Onset Of Contraction Research Articles

Left atrial strain and risk of atrial fibrillation post-aortic valve replacement surgery

Abstract Background Post-operative atrial fibrillation (POAF) occurs in approximately 30% of patients following aortic valve replacement (AVR) surgery. Left atrial dilatation has been proposed as a predictor of POAF. However, very little is known about the predictive value of left atrial strain analysis, which is a surrogate of left atrial mechanical function. This study evaluates the strength of association between left atrial function, assessed using strain echocardiography, and the occurrence of POAF after AVR. Methods and materials Perioperative data was collected retrospectively for patients undergoing surgical aortic valve replacement (n=100) who had appropriate pre-operative echocardiographic characterization, including echocardiography measures of LA strain (Fig. 1). Patients with pre-operative AF (n=3) were excluded. Patients were categorised according to the development of POAF. Results 28 (29%) of 97 patients developed POAF. Initial univariate analysis suggested an association between POAF and increased age, larger LA and LV volumes, diastolic dysfunction, mitral valve E and A values, and lower LA and LV strain. Univariate analysis suggested post-operative associations between POAF and longer durations of intubation, longer durations of noradrenaline requirement, and longer stays in ICU and hospital. Multivariate analysis demonstrated that lower pre-operative left atrial reservoir function had a very strong independent association (mean 12.0% vs 41.5%, odds ratio 0.007, 95% CI 0.0001-0.33, p=0.01) with POAF. Longer post-operative duration of intubation also had a strong association (mean 10hr vs 8hr, odds ratio 67.5, 95% CI 1.1-41.5, p=0.04) with POAF. Conclusion Left atrial reservoir function, a surrogate of left atrial compliance, has a strong independent association with POAF post-AVR. This suggests that patients with underlying mechanical atrial dysfunction are at increased risk of developing POAF. This study supports the inclusion of left atrial reservoir function in any predictive tool for POAF post-AVR. The longer duration of post-operative intubation in the AF group supports the negative impact of POAF. Figure 1. Example of speckle tracking analysis and strain measurements during the three phases of left atrial (LA) cycle using R-R ECG gating with the zero-baseline strain reference. Reservoir strain (yellow line) is the peak strain before mitral valve opening (positive value). Conduit strain (red line) is calculated as difference of the strain value at the onset of atrial contraction minus the peak strain value (negative value). Contraction strain is calculated as difference of the strain value at baseline (0) minus the strain value at onset of atrial contraction (negative value).

The boost of force in unfused tetanic contractions at variable interpulse intervals in fast motor units of the rat medial gastrocnemius

Previously, boost and sag effects seen in unfused tetanic contractions have been studied exclusively at constant stimulation frequency. However, intervals between successive discharges of motoneurons vary during voluntary movements. We therefore aimed to test whether the extra-efficient force production at the onset of contraction (boost) occurs during stimulation with variable intervals, and to what extent it depends on the level of interpulse interval (IPI) variability and history of stimulation. Four sets of three repeated unfused tetani (the first set with constant IPIs at 35 Hz; the other three sets with mean frequency 35 Hz and variable IPIs 28 ± 2 ms, ± 5 ms, and ± 7 ms, respectively) were recorded with 3 min breaks in fast fatigable and fast fatigue-resistant motor units of the rat medial gastrocnemius. We show that boost occurred in the first tetanic contraction of each set for stimulation at both constant and variable IPIs in two fast types of motor units; additionally, it was present in different IPIs variability for a given range. Mathematical decomposition of first (sagging) and second (non-sagging) tetanic contractions into twitch-like responses to successive stimuli in the tested IPIs variability showed that the changes underlying boost are pattern independent. This implies that boost probably occurs in daily activity when motoneurons fire with an unstable firing rate. The effect may therefore contribute to the development and regulation of force in voluntary daily activities, especially in short powerful contractions.

Isosorbide mononitrate for preinduction cervical ripening at or post-term pregnancy: randomised placebo-controlled clinical trial

IntroductionEffective labour induction is marked by the onset of uterine contractions, progressive cervical dilation, and effacement, culminating in a vaginal birth without maternal or fetal complications. The success of induction...

Enteric neuronal substrates underlying spontaneous and evoked neurogenic contractions in mouse colon.

