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Background We aimed to study the predictive value of early two-dimensional echocardiography (2DE) speckle tracking (ST) for left ventricular ejection fraction (LVEF) changes during trastuzumab treatment for HER2-positive breast cancer. Methods HER2-positive breast cancer patients receiving trastuzumab, with or without anthracycline, underwent 2DE-ST at baseline and after 3 and 6 months (m) trastuzumab. Cardiac magnetic resonance (CMR) imaging (with ST) was performed at baseline and 6 m. We studied the correlation between 2DE-ST- and CMR-derived global longitudinal strain (GLS) and global radial strain (GRS) measured at the same time. Additionally, we associated baseline and 3 m 2DE-ST measurements with later CMR-LVEF, and with cardiotoxicity, defined as CMR-LVEF 10% during trastuzumab. Results Forty-seven patients were included. Median baseline LVEF was 60.4%. GLS measurements based on 2DE-ST and CMR showed weak correlation (Pearson’s r = 0.33; p = 0.041); GRS measurements were uncorrelated (r = 0.09; p = 0.979). 2DE-LVEF at baseline and 3 m, and 2DE-ST-GLS at 3 m were predictive of CMR-LVEF at 6 m. In contrast, the change in 2DE-ST-GLS at 3 m was predictive of the change in CMR-LVEF at 6 m, whereas the change in 2DE-LVEF was not. Importantly, the 11 patients who developed cardiotoxicity (28%) had larger 2DE-ST-GLS change at 3 m than those who did not (median 5.2%-points versus 1.7%-points; odds ratio for 1% difference change 1.81, 95% confidence interval 1.11–2.93; p = 0.016; explained variance 0.34). Conclusions Correlations between 2DE-ST and CMR-derived measurements are weak. Nevertheless, ST-measurements appeared useful to improve the performance of 2DE in predicting LVEF changes after 6 m of trastuzumab treatment.

Previous studies showed that postmenopausal women are more likely to have poorly controlled hypertension than men of the same age. Whether this is caused by inadequate treatment or poor response to antihypertensive agents remains unknown. The aim of this study is to analyze treatment response to the most potent renin angiotensin aldosterone system (RAAS) inhibitor perindopril in different age categories in women and men. Individual patient data were used from the combined European Trial on Reduction of Cardiac Events With Perindopril (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), and Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trials, which include patients with vascular disease (n = 29,463). We studied the relative and absolute changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) during a 4-week run-in phase in which all patients were treated with the perindopril-based treatment in different age categories. In total, 8366 women and 21,097 men were included in the analysis. Women greater than 65 years of age showed a significantly smaller blood pressure reduction after perindopril treatment (2.8 mmHg [95% confidence interval {CI} = 0.1–5.5] less reduction compared to women ≤45 years, p = 0.039). In men, the SBP reduction after perindopril in patients greater than 55–65 and greater than 65 years was lower compared to the age category less than or equal to 45 years (adjusted mean difference >55–65: 2.8 mmHg [95% CI = 1.8–3.7], p 65: 3.7 mmHg [95% CI = 2.7–4.7], p

The inlet duct length may affect the gas flow field and performance of a cyclone separator with a contracted inlet duct. In this study, a numerical simulation using the Eulerian-Lagrangian approach with a one-way coupling method was conducted to evaluate the gas flow field and separation efficiency of the cyclone separators with contracted inlet ducts of different lengths. The simulation results indicated that increasing the inlet duct length led to higher gas tangential velocity in the cyclone body. The effect of the inlet duct length on gas axial velocity was inferior to that on gas tangential velocity. A longer inlet duct reduced both the pressure drop and the separation efficiency. The reductions of the expansion loss at the inlet of the cylinder and friction loss inside the cyclone body contributed the most reduction of the pressure drop as the inlet duct length increased. Generally, when the inlet duct was 1.5 times longer than the cylinder diameter, the effect of inlet duct length on the gas flow field and performance of a cyclone separator became slight.

Vascular dysfunctions can progress and lead to stroke and cardiovascular disease, especially in smokers. The presence of particular vascular changes according to sex has been described and they can be identified by the Doppler method. This study evaluated Doppler velocimetry parameters of the Ophthalmic Artery (OA) and the Middle Cerebral Artery (MCA) according to sex in smokers regarding a non-smoker group. This cross-sectional observational study included 178 subjects: 93 women and 85 men. Doppler parameters were assessed in OA and MCA. Student’s t-test was used, with p

Jingfeng Wang,1,2,&ast; Jian Liu,3,&ast; Longfei Gao,3 Guangqiao Li,1,2 Yilin Sun,3 Bo Shi1,2 1School of Medical Imaging, Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of China; 2Anhui Key Laboratory of Computational Medicine and Intelligent Health, Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of China; 3Department of Gynecologic Oncology, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo ShiSchool of Medical Imaging, Bengbu Medical College, Bengbu, Anhui, People’s Republic of ChinaTel +86-18955203003Email shibo@bbmc.edu.cnPurpose: Heart rate variability (HRV) has been reported as a useful biomarker for prognostic factors in a variety of cancers. The purpose of this study was to explore the predictive value of preoperative HRV for lymph node metastasis (LNM) in patients with cervical cancer (CC).Patients and Methods: A total of 77 patients with CC were included, including 18 LNM and 59 non-LNM patients. A five-minute resting electrocardiogram (ECG) was collected before surgery for the analysis of HRV time domain, frequency domain and Poincaré plot parameters (ie, SDNN, RMSSD, LF, HF, LF/HF, SD1, SD2 and SD2/SD1). Student’s t-tests and logistic regression were performed to determine the relationship between HRV and LNM.Results: The LNM group had significantly lower SDNN, LF, and SD2 than the non-LNM group (all p < 0.05; all Cohen’s d > 0.5). Binary logistic regression analysis indicated that SDNN, LF and SD2 were still significantly associated with LNM. Specifically, for each 1 ms decrease in SDNN and SD2 and each 1 logarithmic unit decrease in ln (LF), the odds of LNM increased by 12%, 9%, and 86%, respectively (all p < 0.05).Conclusion: These findings suggest an association between HRV and CC LNM, and HRV could be a potential noninvasive biomarker for the prediction of LNM in CC patients.Keywords: cervical cancer, heart rate variability, lymph node metastasis, autonomic nervous system

