Frequency Of Contractions Research Articles

Human norovirus disturbs intestinal motility and transit time through its capsid proteins.

Human norovirus (HuNoV) accounts for over 700 million cases of gastroenteritis annually. Episodes of HuNoV disease are characterized by vomiting and diarrhea as the two most prominent symptoms. Despite its prevalence, our understanding of the pathophysiological mechanisms triggered upon HuNoV infection is limited, mainly due to a lack of suitable animal models. Our aim was to use the recent HuNoV zebrafish larvae model to study the effect of HuNoV infection on intestinal motility and investigate whether one viral protein could act as an enterotoxin, as seen with rotavirus. We studied whether HuNoV infection affects the contraction frequency of the intestinal bulb and the posterior intestine as well as the transit time. Infection of larvae, following injection of a HuNoV GII.4-containing stool sample in the yolk, resulted in an increased contraction frequency in the intestinal bulb. A comparable effect was observed in serotonin-treated larvae, corresponding to the natural function of serotonin. The higher replication efficacy of HuNoV GII.4 likely explains why they have a more marked effect on gut motility, when compared to other genotypes. Additionally, transit time of fluorescent food was prolonged in HuNoV GII.4 infected larvae, suggesting a loss of coordination in bowel movements upon infection. To identify the proteins responsible for the effect, individual HuNoV non-structural proteins and virus-like particles (VLPs) were injected intraperitoneally (ip). VLPs carrying VP1/VP2, but not those with only VP1, induced increased contraction frequencies in the intestinal bulb in a dose-dependent manner. In conclusion, our findings suggest that the viral capsid and potentially the minor capsid protein VP2 play a crucial role in the aetiology of symptoms associated with HuNoV, potentially acting as a viral enterotoxin. This work contributes to the understanding of the pathophysiological mechanisms in HuNoV-induced disease and further attests zebrafish as a valuable HuNoV disease model.

Evaluation value of ultrasound on gastrointestinal function in patients with acute heart failure

ObjectiveTo study the changes in gastrointestinal wall thickness, blood flow, motility, and symptoms in patients with acute heart failure, and to assess gastrointestinal function by ultrasound.MethodsIn this study, patients diagnosed with acute heart failure were selected as the study group, and healthy individuals were selected as the control group. Both groups collected general data and completed the Chinese version of the gastrointestinal symptom rating scale. Ultrasonography was used to measure several abdominal vascular and gastrointestinal-related indicators. Statistical analysis used grouped comparison and correlation analysis.ResultsThe study group scored higher than the control group in total score, lower abdominal symptom score, constipation score, and difficult defecation score (Z = −2.828, −2.022, −2.015, −2.015, all P < 0.05). The hepatic vein diameter, superior mesenteric vein inner diameter and wall thickness of the ascending colon in the study group were significantly higher than those in the control group (t = 9.543, P < 0.001; t = 2.277, P = 0.025; Z = −2.062, P = 0.039). Antral contraction amplitude, antral contraction frequency, motility index, jejunal peristalsis frequency, and ascending colon peristalsis frequency were significantly lower in the study group compared to the control group (Z = −2.571, −4.196, −3.681, −5.451, −4.061, all P < 0.001). The wall thickness of the antrum, jejunum, and ascending colon were positively correlated with the diameter of the hepatic vein (r = 0.394, P = 0.011; r = 0.352, P = 0.024; r = 0.450, P = 0.003). Motility index and ascending colon peristalsis frequency were positively correlated with the peak velocity of superior mesenteric vein (r = 0.456, P = 0.029; r = 0.507, P = 0.007). The wall thickness of the jejunum was positively correlated with the peak velocity of superior mesenteric artery (r = 0.330, P = 0.035). Peak velocity of superior mesenteric artery, antral contraction frequency, and jejunal peristalsis frequency were negatively correlated with the reflux score (r = −0.409, P = 0.038; r = −0.423, P = 0.032; r = −0.409, P = 0.038). The wall thickness of the ascending colon was positively correlated with the reflux score (r = 0.414, P = 0.035).ConclusionThis study found that patients with acute heart failure exhibited thickening of the gastrointestinal wall and generally reduced gastrointestinal motility, with predominantly lower abdominal symptoms. These findings indicate that ultrasound can effectively monitor the gastrointestinal structure and function of patients with acute heart failure, which is expected to provide help for clinical diagnosis and treatment.