Gastrointestinal motility persists when peripheral cholinergic signaling is blocked genetically or pharmacologically, and a recent study suggests nitric oxide drives propagating neurogenic contractions. To determine the neuronal substrates that underlie these contractions, we measured contractile-associated movements together with calcium responses of cholinergic or nitrergic myenteric neurons in un-paralyzed ex vivo preparations of whole mouse colon. We chose to look at these two subpopulations because they encompass nearly all myenteric neurons. Many but not all cholinergic neurons of the middle colon exhibited contractile-associated calcium responses with distinct features. By contrast, a large population of nitrergic neurons of the middle colon shut their activity off just before contraction onset, whereas another population of nitrergic neurons initiated a response just after contraction onset. When contractions were evoked by a variety of stimuli to the proximal and distal colon, the same neuronal subtypes exhibited the same activity patterns during the contraction. However, stimulation of proximal colon produced a transient, stimulation-locked response before the ensuing contraction in a subpopulation of cholinergic neurons and in nearly all nitrergic neurons, suggesting that distinct neuronal activity patterns underlie specific stimuli. Finally, although blockade of nitric oxide failed to arrest the generation or propagation of neurogenic contractions, chemogenetic elimination of nitrergic activity impaired their propagation to middle and distal colon. Genetic approaches were used to study the activity patterns of enteric neurons underlying spontaneous and evoked neurogenic contractions in un-paralyzed colon. These approaches can be combined with a variety of other approaches to identify the neuronal subtypes and subclasses that coordinate colonic motility.

Comparative in situ characterization of erythroid cells found throughout the developing tongue tissue, circulation, and liver of fetal mice.

Erythroid cells contribute to embryonic organ development and adult tissue repair supplying oxygen to tissues. During mouse development, the primitive erythroid cells produced in the extraembryonic blood islands of the yolk sac begin to circulate as immature and nucleated erythroblasts with the onset of cardiac contractions around embryonic day 9.5 (E9.5). On the other hand, the definitive erythroid progenitors derived from the yolk sac and arterial vessels colonize the fetal liver, where they mature into small, enucleated definitive erythrocytes that are released into circulation at E11.5. In many cases, however, erythroblasts are also generated in situ during the development of tissue vasculature. We hypothesized that the properties of erythroid cells generated by peripheral tissue hematopoiesis may differ from those of contemporaneously circulating erythroid cells because hematopoiesis is spatiotemporally distinct from typical primitive and definitive hematopoiesis. Comparative in situ protein expression analyses of erythroid cells in developing tongue, circulation, and liver of fetal mice were performed at E12.5 and E14.5, using immunofluorescence staining of several marker proteins for erythroid and endothelial cells. At E12.5, irregularly elongated immature vascular endothelial cells, many of which were in contact with nucleated erythroblasts, were distributed in the developing tongue. In the three fetal locations examined (tongue, circulation, and liver), most erythroid cells at E12.5 expressed CD31, which is involved in cell-cell interactions; however, the expression was downregulated by E14.5. Interestingly, at E12.5, several erythroblasts strongly expressing CD31 were found in the tongue, but less abundant in the circulation and fetal liver. Nearly all erythroblasts in E12.5 fetuses expressed primitive erythroid cell-specific βH1-globin; however, those strongly expressing the embryonic globin were scattered, particularly in the tongue, fewer in the circulation and fetal liver. On the contrary, erythroid cells expressing adult β1-globin were scarcely found in the tongue, which is in stark contrast to those in the circulation and fetal liver, where nearly all erythroid cells weakly expressed β1-globin at the embryonic stage. At E14.5, the number of βH1-globin-expressing cells drastically decreased; however, it was still significantly higher in the tongue than in the circulation and fetal liver. In all three locations, β1-globin accumulation and the enucleation of erythroid cells progressed uniformly and rapidly from E12.5 to E14.5. The results indicate that primitive erythroblasts in the tongue highly express CD31, mature more slowly, and are replaced by definitive erythroid cells more slowly than those in the circulation and fetal liver. Primitive erythroblasts produced together with immature vascular endothelial cells during vasculogenesis in the developing tongue may perform functions other than oxygen supply, such as regulating vascular remodeling.

