest reliability was excellent for both the 2D APP (intraclass correlation = 0.993) and the 3D SCAN (intraclass correlation = 0.993) with the SEM <1% BF for both methods. Although the three methods were highly correlated with each other (r = 0.857-0.923), the mean %BF estimations were significantly different (P = 0.001). The 2D APP [19.9 (8.2)%BF] underestimated the Bod Pod value [21.9 (9.4)%BF] and the 3D SCAN [24.0 (6.8)%BF] overestimated. Additionally, the SE of estimate and total error exceeded 4% BF for both 2D APP and 3D SCAN, and both methods tended to overestimate lean participants and underestimate fat participants. CONCLUSIONS: Although highly reliable, neither the 2D APP, nor the 3D SCAN provided valid estimates of %BFBod Pod .

The effects of bolt length on penetration hole characteristics, brain damage and specified-risk material dispersal in finished cattle stunned with a penetrating captive bolt stunner.

The purpose of this study was to determine the effect of captive bolt lengths on penetration hole characteristics, brain damage, and specified risk material (SRM) dispersal. Cattle were stunned with a pneumatic captive bolt stunner using: standard (15.2 cm; STRD), medium (16.5 cm; MED), or long (17.8 cm; LON) bolts. Heads (N = 293) and exsanguination blood (N = 103) were collected for analyses. Penetration hole diameter and depth differed by treatment (P ≤ 0.004); both parameters were greatest for LON (P < 0.05). Presence of damage in frontal, parietal, and occipital lobes, olfactory bulb, and collective area including the corpus callosum, fornix and thalamus were impacted by treatment (P < 0.003). Treatment did not impact SRM dispersal (P = 0.33), determined by presence of glial acidic fibrillary protein. Data suggest that bolt length affects both the extent of brain damage and the specific structures damaged but all bolt lengths are successful in causing substantial brain damage and subsequent insensibility.

Adenosine A1 receptor activation attenuates cardiac hypertrophy and fibrosis in response to α1 -adrenoceptor stimulation in vivo.

BACKGROUND AND PURPOSE: Adenosine has been proposed to exert anti-hypertrophic effects. However, the precise regulation and the role of the different adenosine receptor subtypes in the heart and their effects on hypertrophic signalling are largely unknown. We aimed to characterize expression and function of adenosine A1 receptors following hypertrophic stimulation in vitro and in vivo. EXPERIMENTAL APPROACH: Pro-hypertrophic stimuli and adenosine A1 receptor stimulation of neonatal rat cardiomyocytes and male C57/Bl6 mice, sc. drug administration, real-time PCR, (3) [H]-leucine-incorporation assay, immunostaining, tissue staining, Western blots, gravimetric analyses and echocardiography were applied in this study. KEY RESULTS: In neonatal rat cardiomyocyte cultures, phenylephrine, but not angiotensin II or insulin-like growth factor 1 (IGF1), up-regulated adenosine A1 receptors concentration-dependently. The hypertrophic phenotype (cardiomyocyte size, sarcomeric organization, total protein synthesis, c-fos expression) mediated by phenylephrine (10 µM), but not that by angiotensinII (1 µM) or IGF1 (20 ng·mL(-1) ), was counteracted by the selective A1 receptor agonist, N6-cyclopentyladenosine. In C57/BL6 mice, continuous N6-cyclopentyladenosine infusion (2 mg·kg(-1) ·day(-1) ; 21 days) blunted phenylephrine (120 mg·kg(-1) ·day(-1) ; 21 days) induced hypertrophy (heart weight, cardiomyocyte size and fetal genes), fibrosis, MMP 2 up-regulation and generation of oxidative stress - all hallmarks of maladaptive remodelling. Concurrently, phenylephrine administration increased expression of adenosine A1 receptors. CONCLUSIONS AND IMPLICATIONS: We have presented evidence for a negative feedback mechanism attenuating pathological myocardial hypertrophy following α1 -adrenoceptor stimulation. Our results suggest adenosine A1 receptors as potential targets for therapeutic strategies to prevent transition from compensated myocardial hypertrophy to decompensated heart failure due to chronic cardiac pressure overload.

Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain.

OBJECTIVES: To address the diagnostic value of circulating microRNAs (miRNAs) in patients presenting with acute chest pain. DESIGN: In a prospective, international, multicentre study, six miRNAs (miR-133a, miR-208b, miR-223, miR-320a, miR-451 and miR-499) were simultaneously measured in a blinded fashion in 1155 unselected patients presenting with acute chest pain to the emergency department. The final diagnosis was adjudicated by two independent cardiologists. The clinical follow-up period was 2 years. RESULTS: Acute myocardial infarction (AMI) was the adjudicated final diagnosis in 224 patients (19%). Levels of miR-208b, miR-499 and miR-320a were significantly higher in patients with AMI compared to those with other final diagnoses. MiR-208b provided the highest diagnostic accuracy for AMI (area under the receiver operating characteristic curve 0.76, 95% confidence interval 0.72-0.80). This diagnostic value was lower than that of the fourth-generation cardiac troponin T (cTnT; 0.84) or the high-sensitivity cTnT (hs-cTnT; 0.94; both P < 0.001 for comparison). None of the six miRNAs provided added diagnostic value when combined with cTnT or hs-cTnT (ns for the comparison of combinations vs. cTnT or hs-cTnT alone). During follow-up, 102 (9%) patients died. Levels of MiR-208b were higher in patients who died within 30 days, but the prognostic accuracy was low to moderate. None of the miRNAs predicted long-term mortality. CONCLUSION: The miRNAs investigated in this study do not seem to provide incremental diagnostic or prognostic value in patients presenting with suspected AMI.

The role of calcium signalling in the chondrogenic response of mesenchymal stem cells to hydrostatic pressure.

The object of this study was to elucidate the role of Ca++ signalling in the chondrogenic response of mesenchymal stem cells (MSCs) to hydrostatic pressure (HP). MSCs were seeded into agarose hydrogels, subjected to HP or kept in free swelling conditions, and were cultured either with or without pharmacological inhibitors of Ca++ mobility and downstream targets. Chelating free Ca++, inhibiting voltage-gated calcium channels, and depleting intracellular calcium storessuppressed the beneficial effect of HP on chondrogenesis, indicating that Ca++ mobility may play an important role in the mechanotransduction of HP. However, inhibition of stretch-activated calcium channels in the current experiment yielded similar results to the control group, suggesting that mechanotransduction of HP is distinct from loads that generate cell deformations. Inhibition of the downstream targets calmodulin, calmodulin kinase II, and calcineurin all knocked down the effect of HP on chondrogenesis, implicating these targets in MSCs response to HP. All of the pharmacological inhibitors that abolished the chondrogenic response to HP also maintained a punctate vimentin organisation in the presence of HP, as opposed to the mechanoresponsive groups where the vimentin structure became more diffuse. These results suggest that Ca++ signalling may transduce HP via vimentin adaptation to loading.

Role of MicroRNAs in Endothelial Progenitor Cells: Implication for Cardiac Repair.

Endothelial progenitor cells (EPC) are mobilized after myocardial infarction (MI) from the bone marrow to injured sites of the heart where they participate in cardiac repair by revascularization of ischemic tissues. Endothelial progenitor cells have been actively studied, but their exact phenotype and regenerative properties are still controversial. Small trials with progenitor cells of different origins showed modest clinical benefits. It is assumed that a better understanding of the biology of EPC will contribute to improve their therapeutic potential. MicroRNAs (miRNAs) are small single-stranded non-coding RNAs that modulate gene expression by interacting post transcriptionally with protein-coding RNAs. MicroRNAs regulate multiple biological processes involved in cardiac development and disease. While many studies addressed the role of miRNAs in cardiac cells, less is known of the effect of miRNAs in EPC. Recent studies showed that miRNAs indeed regulate the biology of EPC. Since novel technologies to enhance or blunt the functions of miRNAs have been recently developed, it is conceivable that miRNAs may become promising new therapeutic tools. This article will review the recent advances in the knowledge of the effects of miRNAs in EPC and will discuss how miRNAs could be manipulated to improve the regenerative capacities of EPC in the diseased heart.

