One size does not fit all: Perioperative management of patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is recognized as an important risk factor for perioperative complications. However, anesthesia management of HFpEF patients remains a considerable challenge without clear guidance. HFpEF is heterogeneous in its pathophysiological processes, diverse clinical presentations, adverse remodeling of cardiovascular and other organs, and clinical outcomes. It is difficult to manage the disease with one fixed approach because of this. This review phenotypes HFpEF patients by combining their clinical features and anesthesia care issues. Five phenotypes of HFpEF patients are identified: A, O, P, C, and Y. The clinical features, anesthesia implications, and anesthesia management for each phenotype are highlighted and discussed. Such an approach to HFpEF patients in the operating room could deliver safe, high-quality perioperative care.

[Stapled anoplin peptide combined with photothermal therapy enhances oncolytic immunotherapy of triple-negative breast cancer].

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.

Nanotechnology-based photo-immunotherapy: a new hope for inhibition of melanoma growth and metastasis.

Melanoma is the most aggressive form of skin cancer and there is a need for the development of effective anti-melanoma therapies as it shows high metastatic ability and low response rate. In addition, it has been identified that traditional phototherapy could trigger immunogenic cell death (ICD) to activate antitumor immune response, which could not only effectively arrest primary tumour growth, but also exhibit superior effects in terms of anti-metastasis, anti-recurrence for metastatic melanoma treatment. However, the limited tumour accumulation of photosensitizers/photothermal agents and immunosuppressive tumour microenvironment severely weaken the immune effects. The application of nanotechnology facilitates a higher accumulation of photosensitizers/photothermal agents at the tumour site, which can thus improve the antitumor effects of photo-immunotherapy (PIT). In this review, we summarise the basic principles of nanotechnology-based PIT and highlight novel nanotechnologies that are expected to enhance the antitumor immune response for improved therapeutic efficacy.

Human Resistin Induces Cardiac Dysfunction in Pulmonary Hypertension.

Background Cardiac failure is the primary cause of death in most patients with pulmonary arterial hypertension (PH). As pleiotropic cytokines, human resistin (Hresistin) and its rodent homolog, resistin-like molecule α, are mechanistically critical to pulmonary vascular remodeling in PH. However, it is still unclear whether activation of these resistin-like molecules can directly cause PH-associated cardiac dysfunction and remodeling. Methods and Results In this study, we detected Hresistin protein in right ventricular (RV) tissue of patients with PH and elevated resistin-like molecule expression in RV tissues of rodents with RV hypertrophy and failure. In a humanized mouse model, cardiac-specific Hresistin overexpression was sufficient to cause cardiac dysfunction and remodeling. Dilated hearts exhibited reduced force development and decreased intracellular Ca2+ transients. In the RV tissues overexpressing Hresistin, the impaired contractility was associated with the suppression of protein kinase A and AMP-activated protein kinase. Mechanistically, Hresistin activation triggered the inflammation mediated by signaling of the key damage-associated molecular pattern molecule high-mobility group box 1, and subsequently induced pro-proliferative Ki67 in RV tissues of the transgenic mice. Intriguingly, an anti-Hresistin human antibody that we generated protected the myocardium from hypertrophy and failure in the rodent PH models. Conclusions Our data indicate that Hresistin is expressed in heart tissues and plays a role in the development of RV dysfunction and maladaptive remodeling through its immunoregulatory activities. Targeting this signaling to modulate cardiac inflammation may offer a promising strategy to treat PH-associated RV hypertrophy and failure in humans.

A Four-Stepwise Electrocardiographic Algorithm for Differentiation of Ventricular Arrhythmias Originated from Left Ventricular Outflow Tract.