Purpose of review Red blood cell (RBC) clearance has been studied for decades in many different pathologies, which has revealed different routes of RBC degradation, depending on the situation. This review summarizes the latest mechanistic insights on RBC clearance in different contexts; during homeostatic removal, immune-mediated destruction, and systemic inflammation. Recent findings Besides the recognition of a variety of potential 'eat me' signals on RBCs, recent evidence suggests that normal RBC degradation is driven by the increase of the adhesive properties of RBCs, mediating the retention in the spleen and leading to RBC hemolysis. Furthermore, immune-mediated degradation of RBCs seems to be fine-tuned by the balance between the density of the antigens expressed on RBCs and the presence of 'don't eat me' signals. Moreover, besides RBC clearance by macrophages, neutrophils seem to play a much more prominent role in immune-mediated RBC removal than anticipated. Lastly, RBC clearance during systemic inflammation appears to be driven by a combination of extreme macrophage activity in response to proinflammatory cytokines as well as direct damage of RBC by the inflammation or inflammatory agent. Summary Recent studies on RBC clearance have expanded our knowledge on their destruction in different contexts.

Interoception, the ability to perceive internal bodily sensations, and heart rate variability (HRV) share common physiological pathways, including the baroreflex feedback loop. The baroreflex can be activated by resonance breathing, wherein respiration is paced at 6 times per minute (0.1 Hz), eliciting immediate physiological changes and longer-term therapeutic responses. This registered report characterizes baroreflex functioning as a cardiac mechanism of interoception in a two-session study (n = 67). The heartbeat discrimination task was used to obtain indices of interoceptive accuracy, sensibility and metacognition. Baroreflex functioning was measured as HRV at 0.1 Hz and baroreflex sensitivity (BRS); high frequency (HF) HRV was calculated as a control. Cardiovascular indices were measured at baseline and during active and control paced breathing after which changes in interoception were measured. The first hypothesis was that baseline baroreflex functioning would predict individual differences in interoceptive awareness. The second hypothesis was that resonance breathing would increase participants' ability to detect their own heartbeats, and that this effect would be mediated by increases in 0.1 Hz HRV and BRS. Data were collected upon in principle acceptance of the manuscript. We found a negative relationship of interoceptive accuracy with baseline HF HRV and BRS, and a positive relationship between metacognitive interoception and 0.1HZ HRV, BRS and HF HRV. We found that changes in 0.1 Hz HRV and BRS during resonance breathing positively correlate with increases in interoceptive accuracy. Our results show that the extent to which breathing recruits the resonant properties of the cardiovascular system can facilitate the conscious perception of participants' heartbeats. We interpret this as an increase in vagal afferent signaling and baroreflex functioning following resonance breathing. We put forward an alternative explanation that HRV modulation can reduce interoceptive prediction errors, facilitating the conscious perception of interoceptive signals, and consider the role of resonance breathing on mental health from an interoceptive inference perspective.

To investigate the optimal blood pressure (BP) levels and relative importance of BP and BP variability in the early phase of acute ischemic stroke (AIS) for hypertensive patients with carotid artery stenosis (CAS). A single‐center cohort study included 750 AIS patients with hypertension and tests were performed for CAS. Participants were categorized to Group 1 (SBP

Background Lung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. Methods Acute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n=7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. Results All pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n=4) and early death (n=3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cm H2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. Conclusions During near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.

Drug-induced corrected QT (QTc) prolongation can cause Torsade de Pointes (TdP) which leads to severe arrhythmia or sudden cardiac death. However, information on the prevalence of QTc prolongation in coronavirus disease 2019 (COVID-19) patients and risk factors is limited. A retrospective chart review was conducted in COVID-19 patients admitted to Chonburi Hospital from April to October 2020. The outcomes were the incidence of QTc prolongation and prevalence of risk factor QTc prolongation. We included 29 COVID-19 patients. After treatments were initiated, QTc prolongation occurred in 17 patients (58.62%). QT prolongation could be found as early as two days after the treatment initiation (median = 6 days interquartile range [IQR], 4-7). The median QTc interval in those 17 patients increased from 410 (IQR, 399.5-425.0) ms to 460 (453.50-466.50) ms, with the maximum QTc interval of 488 ms. They were treated with multiple drugs that were reported as a cause of QTc prolongation. 64.71% (n = 11) of them were treated with chloroquine. The median TdP risk score in patients with and without QTc prolongation was 3 (IQR, 2-3) and 2 (IQR, 1-2), respectively. The percentage of patients with comorbidities including atrial fibrillation, bradycardia, concomitant use of diuretics, diabetes, electrolyte imbalance was higher in patients with QTc prolongation. COVID-19 patients were treated with multiple drugs that were reported as a cause of QTc prolongation. COVID-19 patients with QTc prolongation had more comorbidities that are risk factors for QTc prolongation.

Slow flow (SF) that develops after percutaneous coronary intervention (PCI) is significantly associated with poor prognosis in Non-ST elevation myocardial infarction (Non-STEMI) patients. Increased Selvester QRS score and Frontal QRS-T angle [f(QRS-T)] are related to adverse cardiovascular outcomes. We aimed to investigate the predictive role of the Selvester QRS score and f(QRS-T) for the development of post-PCI SF in patients with Non-STEMI.In a retrospective study, 210 patients with Non-STEMI were divided into two groups as SF (29) and Non-SF (181) according to their TIMI coronary flow grade. For all patients the Selvester QRS score and f(QRS-T) were calculated from automatic electrocardiography (ECG) reports. The mean age of the study population was 63 (55-75) years and 102 (68.6%) of patients were male. The Selvester QRS score and f(QRS-T) were higher in the SF group than in the Non-SF group [(5[3-8], 3[2-5]); (67° [42°-88°], 39° [24°-59°]), respectively, all p 0.01]. In a logistic regression analysis, the Selvester QRS score (OR = 4,862; 95% (CI) = 1,131-20,904, p =0.03) and f(QRS-T) (OR = 5,489; 95% (CI)= 11,433-21,034, p =0.01) were found independent predictors of post-PCI SF in Non-STEMI patients. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic values of the Selvester QRS score [86% sensitivity; 44% specificity; cut off 2; (AUC, 0.693)] and f(QRS-T) [62% sensitivity; 73% specificity; cut off 58°; (AUC, 0.778)].The Selvester QRS score and f(QRS-T), both easy-to-calculate ECG parameters, are predictors of post-PCI SF in Non-STEMI patients.