An Observation of Outcome in Association with Spontaneous Onset of Labor and Induced Labour of Primigravida at Term

Introduction: Labour is a usual physiological process considered by progressive rise in frequency, intensity and duration of uterine contractions resulting in effacement and dilatation of the cervix with descent of the fetus over the birth canal. Initiation of labour is defined as iatrogenic stimulation of uterine reductions to cause the delivery of fetus before the onset of spontaneous labour. Aim of the study: To observe the outcome in association with spontaneous onset of labor and induced labour of primigravida at term. Methods: This cross-sectional study was conducted in the Department of Obstetrics and Gynecology in Ashiyan Medical College Hospital, Barua Khilkhet, and Dhaka, Bangladesh during the period from January 2018 to December 2018. Initially, all pregnant mothers at term (410/7 – 416/7 Weeks) were enrolled by purposive sampling. Thereafter, they were scrutinized according to the eligibility criteria. Finally, 80 participants were grouped in each category; namely spontaneous labor group. Thereafter, they were explained regarding the study procedure and informed written consent was charted on the partograph. A structure data sheet was used to obtain socio-demographic profile, obstetric profile, maternal and neonatal outcome profile were recorded using a pre structured, peer reviewed, interview and observation-based data collection sheet. All data were recorded, managed and analyzed using software Statistical Package for Social Science (SPSS) version 20.

Obesogenic Cafeteria Diet Induces Dynamic Changes in Gut Microbiota, Reduces Myenteric Neuron Excitability, and Impairs Gut Contraction in Mice.

The cafeteria diet (CAF) is a superior diet model in animal experiments compared to the conventional high-fat diet (HFD), effectively inducing obesity, metabolic disturbances and multi-organ damage. Nevertheless, its impact on gut microbiota composition during the progression of obesity, along with its repercussions on the enteric nervous system (ENS) and gastrointestinal motility has not been completely elucidated. To gain more insight into the effects of CAF diet in the gut, C57BL/6 mice were fed with CAF or standard diet for 2 or 8 weeks. CAF-fed mice experienced weight gain, disturbed glucose metabolism, dysregulated expression of colonic IL-6, IL-22, TNFα and TPH1, and altered colon morphology, starting at week 2. Fecal DNA was isolated and gut microbiota composition was monitored by sequencing the V3-V4 16S rRNA region. Sequence analysis revealed that Clostridia and Proteobacteria were specific biomarkers associated with CAF-feeding at week 2, while Bacteroides, Actinobacteria were prominent at week 8. Additionally, the impact of CAF diet on ENS was investigated (week 8), where HuC/D+ neurons were measured and counted, and their biophysical properties were evaluated by patch-clamp. Gut contractility was tested in whole-mount preparations. Myenteric neurons in CAF-fed mice exhibited reduced body size, incremented cell density and decreased excitability. The amplitude and frequency of the rhythmic spontaneous contractions in colon and ileum were affected by the CAF diet. Our findings demonstrate, for the first time, that CAF diet gradually changes the gut microbiota and promotes low-grade inflammation, impacting the functional properties of myenteric neurons and gut contractility in mice.

Uterine contraction frequency after initiation of labour epidural analgesia using electrohysterography monitoring: A prospective pilot study

BackgroundThe introduction of electrohysterography into clinical practice provides new opportunities to study the impact of labour epidural analgesia on uterine contractility because electrohysterography has a greater sensitivity in detecting uterine contractions than external tocodynamometry. We determined the uterine contraction frequency before and after initiation of labour epidural analgesia using an electrohysterography-derived tocogram. MethodsThis prospective study included 23 pregnant women between 36–42 weeks’ gestation with a singleton cephalic presentation who requested epidural analgesia in active labour. The primary study outcome was the difference in mean uterine contraction frequency 60 min before and 120 min after epidural analgesia initiation. The secondary aim was to measure changes in mean contraction frequency over time, using the mean uterine contraction frequency per 10 min, derived from 30-minute averages. ResultsIn the 120 min after epidural analgesia initiation, the average contraction frequency decreased significantly (−0.37 contractions/10 min [95 % CI −0.64 to −0.11]; p = 0.007 compared to the 60 min before epidural analgesia initiation. The largest decrease occurred 60–90 min after epidural analgesia initiation (−0.47 contractions/10 min [95 % CI −0.89 to −0.05]; p = 0.029). ConclusionDuring active labour, electrohysterography identified a statistically significant, although clinically small, reduction in uterine contraction frequency after epidural analgesia initiation. This pilot study demonstrates the potential value of electrohysterography monitoring for obstetric anaesthesia research and might renew interest in the still poorly understood interaction between labour epidural analgesia and uterine activity.