Several electrocardiographic algorithms have been proposed to identify the site of origin for the ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) versus right ventricular outflow tract. However, the electrocardiographic criteria for distinguishing VAs originated from the different sites of LVOT is lacking. We aimed to develop a simple and efficient ECG algorithm to differentiate LVOT VAs originated from the aortic root, AMC and LV summit. We analyzed 12-lead ECG characteristics of 68 consecutive patients who underwent successful radiofrequency catheter ablation of symptomatic VAs from LVOT. Patients were divided into RCC (right coronary cusp) group (n = 8), the L-RCC (the junction between the LCC and RCC) group (n = 21), the LCC (left coronary cusp) group (n = 24), the aortomitral continuity (AMC) group (n = 9) and the LV summit group (n = 6) according to the final ablation sites. Measurements with the highest diagnostic performance were modeled into a 4-stepwise algorithm to discriminate LVOT VAs. The performance of this novel algorithm was prospectively tested in a validation cohort of 43 consecutive patients undergoing LVOT VAs ablation. Based on the accuracy of AUC, a 4-stepwise ECG algorithm was developed. First, the QS duration in aVL > 134 ms was used to distinguish VAs from AMC, LV summit and VAs from aortic root (80% sensitivity and 76% specificity). Second, the R duration in II > 155 ms was used to differentiate VAs from LV summit and VAs from AMC (67% sensitivity and 56% specificity). Third, the ratio of III/II < 0.9 was used to discriminate VAs from RCC and VAs from LCC, L-RCC (82% sensitivity and 63% specificity). Fourth, the QS duration of aVR > 130 ms was used to discern VAs from LCC and VAs from L-RCC (75% sensitivity and 62% specificity). In the prospective evaluation, our 4-stepwise ECG algorithm exhibited a good predictive value. We have developed a novel and simple 4-stepwise ECG algorithm with good predictive value to discriminate the AVs from different sites of LVOT.

Preoperative Liver Stiffness is Associated With Hospital Length of Stay After Cardiac Surgery.

OBJECTIVES: Risk assessment models for cardiac surgery do not account for the degrees of liver dysfunction. Ultrasound shear-wave elastography measures liver stiffness (LSM), a quantitative measurement related to fibrosis, congestion, and inflammation. The authors hypothesized that preoperative liver stiffness would be associated with hospital length of stay after cardiac surgery. DESIGN: Prospective observational study. SETTING: University hospital, single center. PARTICIPANTS: One hundred five adult patients undergoing nonemergent cardiac surgery. INTERVENTIONS: Preoperative liver stiffness measured by ultrasound elastography. MEASUREMENTS AND MAIN RESULTS: The associations were analyzed using linear mixed models, with adjustments for preoperative variables, duration of cardiopulmonary bypass, and type of surgery. Median liver stiffness was 6.4 kPa (range, 4.1-18.6 kPa). The median length of hospital stay was 6 days (range, 3-18 d). Each unit increase in liver stiffness, treated as a continuous variable, was associated with an increase of 0.32 ± 0.10 days in the hospital (p = 0.002). When treated as a categorical variable (<6 kPa, 6-9.4 kPa, and ≥9.5 kPa), LSM ≥9.5 kPa v LSM <6 kPa was associated strongly with an increase in hospital length of stay of 3.25 ± 0.87 days (p = 0.0003). CONCLUSIONS: A preoperative LSM ≥9.5 kPa was associated with a significantly longer postoperative hospital length of stay. This association appeared independent of preoperative comorbidities commonly associated with coronary disease. Preoperative liver stiffness is a novel risk metric that is associated with the postoperative hospital length of stay after cardiac surgery.

Selected Transesophageal Echocardiographic Parameters of Left Ventricular Diastolic Function Predict Length of Stay Following Coronary Artery Bypass Graft-A Prospective Observational Study.