Background Timely diagnosis of disseminated intravascular coagulation (DIC) in hemophagocytic lymphohistiocytosis (HLH) patients is crucial but challenging, as HLH interferes with the results of the laboratory tests included in the DIC score system. Case presentation Here, we reported a case of lymphoma-associated HLH, in which coagulation-fibrinolysis activation /inhibition markers (TAT, tPAIC, and PIC), prompted timely diagnosis of early stage DIC (initial phase of microvascular thrombosis, yet non-overt), prior to the development of organ failures and/or bleedings. Conclusions This report highlights the importance of the implementation of new biomarkers (such as TAT, tPAIC, and PIC), into the diagnostic work-up for coagulation disorders. These biomarkers are directly suggestive of microthrombus formation, therefore they can be of paramount importance in diagnosing DIC with complicated etiologies, such as hematological diseases-related DIC.

Introduction This study aimed to evaluate the sensitivity of the erect chest X-ray for diagnosing subdiaphragmatic free air. Furthermore, we examined the effects of different parameters, including sex, age, size of perforation, and the location of perforation on the sensitivity of the erect CXR. Methods This study included all patients with perforated peptic ulcer (107 cases) referred to the Shahid Rajaei hospital of Tonekabon from April 2015 to August 2020. The perforated peptic ulcer was confirmed by laparotomy, and the erect chest X-ray was performed as a preoperative procedure. The collected checklist was analyzed using the IBM SPSS Statistics V22.0 software. Results Achieved results showed total sensitivity of 86% for the erect chest X-ray. The sensitivity of the erect CXR was calculated, 88.5% and 82.6% at males and females, respectively. However, the sensitivity for different age groups was about 86%. The larger perforations resulted in higher sensitivity. Furthermore, the erect chest X-ray sensitivity for duodenal perforations (92.5%) was significantly greater than the gastric perforations (75%). Conclusion Based on this study, the erect chest X-ray could be utilized as a preoperative procedure with total sensitivity of 86% for gastroduodenal perforations. Patients' age and sex have no significant impact on the sensitivity (P-value > 0.05). However, the size and location of perforation significantly influenced the sensitivity (P-value Implications for practice The erect chest X-ray is used as a routine procedure to detect subdiaphragmatic free air in gastroduodenal perforations. The effects of different factors such as age, sex, size of perforation, and the location of perforation on the sensitivity of the erect chest X-ray are discussed for the first time in this study.

Background: Predicting postoperative lung function after pneumonectomy is essential. We retrospectively compared postoperative lung function to predicted postoperative lung function based on computed tomography (CT) volumetry and perfusion scintigraphy in patients who underwent pneumonectomy. Methods: Predicted postoperative lung function was calculated based on perfusion scintigraphy and CT volumetry. The predicted function was compared to the postoperative lung function in terms of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV₁), using 4 parameters: FVC, FVC%, FEV₁, and FEV₁%. Results: The correlations between postoperative function and predicted function based on CT volumetry were r=0.632 (p=0.003) for FVC% and r=0.728 (p

In this study, a series of experiments was conducted to examine the mechanical and damage properties of cemented paste backfill (CPB) with different water saturations (ws = 0%, 22.1%, 47.0%, 65.3%, 82.8%, and 100%). The results reveal that the UCS, peak strain, and elastic modulus first increased and then decreased, and the porosity and fractal dimension of cracks first decrease and then increase with the increase of ws. In addition, the UCS, peak strain, and elastic modulus is maximum, and the porosity and fractal dimension are minimum when the ws is 65.3%. The UCS increases with the increase of peak strain and elastic modulus, and decreases with the increase of porosity and fractal dimension, and the UCS present good quadratic polynomial functions relationship with the porosity and fractal dimension. The SEM images show that with the increase of ws from 0% to 65.3%, the hydration products increases and the pore structure decreases. When the ws exceeds 65.3%, and the pore structure begins to increase. The failure mode of the CPB is mainly tensile failure. A new damage constitutive model of CPB with different ws was constructed. The total damage D of the CPB is composed of initial damage Dp and load damage DL. The total damage evolution curve shows an S-shaped distribution, and the total damage rate evolution curve shows a normal distribution. With the increase of ws, the damage rate and the peak value of damage rate of CPB first increases and then decreases.

Despite their limitations, unfractionated heparin (UFH) and bivalirudin remain standard-of-care parenteral anticoagulants for percutaneous coronary intervention (PCI). We discovered novel direct thrombin inhibitors (DTIs) from tick salivary transcriptomes and optimised their pharmacologic activity. The most potent, ultravariegin, inhibits thrombin with a Ki of 4.0 pM, 445-fold better than bivalirudin. Unexpectedly, despite their greater antithrombotic effect, variegin/ultravariegin demonstrated less bleeding, achieving a 3-to-7-fold wider therapeutic index in rodent thrombosis and bleeding models. When used in combination with aspirin and ticagrelor in a porcine model, variegin/ultravariegin reduced stent thrombosis compared with antiplatelet therapy alone but achieved a 5-to-7-fold lower bleeding time than UFH/bivalirudin. Moreover, two antibodies screened from a naïve human antibody library effectively reversed the anticoagulant activity of ultravariegin, demonstrating proof-of-principle for antidote reversal. Variegin and ultravariegin are promising translational candidates for next-generation DTIs that may reduce peri-PCI bleeding in the presence of antiplatelet therapy., Bleeding complications limits the use of effective antithrombotics therapeutics. Here, the authors developed next-generation direct thrombin inhibitors with low bleeding risks as safe peri-percutaneous coronary intervention anticoagulants when used in combination with antiplatelets.