The role of progesterone preparations in the prevention of premature birth: a modern view of the problem

Despite significant progress achieved in healthcare, preterm birth is an urgent problem in modern obstetrics. The preterm birth can be caused by various risk factors: for example, an ascending infection can trigger the onset of uterine contractions, cervical shortening followed by infection of the fetal membranes, amniotic fluid, and, in rare cases, the fetus itself. In most cases, the infectious and inflammatory process is the etiopathogenetic factor of isthmic-cervical insufficiency (ICI), one of the common causes of late miscarriages and preterm births. The period between 14 and 20 weeks of gestation is the most critical time for the development of ICI. The dynamic ultrasound cervicometry once every 7–14 days from week 16 through week 24 of pregnancy is recommended to the patients with ICI, as well as pregnant women in the high-risk group. Most professional societies guidelines addressing this issue recommend all pregnant women to perform routine transvaginal cervicometry during the second ultrasound screening for the timely formation of risk groups and optimization of approaches to the patient management. The following groups of drugs are used to prevent preterm birth: micronized progesterone, slow calcium channel blockers, β-adrenergic agonists, and non-steroidal anti-inflammatory drugs. The use of progesterone drugs to prevent preterm birth has generated much debate. Thus, the availability of several forms of progesterone and various routes of administration determine the complexity of the drug therapy. Micronized progesterone is the only progesterone drug that was approved for use after 20 weeks of gestation. The vaginal micronized progesterone has been found to be highly effective in the prevention of preterm birth, significantly reduce neonatal mortality and improve infant morbidity outcomes.

Ultrasound Evaluation of Onset Core Muscle Activity in Subjects with Non-Specific Lower Back Pain and Without Lower Back Pain: An Observational Case-Control Study.

Lower back pain (LBP) has been the leading cause of disability since 1990. Objectives: The main objective of this observational case-control study was to evaluate, using ultrasound, whether there were differences in the onset and ratio of core muscle contraction between subjects with non-specific chronic lower back pain and healthy subjects. Methods: A total of 60 participants (52% women), split between those with non-specific chronic lower back pain (n = 26) and healthy (n = 34) subjects, were recruited. Initial muscle contraction of the lateral abdominal wall, pelvic floor, lumbar multifidus, and respiratory diaphragm was measured using ultrasound. The abdominal drawing-in maneuver, contralateral arm elevation, the Valsalva maneuver, and voluntary contraction of the pelvic floor in seated and standing positions were performed. The muscle thickness of the lateral abdominal wall and lumbar multifidus and excursion of the pelvic floor and diaphragm at rest and during testing were also analyzed. Results: No differences were found between the groups in the initial contraction. Statistically significant differences were found in the following variables: diaphragm excursion (p = 0.032, r = 0.277) and lumbar multifidus ratio (p = 0.010, r = 0.333) in the standing-abdominal retraction maneuver; pelvic floor excursion (p = 0.012, r = 0.325) in the standing-contralateral arm raise; and transverse abdominis ratio (p = 0.033, r = 0.275) in the sitting-contralateral arm raise. A statistically significant interaction between the groups and body mass index was observed in resting diaphragm excursion (p = 0.018, partial eta squared = 0.096) during sitting-voluntary pelvic floor contraction. Conclusions: It cannot be concluded that there is a specific pattern of core activation in any of the groups. However, statistically significant differences were found in the contraction indexes of the lumbopelvic musculature.

A comparative study between modified Bishop score and transvaginal sonography to predict successful induction of labor

ABSTRACT Background: Modified Bishop score (MBS) and cervical length determination by transvaginal sonography (TVS) are the two methods for predicting successful vaginal delivery based on pre-induction favourability of the cervix. Aims and Objectives: This study compared both methods for predicting successful vaginal delivery. The primary objective was to compare the predictive value of MBS and TVS in predicting successful induction of labor. The secondary objective was to obtain the cut-off score of MBS and TVS for successful induction of labor. Methods: A prospective study was done involving 100 pregnant women admitted for induction of labor. TVS was done to measure the cervical length before induction of labor. MBS was also calculated for all the patients. Labor was induced with prostaglandins. Labor induction was considered successful if there was an onset of uterine contractions and cervical dilatation within 24 h of induction. Results: For successful induction of labor, the cutoff of cervical length by TVS and MBS was 2.5 cm and 6, respectively. Cervical length assessment by TVS performed better than the MBS (sensitivity 61.8% vs. 28.9%, Specificity 95.8% vs. 100%). Conclusion: MBS and cervical length measurement by sonography both are good predictors of successful induction of labor. Cervical length measurement by TVS provides a better prediction of the likelihood of vaginal delivery.

Relative uteroplacental insufficiency of labor.