(1) Importance: Abnormal left ventricular (LV) diastolic function, with or without a diagnosis of heart failure, is a common finding that can be easily diagnosed by intra-operative transesophageal echocardiography (TEE). The association of diastolic function with duration of hospital stay after coronary artery bypass (CAB) is unknown. (2) Objective: To determine if selected TEE parameters of diastolic dysfunction are associated with length of hospital stay after coronary artery bypass surgery (CAB). (3) Design: Prospective observational study. (4) Setting: A single tertiary academic medical center. (5) Participants: Patients with normal systolic function undergoing isolated CAB from September 2017 through June 2018. (6) Exposures: LV function during diastole, as assessed by intra-operative TEE prior to coronary revascularization. (7) Main Outcomes and Measures: The primary outcome was duration of postoperative hospital stay. Secondary intermediate outcomes included common postoperative cardiac, respiratory, and renal complications. (8) Results: The study included 176 participants (mean age 65.2 ± 9.2 years, 73% male); 105 (60.2%) had LV diastolic dysfunction based on selected TEE parameters. Median time to hospital discharge was significantly longer for subjects with selected parameters of diastolic dysfunction (9.1/IQR 6.6−13.5 days) than those with normal LV diastolic function (6.5/IAR 5.3−9.7 days) (p < 0.001). The probability of hospital discharge was 34% lower (HR 0.66/95% CI 0.47−0.93) for subjects with diastolic dysfunction based on selected TEE parameters, independent of potential confounders, including a baseline diagnosis of heart failure. There was a dose−response relation between severity of diastolic dysfunction and probability of discharge. LV diastolic dysfunction based on those selected TEE parameters was also associated with postoperative cardio-respiratory complications; however, these complications did not fully account for the relation between LV diastolic dysfunction and prolonged length of hospital stay. (9) Conclusions and Relevance: In patients with normal systolic function undergoing CAB, diastolic dysfunction based on selected TEE parameters is associated with prolonged duration of postoperative hospital stay. This association cannot be explained by baseline comorbidities or common post-operative complications. The diagnosis of diastolic dysfunction can be made by TEE.

Right ventricular diastolic dysfunction and failure: a review.

Right ventricular diastolic dysfunction and failure (RVDDF) has been increasingly identified in patients with cardiovascular diseases, including heart failure and other diseases with cardiac involvement. It is unknown whether RVDDF exists as a distinct clinical entity; however, its presence and degree have been shown to be a sensitive marker of end-organ dysfunction related to multiple disease processes including systemic hypertension, pulmonary hypertension, heart failure, and endocrine disease. In this manuscript, we review issues pertaining to RVDDF including anatomic features of the right ventricle, physiologic measurements, RVDDF diagnosis, underlying mechanisms, clinical impact, and clinical management. Several unique features of RVDDF are also discussed.

Severe Patients With ARDS With COVID-19 Treated With Extracorporeal Membrane Oxygenation in China: A Retrospective Study.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis affecting over 200 countries worldwide. Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the management of COVID-19-associated end-stage respiratory failure. However, the exact effect of ECMO in the management of these patients, especially with regards to complications and mortality, is unclear. Methods: This is the largest retrospective study of ECMO treated COVID-19 patients in China. A total of 50 ECMO-treated COVID-19 patients were recruited. We describe the main characteristics, the clinical features, ventilator parameters, ECMO-related variables and management details, and complications and outcomes of COVID-19 patients with severe acute respiratory distress syndrome (ARDS) that required ECMO support. Results: For those patients with ECMO support, 21 patients survived and 29 died (mortality rate: 58.0%). Among those who survived, PaO2 (66.3 mmHg [59.5-74.0 mmHg] and PaO2/FiO2 (68.0 mmHg [61.0-76.0 mmHg]) were higher in the survivors than those of non-survivors (PaO2: 56.8 mmHg (49.0-65.0 mmHg), PaO2/FiO2 (58.2 mmHg (49.0-68.0 mmHg), all P < 0.01) prior to ECMO. Patients who achieved negative fluid balance in the early resuscitation phase (within 3 days) had a higher survival rate than those who did not (P = 0.0003). Conclusions: In this study of 50 cases of ECMO-treated COVID-19 patients, a low PO2/FIO2 ratio before ECMO commencement may indicate a poor prognosis. Negative fluid balance in the early resuscitation phase during ECMO treatment was a predictor of increased survival post-ECMO treatment.

A New Fitness Test of Estimating VO2max in Well-Trained Rowing Athletes.