[Percutaneous aortic valve replacement using the Direct Flow Medical system: results of the Luxembourg registry]. / Remplacement valvulaire aortique percutané par le système Direct Flow Medical: résultats du registre Luxembourgeois.

Percutaneous aortic valve replacement (TAVI) is one of the most innovative procedure in interventional cardiology. The Direct Flow Medical transcatheter aortic valve (DFM) is a new nonmetallic valve which allows perfect repositioning and valve retrieval prior to the final deployment. This study is a prospective non-randomized evaluation of the DFM system in the Luxembourg registry. The study focused on 15 patients who received between March 2013 and October 2013 a percutaneous aortic valve replacement by DFM prosthesis. All clinical and echocardiographic data have been collected prospectively. Fifteen inoperable patients with severe aortic stenosis were evaluated. The average age of our population was 83 +/- 4.16 years, mean STS score was 16%. 46% of patients were in NYHA class III and 33.3% in NYHA class IV. Mean ejection fraction was 59% +/- 12.7, the average mean gradient was 52.86 +/- 18.5 mm Hg and mean aortic orifie was 0.63 +/- 0.15 cm2. Procedural success rate was 100%. The mean trans- valvular gradient decreased from 52.86 +/- 18.5 mm Hg to 12 +/- 4.2 mm Hg (p < 0.001). The average hospital stay was 14 +/- 7.6 days. The non-fatal major event rate at one month was 33.3%. The mortality rate at one month was limited to 6.6%. These results allow us to confirm the efficacy and safety of the DFM valve.

Regulation of endothelial progenitor cell function by micrornas.

After cardiac injury, endothelial progenitor cells (EPC) are mobilized from the bone marrow and participate in cardiac repair by increasing revascularization of injured tissues. These cells have been studied actively in the past few years, but their exact phenotype and function are still controversial. In clinical trials, injection of progenitor cells has shown modest benefits. A better understanding of the biology of EPC will allow improving their therapeutic potential. MicroRNAs (miRNAs) are tiny single-stranded non-coding RNAs that negatively regulate gene expression post transcriptionally. They are involved in multiple biological pathways regulating cardiac pathophysiology. Modern technologies using miRNA inhibitors and miRNA mimics have been developed and allow modifying the expression and hence the biological effects of miRNAs. The role of miRNAs in cardiac cells has been extensively investigated. Recent studies suggest that miRNAs play significant roles in EPC, and therefore might be used to improve the regenerative capacities of EPC. In this review, we will first provide a brief overview of the role of EPC in cardiovascular disease. Then, we will summarize current knowledge on the role of miRNAs in EPC and we will discuss how miRNAs may be used to enhance the capacity of EPC to repair the injured heart.

The pericellular environment regulates cytoskeletal development and the differentiation of mesenchymal stem cells and determines their response to hydrostatic pressure.

The objective of this study was to examine the interplay between matrix stiffness and hydrostatic pressure (HP) in regulating chondrogenesis of mesenchymal stem cells (MSCs) and to further elucidate the mechanotransductive roles of integrins and the cytoskeleton. MSCs were seeded into 1 %, 2 % or 4 % agarose hydrogels and exposed to cyclic hydrostatic pressure. In a permissive media, the stiffer hydrogels supported an osteogenic phenotype, with little evidence of chondrogenesis observed regardless of the matrix stiffness. In a chondrogenic media, the stiffer gels suppressed cartilage matrix production and gene expression, with the addition of RGDS (an integrin blocker) found to return matrix synthesis to similar levels as in the softer gels. Vinculin, actin and vimentin organisation all adapted within stiffer hydrogels, with the addition of RGDS again preventing these changes. While the stiffer gels inhibited chondrogenesis, they enhanced mechanotransduction of HP. RGDS suppressed the mechanotransduction of HP, suggesting a role for integrin binding as a regulator of both matrix stiffness and HP. Intermediate filaments also appear to play a role in the mechanotransduction of HP, as only vimentin organisation adapted in response to this mechanical stimulus. To conclude, the results of this study demonstrate that matrix density and/or stiffness modulates the development of the pericellular matrix and consequently integrin binding and cytoskeletal structure. The study further suggests that physiological cues such as HP enhance chondrogenesis of MSCs as the pericellular environment matures and the cytoskeleton adapts, and points to a novel role for vimentin in the transduction of HP.