Lymphatic dysfunction is associated with the progression of several vascular disorders, though currently, there are limited strategies to promote new lymphatic vasculature (i.e., lymphangiogenesis) to restore lost lymphatic function. One promising approach to stimulate lymphangiogenesis involves delivering endothelial progenitor cells (EPCs), which are naturally involved in de novo blood vessel formation and have recently been identified to include a lymphatic subpopulation. However, the contribution of lymphatic EPCs in lymphangiogenesis is not clear and challenges with maintaining the activity of transplanted EPCs remain. Thus, the objective of this study was to isolate lymphatic EPCs from human umbilical cord blood and characterize their role in the initial stages of blood or lymphatic vasculature formation. Furthermore, this study also tested the applicability of alginate hydrogels to deliver lymphatic EPCs for a possible therapeutic application. We postulated and confirmed that blood and lymphatic EPC colonies could be isolated from human umbilical cord blood. Additionally, EPC populations responded to either angiogenic or lymphangiogenic growth factors and could stimulate their respective mature endothelial cells in vasculature models in vitro. Finally, lymphatic EPCs maintained their ability to promote lymphatic sprouts after prolonged interactions with the alginate hydrogel microenvironment. These results suggest EPCs have both a blood and a lymphatic population that have specific roles in promoting revascularization and highlight the potential of alginate hydrogels for the delivery of lymphatic EPCs. STATEMENT OF SIGNIFICANCE: Despite the potential therapeutic benefit of promoting lymphatic vasculature, lymphangiogenesis remains understudied. One appealing strategy for promoting lymphangiogenesis involves delivering lymphatic endothelial progenitor cells (EPCs), which are a subpopulation of EPCs involved in de novo vessel formation. Here, we investigate the role of isolated blood and lymphatic EPC subpopulations in promoting the early stages of vascularization and the utility of alginate hydrogels to deliver lymphatic EPCs. We determined that EPCs had two populations that expressed either blood or lymphatic markers, could stimulate their respective mature vasculature in tissue constructs and that alginate hydrogels maintained the therapeutic potential of lymphatic EPCs. We anticipate this work could support promising biomaterial applications of EPCs to promote revascularization, which could have many therapeutic applications.

Sinus of Valsalva aneurysms are abnormal bulges of the aortic root caused by a tissue deficiency resulting in an enlargement of the aortic root in the area between the aortic annulus and the sinotubular junction. Frequently, sinus of Valsalva aneurysms are asymptomatic. However, sinus of Valsalva aneurysms can also be potentially fatal due to their risk of rupture. We present a case of a 49-year old asymptomatic male patient with a rare image of a sinus of Valsalva aneurysm of the non-coronary cusp which was initially mistaken for a right ventricular thrombus. Surgical repair of the sinus of Valsalva aneurysm was eventually achieved by a valve sparing root replacement and the patient was discharged 7 days after surgery. This case report shows that sinus of Valsalva aneurysms are vulnerable to misdiagnosis when it is not initially suspected. Because of the potential fatality of this phenomenon we would like to underline the necessary vigilance in the diagnostic process, as sinus of Valsalva aneurysms can be missed when the physician is not aware of this potential rare diagnosis.

Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. Acute ischemic priapism, characterized by little or no cavernous blood flow and abnormal cavernous blood gases (ie, hypoxic, hypercarbic, acidotic) represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction.A comprehensive search of the literature was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full texts for the remaining 432 articles were reviewed, and ultimately 137 unique articles were included in the report.This Guideline was developed to inform clinicians on the proper diagnosis and surgical and non-surgical treatment of patients with acute ischemic priapism. This Guideline addresses the role of imaging, adjunctive laboratory testing, early involvement of urologists when presenting to the emergency room, discussion of conservative therapies, enhanced data for patient counseling on risks of erectile dysfunction and surgical complications, specific recommendations on intracavernosal phenylephrine with or without irrigation, the inclusion of novel surgical techniques (eg, tunneling), and early penile prosthesis placement.All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention. Treatment of the acute ischemic patient must be based on patient objectives, available resources, and clinician experience. As such, a single pathway for managing the condition is oversimplified and no longer appropriate. Using a diversified approach, some men may be treated with intracavernosal injections of phenylephrine alone, others with aspiration/irrigation or distal shunting, and some may undergo non-emergent placement of a penile prosthesis.

Background Maximal respiratory pressures (MRP) obtained at functional residual capacity (FRC) may reflect the real respiratory muscle pressure. Objectives To evaluate concurrent validity, test-retest, and inter-rater reliability of MRP performed with a new instrument in healthy individuals, and to compare values obtained at different volumes in healthy individuals and individuals with COPD. Methods MRP of 100 healthy individuals were obtained using the TrueForce and the MicroRPM® at residual volume (RV) and total lung capacity (TLC) to evaluate concurrent validity. MRP were obtained at FRC using the TrueForce to evaluate reliability. Comparisons of inspiratory pressure values (FRC compared to RV) and expiratory pressure values (FRC compared to TLC) were performed with 100 healthy individuals and 15 individuals with COPD. Results The intraclass correlation coefficient (ICC) was 0.77 and 0.86 for concurrent validity for inspiratory and expiratory pressures, respectively. Test-retest reliability showed an ICC of 0.87 for inspiratory pressure, and 0.78 for expiratory pressure; inter-rater reliability showed an ICC of 0.91 for inspiratory pressure, and 0.84 for expiratory pressure. Measurements performed at RV and TLC were higher when compared to FRC [mean difference (95%CI)= -8.30 (-11.82, -4.78) cmH2O; -37.29 (-42.63, -31.96) cmH2O] in healthy individuals, and -11.09 (-15.83, -6.35) cmH2O; -57.14 (-71.05, -43.05) cmH2O in COPD, for inspiratory and expiratory pressures, respectively. Conclusion MRP performed with the TrueForce presented good concurrent validity, good test-retest reliability, excellent inter-rater reliability for inspiratory pressure and good inter-rater reliability for expiratory pressure. MRP were lower when obtained at FRC for healthy individuals and with COPD.

Polycythaemia vera (PV) is a haematological disorder caused by an overproduction of erythroid cells. To date, the molecular mechanisms involved in the disease pathogenesis are still ambiguous. This study aims to identify aberrantly expressed proteins in erythroblasts of PV patients by utilizing mass spectrometry-based proteomic analysis. Haematopoietic stem cells (HSCs) were isolated from newly-diagnosed PV patients, PV patients who have received cytoreductive therapy, and healthy subjects. In vitro erythroblast expansion confirmed that the isolated HSCs recapitulated the disease phenotype as the number of erythroblasts from newly-diagnosed PV patients was significantly higher than those from the other groups. Proteomic comparison revealed 17 proteins that were differentially expressed in the erythroblasts from the newly-diagnosed PV patients compared to those from healthy subjects, but which were restored to normal levels in the patients who had received cytoreductive therapy. One of these proteins was S-methyl-5′-thioadenosine phosphorylase (MTAP), which had reduced expression in PV patients’ erythroblasts. Furthermore, MTAP knockdown in normal erythroblasts was shown to enhance their proliferative capacity. Together, this study identifies differentially expressed proteins in erythroblasts of healthy subjects and those of PV patients, indicating that an alteration of protein expression in erythroblasts may be crucial to the pathology of PV.