BACKGROUND: This study was designed to investigate the validity of maximal oxygen consumption (VO2max) estimation through the Firstbeat fitness test (FFT) method when using submaximal rowing and running programs for well-trained athletes. METHODS: Well-trained flatwater rowers (n = 45, 19.8 ± 3.0 years, 184 ± 8.7 cm, 76 ± 12.9 kg, and 58.7 ± 6.0 mL⋅kg-1⋅min-1) and paddlers (n = 45, 19.0 ± 2.5 years, 180 ± 7.7 cm, 74 ± 9.4 kg, and 59.9 ± 4.8 mL⋅kg-1⋅min-1) completed the FFT and maximal graded exercise test (GXT) programs of rowing and running, respectively. The estimated VO2max was calculated using the FFT system, and the measured VO2max was obtained from the GXT programs. Differences between the estimated and measured VO2max values were analyzed to assess the accuracy and agreement of the predictions. Equations from the previous study were also used to predict the VO2max in the submaximal programs to compare the accuracy of prediction with the FFT method. RESULTS: The FFT method was in good agreement with the measured VO2max in both groups based on the intraclass correlation coefficients (>0.8). Additionally, the FFT method had considerable accuracy in VO2max estimation as the mean absolute percentage error (≤5.0%) and mean absolute error (<3.0 mL⋅kg-1⋅min-1) were fairly low. Furthermore, the FFT method seemed more accurate in the estimation of VO2max than previously reported equations, especially in the rowing test program. CONCLUSION: This study revealed that the FFT method provides a considerably accurate estimation of VO2max in well-trained athletes.

Resistin-Like Molecule α Dysregulates Cardiac Bioenergetics in Neonatal Rat Cardiomyocytes.

Heart (right) failure is the most frequent cause of death in patients with pulmonary arterial hypertension. Although historically, increased right ventricular afterload has been considered the main contributor to right heart failure in such patients, recent evidence has suggested a potential role of load-independent factors. Here, we tested the hypothesis that resistin-like molecule α (RELMα), which has been implicated in the pathogenesis of vascular remodeling in pulmonary artery hypertension, also contributes to cardiac metabolic remodeling, leading to heart failure. Recombinant RELMα (rRELMα) was generated via a Tet-On expression system in the T-REx 293 cell line. Cultured neonatal rat cardiomyocytes were treated with purified rRELMα for 24 h at a dose of 50 nM. Treated cardiomyocytes exhibited decreased mRNA and protein expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and transcription factors PPARα and ERRα, which regulate mitochondrial fatty acid metabolism, whereas genes that encode for glycolysis-related proteins were significantly upregulated. Cardiomyocytes treated with rRELMα also exhibited a decreased basal respiration, maximal respiration, spare respiratory capacity, ATP-linked OCR, and increased glycolysis, as assessed with a microplate-based cellular respirometry apparatus. Transmission electron microscopy revealed abnormal mitochondrial ultrastructure in cardiomyocytes treated with rRELMα. Our data indicate that RELMα affects cardiac energy metabolism and mitochondrial structure, biogenesis, and function by downregulating the expression of the PGC-1α/PPARα/ERRα axis.

Acetate, a Short-Chain Fatty Acid, Acutely Lowers Heart Rate and Cardiac Contractility Along with Blood Pressure.