Relative uteroplacental insufficiency of labor (RUPI-L) is a clinical condition that refers to alterations in the fetal oxygen "demand-supply" equation caused by the onset of regular uterine activity. The term RUPI-L indicates a condition of "relative" uteroplacental insufficiency which is relative to a specific stressful circumstance, such as the onset of regular uterine activity. RUPI-L may be more prevalent in fetuses in which the ratio between the fetal oxygen supply and demand is already slightly reduced, such as in cases of subclinical placental insufficiency, post-term pregnancies, gestational diabetes, and other similar conditions. Prior to the onset of regular uterine activity, fetuses with a RUPI-L may present with normal features on the cardiotocography. However, with the onset of uterine contractions, these fetuses start to manifest abnormal fetal heart rate patterns which reflect the attempt to maintain adequate perfusion to essential central organs during episodes of transient reduction in oxygenation. If labor is allowed to continue without an appropriate intervention, progressively more frequent, and stronger uterine contractions may result in a rapid deterioration of the fetal oxygenation leading to hypoxia and acidosis. In this Commentary, we introduce the term relative uteroplacental insufficiency of labor and highlight the pathophysiology, as well as the common features observed in the fetal heart rate tracing and clinical implications.

Effect of Obesity on Aquaporin5 Expression in Human Placental and Uterus Tissues.

Background: Obesity and overweight are also becoming more prevalent among women of childbearing age and pregnant women. In maternal obesity, the activation of metabolic, inflammatory, and oxidative stress pathways is proven, which appears to be a key step in the pathological changes observed in placental and uterine function. Several recent studies have evidenced that aquaporins (AQPs) are critical players in adipose tissue biology and are involved in the onset of obesity. Methods: Our studies aimed to investigate the changes in placental volume and vascularization and measure the AQP5 expression and total antioxidant capacity (TAC) in the placenta and uterus tissues in obese and typical-weight mothers. We also aim to measure the AQP5 plasma concentration. Results: We found AQP5 dominance in the uterus and plasma at 34 weeks of normal pregnancy. The placental volume increased and the vascularization decreased in obese mothers compared to the control. The AQP5 expression increased in the uterus of the obese group and did not change in the placenta. The TAC decreased in the plasma of overweight mothers. Conclusions: We hypothesize that increased AQP5 expression prolongs the length of pregnancy and inhibits the onset of contractions. Based on our findings, we can develop diagnostic tests and provide new targets for tocolytic drug development.

Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis

Premature rupture of membranes (PROM) is defined as the leakage of amniotic fluid before the onset of labor and delivery contractions. Some studies found that women who experienced PROM had significantly lower vitamin C blood levels than those who did not, while others found no significant differences. Previous systematic reviews and meta-analyses on the efficacy of vitamin C in the prevention of PROM had conflicting results. Conduct a systematic review and meta-analysis to determine if there was a significant difference in vitamin C blood levels in women who had PROM versus the control group who did not and to determine if vitamin C supplements could help prevent it. Systematic review and meta-analysis. We registered our protocol with PROSPERO (CRD42022371644). We searched PubMed/MEDLINE, Web of Science, and Scopus through February 15, 2024. Additionally, backward and forward citation searches were conducted. Studies were selected based on predetermined inclusion and exclusion criteria. Meta-Essentials: Workbooks for Meta-Analysis (version 1.5) was used for analysis. Twenty-five studies (26 reports) met all eligibility criteria, with 18 studies (18 reports) assessing vitamin C levels and seven studies (eight reports) evaluating efficacy. Women with PROM, whether preterm or term, had significantly lower vitamin C levels [Hedges’ g, -1.48; 95% confidence interval (CI): -2.82, -0.14; p = 0.020; I2 = 94.08%) and specifically preterm PROM after removing the outlying study [Hedges’ g, -1.29; 95% CI: -1.85, -0.73; p < 0.001; I2 = 87.35%). Vitamin C supplementation significantly reduced the risk of preterm or term PROM [risk ratio (RR), 0.57; 95% CI: 0.39, 0.81; p < 0.001; I2 = 12.17%), particularly for preterm PROM (RR, 0.67; 95% CI: 0.45, 0.99; p = 0.001; I2 = 0.00%). There were no significant differences in vitamin C levels between women with term PROM and controls, and there were no differences in the risk of developing term PROM between women taking vitamin C supplements and controls. Results were not robust in all sensitivity analyses. Women with PROM, particularly those who developed it preterm, appear to have significantly lower vitamin C levels, and vitamin C supplementation appears to be effective in reducing the risk of PROM, particularly preterm PROM. More high-quality studies with low risk of bias, more homogenous, and larger samples are needed to confirm these findings.

