Abstract 150: Determining Changes in Contractility, Myofilament Expression and Myofilament Sensitivity in the Developing Human Ventricle

As pediatric cardiac surgery is increasingly performed in the first year of life, the need for understanding contractility regulation becomes increasingly important. We examined contractility and myofilament changes in ventricular biopsies removed as part of the surgical correction of congenital heart defects from newborns (NB) (hypoplastic left heart syndrome, < 1 wk old) and infants (IF) (tetralogy of Fallot, 3-12 mo old). Sarcomere shortening and calcium (Ca) transients were measured in isolated ventricular cells stimulated at 0.5 and 1 Hz. Increasing pacing frequency caused a significant increase in sarcomere shortening (p< 0.05)in only the IF, but the Ca transient amplitude was relatively unchanged in both groups. Consistent with work in the developing rat heart, we found an isoform switch with increasing developmental age in myofilament proteins, troponin T (TnT) and troponin I (TnI). Western blot analysis revealed that total TnI (the sum of cardiac TnI (cTnI) and slow skeletal TnI (ssTnI)) was not significantly different between the two age groups. However, when comparing only the cTnI isoforms, we found that the NB had a significantly lower levels compared to the IF (11556±789 a.u. vs. 21770±1700 a.u., p<0.001). Analysis of the RT-PCR revealed nearly significant lower levels of TnT isoform 1 in the IF group than the NB group (p=0.078), no significant difference in the levels of TnT isoform 2 (p= 0.536), and significantly higher levels of TnT isoform 3 in the IF group than the NB group (p= 0.039). We also observed developmental changes in myofilament sensitivity to calcium as assessed by measuring the gradient of the fura-2 cell length trajectory on phase-plane diagrams during the late relaxation of the twitch contraction. These results collectively suggest that contractility and myofilament changes, or the lack of changes, may serve as targets for clarifying elements associated with cardiac dysfunction in the developing human ventricle.

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The underestimated issue of non-reproducible cardiac troponin I and T results: case series and systematic review of the literature

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-1564 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Julien Favresse ◽

Jean-Louis Bayart ◽

Damien Gruson ◽

Sergio Bernardini ◽

Aldo Clerico ◽

...

Keyword(s):

Systematic Review ◽

Clinical Judgment ◽

Troponin I ◽

Troponin T ◽

Case Reports ◽

False Negative ◽

Case Series ◽

Elevated Alkaline Phosphatase ◽

Negative Results ◽

Significant Difference

Abstract Cardiac troponins (cTn) are the preferred biomarkers for the evaluation of myocardial injury and play a key role in the diagnosis of acute myocardial infarction (MI). Pre-analytical or analytical issues and interferences affecting troponin T and I assays are therefore of major concern given the risk of misdiagnosis. False positive troponin results have been related to various interferences including anti-troponin antibodies, heterophilic antibodies, or elevated alkaline phosphatase level. On the other hand, false negative results have been reported in the case of a large biotin intake. These interferences are characterized with erroneous but reproducible troponin results. Of interest, non-reproducible results have also been reported in the literature. In other words, if the sample is reanalyzed a second time, a significant difference in troponin results will be observed. These interferences have been named “fliers” or “outliers”. Compared to the biotin interference that received major attention in the literature, troponin outliers are also able to induce harmful clinical consequences for the patient. Moreover, the prevalence of outliers in recent studies was found to be higher (0.28–0.57%) compared to the biotin interference. The aim of this systematic review is to warn clinicians about these non-reproducible results that may alter their clinical judgment. Four case reports that occurred in the Clinique of Saint-Luc Bouge are presented to attest this point. Moreover, we aimed at identifying the nature of these non-reproducible troponin results, determining their occurrence, and describing the best way for their identification.