Short-chain fatty acids (SCFAs) are metabolites produced almost exclusively by the gut microbiota and are an essential mechanism by which gut microbes influence host physiology. Given that SCFAs induce vasodilation, we hypothesized that they might have additional cardiovascular effects. In this study, novel mechanisms of SCFA action were uncovered by examining the acute effects of SCFAs on cardiovascular physiology in vivo and ex vivo. Acute delivery of SCFAs in conscious radiotelemetry-implanted mice results in a simultaneous decrease in both mean arterial pressure and heart rate (HR). Inhibition of sympathetic tone by the selective ß-1 adrenergic receptor antagonist atenolol blocks the acute drop in HR seen with acetate administration, yet the decrease in mean arterial pressure persists. Treatment with tyramine, an indirect sympathomimetic, also blocks the acetate-induced acute drop in HR. Langendorff preparations show that acetate lowers HR only after long-term exposure and at a smaller magnitude than seen in vivo. Pressure-volume loops after acetate injection show a decrease in load-independent measures of cardiac contractility. Isolated trabecular muscle preparations also show a reduction in force generation upon SCFA treatment, though only at supraphysiological concentrations. These experiments demonstrate a direct cardiac component of the SCFA cardiovascular response. These data show that acetate affects blood pressure and cardiac function through parallel mechanisms and establish a role for SCFAs in modulating sympathetic tone and cardiac contractility, further advancing our understanding of the role of SCFAs in blood pressure regulation. SIGNIFICANCE STATEMENT: Acetate, a short-chain fatty acid, acutely lowers heart rate (HR) as well as mean arterial pressure in vivo in radiotelemetry-implanted mice. Acetate is acting in a sympatholytic manner on HR and exerts negative inotropic effects in vivo. This work has implications for potential short-chain fatty acid therapeutics as well as gut dysbiosis-related disease states.

Remote liver ischemic preconditioning attenuates myocardial ischemia/reperfusion injury in streptozotocin-induced diabetic rats.

Diabetes mellitus (DM) exhibits a higher sensitivity to myocardial ischemia/reperfusion (I/R) injury and may compromise the effectiveness of cardioprotective interventions, including ischemic preconditioning. We previously found that liver ischemic preconditioning (RLIPC) could limit infarct size post I/R in non-diabetic rat hearts and further exerted anti-arrhythmic effects in diabetic or non-diabetic rats after myocardial I/R, however, little is known regarding the effect of RLIPC on infarct-sparing in diabetic hearts. In this study, we evaluated the protective effects of RLIPC on I/R injury in streptozotocin-induced type 1 diabetic rats. Type 1 diabetes mellitus was induced by one-time intraperitoneal injection of streptozotocin in Sprague-Dawley rats. Rats were exposed to 45 min of left anterior descend in (LAD) coronary artery occlusion, followed by 3 h of reperfusion. For liver ischemic preconditioning, four cycles of 5 min of liver I/R stimuli were performed before LAD occlusion. The cardioprotective effect of RLIPC was determined in diabetic rats. Compared to non-RLIPC treated DM rats, RLIPC treatment significantly reduced infarct size and cardiac tissue damage, inhibited apoptosis in diabetic hearts post I/R. RLIPC also improved cardiac functions including LVESP, LVEDP, dp/dtmax, and - dp/dtmax. In addition, RLIPC preserved cardiac morphology by reducing the pathological score post I/R in diabetic hearts. Finally, Westernblotting showed that RLIPC stimulated phosphorylation of ventricular GSK-3ß and STAT-5, which are key components of RISK and SAFE signaling pathways. Our study showed that liver ischemic preconditioning retains strong cardioprotective properties in diabetic hearts against myocardial I/R injury via GSK-3ß/STAT5 signaling pathway.

Resibufogenin inhibited colorectal cancer cell growth and tumorigenesis through triggering ferroptosis and ROS production mediated by GPX4 inactivation.

Resibufogenin (RB) has been used for cancer treatment, but the underlying mechanisms are still unclear. This study aimed to investigate the effects of RB treatment on colorectal cancer (CRC) cells, and to determine the underlying mechanisms. The cell counting kit-8 assay was used to determine cell viability. Cell morphology was observed under light microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was employed to detect cell apoptosis. Intracellular ferrous iron (Fe2+ ), malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species levels were detected by using commercial iron assay kit, MDA assay kit, GSH assay kit, and 2,7-dichlorodihydrofluorescein diacetate probes, respectively. The protein expressions were determined by Western blot and immunohistochemistry. RB inhibited cell viability in the CRC cell lines (HT29 and SW480) in a dose- and time-dependent manner, and caused cytotoxicity to the normal colonic epithelial cell line (NCM460) at high dose. Similarly, RB induced morphological changes in CRC cells from normal to round shape, and promoted cell death. Of note, RB triggered oxidative stress and ferroptotic cell death in CRC cells, and only ferroptosis inhibitors (deferoxamine and ferrostatin-1), instead of inhibitors for other types of cell death (apoptosis, autophagy, and necroptosis), reversed the inhibitory effects of RB on CRC cell proliferation. Furthermore, glutathione peroxidase 4 (GPX4) was inactivated by RB treatment, and overexpression of GPX4 alleviated RB-induced oxidative cell death in CRC cells. Consistently, the in vivo experiments validated that RB also triggered oxidative stress, and inhibited CRC cells growth and tumorigenicity in mice models. RB can inhibit CRC cells growth and tumorigenesis by triggering ferroptotic cell death in a GPX4 inactivation-dependent manner.