Segmental regulation of intestinal motility by colitis and the adaptive immune system in the mouse ileum and colon.

Gastrointestinal motility disturbances are a hallmark of inflammatory bowel disease (IBD); however, their mechanisms remain unclear. This study utilized a dextran sulfate sodium (DSS)-induced colitis mouse model, deficient in mature B and T lymphocytes, to assess intestinal motility and the role of the adaptive immune system in health and IBD. In healthy mice, the absence of adaptive lymphocytes reduced acetylcholine (ACh) sensitivity in the ileum. During colitis, it decreases motility by reducing the intensity and frequency of spontaneous contractions while increasing cholinergic responsiveness. In the proximal colon, adaptive immunity deficiency led to increased contractility and reduced ACh sensitivity in homeostasis, while colitis reduced contractile capacity. In the mid-colon, immune-deficient mice have reduced ACh sensitivity in homeostasis and exacerbated contractile responses during colitis. In the distal colon, adaptive immunity loss reduced contractility in health and cholinergic responsiveness during colitis. These motility alterations were associated with altered acetylcholinesterase and M2/M3 muscarinic receptor expression. Notably, adaptive lymphocyte deficiency resulted in reduced tissue damage and lower TNF-α expression in the colon during colitis paralleling intestinal motility changes. Overall, the adaptive immune system critically regulates motility and inflammation across different intestinal segments in IBD.

Use of uterine electromyography in the prediction of preterm birth after transvaginal cervical cerclage

BackgroundPreterm birth (PTB), complications of which account for approximately 35% of deaths among neonates, remains a crucial issue. Cervical insufficiency (CI) is defined as the inability of the utrine cervix to retain a pregnancy, leading to PTB. Cervical cerclage is an efficient surgery for CI patients by preventing the cervix from being further mechanically shortened. Unfortunately, a certain number of patients who had cerclage still delivered prematurely, raising the urgent need to accurately assess the risk of PTB in patients with cerclage. Uterine electromyography (uEMG) is an emerging technology that characterizes uterine contractions by describing the actual evolution process of uterine activity and has been used to predict PTB in recent years.MethodIn this single-center retrospective case-control study, singleton pregnancy women who received cervical cerclage and uEMG assessment between January 2018 and January 2022 at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled.Results32 PTBs were observed of the 69 women who underwent assessment. Based on multivariate logistic regression analysis, PTB after cerclage was significantly associated with previous PTB history or mid-trimester pregnancy loss (OR: 2.87, 95%CI: 1.49–5.54) and contraction frequency detected by uEMG (OR: 2.24, 95%CI: 1.44–3.49). The AUC of contraction frequency (0.766, P<0.001) was observed, and the optimal cut-off value suggested by Youden Index was 1.75 times per hour. Combined with previous preterm history and cervical length, the AUC of contraction frequency reached 0.858. After stratification by contraction frequency, the median duration was 11 weeks in the high frequency group (> 1.75 times per hour) and 15 weeks in the low frequency group (≤ 1.75 times per hour) (P<0.001).ConclusionsThe uEMG effectively predicts PTB after transvaginal cervical cerclage and provides a new method for clinicians to evaluate the pregnancy outcome of CI patients.

Conditional deletion of IP3R1 by Islet1-Cre in mice reveals a critical role of IP3R1 in interstitial cells of Cajal in regulating GI motility.

Inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) has been proposed to play a physiological role in regulating gastrointestinal (GI) motility, but the underlying cell-dependent mechanism remains unclear. Here, we utilized cell-specific IP3R1 deletion strategies to address this question in mice. Conditional IP3R1 knockout mice using Wnt1-Cre, Islet1-Cre mice, and smMHC-CreEGFP were generated. Cell lineage tracing was performed to determine where gene deletion occurred in the GI tract. Whole-gut transit assay and isometric tension recording were used to assess GI function in vivo and in vitro. In the mouse GI tract, Islet1-Cre targeted smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs), but not enteric neurons. IP3R1 deletion by Islet1-Cre (isR1KO) caused a phenotype of intestinal pseudo-obstruction (IPO), evidenced by prolonged whole-gut transit time, enlarged GI tract, abdominal distention, and early lethality. IP3R1 deletion by Islet1-Cre not only reduced the frequency of spontaneous contractions but also decreased the contractile responses to the muscarinic agonist carbachol (CCh) and electrical field stimulation (EFS) in colonic circular muscles. By contrast, smMHC-CreEGFP only targeted SMCs in the mouse GI tract. Although IP3R1 deletion by smMHC-CreEGFP (smR1KO)also reduced the contractile responses to CCh and EFS in colonic circular muscles, the frequency of spontaneous contractions was less affected, and neither global GI abnormalities nor early lethality was found in smR1KO mice. IP3R1 deletion in both ICCs and SMCs but not in SMCs alone causes an IPO phenotype, suggesting that IP3R1 in ICCs plays an essential role in regulating GI motility in vivo.

The genetic architecture of exercise-induced ventricular ectopy

Abstract Background Previously, we have shown that the frequency of exercise-induced premature ventricular contractions (PVCs) during and after exercise are associated with increased risk of major adverse cardiovascular events in asymptomatic individuals from the UK Biobank study1. The underlying mechanisms are, however, unclear. Several electrocardiographic markers associated with arrhythmogenesis have a known hereditary component, but the genetic underpinnings of exercise-induced ventricular ectopy have not been investigated. Purpose Our aim was to explore the genetic basis of premature ventricular ectopy during and after exercise and unveil plausible candidate genes and biological mechanisms. Methods We conducted a genome-wide association study (GWAS) for PVC frequency during exercise and recovery in &amp;gt;44,000 asymptomatic individuals of European ancestry without known cardiovascular disease from the UK Biobank study. As the distribution of PVC frequency is highly skewed (e.g. absence of negative values and excess of zero values), we first applied Gaussian transformation. Simulation studies were performed to justify that this approach would lead to valid inference. In the GWAS model, we included sex, age, UK Biobank genotyping array, and the first 10 genetic principal components as covariates. Statistical power was boosted by joint analysis of exercise and recovery PVC traits using multi-trait analysis of GWAS (MTAG)2. Genetic risk scores were constructed in independent samples from UK Biobank (N=341,948) and were tested for association with heart failure and life-threatening ventricular arrhythmias. Results We identified 4 loci for PVC frequency during exercise, and 1 locus for PVC frequency during recovery (Picture 1). Candidate genes included CRIM1, FLNC, and BAG3 for which mutations have been linked in the pathogenesis of (arrhythmogenic) cardiomyopathy. Subjects in the top 10% of the genetic risk scores had a significantly higher risk of heart failure and life-threatening ventricular arrhythmias compared to the bottom 90%, (odds ratio (OR) (95% confidence interval): 1.14 (1.08 – 1.20), p &amp;lt; 0.001; and 1.13 (1.02 – 1.24), p &amp;lt; 0.001, respectively). Conclusions Ventricular ectopic burdens during exercise and recovery have a significant heritable component. Candidate genes highlight a possible shared genetic background with inherited cardiomyopathy and a genetic risk score was associated with heart failure and ventricular arrhythmias. These findings substantial advance our understanding of the genetic basis of exercise-induced ventricular ectopy in a population-based cohort without cardiovascular disease.Miami plot of ventricular ectopic burden

Disorders of secondary peristalsis are associated with the development of esophagitis.

Disorders of primary peristalsis are associated with a higher percent time pH <4 in the esophagus suggesting poor acid clearance. However, there are no studies of secondary peristalsis and its relationship to microscopic or erosive esophagitis. The goal of this study was to determine the relationship between secondary peristalsis using functional luminal imaging probes (EndoFLIP) and the presence or absence of esophagitis. We reviewed the endoscopic and EndoFLIP 2.0 tracings for 103 consecutive patients including those with a history of upper gastrointestinal surgery undergoing upper endoscopy. Esophagogastric junction (EGJ) distensibility and diameter, repetitive antegrade contraction (RACs) presence and frequency, and occlusive diameters were measured. Measurements were then compared between patients with and without microscopic and/or erosive esophagitis. Means were compared using t-tests. Proportions were compared using Chi-Squared analyses. One hundred and three patients were included (mean age: 14.4 + 6.4 years). Ten patients had erosive esophagitis and 28 patients had microscopic esophagitis. Erosive and microscopic esophagitis were associated with abnormal or absent of RACs (p < 0.001). Occlusive diameters were higher in patients with esophagitis compared to those without (p < 0.001). There was no relationship between EGJ distensibility and the presence of erosive or microscopic esophagitis (p = 0.4). The absence of RACs was the only independent predictor of esophagitis (erosive and microscopic), after controlling for age, proton pump inhibitors (PPI) use and EGJ distensibility (p < 0.001). Abnormal secondary peristalsis is associated with microscopic and gross esophagitis, suggesting that EndoFLIP should be part of the diagnostic algorithm for esophagitis.