Central and peripheral haemodynamics at exercise onset: the role of central command

PurposeThe involvement of central command in central hemodynamic regulation during exercise is relatively well-known, although its contribution to peripheral hemodynamics at the onset of low-intensity contractions is debated. This study sought to examine central and peripheral hemodynamics during electrically-evoked muscle contractions (without central command) and voluntary muscle activity (with central command).MethodsCyclic quadriceps isometric contractions (1 every second), either electrically-evoked (ES; 200 ms trains composed of 20 square waves) or performed voluntarily (VC), were executed by 10 healthy males (26 ± 3 years). In both trials, matched for force output, peripheral and central hemodynamics were analysed.ResultsAt exercise onset, both ES and VC exhibited equal peaks of femoral blood flow (1276 ± 849 vs. 1117 ± 632 ml/min, p > 0.05) and vascular conductance (15 ± 11 vs. 13 ± 7 ml/min/mmHg, p > 0.05), respectively. Similar peaks of heart rate (86 ± 16 bpm vs. 85 ± 16 bpm), stroke volume (100 ± 20 vs. 99 ± 27 ml), cardiac output (8.2 ± 2.5 vs. 8.5 ± 2.1 L/min), and mean arterial pressure (113 ± 13 vs. 113 ± 3 mmHg), were recorded (all, p > 0.05). After ~ 50 s, all the variables drifted to lower values. Collectively, the hemodynamics showed equal responses.ConclusionThese results suggest a similar pathway for the initial (first 40 s) increase in central and peripheral hemodynamics. The parallel responses may suggest an initial minimal central command involvement during the onset of low-intensity contractions, likely associated with a neural drive activation delay or threshold.

Prediction of Failure to Progress after Labor Induction: A Multivariable Model Using Pelvic Ultrasound and Clinical Data.

Objective: Labor induction is one of the leading causes of obstetric admission. This study aimed to create a simple model for predicting failure to progress after labor induction using pelvic ultrasound and clinical data. Material and Methods: A group of 387 singleton pregnant women at term with unruptured amniotic membranes admitted for labor induction were included in an observational prospective study. Clinical and ultrasonographic variables were collected at admission prior to the onset of contractions, and labor data were collected after delivery. Multivariable logistic regression analysis was applied to create several models to predict cesarean section due to failure to progress. Afterward, the most accurate and reproducible model was selected according to the lowest Akaike Information Criteria (AIC) with a high area under the curve (AUC). Results: Plausible parameters for explaining failure to progress were initially obtained from univariable analysis. With them, several multivariable analyses were evaluated. Those parameters with the highest reproducibility included maternal age (p < 0.05), parity (p < 0.0001), fetal gender (p < 0.05), EFW centile (p < 0.01), cervical length (p < 0.01), and posterior occiput position (p < 0.001), but the angle of descent was disregarded. This model obtained an AIC of 318.3 and an AUC of 0.81 (95% CI 0.76-0.86, p < 0.0001) with detection rates of 24% and 37% for FPRs of 5% and 10%. Conclusions: A simplified clinical and sonographic model may guide the management of pregnancies undergoing labor induction, favoring individualized patient management.

Skeletal muscle contractions attenuate the norepinephrine-related reduction in interstitial oxygen pressures in the rat spinotrapezius