The Effect of the No Pain Labor & Delivery-Global Health Initiative on Cesarean Delivery and Neonatal Outcomes in China: An Interrupted Time-Series Analysis.

BACKGROUND: The proportion of live births by cesarean delivery (CD) in China is significant, with some, particularly rural, provinces reporting up to 62.5%. The No Pain Labor & Delivery-Global Health Initiative (NPLD-GHI) was established to improve obstetric and neonatal outcomes in China, including through a reduction of CD through educational efforts. The purpose of this study was to determine whether a reduction in CD at a rural Chinese hospital occurred after NPLD-GHI. We hypothesized that a reduction in CD trend would be observed. METHODS: The NPLD-GHI program visited the Weixian Renmin Hospital, Hebei Province, China, from June 15 to 21, 2014. The educational intervention included problem-based learning, bedside teaching, simulation drill training, and multidisciplinary debriefings. An interrupted time-series analysis using segmented logistic regression models was performed on data collected between June 1, 2013 and May 31, 2015 to assess whether the level and/or trend over time in the proportion of CD births would decline after the program intervention. The primary outcome was monthly proportion of CD births. Secondary outcomes included neonatal intensive care unit (NICU) admissions and extended NICU length of stay, neonatal antibiotic and intubation use, and labor epidural analgesia use. RESULTS: Following NPLD-GHI, there was a level decrease in CD with an estimated odds ratio (95% confidence interval [CI]) of 0.87 (0.78-0.98), P = .017, with odds (95% CI) of monthly CD reduction an estimated 3% (1-5; P < .001), more in the post- versus preintervention periods. For labor epidural analgesia, there was a level increase (estimated odds ratio [95% CI] of 1.76 [1.48-2.09]; P < .001) and a slope decrease (estimated odds ratio [95% CI] of 0.94 [0.92-0.97]; P < .001). NICU admissions did not have a level change (estimated odds ratio [95% CI] of 0.99 [0.87-1.12]; P = .835), but the odds (95% CI) of monthly reduction in NICU admission was estimated 9% (7-11; P < .001), greater in post- versus preintervention. Neonatal intubation level and slope changes were not statistically significant. For neonatal antibiotic administration, while the level change was not statistically significant, there was a decrease in the slope with an odds (95% CI) of monthly reduction estimated 6% (3-9; P < .001), greater post- versus preintervention. CONCLUSIONS: In a large, rural Chinese hospital, live births by CD were lower following NPLD-GHI and associated with increased use of labor epidural analgesia. We also found decreasing NICU admissions. International-based educational programs can significantly alter practices associated with maternal and neonatal outcomes.

Fropofol prevents disease progression in mice with hypertrophic cardiomyopathy.