Weight and body composition change over a six-week holiday period.

Change in weight and body composition was assessed over a six-week holiday period. Baseline testing occurred the Monday or Tuesday prior to Thanksgiving Day (November 24 or 25, 2008), and the post-holiday assessment was the Monday or Tuesday after New Year's Day (January 5 or 6, 2009). Thirteen men and 21 women ranging in age from 23-61 years completed the study. The majority of participants (24 of 34) perceived that they had gained weight, and four did gain ≥2 kg. However, despite some changes to dietary and exercise habits, on average there was no difference between pre-holiday weight (74.0±17.8 kg) and post-holiday weight (73.9±18.1 kg), nor between pre-holiday body fat percentage (25.4±9.0%) and post-holiday body fat percentage (25.4±8.9%). Despite a perception of substantial weight gain, body weight and body fat remained unchanged over a six-week holiday period.

Cell-matrix interactions regulate mesenchymal stem cell response to hydrostatic pressure.

Both hydrostatic pressure (HP) and cell-matrix interactions have independently been shown to regulate the chondrogenic differentiation of mesenchymal stem cells (MSCs). The objective of this study was to test the hypothesis that the response of MSCs to hydrostatic pressure will depend on the biomaterial within which the cells are encapsulated. Bone-marrow-derived MSCs were seeded into either agarose or fibrin hydrogels and exposed to 10 MPa of cyclic HP (1 Hz, 4 h per day, 5 days per week for 3 weeks) in the presence of either 1 or 10 ng ml(-1) of TGF-ß3. Agarose hydrogels were found to support a spherical cellular morphology, while MSCs seeded into fibrin hydrogels attached and spread, with clear stress fiber formation. Hydrogel contraction was also observed in MSC-fibrin constructs. While agarose hydrogels better supported chondrogenesis of MSCs, HP only enhanced sulfated glycosaminoglycan (sGAG) accumulation in fibrin hydrogels, which correlated with a reduction in fibrin contraction. HP also reduced alkaline phosphatase activity in the media for both agarose and fibrin constructs, suggesting that this stimulus plays a role in the maintenance of the chondrogenic phenotype. This study demonstrates that a complex relationship exists between cell-matrix interactions and hydrostatic pressure, which plays a key role in regulating the chondrogenic differentiation of MSCs.

7-year results of cell therapy in patients with severe ischemic cardiomyopathy.

BACKGROUND: Intracoronary infusion of autologous bone marrow cells (CTX) has been shown to improve myocardial function in post infarct patients and in patients with chronic ischemic cardiomyopathy. Long term results of CTX are unknown. METHODS AND RESULTS: In this small pilot study, eleven patients with chronic ischemic cardiomyopathy and ejection fraction (EF) of 19 +/- 1% were treated with CTX and followed for 7 years. Four patients died during follow-up, all because of progressive heart failure. All patients received an implantable cardioverter defibrillator (ICD) during the course of the study but only 1 patients developed ventricular tachycardia after CTX. One patient received resynchronization therapy. The overall clinical benefit of CTX was modest (NYHA 3.0 +/- 0.1 pre and 2.5 +/- 0.2 post CTX, p= 0.06). CTX was not associated with reverse remodeling. However, left ventricular EF (19 +/- 1% pre and 18 +/- 6% post) and left ventricular end-diastolic volumes (289 +/- 71 ml pre and 294 +/- 123 ml post) remained remarkably stable over 7-year follow-up in the survivors of this very sick population. CONCLUSIONS: During 7-year follow-up, CTX was associated with stabilization of EF and ventricular volumes but without significant clinical benefit or evidence of reverse remodeling.