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Dendritic cells in the mucosa of the human trachea are not regularly found in the first year of life

Thorax ◽

10.1136/thx.56.6.427 ◽

2001 ◽

Vol 56 (6) ◽

pp. 427-431 ◽

Cited By ~ 1

Author(s):

T Tschernig ◽

A S Debertin ◽

F Paulsen ◽

W J Kleemann ◽

R Pabst

Keyword(s):

Dendritic Cells ◽

Sudden Death ◽

Respiratory Tract ◽

Age Groups ◽

First Year ◽

Tracheal Mucosa ◽

Transmission Electron ◽

Human Airways ◽

Tract Infections ◽

First Year Of Life

BACKGROUNDDendritic cells (DCs) in the mucosa of the respiratory tract might be involved in the early development of pulmonary allergy or tolerance. To date, little is known about when the first DCs occur in human airways.METHODSSpecimens of the distal trachea from patients who had died from sudden death in the first year of life (n=29) and in older age groups (n=59) as well as from those who had died from respiratory tract infections in the first year of life (n=8) were examined by immunohistochemistry. Transmission electron microscopy was performed in additional samples from two adults.RESULTSIn the sudden death subgroup DCs were absent in 76% of those who died in the first year of life but were present in 53 of the 59 older cases. All infants who had died of respiratory infectious diseases had DCs in the tracheal mucosa.CONCLUSIONSMature DCs are not constitutively present in the human tracheobronchial mucosa in the first year of life, but their occurrence seems to be triggered by infectious stimuli. These data support the hypothesis that DCs play a crucial role in immunoregulation in early childhood.

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Abstract 69: Diminished T-Tubule Density in Newborn Human Ventricular Cells Is Associated with Heterogeneity of Calcium Transients

Circulation Research ◽

10.1161/res.111.suppl_1.a69 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Talib Saafir ◽

Brian Crawford ◽

Ming Shen ◽

Guoliang Ding ◽

Paul M Kirshbom ◽

...

Keyword(s):

Age Groups ◽

Ventricular Myocardium ◽

Outer Edge ◽

Calcium Transients ◽

Calcium Handling ◽

Live Cells ◽

Ventricular Cells ◽

T Tubules ◽

Human Ventricular Myocardium ◽

First Year Of Life

For children with congenital heart disease (CHD), therapies developed for adults may have different effects on immature myocardium. Thus, it is critical to understand calcium handling in the young human ventricle. Methods: Human ventricular cells were isolated from tissue removed as part of the surgical repair for CHDs from two age groups: newborns (<1 week old) and infants (2-12 months old). Developmental changes in t-tubules were examined in live cells with Di-8 ANEPPS which highlights the cell membrane. We measured the T-index (percent of cell interior occupied by t-tubules), averaged for at least 3 confocal z-sections per cell. Changes in calcium transients were measured by confocal line scans in cells loaded with Fluo-4 and field stimulated (37°C). Results: Newborn human myocytes have very few t-tubules whereas infant myocytes have a range of t-tubule densities. The T-index in newborn myocytes was significantly less than in infant myocytes (4.4±0.2%, n=8 cells, 3 newborns vs. 9.1±0.9%, n=55 cells, 7 infants). Furthermore, there was sizable heterogeneity in the T-index for each patient in the infant group, in which some cells had few t-tubules and others had many t-tubules. We calculated the coefficient of variation (CV=SD/mean*100) for each patient and compared CV values for newborns vs. infants. CV was significantly greater in infants compared to newborns (46.5±7.4%, n=7, vs. 9.4±1.9%, n=3, p<0.02). In addition, calcium transients from newborn cells had a ‘U’ shaped wavefront with calcium first increasing at the outer edge of the cell then propagating toward the center. In contrast, infant cells had a homogenous calcium wavefront. The delay of peak calcium from the edge to center was significantly longer in newborns compared to infants (61.7±8.9 ms, n=8 cells, 3 newborns vs. 10.6±1.6 ms, n=6 cells, 4 infants, p<0.001). Conclusions: There are heterogeneous calcium transients in newborn human myocytes that correspond to a lack of t-tubules. Furthermore, t-tubule development occurs in a heterogeneous manner throughout the first year of life with cells from the same patient exhibiting different degrees of t-tubule development. This is the first study to examine t-tubule development and calcium transients in the very young human ventricular myocardium.