Increased sympathetic nerve activity with exercise plays a key role in the control of arterial blood pressure and redistribution of blood flow. Within the microcirculation, elevated sympathetic outflow promotes the release of norepinephrine and smooth muscle contraction. Exercise-induced attenuation of sympathetic vasoconstriction (i.e., functional sympatholysis) is thus critical for active muscle oxygen delivery-utilization matching. However, the extent to which muscle contractions impact noradrenergic regulation of interstitial oxygen pressures (PO2is) is unknown. This is important because, as dictated by Fick’s law, PO2is provides the sole driving force for oxygen diffusion into the myocyte thereby supporting oxidative phosphorylation. PURPOSE: To determine the effects of norepinephrine administration on resting and contracting rat skeletal muscle PO2is. We tested the hypothesis that topical application (superfusion) of norepinephrine would result in blunted decreases in skeletal muscle PO2is during contractions compared to rest. METHODS: PO2is was determined via phosphorescence quenching in the exposed spinotrapezius muscle of anesthetized male Sprague-Dawley rats (n=7, 2-3 months old) at rest and during electrically-induced submaximal contractions (0.5 Hz, 3-6 V) for 6 minutes in response to norepinephrine superfusion (5x10−4 M). Functional sympatholysis was determined as the difference between the norepinephrine-induced changes in PO2is at rest and during the contraction steady-state (i.e., 2 min following the onset of muscle contractions) using (i) the absolute PO2is fall with norepinephrine (ΔPO2is), and (ii) the area under the PO2is curve plotted as a function of time (AUC). The tail (caudal) artery was cannulated for measurements of mean arterial pressure (MAP) and heart rate (HR). RESULTS: Consistent with our hypothesis, skeletal muscle contractions attenuated norepinephrine-evoked reductions in spinotrapezius interstitial oxygenation as evaluated by ΔPO2is (rest: -8.7±1.4, contractions: -4.3±1.1 mmHg, p&lt;0.05) and AUC (rest: 2246±368, contractions: 1066±273 mmHg·s, p&lt;0.05). Although MAP increased significantly with norepinephrine both at rest (+5±1%, p&lt;0.05) and during contractions (+8±1%, p&lt;0.05), this mild hypertensive response to norepinephrine was not different between conditions (p&gt;0.05). Norepinephrine superfusion did not affect HR at rest or during contractions (p&gt;0.05). CONCLUSIONS: That muscle contractions blunted the decrease in spinotrapezius PO2is with norepinephrine compared to the resting condition is consistent with functional sympatholysis. The latter serves to match active muscle O2 delivery-utilization in the face of elevated sympathetic nerve activity during exercise. The current results indicate that a novel combination of phosphorescence quenching (interstitial oxygenation, PO2is) and superfusion techniques may be used to evaluate functional sympatholysis in the intact rat spinotrapezius muscle. Showalter Research Trust, Purdue University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The role of pennation angle and architectural gearing to rate of force development in dynamic and isometric muscle contractions.

Associations between muscle architecture and rate of force development (RFD) have been largely studied during fixed-end (isometric) contractions. Fixed-end contractions may, however, limit muscle shape changes and thus alter the relationship between muscle architecture an RFD. We compared the correlation between muscle architecture and architectural gearing and knee extensor RFD when assessed during dynamic versus fixed-end contractions. Twenty-two recreationally active male runners performed dynamic knee extensions at constant acceleration (2000°s-2) and isometric contractions at a fixed knee joint angle (fixed-end contractions). Torque, RFD, vastus lateralis muscle thickness, and fascicle dynamics were compared during 0-75 and 75-150 ms after contraction onset. Resting fascicle angle was moderately and positively correlated with RFD during fixed-end contractions (r = 0.42 and 0.46 from 0-75 and 75-150 ms, respectively; p < 0.05), while more strongly (p < 0.05) correlated with RFD during dynamic contractions (r = 0.69 and 0.73 at 0-75 and 75-150 ms, respectively; p < 0.05). Resting fascicle angle was (very) strongly correlated with architectural gearing (r = 0.51 and 0.73 at 0-75 ms and 0.50 and 0.70 at 75-150 ms; p < 0.05), with gearing in turn also being moderately to strongly correlated with RFD in both contraction conditions (r = 0.38-0.68). Resting fascicle angle was positively correlated with RFD, with a stronger relationship observed in dynamic than isometric contraction conditions. The stronger relationships observed during dynamic muscle actions likely result from different restrictions on the acute changes in muscle shape and architectural gearing imposed by isometric versus dynamic muscle contractions.

Cretaceous extensional and contractional stages in the Colombian Andes unraveled by a source-to-sink geochronological and thermochronological study in the Upper Magdalena Basin

Extensional and flexural basins can evolve through multiple stages under the same plate tectonic regime over tens of millions of years. The Cretaceous tectonic evolution of the Colombian Andes is characterized by shifts between contractional and extensional tectonics. The upper plate response to these changes is recorded in the Cretaceous sedimentary rocks along the Western, Central, and Eastern cordilleras, and their adjacent basins, including the Upper Magdalena hinterland basin. We integrated field observations, petrography, geochronology, and thermochronology in the Cretaceous sedimentary units in the southern Upper Magdalena Basin and in the adjacent crystalline basement to decipher the provenance of these units and the exhumation patterns of the source areas. These results suggest that the source areas were exhumed between the Late Jurassic to Early Cretaceous, which may have resulted from the combination of Jurassic contraction and the Early Cretaceous extension. Between ∼120 and 100 Ma, a major stage of crustal extension is recorded in the Caballos Formation. Subsequently, between ∼100 and 80 Ma, sedimentation in the Villeta Group marks the end of the extension and the onset of contraction. This contractional phase was characterized by minor rock uplift within the basin. Basin modification continued between 80 and 65 Ma, involving two successive contractional stages that changed the sedimentary patterns, leading to the burial of a previously exhumed horst block and the appearance of new source areas. These major changes in source areas and sedimentary systems are the result of deformation episodes during prolonged extensional and contractional phases. This geologic evolution highlights the stages that characterize extensional to contractional settings.