Marine Streptomyces S073 was previously shown to have strong anti-Vibrio activity, and its antibacterial mechanism was proposed to be associated with siderophore-mediated iron competition and other antagonistic agents. In this study, anti-Vibrio compounds produced by S073 were isolated by bioassay-guided fractionation using column chromatography and HPLC, and the target compound in the most active fraction was identified as dibutyl phthalate (DBP) by various spectroscopic analyses, including EI-MS, 1H NMR and 13C NMR. The DBP-producing capacity of S073 was 2.39 mg/L in ISP1 culture media. Pure DBP was demonstrated to have strong inhibitory activity on Vibiro parahaemolyticus growth with an MIC of 31.25 mg/L. When standard DBP was supplemented into the S073 fermentation broth in a gradient method, an additive inhibitory effect on V. parahaemolyticus was observed, indicating the important role of DBP in driving anti-Vibrio activity in S073 metabolites pool. A synergistic additive effect between DBP and florfenicol was observed in the Vibrio inhibition. These results indicate that, to achieve Vibrio-inhibition, S073 exerted multifaceted strategies, which included DBP-mediated antagonism and siderophore-governed iron competition. The application potential of S073 as an aquaculture probiotic was evaluated, and the safety risks associated with the endocrine disruptor attributes of DBP were discussed.

This study sought to compare 2 ways of achieving cardiac resynchronization.Cardiac resynchronization therapy (CRT) in patients with symptomatic heart failure and left bundle branch block (LBBB) can be achieved with His-bundle pacing correcting the bundle branch block (His-CRT). The present study is the largest randomized study comparing His-CRT and biventricular pacing (BiV-CRT) to date.Fifty patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤35% and LBBB according to electrocardiography were randomized 1:1 to His-CRT or BiV-CRT and followed for 6 months. At implantation, 7 patients crossed over from His-pacing to LV-pacing in the His-CRT group and 1 patient crossed over from LV-pacing to His-pacing in the BiV-CRT group.His-corrective pacing was achieved in 72% of the patients in the His-CRT group. Intention-to-treat 6-month follow-up LVEF increased by 16 ± 7% in the His-CRT group compared with 13 ± 6% in the BiV-CRT group (nonsignificant) and improvements were seen in clinical and physical parameters in both treatment arms with no significant differences between the groups. Pacing thresholds were higher for His-CRT compared with BiV-CRT both at implantation (1.8 ± 1.2 V vs. 1.2 ± 0.8 V; p 0.01) and at 6-month follow-up (2.3 ± 1.4 V vs. 1.4 ± 0.5 V; p 0.01). The per-protocol LVEF was significantly higher at 6 months (48 ± 8% vs. 42 ± 8%; p 0.05) and the end-systolic volume was lower (65 ± 22 ml vs. 83 ± 27 ml; p 0.05) in His-CRT patients compared with BiV-CRT.In heart failure patients with LBBB, His-CRT provided similar clinical and physical improvement compared with BiV-CRT at the expense of higher pacing thresholds.

Background Heart rate variability (HRV) is determined by intrinsic sinoatrial node (SAN) activity and the autonomic nervous system (ANS). HRV is reduced in aging; however, aging is heterogeneous. Frailty, which can be measured using a frailty index (FI), can quantify health status in aging separately from chronological age. Objective The purpose of this study was to investigate the impacts of age and frailty on HRV in mice. Methods Frailty was measured in aging mice between 10 and 130 weeks of age. HRV was assessed using time domain, frequency domain, and Poincare plot analyses in anesthetized mice at baseline and after ANS blockade, as well as in isolated atrial preparations. Results HRV was reduced in aged mice (90–130 weeks and 50–80 weeks old) compared to younger mice (10–30 weeks old); however, there was substantial variability within age groups. In contrast, HRV was strongly correlated with FI score regardless of chronological age. ANS blockade resulted in reductions in heart rate that were largest in 90- to 130-week-old mice and were correlated with FI score. HRV after ANS blockade or in isolated atrial preparations was increased in aged mice but again showed high variability among age groups. HRV was correlated with FI score after ANS blockade and in isolated atrial preparations. Conclusion HRV is reduced in aging mice in association with a shift in sympathovagal balance and increased intrinsic SAN beating variability; however, HRV is highly variable within age groups. HRV was strongly correlated with frailty, which was able to detect differences in HRV separately from chronological age.

Background The mechanisms underlying functional impairments in symptomatic PAD patients are controversial and poorly understood. Endothelial dysfunction and arterial stiffness have been proposed as potential mechanisms related to functional impairment in symptomatic PAD patients, however, more studies are needed to confirm these associations. Objective To analyze the association between vascular function and walking impairment in patients with peripheral arterial disease (PAD) and symptoms of claudication. Methods This was a cross-sectional study that included 68 patients with symptomatic PAD. All patients underwent an objective (Six-minute walk test [6MWT], 4-meter walk test) and a subjective (Walking Impairment Questionnaire [WIQ]) measurement of walking impairment. Vascular parameters measured were pulse-wave velocity (PWV) and flow-mediated dilation (FMD). Multiple linear regression was performed to investigate the association among walking impairment variables with vascular function parameters. Results No significant associations between the claudication onset distance (PWV: b=.060, P = 0.842; FMD: b=-.192, P = 0.456), 6MWT (PWV: b=.007, P = 0..975; FMD: b=.090, P = 0.725), WIQ distance (PWV: b=.337, P = 0.117; FMD: b=-.025, P = 0.895) WIQ speed (PWV: b=.320, P = 0.181; FMD: b=-.028, P = 0.497), WIQ stairs (PWV: b=.256, P = 0.204; FMD: b=-.228, P = 0.230), 4-meter usual walk (PWV: b=-.421, P = 0.107; FMD: b=-.338, P = 0.112), 4-meter fast walk (PWV: b=-.496, P = 0.063; FMD: b=-.371, P = 0.086) and vascular function were found. Conclusions In symptomatic PAD patients, vascular function is not associated to walking impairment, even when adjusting for comorbid conditions and diabetes.