Diacerein and myo-inositol alleviate letrozole-induced PCOS via modulation of HMGB1, SIRT1, and NF-kB: A comparative study.

Polycystic ovary syndrome (PCOS) is the most prevalent cause of anovulatory infertility in women. Myo-inositol supplementation has displayed effectiveness in curing PCOS patients. Diacerein, an anti-inflammatory medication, has not been extensively studied in the context of reproductive disorders. This study aimed to compare the role of myo-inositol and diacerein in PCOS and the probable mechanisms mediating their actions. Forty adult female rats were divided equally into the following: control, PCOS, PCOS+Myo-inositol, and PCOS+Diacerein groups. Rats were subjected to arterial blood pressure (ABP), electromyography (EMG), and uterine reactivity measurements. Blood samples were collected for measuring hormonal assays, glycemic state, lipid profile, oxidative stress, and inflammatory markers. Ovaries and uteri were extracted for histological examination, including hematoxylin and eosin staining, Masson's trichrome staining, immunohistochemistry, and rt-PCR analysis of ovarian tissues. PCOS was associated with significant increases in ABP, uterine frequency and amplitude of contraction, luteinizing hormone, testosterone, lipid, glycemic and inflammatory markers, malondialdehyde, high-mobility group box 1 (HMGB1), nuclear factor kappa (NF-kB), ovarian fibrosis, and endometrial thickening. In contrast, there was a significant reduction in follicular stimulating hormone, reduced glutathione, and Sirtuin 1 (SIRT1) when compared with control group. Both myo-inositol and diacerein counteract PCOS changes; but diacerein's effectswere superiorto myo-inositol's for all parameters, except for lipid and glycemic markers. Diacerein possessed anti-inflammatory properties and showed significant efficacy in mitigating the endocrinal, metabolic, and ovarian structural alterations linked to PCOS. Its beneficial actions likely stem from reducing oxidative stress, dyslipidemia, and hyperglycemia, potentially through the modulation of HMGB1, SIRT1, and NF-kB pathways.

On the rate-limiting dynamics of force development in muscle.

Skeletal muscles produce forces relatively slowly compared with the action potentials that excite them. The dynamics of force production are governed by multiple processes, such as calcium activation, cycling of cross-bridges between myofilaments, and contraction against elastic tissues and the body. These processes have been included piecemeal in some muscle models, but not integrated to reveal which are the most rate limiting. We therefore examined their integrative contributions to force development in two conventional types of muscle models: Hill-type and cross-bridge. We found that no combination of these processes can self-consistently reproduce classic data such as twitch and tetanus. Rather, additional dynamics are needed following calcium activation and facilitating cross-bridge cycling, such as for cooperative myofilament interaction and reconfiguration. We provisionally lump such processes into a simple first-order model of 'force facilitation dynamics' that integrate into a cross-bridge-type muscle model. The proposed model self-consistently reproduces force development for a range of excitations including twitch and tetanus and electromyography-to-force curves. The model's step response reveals relatively small timing contributions of calcium activation (3%), cross-bridge cycling (3%) and contraction (27%) to overall force development of human quadriceps, with the remainder (67%) explained by force facilitation. The same set of model parameters predicts the change in force magnitude (gain) and timing (phase delay) as a function of excitatory firing rate, or as a function of cyclic contraction frequency. Although experiments are necessary to reveal the dynamics of muscle, integrative models are useful for identifying the main rate-limiting processes.

Pirfenidone mitigates demyelination and electrophysiological alterations in multiple sclerosis: Targeting NF-κB, sirt1, and neurotrophic genes.