Constraining the onset of orogenic contraction in fold-and-thrust belts using sedimentary stylolite populations (Umbria-Marche Apennines, Italy)

Stylolites are pressure solution structures, the roughness of which yields quantitative information about the magnitude of the normal stress applied to the stylolite plane. The stress magnitude is calculated from the cross over length (Lc) determined using the signal analysis of a 2D track. For a sedimentary, bedding-parallel stylolite (BPS), Lc scales to the magnitude of the vertical maximum principal stress σ1, hence to the burial depth at the time the roughness of the stylolite froze. We present a dataset of nearly 200 BPS from Meso-Cenozoic folded carbonates across the Umbria Marche Apennine Ridge. The BPS population is used to address the discrepancies between Lc values obtained by using different signal analysis methods. Assuming that in compressional settings burial-related pressure-solution more probably halts because of the switch of σ1 from a burial-related vertical attitude to a tectonic-related horizontal attitude, the vertical stress magnitudes derived from the inversion of the BPS roughness were combined to burial models at each investigated fold to reconstruct the absolute timing at which the orogenic stress started to prevail. The results indicate that the onset of horizontal compression started at ∼10 Ma and ∼8 Ma in the innermost and outermost folds, respectively, and predated fold development as indicated by the age of growth strata. These results establish Stylolite Roughness Inversion Technique as a reliable depth gauge that enables refining the timing of the onset of contraction in fold-and-thrust belts.

P114 Role of NLRX1 Agonist NX-13 in Reducing Visceral Hypersensitivity in Preclinical Gastrointestinal Inflammation

Abstract Background NLRX1 activation reduces inflammation by decreasing oxidative stress and altering cellular metabolism within multiple cell types implicated in ulcerative colitis (UC). Colitis animal models demonstrated reduced disease severity and a phase 1b clinical trial showed signs of rapid symptom and endoscopic improvement in patients with active UC.1, 2 Abdominal pain driven by visceral hypersensitivity may persist in patients even after inflammation has resolved, negatively affecting their quality of life.3, 4 Therapeutic agents which address inflammation, epithelial healing, and visceral hypersensitivity concurrently may provide greater symptomatic relief and improved quality of life as many patients, even in remission, still complain of abdominal pain. We here describe the effects of oral NX-13 in a rat model of visceral hypersensitivity. Methods Rats (n=8) were dosed daily for a period of 3 days with NX-13 or vehicle. Under anesthesia, electrodes were positioned to monitor oblique abdominal muscle contraction and a colonic balloon catheter was inserted intra-anally. Visceral pain was assessed at baseline and 3 h post lipopolysaccharide injection (1 mg/kg subcutaneous) through measuring of visceromotor response (VMR) via electromyogram (EMG) recording and visual assessment of abdominal withdrawal reflex (AWR). Data are represented as median (IQR) and statistical significance determined by non-parametric Mann-Whitney U test. Results Compared to the vehicle control, oral NX-13 delayed the onset of muscle contraction in response to colonic distension in LPS-treated rats. Further, NX-13 treated rats experienced reduced contraction intensity and reduced sustained abdominal muscle contraction period compared to the vehicle control. Specifically, NX-13 decreased the number of AWR during colonic expansion compared to the control group (p=0.01, Fig1A). Moreover, NX-13 desensitized the VMR response by numerically increasing the minimum volume of the colonic distension balloon required to induce significant VMR. The mean minimum volume of water injected required to induce significant VMR increased 23%, from 650 μL in the vehicle group to 800 μL in the NX-13 treated rats (p=0.16, Fig1B). Lastly, NX-13 visually reduced the maximum abdominal EMG amplitude during colonic distention (p=0.19, Fig1C). Conclusion Adequate management of persistent pain in IBD patients with or without active bowel inflammation remains an unmet need in the treatment of IBD. The potential for NX-13 to specifically reduce visceral hypersensitivity and abdominal pain will be evaluated further in the ongoing phase 2 human NEXUS trial in patients with UC. 1Leber et al. J Immunol 203(12) 2Peyrin-Biroulet et al. JCC (17)Supp 3Abreu et al. JCC (14)Supp 4Wils et al. J Clin Med 11(15)

Evaluation of Left Atrial Function in Patients with Paroxysmal Atrial Fibrillation Using Left Atrial Automatic Myocardial Functional Imaging Ultrasonography.