[Measurement of ventricular twist by 2D speckle tracking early after acute myocardial infarction. Comparison between anterior and inferior infarction]. / Mesure du twist ventriculaire par 2D speckle tracking dans la phase précoce de l'infarctus du myocarde. Comparaison entre l'infarctus antérieur, l'infarctus inférieur et un groupe contrôle.

INTRODUCTION: Left Ventricular twist (LV twist) is defined as the apical counter-clockwise rotation relative to the clockwise basal rotation. It has been shown that LV twist decreases after myocardial infarction (MI) and that it is well correlated with left ventricular ejection fraction. Most studies have only evaluated anterior wall MI. The aim of our study was to determine whether LV twist is dependent on the infarct territory (anterior vs. inferior) and whether there is a correlation between LV twist and matrix metalloproteinase-9, a marker of LV remodeling. METHODS: We measured LV twist using echocardiography with 2D speckle tracking in patients with acute MI and in a control group. RESULTS: We evaluated 27 controls and 35 patients with acute MI, 15 with anterior wall and 20 with inferior wall MI. LV twist was significantly decreased after MI, compared to the control group (10.93 +/- 2.05 vs 15.5 +/- 2.29; p = 0.003). There was no difference between anterior and inferior MI. LV rotation was decreased in the infarct area. We did not observe a correlation between LV twist and MMP-9, or creatine phosphokinase. CONCLUSION: With this study we confirm that LV twist decreases after acute MI. Moreover, we show that LV apical rotation is mostly decreased after large anterior MI. As apical rotation is important for ejection and aspiration (untwisting), this could be a possible mechanism of LV dysfunction after MI.

Inheritance of hypoadrenocorticism in bearded collies.

OBJECTIVE: To assess heritability and mode of inheritance for hypoadrenocorticism in Bearded Collies. ANIMALS: 635 Bearded Collies. PROCEDURES: Dogs were classified as affected by hypoadrenocorticism or unaffected. Phenotypic and pedigree data were analyzed. Heritability was estimated by use of Bayesian statistical methods. Regressive logistic models for complex segregation analyses were used to characterize mode of inheritance. RESULTS: Hypoadrenocorticism was diagnosed in 60 (9.4%) dogs. Heritability of hypoadrenocorticism was estimated to be 0.76 with both sexes affected with equal probability. Evaluation of the pedigrees did not support a Mendelian autosomal dominant mode of inheritance. Evidence from the complex segregation analysis for a single locus of large effect on hypoadrenocorticism was not convincing. CONCLUSIONS AND CLINICAL RELEVANCE: Hypoadrenocorticism in Bearded Collies is highly heritable. Although a precise genetic mechanism responsible for inheritance of the disorder remains undetermined, breeding decisions must include consideration of the genetic likelihood of passing on this deleterious disorder to offspring of affected dams and sires.

NFL1, a Nicotiana tabacum LEAFY-like gene, controls meristem initiation and floral structure.

The Arabidopsis LEAFY (LFY) gene product induces cells of the shoot apical meristem to differentiate into floral primordia by acting as a master regulator of downstream floral homeotic genes. Tobacco, an allotetraploid, possesses two homologous genes, NFL1 and NFL2, which are 97% identical in amino acid sequence and share 73% amino acid sequence identity with LFY. In order to test whether the highly conserved tobacco orthologue, NFL1, shares functional identity with LFY, we created transgenic tobacco and Arabidopsis plants that constitutively express the NFL1 cDNA. Our results indicate that NFL1 plays a critical role in the allocation of meristematic cells that differentiate lateral structures such as leaves and branches, thereby determining the architecture of the wild-type tobacco shoot. NFL1 also regulates floral meristem development and does so through the control of cell proliferation as well as cell identity. Surprisingly, unlike ectopic LFY expression, which can act as a floral trigger, ectopic NFL1 expression does not promote severe precocious flowering in Nicotiana tabacum suggesting that variations in amino acid sequence among members of the LFY-like gene family have led to divergence in the functional roles of these genes.