Multiple sclerosis (MS) is a demyelinating disease affecting thecentral nervous system associated with progressive neurodegeneration. Pirfenidone (Pir) is a well-known antifibrotic agent; however, Pir's function in MS is little explored. We evaluated the neuroprotective effects of Pir in MS and its possible underlying mechanisms. Forty male Swiss mice were divided equally into control, cuprizone (CPZ), Pir, and CPZ + Pir groups. Assessment of motor function was conducted using neurobehavioral tests, EMG, and nerve conduction velocity (NCV). Mice's brains were extracted to measure oxidative stress, neuroinflammatory markers, and the expression of neurotrophic genes. The corpus callosum and the sciatic nerve were subjected to histopathological and immunohistochemical studies. The CPZ group was associated with significant reductions in muscle power, frequency of contraction, sciatic NCV, SOD, IL-10, SIRT1, NGF, and neuregulin-1. Significant increases in MDA, TNF-α, INF-γ, IL-17, TGF-β, and NF-κB were also detected. Multiple areas of partially demyelinated nerve fibers in the corpus callosum, the loss of oligodendrocyte nuclei, and increased microglia and astrocytes were also observed. The sciatic nerve revealed partial demyelination with significantly reduced myelin basic protein (MBP) expression. Pir significantly restored motor function, demyelination, and neurodegenerative changes induced by CPZ. Besides the antifibrotic action of Pir, we concluded that it improves motor function in MS by alleviating the demyelinating process and neurodegeneration. Its potential anti-inflammatory, antioxidant, and antifibrotic properties could be contributing factors. These effects could be mediated by modulating the NF-κB, SIRT1, NGF, and neuregulin-1 pathways. Pir is a promising agent for treating MS.

Real‐Time Force Monitoring of Electrically Stimulated 3D‐Bioengineered Muscle Bioactuators Using Organic Sensors with Tunable Sensitivity

The contractile nature of skeletal muscle tissue makes it especially attractive for powering biohybrid actuators. Significant efforts have been dedicated to the improvement and control of contraction force, going one step forward toward the automation of these biohybrid platforms. Herein, 3D‐bioengineered skeletal muscle tissues are integrated with organic transistor‐based sensors to define a soft bioactuator with real‐time force monitoring capabilities. The muscle tissue is electrically stimulated while the organic sensor ensures transduction of the exerted force into an electrical signal that allows direct monitoring of the bioactuator performance. Sensor calibration is carried out to define its sensitivity at different biasing conditions: as opposed to standard, two‐terminal piezoresistive devices, transistor‐based strain sensors show tunable sensitivity by acting on the voltage applied to a third terminal—the gate. A complete evaluation of sensing performances is provided, demonstrating that real‐time monitoring is effective under different conditions, including stimulation signal frequency and chemical modulation of the bioactuator contraction, demonstrating its potential use as a drug testing platform. In the reported results, the way is paved for a complete exploitation of organic devices in soft robotic applications and to the development of novel biohybrid machines in bioengineering and biomedicine.

Rotigaptide inhibits spontaneous contractions of gastric smooth muscle in diabetic rats via the PKCα-Cx43 pathway.

The study aimed to investigate the effect of rotigaptide (ZP123) on spontaneous contractions of gastric smooth muscle in diabetic rats and explore the underlying mechanisms. Twelve rats were randomly divided into model and normal control groups. Changes in gastric smooth muscle spontaneous contractions in each group were observed. Western blot analysis was performed to detect Cx43 and PKCα expression. Rat gastric smooth muscle cells were cultured in vitro and divided into normal glucose, high glucose and high glucose+rotigaptide group. The intracellular Ca2+ content was observed by immunofluorescence. The amplitude and frequency of gastric smooth muscle spontaneous contractions were reduced in the model group than the normal control group (all p < .01), which were reduced after rotigatide treatment than before treatment in the model group (all p < .01). The model+rotigaptide group showed decreased membrane expression of Cx43, increased cytoplasmic expression of Cx43, increased membrane expression of p-PKCα Thr497 and lower membrane/cytoplasm ratio of Cx43 expression compared with the model group (all p < .01). The intracellular Ca2+ content was increased in the high glucose group than the normal glucose group (p < .01), while no significant difference was observed between the high glucose+rotigaptide and high glucose groups. Our findings suggest that rotigatide can stabilize the intracellular Ca2+ concentration in gastric smooth muscle cells under high glucose condition by upregulating PKCα activity and downregulating the number of GJs and the opening rate of GJ hemichannels through the PKCα-Cx43 pathway, thus inhibiting spontaneous contractions of gastric smooth muscle in diabetic rats.