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HEMATOPOIESIS IN PREMATURE INFANTS WITH SPECIAL CONSIDERATION OF THE EFFECT OF IRON AND OF ANIMAL-PROTEIN FACTOR

PEDIATRICS ◽

10.1542/peds.16.6.753 ◽

1955 ◽

Vol 16 (6) ◽

pp. 753-762

Author(s):

James A. Wolff ◽

Alice M. Goodfellow

Keyword(s):

Premature Infants ◽

Animal Protein ◽

Iron Therapy ◽

First Year ◽

Protein Factor ◽

Anemia Of Prematurity ◽

Significant Difference ◽

One Year ◽

First Year Of Life ◽

Weight Groups

Normal values in the first 3 months of life have been determined for hemoglobin, erythrocytes, reticulocytes, platelets, leukocytes and differential counts for premature infants with birth weights less than 1200 gm., and for those between 1200 and 1500 gm. at birth. No significant difference was found in the degree of depression of levels of hemoglobin and erythrocytes when values in the 2 weight groups were compared. Two reticulocyte peaks occur during the first 3 months of life. The first peak is present immediately after birth. The second peak, at about the eighth week, coincides with the occurrence of the greatest degree of anemia. Neither iron therapy nor treatment with animal-protein factor containing vitamin B12 and Aureomycin®, started before the end of the third week of life, had a statistically significant effect on the early phase of the anemia of prematurity. Untreated premature infants and those given animal-protein factor were anemic at the end of the first year of life. Subjects given iron therapy had normal hemoglobin values at one year of age. Blood transfusion is rarely necessary in the treatment of the anemia of prematurity.

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The intensity of natural selection in man

Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character ◽

10.1098/rspb.1912.0073 ◽

1912 ◽

Vol 85 (581) ◽

pp. 469-476 ◽

Cited By ~ 18

Keyword(s):

Natural Selection ◽

Death Rate ◽

Age Groups ◽

First Year ◽

Human Beings ◽

High Infant Mortality ◽

Total Death ◽

Selective Death ◽

First Year Of Life ◽

Varying Environment

(1) In a paper communicated to the Royal Society in 1899, and later in greater elaboration published in ‘Biometrika,’ 1901, it has been shown on the basis of the inheritance of longevity that the selective death-rate in man amounted to at least 60 per cent. to 80 per cent. of the total death-rate. The matter has been recently reconsidered by Prof. Ploetz, who, dealing with material wholly different from that of Beeton and Pearson came to similar conclusions. The point is a very vital one, for, combined with: (i) the heredity of physical and mental characters in man, and (ii) the demonstration that the longer-lived have more offspring, we reach a definite knowledge that Darwinism does apply, and very intensely applies, even to man under civilised conditions. The difficulty of a direct investigation of the problem lies in securing uniformity of environment. W e have to demonstrate that when under the same environment there is a heavier death-rate among a given group of human beings, then among the survivors of this group in a given later period the death-rate will be lessened. Now each group of individuals we attempt to deal with has its own environment, and if that is a bad environment we should expect to find a heavy death-rate both at the earlier and later periods; this obviously must obscure the action of natural selection. For example in districts with a high infant mortality we might expect a high child mortality, say deaths from two to five years of life, because a bad environment sends up the intensity of both. The correlation between deaths in the first year of life (0—1) and in the next four years of life (1—5) for a given district will certainly be positive if no correction be made for varying environment. Quite recently this matter has been discussed by determining the correlation between the ages 0—1 and 1—5 in the administrative counties of England and Wales. As ( a ) the group 0—1 was not followed to 1—5, but the deaths in these age-groups for the same years were dealt with, and ( b ) no allowance whatever was made for the differential environment of the administrative counties, it is difficult to find any real bearing of the data on the problem of natural selection in man.

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Kinetics of high-sensitivity cardiac troponin T or troponin I compared to creatine kinase in patients with revascularized acute myocardial infarction

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-0475 ◽

2015 ◽

Vol 53 (5) ◽

Cited By ~ 16

Author(s):