Objective: To compare the Salbutamol alone and Ipratropium Bromide supplemented Salbutamol in children with exacerbation of asthma in terms of PEFR. Study Design: Randomized Controlled Trial. Setting: Pediatrics Emergency, KRL Hospital Islamabad. Period: 1st August 2016 to 31 January 2017. Material & Methods: Group A patients were given only Salbutamol (0.15mg/kg per dose with minimum 2.5 mg, maximum 5 mg/dose). Group B was given Ipratropium Bromide supplemented Salbutamol (250 mcg/dose for 20kg of Ipratropium Bromide with same dose of Salbutamol as prescribed for Group A). Baseline spirometry was performed on each patient and after measurement of baseline peak expiratory flow. The outcome was measured by Peak flow meter and reassessed at 60 minutes. Results: Comparison of salbutamol alone and ipratropium bromide supplemented salbutamol in children with exacerbation of asthma in terms of PEFR shows that 40.5 + 4.28 in Group-A and 59.5 +4.75 in Group-B, P-value was calculated as 0.0001, showing a significant difference between the two groups while the difference in increase was recorded as 19%. Conclusion: We concluded that salbutamol alone is significantly less effective when compared with Ipratropium Bromide supplemented Salbutamol in children with exacerbation of asthma in terms of PEFR.

The present study was conducted to correlate PCWP estimated by Doppler Echocardiography with that obtained by Swan-Ganz catheter in patients with post coronary artery bypass graft surgery and to evaluate the feasibility and accuracy of Doppler Echocardiographic data. The present study provides evidence that in patients with coronary artery disease who underwent elective CABG surgery, PCWP can be reliably and accurately estimated by combining Doppler Echocardiographic variables of mitral flow and Tissue Doppler imaging and the relationship between E/Ea ratio and measured PCWP by Swan Ganz catheter was the strongest of all Doppler variables determined.

The posterior condylar offset (PCO) has been proposed as a determinant of a postoperative range of motion after total knee arthroplasty, although there is no consensus. This study aimed to demonstrate the error introduced by forcing the femoral rotation to overlap both condyles for the "true" lateral X-ray projection for the PCO measurement. We hypothesize that the angular discrepancy between the posterior femoral cortical reference plane and the posterior condylar axis plane due to rotation invalidates the acquisition of reliable measurements on X-rays. We have measured the PCO in 50 "true" lateral X-rays and compared it with the medial and lateral condyles PCO's assessed on a computed tomography-scan-based three-dimensional (3D) model of each knee. PCO based on the 3D imaging differed significantly between the medial (25.8 ± 3.67 mm) and lateral (16.59 ± 2.92 mm) condyle. Three-dimensional PCO values differ significantly from those determined in the radiographic studies. Also, the mean values of the medial and lateral condyle PCO measurements differed significantly (p < 0.001) with all PCO measurements on radiographs. We have identified a difference between the posterior cortical plane and the posterior condylar axis projections, both on the axial plane with a mean value of 11.23° ± 3.64°. Our data show an interplane discrepancy angle between the posterior femoral diaphyseal cortical and the posterior condylar axis plane (due to the femur's necessary rotation to overlap both condyles) may invalidate the 2D X-ray PCO assessment as a reliable measurement.

Background and purpose Overweight or obese patients exhibit poorer platelet responses to clopidogrel; however, the mechanisms behind this phenotype remain to be elucidated. Here, we sought to dissect whether and why obesity could affect the metabolic activation of and/or platelet response to clopidogrel in obese patients and high-fat diet-induced obese mice. Experimental approach A post hoc stratified analysis of an observational clinical study was performed to investigate changes in residual platelet reactivity with increasing body weight in patients taking clopidogrel. Furthermore, high-fat diet-induced obese mice were used to reveal alterations in systemic exposure of clopidogrel thiol active metabolite H4, ADP-induced platelet activation and aggregation, the expression of genes responsible for the metabolic activation of clopidogrel, count of circulating reticulated and mature platelets, and proliferation profiles of megakaryocyte in bone marrow. The relevant genes and potential signaling pathways were predicted and enriched according to the GEO datasets available from obese patients. Key results Obese patients exhibited significantly attenuated antiplatelet effect of clopidogrel. In diet-induced obese mice, systemic exposure of clopidogrel active metabolite H4 was significantly reduced but that of its hydrolytic metabolite was increased due to down-regulation of certain P450s but up-regulation of Ces1 in the liver. Moreover, enhanced proliferation of megakaryocytes and elevated platelet count also contributed. Conclusion and implications Obesity attenuates metabolic activation of clopidogrel and increases counts of circulating reticulated and mature platelets, leading to impaired platelet responsiveness to the drug in mice, suggesting that clopidogrel dosage may need to be adjusted adequately in overweight or obese patients.

Objectives/hypothesis To compare the 12-month evolution of voice quality outcomes in patients who benefited from types 1-2 transoral CO2 laser cordectomy (TLC) for an early-stage vocal fold squamous cell carcinoma (VFSCC). Study design Prospective uncontrolled study. Methods Sixty patients with cT1 VFSCC were consecutively recruited from a single medical center. Thirty patients benefited from type 1 TLC, while type 2 TCL was performed in 30 patients. The following voice quality outcomes were evaluated at baseline, 3-, 6-, and 12-month post-TLC: voice handicap index (VHI), GRBAS, speech rate, maximum phonation time (MPT), and acoustic parameters. Voice quality evolution was compared between type 1 and type 2 TLC. Results Fifty-seven patients completed the evaluations. Type 1 TLC patients reported significant improvements of VHI, grade of dysphonia, and breathiness at 3-, 6-, and 12-month post-TLC. Speech rate and jitter values improved 6- and 12-month post-TLC. A few voice quality outcomes reported 3- or 6-month post-TLC improvements in type 2 TLC group, while VHI, grade of dysphonia improved at 6- and 12-month post-TLC. MPT significantly decreased at 6- and 12-month post-TLC, while there were no acoustic measurement changes in type 2 TLC. Conclusions The effect of TLC on voice quality may depend on the type of TLC. Type 1 TLC was associated with faster voice quality improvements compared with type 2 TLC. VHI and dysphonia grade were identified as the most relevant tool of voice changes irrespective to the TLC type. Level of evidence 3 Laryngoscope, 2021.