Predicting Vaginal Delivery Success: Role of Intrapartum Transperineal Ultrasound Angle of Descent at a Single Center.

BACKGROUND Assessment of labor progress via digital vaginal examination is subjective, while intrapartum transperineal ultrasonography is deemed more objective and effective. The angle of descent (AoD) is a reliable intrapartum transperineal ultrasound parameter with minimal inter-observer and intra-observer errors. This study compared intrapartum transperineal ultrasonography with digital vaginal examination in evaluating the angle of descent for vaginal delivery selection in 70 women. MATERIAL AND METHODS This cross-sectional study was conducted at Dr. Mohammad Hoesin Hospital Palembang in Indonesia, using a consecutive sampling method to measure AoD of 70 patients at admission and every 2 h during labor progression. Patients were monitored until childbirth, and outcomes of successful vaginal or cesarean delivery were reported. A diagnostic test determined the optimal AoD for predicting successful vaginal delivery and its predictive value. RESULTS The study included 70 patients with a mean age of 28.29±6.09 years and a body mass index of 30.59±3.49 kg/m². Among them, 29 (41%) had successful vaginal deliveries. Adequate contraction frequency at admission was strongly associated with successful vaginal delivery (P<0.001). The optimal AoD for predicting successful vaginal delivery was 94.5°, with an area under the curve of 0.567 (95% CI 0.425-0.710), sensitivity of 84.2%, specificity of 45.7%, and accuracy of 54.3%. CONCLUSIONS Intrapartum transperineal ultrasonography for measuring AoD can be a valuable adjunct in labor management. Further investigations are needed to validate the optimal AoD in Indonesian pregnant women.

The role of NAADP in maintaining spontaneous heart contractions: comparative physiological studies

The goal of the work was to study the role of the second messenger NAADP (Nicotinic Acid Adenine Dinucleotide Phosphate), which causes the release of Ca2+ ions from lysosomes and endosomes, in the regulation of heart contractions. Isolated hearts of the grape snail Helix pomatia and a chicken embryo were used as models. Using the membrane-permeable acetooxymethyl ester NAADP-AM, we showed that NAADP at nanomolar concentrations increases the frequency and amplitude of spontaneous cardiac contractions in H. pomatia. The NAADP antagonist NED19, without affecting the amplitude of contractions, dose-dependently reduces their frequency, completely blocking spontaneous contractions of the mollusk heart at a concentration of 5 μM. The V-type H+-ATPase inhibitor bafilomycin A1 suppresses the accumulation of calcium ions in lysosomes and acidic endosomes. We have shown that bafilomycin A1 causes attenuation of spontaneous contractions and cardiac arrest in H. pomatia. Serotonin increases the amplitude of contractions of the H. pomatia heart without affecting heart rate. NED19 at saturating concentrations (10 μM) reduces the frequency of contractions when the snail heart is activated by serotonin, but only partially reduces their amplitude. In experiments with the isolated chick embryo heart, we showed that NED19 reduces the frequency of spontaneous contractions without affecting the amplitude of contractions. Based on the data obtained, a hypothesis was put forward that the release of calcium ions from lysosomes and endosomes under the influence of endogenous NAADP ensures the maintenance of spontaneous contractions of the heart.

The hanging‐heart chip: A portable microfluidic device for high‐throughput generation of contractile embryonic stem cell‐derived cardiac spheroids

AbstractStem cell‐derived cardiac spheroids are promising models for cardiac research and drug testing. However, generating contracting cardiac spheroids remains challenging because of the laborious experimental procedure. Here, we present a microfluidic hanging‐heart chip (HH‐chip) that uses a microchannel and flow‐driven system to facilitate cell loading and culture medium replacement operations to reduce the laborious manual handling involved in the generation of a large quantity of cardiac spheroids. The effectiveness of the HH‐chip was demonstrated by simultaneously forming 50 mouse embryonic stem cell‐derived embryonic bodies, which sequentially differentiated into 90% beating cardiac spheroids within 15 days of culture on the chip. A comparison of our HH‐chip method with traditional hanging‐drop and low‐attachment plate methods revealed that the HH‐chip could generate higher contracting proportions of cardiac spheroids with higher expression of cardiac markers. Additionally, we verified that the contraction frequencies of the cardiac spheroids generated from the HH‐chip were sensitive to cardiotoxic drugs. Overall, our results suggest that the microfluidic hanging drop chip‐based approach is a high‐throughput and highly efficient method for generating contracting mouse embryonic stem cell‐derived cardiac spheroids for cardiac toxicity and drug testing applications.