Kamila Solecki ◽

Anne Marie Dupuy ◽

Nils Kuster ◽

Florence Leclercq ◽

Richard Gervasoni ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

Troponin T ◽

High Sensitivity ◽

Cardiac Troponin T ◽

Significant Difference ◽

Kinetics Of

AbstractCardiac biomarkers are the cornerstone of the biological definition of acute myocardial infarction (AMI). The key role of troponins in diagnosis of AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine kinase (CK) after AMI are correlated to the prognosis. New technical assessment like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its unclear kinetic following the peak. This study aims to compare kinetics of cTnI and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous coronary intervention (PCI).We prospectively studied 62 patients with anterior AMI successfully reperfused with primary angioplasty. We evaluated two consecutive groups: the first one regularly assessed by both CK and cTnI methods and the second group by CK and hs-cTnT. Modeling of kinetics was realized using mixed effects with cubic splines.Kinetics of markers showed a peak at 7.9 h for CK, at 10.9 h (6.9–12.75) for cTnI and at 12 h for hs-cTnT. This peak was followed by a nearly log linear decrease for cTnI and CK by contrast to hs-cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h. There was no significant difference between the decrease of cTnI and CK (p=0.63). CK fell by 79.5% (76.1–99.9) vs. cTnI by 86.8% (76.6–92.7). In the hs-cTnT group there was a significant difference in the decrease by 26.5% (9–42.9) when compared with CK that fell by 79.5% (64.3–90.7).Kinetic of hs-cTnT and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be investigated.

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P01-303-Vegetative status in infants of high-risk for schizophrenia

European Psychiatry ◽

10.1016/s0924-9338(11)72014-4 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 305-305

Author(s):

M.A. Kalinina ◽

G.N. Schimonova

Keyword(s):

High Risk ◽

Mental State ◽

Motor Development ◽

Prognostic Significance ◽

Age Groups ◽

Control Group ◽

First Year ◽

Autonomic Tone ◽

Autonomic Disorders ◽

First Year Of Life

IntroductionThe study of clinical features and prognostic significance of autonomic disorders are among the most pressing problems of modern medicine.ObjectivesDynamically within 5 years were observed 50 children at high risk for schizophrenia and 40 children with hypoxic-ischemic encephalopathy of the general population. Aims. Evaluation of prognostic significance of autonomic disorders in infancy for mental health in older age groups.MethodsAll patients were examined by clinical methods and EEG, neurosonografia, original screening tables for early childhood.ResultsIn the first year of life in children at high risk for schizophrenia observed mental and motor development within the syndrome of PDD.In infancy the vagotonic orientation prevailed 72, 5%. By 3 years it changed to the amphotonic orientation reaching 76, 0% of children, while the 10, 0% acquired sympathotony, the rest remained vagotonic.The mental state of 37 children to 5 years qualified as schizotipical disorder (F 21.8). In 13 children it was diagnosed schizophrenia, children's type (F20.8). Frequent and sudden changes in the type of tonus correlated with the deterioration of the mental state of a different nature.In the control group at the first year of life prevailed vagotonic orientation, which gradually to age of one year changed by eutonic. During the first 3–5 months of infancy revealed some unstable circulatory, sleep disorders.ConclusionsThe instability of autonomic tone and an abundance of vegetative violations indicate the risk of mental pathology.

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Effectiveness of Rotarix® vaccine in Africa in the first decade of progressive introduction, 2009-2019: systematic review and meta-analysis

Wellcome Open Research ◽

10.12688/wellcomeopenres.16174.2 ◽

2020 ◽

Vol 5 ◽

pp. 187

Author(s):

Nickson Murunga ◽

Grieven P. Otieno ◽

Marta Maia ◽

Charles N. Agoti

Keyword(s):

Meta Analysis ◽

Age Groups ◽

Developed Countries ◽

Point Estimate ◽

First Year ◽

Full Dose ◽

Newcastle Ottawa Scale ◽

Group A ◽

First Year Of Life

Background: Randomized controlled trials of licensed oral rotavirus group A (RVA) vaccines, indicated lower efficacy in developing countries compared to developed countries. We investigated the pooled effectiveness of Rotarix® in Africa in 2019, a decade since progressive introduction began in 2009. Methods: A systematic search was conducted in PubMed to identify studies that investigated the effectiveness of routine RVA vaccination in an African country between 2009 and 2019. A meta-analysis was undertaken to estimate pooled effectiveness of the full-dose versus partial-dose of Rotarix® (RV1) vaccine and in different age groups. Pooled odds ratios were estimated using random effects model and the risk of bias assessed using Newcastle-Ottawa scale. The quality of the evidence was assessed using GRADE. Results: By December 2019, 39 (72%) countries in Africa had introduced RVA vaccination, of which 34 were using RV1. Thirteen eligible studies from eight countries were included in meta-analysis for vaccine effectiveness (VE) of RVA by vaccine dosage (full or partial) and age categories. Pooled RV1 VE against RVA associated hospitalizations was 44% (95% confidence interval (CI) 28-57%) for partial dose versus 58% (95% CI 50-65%) for full dose. VE was 61% (95% CI 50-69%), 55% (95% CI 32-71%), 56% (95% CI 43-67%), and 61% (95% CI 42-73%) for children aged <12 months, 12-23 months, <24 months and 12-59 months, respectively. Conclusion: RV1 vaccine use has resulted in a significant reduction in severe diarrhoea in African children and its VE is close to the efficacy findings observed in clinical trials. RV1 VE point estimate was higher for children who received full dose than those who received partial dose, and its protection lasted beyond the first year of life.