To evaluate volume and strain of the left atrium (LA) in people suffering from paroxysmal atrial fibrillation which is not valvular (NVPAF) using the new technology of left atrial automatic myocardial function imaging (AFILA) and to analyze prognostic factors in patients with NVPAF by follow-up. Between August 2019 and August 2022, a total of 80 NVPAF patients and 60 normal control patients who were hospitalized in the Department of Cardiology were included in the study. The LA volume and strain parameters of the two groups were analyzed. The differences in LA function (LAF) parameters were compared between the two groups to generate the receiver operating characteristic curve (ROC) and calculate the area under the curve (AUC), sensitivity, and specificity of each parameter. Follow-up was conducted on the 80 NVPAF patients included, their treatment methods after admission and their rehospitalization due to heart events were recorded, and independent risk factors influencing the prognosis of NVPAF were obtained. A total of 140 patients participated in the study, including 80 in the NVPAF group and 60 in the normal control group. There was no statistically significant difference in age and sex between the two groups. Compared to the normal group, the LA minimum volume (LAVmin), LA maximum volume (LAVmax), and volume at onset of LA contraction (LAVpreA) in the NVPAF group were significantly increased. The LA emptying fraction (LAEF) was significantly decreased, and LA reservoir strain (S_R), LA conduit strain (S_CD), and LA contractile strain (S_CT) were significantly compromised (P < 0.05). There was no significant difference in LA evacuation volume (LAEV) reduction (P > 0.05). Logistic regression analysis of LAF parameters in NVPAF patients showed that LAEF and S_R were independently correlated with NVPAF (odds ratio values: 0.883 (0.827-0.943), P < 0.001; 0.916 (0.569-1.474), P = 0.047). The ROC curve results showed that LAEF had a high efficiency in the diagnosis of NVPAF, with P < 0.001, AUC of 0.843, sensitivity of 0.788, and specificity of 0.867. For the LA strain parameters, the S_R test efficiency was higher, with P < 0.001, AUC of 0.762, sensitivity of 0.713, and specificity of 0.783. There was a strong correlation between S_R and LAEF in patients with no end event and those with end event. The ROC curve revealed that the S_R was better than LAEF in predicting prognosis of patients with AF (AUC = 0.914, P < 0.0001 vs. AUC = 0.876, P < 0.0001). S_R of 10.5 and LAEF of 21 were the cut-off values for endpoint events in NVPAF patients, with sensitivity of 0.909 and 0.727 and specificity of 0.904 and 0.901, respectively. AFILA ultrasound technology comprehensively evaluated the LA size and function in patients with NVPAF. The LAEF and S_R were independently correlated with NVPAF and can determine the prognosis of patients with NVPAF.

Three-year follow-up results of two children born from a transplanted uterus.

To evaluate the 3-year follow-up results of two children delivered at our institution in 2019 from mothers with a transplanted uterus. Observational data on pregnancy outcomes, neonatal course, and growth trajectory in two children born to mothers after uterus transplantation, including 3-year follow-up and neurodevelopmental status assessed using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). Both children were born prematurely via uneventful caesarean sections, to mothers with Mayer-Rokitansky-Küster-Hauser syndrome and a transplanted uterus. An acute caesarean section was performed in one mother because of the onset of regular uterine contractions at 34 weeks and 6 days of pregnancy; in the other mother, an elective caesarean section was performed at 36 weeks and 2 days of gestation. The children were born healthy with no congenital malformations. They had an uneventful postnatal course and showed a normal growth trajectory during 3 years of follow-up. The Bayley-III neurodevelopmental scores of both children were within the normal ranges at ages 2 and 3 years. Though pregnancy after uterus transplantation is associated with the risk of premature delivery, no abnormalities were observed in the neonatal course and 3-year follow-up results, including the neurodevelopmental status, of two children born prematurely to mothers with a transplanted uterus. This is the first report on neurodevelopmental outcomes in children born after uterus transplantation. More data on children born after this radical procedure of uterine factor infertility treatment are required to support our promising results.