Cardiac glycosides, including digitalis and digoxin, have long-standing use in clinical practice. Digoxin has a half-life that varies from 36 to 48 hours, which may increase in cases of renal failure. Approximately 1% of Congestive Heart Failure patients treated with digoxin develop toxicity. The clinical features of toxicity are often non-specific. Diagnosis is difficult and usually made clinically, as levels of digoxin in the blood do not necessarily correlate with toxicity. Treatment involves early recognition and the administration of antibodies specifically against digoxin also known as Fab fragments. Digoxin concentration does not necessarily correlate with clinical symptoms of toxicity however digoxin concentrations may be used for calculating the amount of antidote therapy. Digoxin-specific antibody fragments are used when there is a risk of a life-threatening arrhythmia.

Sacubitril/valsartan was approved by the Food and Drug Administration in 2015 to reduce the risk of cardiovascular death and hospitalization for heart failure (HHF) in patients with chronic heart failure with reduced ejection fraction defined as left ventricular ejection fraction (LVEF) ≤ 40%. This approval was based on PARADIGM-HF trial. Subsequently, PARAGON-HF was conducted to support a claim for sacubitril/valsartan in patients with heart failure with preserved ejection fraction (HFpEF), defined as LVEF ≥ 45%. PARAGON-HF failed to meet the pre-defined threshold for statistical significance for the primary composite endpoint. However, analysis of the primary endpoint by LVEF as a continuous variable demonstrated that sacubitril/valsartan was efficacious in patients with mildly abnormal LVEF similar to patients with LVEF ≤ 40% evaluated in PARADIGM-HF. This led to a broader indication for sacubitril/valsartan-"to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. LVEF is a variable measure, so use clinical judgment in deciding whom to treat." This article describes the rationale for a revised indication for sacubitril/valsartan, emphasizes the need to go beyond a dichotomous classification of HF based on a traditional LVEF cut-off and clarifies that the product label for sacubitril/valsartan does not refer to HFpEF.

Afterload is an important determinant of left ventricular (LV) and atrial (LA) function, including myocardial strain. Central blood pressure (CBP) is the major component of cardiac afterload and independently associated with cardiovascular risk. However, the optimal means of calibrating CBP is unclear—standard CBP assessment uses systolic (SBP) and diastolic blood pressure (DBP) from brachial waveforms, but calibration with mean pressure (MAP) and DBP purports to be more accurate. Therefore, we sought to determine which CBP is best associated with LA and LV strain. CBP was measured using both standard and MAP based calibration methods in 546 participants (age 70.7±4.7 years, 45% male) with risk factors for heart failure. Echocardiography was performed in all patients and strain analysis conducted to assess LA/LV function. The associations of CBP with LA and LV strain were assessed using linear regression. MAP-derived CSBP (150±20 mmHg) was higher than standard CSBP (128±15 mmHg) and brachial SBP (140±17 mmHg, p0.05), however was independently associated with LA reservoir strain (p0.05). MAP-derived CBP was more accurate in identifying patients with abnormal LA and LV strain than brachial SBP and standard CBP calibration. In conclusion, CBP calibrated using MAP and DBP may be more accurate in identifying patients with abnormal LA and LV function than standard brachial calibration methods.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder caused by a reduced concentration and/or function of von Willebrand factor (VWF) with no prior or family history of congenital vo...

To assess the therapeutic efficacy of PDGF-D-overexpressing endothelial progenitor cells (EPCs) in deep vein thrombosis. Inferior vena cava thrombosis was induced in female Sprague Dawley (SD) rats. Animals were injected via the distal vena cava with EPCs overexpressing PDGF-D after transfection with a lentiviral vector containing the PDGF-D gene. The effect on thrombosis in animals who received EPCs was evaluated using MSB staining, immunohistochemistry, immunofluorescence, and venography; the steady-state mRNA and protein levels of PDGF-D and its receptor (PDGF-Rβ) were determined by RT-PCR and Western blotting, respectively; and the PDGF-D-induced mobilization of circulating EPCs was estimated by flow cytology. Compared with controls, injection of EPCs overexpressing PDGF-D was associated with increased thrombosis resolution; recanalization; PDGF-D and PDGF-Rβ expression; induction of monocyte homing; and mobilization of EPCs to the venous circulation. In a rat model, transplantation of PDGF-D-overexpressing EPCs facilitated the resolution of deep vein thrombosis.

BACKGROUND The Colorado potato beetle (CPB) is the most harmful pest of potato in potato cultivation regions globally. Although it is an economically important agricultural pest, the population structure and colonization route of this species in Turkey are uncertain. We used microsatellite and mitochondrial DNA (mtDNA) markers to obtain information about the population source, structure and bio-invasion route of CPB populations in Turkey. RESULTS The common single mtDNA haplotype in European CPB populations was obtained in all Turkish CPB populations based on mtDNA data analysis. However, microsatellites revealed a low level of genetic variation in CPB populations. The results of microsatellite analysis [factorial correspondence analysis (FCA), Bayesian analysis of genetic population structure (BAPS), unweighted pair group method with arithmetic mean (UPGMA) dendrogram, F-statistics and Nei's distances] indicated three groups for invasive CPB: Thrace-Marmara and Aegean; Black Sea, Central Anatolia and Mediterranean; Northeastern Anatolia. Region-specific alleles have been identified in regions, where commercial potato cultivation and insecticide use are intensive. CONCLUSION The detection of a single fixed European haplotype in all Turkish populations has proved that CPB in Turkey originated from Europe as a result of a founder event occurred in European populations. Low genetic variation was due to the short time period since the spread of CPB from America to Europe. The highest number of private alleles were found in the top commercial potato cultivation region-Central Anatolia from where the CPB populations spread to other parts of Turkey.

Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular neoplasm that requires long-term management. Several reports describe disseminated intravascular coagulation (DIC) associated with angiosarcoma, but no association with EHE has been reported. We encountered a patient with DIC complicated by multifocal EHE. The patient was an 83-year-old woman with spinal lesions, small lung nodules, and a soft tissue mass in the right buttock. The tumor was biopsied and diagnosed as EHE. The patient received pain control therapy without antitumor therapy. One month later, DIC developed with tumor progression. DIC subsided with nafamostat mesylate infusion, and oral apixaban was administered. DIC was managed for 5 months until the patient died of brain metastases. This is the first report of a patient with DIC complicated by EHE. It should be noted that progression of EHE can cause DIC. We were able to manage DIC using anticoagulant agents.