AIMS: Increased myofilament contractility is recognized as a crucial factor in the pathogenesis of hypertrophic cardiomyopathy (HCM). Direct myofilament desensitization might be beneficial in preventing HCM disease progression. Here, we tested whether the small molecule fropofol prevents HCM phenotype expression and disease progression by directly depressing myofilament force development. METHODS AND RESULTS: Force, intracellular Ca2+, and steady-state activation were determined in isolated trabecular muscles from wild-type (WT) and transgenic HCM mice with heterozygous human α-myosin heavy chain R403Q mutation (αMHC 403/+). αMHC 403/+ HCM mice were treated continuously with fropofol by intraperitoneal infusion for 12 weeks. Heart tissue was analysed with histology and real-time PCR of prohypertrophic and profibrotic genes. Fropofol decreased force in a concentration-dependent manner without significantly altering [Ca2+]i in isolated muscles from both WT and αMHC 403/+ HCM mouse hearts. Fropofol also depressed maximal Ca2+-activated force and increased the [Ca2+]i required for 50% activation during steady-state activation. In whole-animal studies, chronic intra-abdominal administration of fropofol prevented hypertrophy development and diastolic dysfunction. Chronic fropofol treatment also led to attenuation of prohypertrophic and profibrotic gene expression, reductions in cell size, and decreases in tissue fibrosis. CONCLUSIONS: Direct inhibition of myofilament contraction by fropofol prevents HCM disease phenotypic expression and progression, suggesting that increased myofilament contractile force is the primary trigger for hypertrophy development and HCM disease progression.

Anesthetic Agents Isoflurane and Propofol Decrease Maximal Ca2+-Activated Force and Thus Contractility in the Failing Myocardium.

In the normal heart, frequently used anesthetics such as isoflurane and propofol can reduce inotropy. However, the impact of these agents on the failing myocardium is unclear. Here, we examined whether and how isoflurane and propofol influence cardiac contractility in intact cardiac muscles from rats treated with monocrotaline to induce heart failure. We measured force and intracellular Ca2+ ([Ca2 +]i) in trabeculae from the right ventricles of the rats in the absence or presence of propofol or isoflurane. At low to moderate concentrations, both propofol and isoflurane dose-dependently depressed cardiac force generation in failing trabeculae without altering [Ca2+]i At high doses, propofol (but not isoflurane) also decreased amplitude of [Ca2+]i transients. During steady-state activation, both propofol and isoflurane impaired maximal Ca2+-activated force (Fmax) while increasing the amount of [Ca2+]i required for 50% of maximal activation (Ca50). These events occurred without apparent change in the Hill coefficient, suggesting no impairment of cooperativity. Exposing these same muscles to the anesthetics after fiber skinning resulted in a similar decrement in Fmax and rise in Ca50 but no change in the myofibrillar ATPase-Ca2+ relationship. Thus, our study demonstrates that challenging the failing myocardium with commonly used anesthetic agents such as propofol and isoflurane leads to reduced force development as a result of lowered myofilament responsiveness to Ca2+ SIGNIFICANCE STATEMENT: Commonly used anesthetics such as isoflurane and propofol can impair myocardial contractility in subjects with heart failure by lowering myofilament responsiveness to Ca2+. High doses of propofol can also reduce the overall amplitude of the intracellular Ca2+ transient. These findings may have important implications for the safety and quality of intra- and perioperative care of patients with heart failure and other cardiac disorders.

Obstructive sleep apnea syndrome detection based on ballistocardiogram via machine learning approach.

Obstructive sleep apnea (OSA) is a common sleep-related respiratory disease that affects people's health, especially in the elderly. In the traditional PSG-based OSA detection, people's sleep may be disturbed, meanwhile the electrode slices are easily to fall off. In this paper, we study a sleep apnea detection method based on non-contact mattress, which can detect OSA accurately without disturbing sleep. Piezoelectric ceramics sensors are used to capture pressure changes in the chest and abdomen of the human body. Then heart rate and respiratory rate are extracted from impulse waveforms and respiratory waveforms that converted by filtering and processing of the pressure signals. Finally, the Heart Rate Variability (HRV) is obtained by processing the obtained heartbeat signals. The features of the heartbeat interval signal and the respiratory signal are extracted over a fixed length of time, wherein a classification model is used to predict whether sleep apnea will occur during this time interval. Model fusion technology is adopted to improve the detection accuracy of sleep apnea. Results show that the proposed algorithm can be used as an effective method to detect OSA.