The arabidopsis serrate gene encodes a zinc-finger protein required for normal shoot development.

Organogenesis in plants depends upon the proper regulation of many genes, but how such necessary changes in gene expression are coordinated is largely unknown. The serrate (se) mutant of Arabidopsis displays defects in the initiation and elaboration of cotyledons and post-embryonic lateral organs. Cloning the SE gene revealed that it encodes a protein with a single, C(2)H(2)-type, zinc finger related to genes in other eukaryotes. Consistent with a role in organogenesis, the SE gene is transcribed in shoot meristems and in emerging organ primordia throughout development. Expression of the SE cDNA under the control of a heterologous promoter caused both accelerated and arrested plant growth, and these phenotypes were due to overexpression and co-suppression of the SE gene, respectively. Our analysis of the se mutant and the SE gene suggests a role for the SE gene product in regulating changes in gene expression via chromatin modification. Consistent with this proposed function, a synergistic double mutant phenotype was seen for plants mutant at both the SE locus and the locus encoding the largest subunit of chromatin assembly factor I.

EARLY FLOWERING3 encodes a novel protein that regulates circadian clock function and flowering in Arabidopsis.

Higher plants use photoperiodic cues to regulate many aspects of development, including the transition from vegetative to floral development. The EARLY FLOWERING3 (ELF3) gene is required for photoperiodic flowering and normal circadian regulation in Arabidopsis. We have cloned ELF3 by positional methods and found that it encodes a novel 695-amino acid protein that may function as a transcriptional regulator. ELF3 transcript level is regulated in a circadian manner, as is expected of a zeitnehmer input pathway component. Overexpression of the LATE ELONGATED HYPOCOTYL gene, which has been proposed to function as a clock component, did not abolish circadian regulation of ELF3 transcription, providing further evidence that ELF3 is a circadian clock input pathway component.

ELF3 encodes a circadian clock-regulated nuclear protein that functions in an Arabidopsis PHYB signal transduction pathway.

Many aspects of plant development are regulated by photoreceptor function and the circadian clock. Loss-of-function mutations in the Arabidopsis EARLY FLOWERING 3 (ELF3) and PHYTOCHROME B (PHYB) genes cause early flowering and influence the activity of circadian clock-regulated processes. We demonstrate here that the relative abundance of the ELF3 protein, which is a novel nucleus-localized protein, displays circadian regulation that follows the pattern of circadian accumulation of ELF3 transcript. Furthermore, the ELF3 protein interacts with PHYB in the yeast two-hybrid assay and in vitro. Genetic analyses show that ELF3 requires PHYB function in early morphogenesis but not for the regulation of flowering time. This suggests that ELF3 is a component of a PHYB signaling complex that controls early events in plant development but that ELF3 and PHYB control flowering via independent signal transduction pathways.

ELF3 modulates resetting of the circadian clock in Arabidopsis.

The Arabidopsis early flowering 3 (elf3) mutation causes arrhythmic circadian output in continuous light, but there is some evidence of clock function in darkness. Here, we show conclusively that normal circadian function occurs with no alteration of period length in elf3 mutants in dark conditions and that the light-dependent arrhythmia observed in elf3 mutants is pleiotropic on multiple outputs normally expressed at different times of day. Plants overexpressing ELF3 have an increased period length in both constant blue and red light; furthermore, etiolated ELF3-overexpressing seedlings exhibit a decreased acute CAB2 response after a red light pulse, whereas the null mutant is hypersensitive to acute induction. This finding suggests that ELF3 negatively regulates light input to both the clock and its outputs. To determine whether ELF3's action is phase dependent, we examined clock resetting by using light pulses and constructed phase response curves. Absence of ELF3 activity causes a significant alteration of the phase response curve during the subjective night, and constitutive overexpression of ELF3 results in decreased sensitivity to the resetting stimulus, suggesting that ELF3 antagonizes light input to the clock during the night. The phase of ELF3 function correlates with its peak expression levels in the subjective night. ELF3 action, therefore, represents a mechanism by which the oscillator modulates light resetting.