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Bovine cardiac troponin I gene (<i>TNNI3</i>) as a candidate gene for bovine dilated cardiomyopathy

Archives Animal Breeding ◽

10.5194/aab-52-113-2009 ◽

2009 ◽

Vol 52 (2) ◽

pp. 113-123

Author(s):

M. Owczarek-Lipska ◽

G. Dolf ◽

K. E. Guziewicz ◽

T. Leeb ◽

C. Schelling ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Dilated Cardiomyopathy ◽

Candidate Gene ◽

Expression Analysis ◽

Cardiac Troponin ◽

Troponin I ◽

Troponin T ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Significant Difference

Abstract. The cardiac troponin complex, which is an important component of the contractile apparatus, is composed of the three subunits troponin I (TnI), troponin C (TnC) and troponin T (TnT). Troponin I is the inhibitory subunit and consists of three isoforms encoded by TNNI1, TNNI2 and TNNI3 genes, respectively. Due to the different types of cardiomyopathies caused by mutations in the TNNI3 gene and its fluorescence in situ hybridization (FISH) mapping on bovine chromosome 18q26, which was shown to be linked to the recessively inherited bovine dilated cardiomyopathy (BDCMP), bovine TNNI3 was considered as candidate gene for BDCMP. Real-time polymerase chain reaction (PCR) TNNI3 expression analysis resulted in a significant difference between BDCMP affected and unaffected animals when normalized to ACTB gene expression, but there was no significant difference in expression when normalized to GAPDH. Northen blotting experiment was in agreement with the expression analysis and did not reveal a significant difference between the group of BDCMP affected and unaffected animals. Sequencing of the bovine TNNI3 gene revealed a single nucleotide polymorphism in intron 6 (c.378+315G>A), but this single nucleotide polymorphism (SNP)was present regardless of the BDCMP status. In summary our data provide evidence to exclude the bovine TNNI3 gene as a candidate for BDCMP.

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Observations on carapace color change in the juvenile big-headed turtle (Platysternon megacephalum)

PeerJ ◽

10.7717/peerj.7331 ◽

2019 ◽

Vol 7 ◽

pp. e7331

Author(s):

Dainan Cao ◽

Yan Ge ◽

Yufeng Wei ◽

Haoran Duan ◽

Shiping Gong

Keyword(s):

Color Change ◽

Ventral Side ◽

First Year ◽

Melanin Content ◽

Dermal Layer ◽

Significant Difference ◽

Before And After ◽

First Year Of Life ◽

Olive Green

The carapace color of newborn big-headed turtles (Platysternon megacephalum) is polymorphic and usually consists of two phenotypes: yellowish brown and olive green. As the turtles grew, over the first year of life, its carapace gradually turned from yellowish brown to chestnut brown, or from olive green to dark brown, depending on the phenotype. Meanwhile, the turtle’s plastron remained an orange and black pattern and did not change much. In this study, we primarily used HE staining to observe the carapace color change with age in big-headed turtle juveniles. We took the carapace marginal scute tissues twice from the same turtles before and after the carapace color change. Histological observations show that in the marginal scutes of the four tested turtles with different carapace color phenotypes, melanin granules are all concentrated in the dermal layer underneath the dorsal corneous layer, but rarely on the ventral side. Melanin deposits in the dorsal corneous layer were found to increase as the corneous layers thickened, while the melanin deposits in the ventral corneous layer did not change significantly. However, there was no significant difference in melanin deposition in the epidermis and dermis of the carapace among the yellowish brown, chestnut brown, olive green, and dark brown big-headed turtles. The results of our study indicate that the carapace color darkening in big-headed turtles may not be due to changes in melanin content of the carapace, but is the result of melanin accumulation and superposition in the dorsal corneous layer.

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