Characterization of the cellular components of mouse collecting lymphatic vessels reveals that lymphatic muscle cells are the innate pacemaker cells regulating lymphatic contractions.

Collecting lymphatic vessels (cLVs) exhibit spontaneous contractions with a pressure-dependent frequency, but the identity of the lymphatic pacemaker cell is still debated. By analogy to pacemakers in the GI and lower urinary tracts, proposed cLV pacemaker cells include interstitial cells of Cajal like cells (ICLC) or the lymphatic muscle (LMCs) cells themselves. Here we combined immunofluorescence and scRNAseq analyses with electrophysiological methods to examine the cellular constituents of the mouse cLV wall and assess whether any cell type exhibited morphological and functional processes characteristic of pacemaker cells: a continuous if not contiguous network integrated into the electrical syncytium; spontaneous Ca2+ transients; and depolarization-induced propagated contractions. We employed inducible Cre (iCre) mouse models routinely used to target these specific cell populations including: c-kitCreER T2 to target ICLC; PdgfrβCreER T2 to target pericyte-like cells; PdgfrαCreER ™ to target CD34+ adventitial cells and ICLC; and Myh11CreER T2 to target LMCs directly. These specific inducible Cre lines were crossed to the fluorescent reporter ROSA26mT/mG, the genetically encoded Ca2+ sensor GCaMP6f, and the light-activated cation channel rhodopsin2 (ChR2). c-KitCreER T2 labeled both a sparse population of LECs and round adventitial cells that responded to the mast cell activator compound 48-80. PdgfrβCreER T2 drove recombination in both adventitial cells and LMCs, limiting its power to discriminate a pericyte-specific population. PdgfrαCreER ™ labeled a large population of interconnected, oak leaf-shaped cells primarily along the adventitial surface of the vessel. Of these cells, only LMCs consistently, but heterogeneously, displayed spontaneous Ca2+ events during the diastolic period of the contraction cycle, and whose frequency was modulated in a pressure-dependent manner. Optogenetic depolarization through the expression of ChR2 under control of Myh11CreER T2 , but not PdgfrαCreER ™ or c-KitCreER T2 , resulted in propagated contractions upon photo-stimulation. Membrane potential recordings in LMCs demonstrated that the rate of diastolic depolarization significantly correlated with contraction frequency. These findings support the conclusion that LMCs, or a subset of LMCs, are responsible for mouse cLV pacemaking.

Assessing the Risk of Interfacility Transport in Pregnant Patients Due to Progression of Labor: Lessons From a Specialized Maternal-Fetal Transport Program.

Background Pregnant laboring patients sometimes require interfacility transfer to a higher level of care. There is a paucity of evidence to inform when it is safe to transfer a laboring patient and when delivery may be too imminent to transfer. Methods This is a retrospective study of pregnant patients undergoing interfacility transfer with a specialized obstetric transport team deployed from a large Midwest regional healthcare system. The primary outcome was delivery prior to or within one hour of arrival at the receiving institution due to progression of labor. Data collected included basic demographics, vital signs, gravidity, parity, gestational age, contraction frequency if contractions were present, and cervical dilation. We sought to define the association between these variables and the primary outcome to inform risk assessment for precipitous delivery among patients being considered for interfacility transfer. Results Of the 370 pregnant patients for whom the specialized transfer team was requested, 11 (3%) met the primary outcome. Those with more advanced cervical dilation and those who did not receive regular prenatal care were more likely to meet the criteria for the primary outcome. For every centimeter of cervical dilation, the odds of meeting the primary outcome increased 2.3-fold (95% CI: 1.5-3.4). Conclusions We identified risk factors for early delivery among pregnant patients for whom an interfacility transfer was requested and described patients who were high-risk for obstetric interfacility transport due to the progression of labor. Our results can help inform risk assessments for transferring potentially high-risk laboring patients.