Disseminated intravascular coagulation (DIC) is life threatening disease it’s often associated with sepsis, which require ICU management. In individuals with sepsis, the risk of DIC is especially high, DIC affects 30 to 50 percent of these individuals. Also it affects only about ten percent of patients with solid tumors, trauma, or obstetric emergencies. Hematological malignancies, aneurysms, and liver diseases can also cause the disease, the treatment for DIC focuses on resolving the underlying problem that led to this condition in the first place. As a result, antibiotics for severe sepsis, delivery in the case of placental abruption, and exploratory surgical intervention in the case of trauma are the pillars of DIC treatment, Patients with active bleeding or a high risk of bleeding, as well as those who require an invasive surgery, should consider platelet and plasma transfusions. Other anti-coagulant drugs can also be used. Prothrombin complex concentrates should only be administered in an emergency, due to their possible dangers. Recombinant human soluble thrombomodulin rhTM it was developed and licensed for clinical usage in Japan in 2008, and it’s one of the novel treatments for DIC. Anti-Xa agents, Synthetic protease inhibitors, and antithrombin are another options for treatment. In this article we will be making overview of the disease, it’s etiology an what’s the current management options.

C-repeat binding factors (CBFs) are key cold-responsive transcription factors that play pleiotropic roles in the cold acclimation, growth, and development of plants. Cold-sensitive cbf knockout mutants and cold-tolerant CBF overexpression lines exhibit abnormal phenotypes at warm temperatures, suggesting that CBF activity is precisely regulated, and a critical threshold level must be maintained for proper plant growth under normal conditions. Cold-inducible CBFs also exist in warm-climate plants but as inactive disulfide-bonded oligomers. However, upon translocation to the nucleus under a cold snap, the h2-isotype of cytosolic thioredoxin (Trx-h2), reduces the oxidized (inactive) CBF oligomers and the newly synthesized CBF monomers, thus producing reduced (active) CBF monomers. Thus, the redox-dependent structural switching and functional activation of CBFs protect plants under cold stress.

In the surgery patient under general anesthesia doesn’t breathe spontaneously, and lung movement is completely dependent on the mechanical ventilation of the anesthesia machine. In order to achieve effective and safe mechanical ventilation of the patient’s lungs during the operation, the concept of lung protective ventilation strategy (LPVS) was proposed, that is, the use of a low tidal volume and an appropriate level of positive end expiratory pressure (PEEP) to reduce alveolar overexpansion and prevent alveolar collapse. In the past, PEEP was an important measure to treat acute lung injury(ALI) or acute respiratory distress syndrome(ARDS) by improving oxygenation and reducing pulmonary edema. Subsequent studies found that PEEP not only be used to treat patients with ALI or ARDS, but also can reduce the incidence of postoperative pulmonary complications(PPCs) in some thoracoabdominal operations. Moreover, PEEP can prevent atelectasis during and after surgery in patients undergoing thoracic and abdominal surgery under general anesthesia, and decrease the incidence of postoperative infection. However, PEEP can affect venous return by increasing intrathoracic pressure, thereby causing changes in heart function and hemodynamics, and indirectly affecting intracranial pressure and renal function. Therefore, with the widespread clinical application of PEEP, more and more people are starting to focus on how to choose the appropriate PEEP. This article reviews the research progress of PEEP selection method, the influence of PEEP on physiological function and the clinical application of PEEP during mechanical ventilation.

Rationale: Natural history of preserved ratio impaired spirometry (PRISm), often defined as FEV1/FVC ≥lower limit of normal and FEV1

In this paper, the analysis of intracavitary electrocardiograms is used to guide the mining of abnormal cardiac rhythms in patients with hidden heart disease, and the algorithm is improved to address the data imbalance problem existing in the abnormal electrocardiogram signals, and a weight-based automatic classification algorithm for deep convolutional neural network electrocardiogram signals is proposed. By preprocessing the electrocardiogram data from the MIT-BIH arrhythmia database, the experimental dataset training algorithm model is obtained, and the algorithm model is migrated into the project. In terms of system design and implementation, by comparing the advantages and disadvantages of the electrocardiogram monitoring system platform, the overall design of the system was carried out in terms of functional and performance requirements according to the system realization goal, and a mobile platform system capable of classifying common abnormal electrocardiogram signals was developed. The system is capable of long-term monitoring and can invoke the automatic classification algorithm model of electrocardiogram signals for analysis. In this paper, the functional logic test and performance test were conducted on the main functional modules of the system. The test results show that the system can run stably and monitor electrocardiogram signals for a long time and can correctly call the deep convolutional neural network-based automatic electrocardiogram signal classification algorithm to analyze the electrocardiogram signals and achieve the requirements of displaying the electrocardiogram signal waveform, analyzing the heartbeat type, and calculating the average heart rate, which achieves the goal of real-time continuous monitoring and analysis of the electrocardiogram signals.

Transient receptor potential channel TRPV4 and nicotinamide adenine dinucleotide phosphate oxidase (Nox2) are involved in oxidative stress that increases endothelial permeability. It has been shown that obesity enhances the physical association of TRPV4 and Nox2, but the role of TRPV4–Nox2 association in obesity has not been clarified. In this study we investigated the function of TRPV4–Nox2 complex in reducing oxidative stress and regulating abnormal vascular permeability in obesity. Obesity was induced in mice by feeding a high-fat diet (HFD) for 14 weeks. The physical interaction between TRPV4 and Nox2 was measured using FRET, co-immunoprecipitation and GST pull-down assays. The functional interaction was measured by rhodamine phalloidin, CM-H(2)DCFDA in vitro, the fluorescent dye dihydroethidium (DHE) staining assay, and the Evans blue permeability assay in vivo. We demonstrated that TRPV4 physically and functionally associated with Nox2, and this physical association was enhanced in aorta of obese mice. Furthermore, we showed that interrupting TRPV4–Nox2 coupling by TRPV4 knockout, or by treatment with a specific Nox2 inhibitor Nox2 dstat or a specific TRPV4 inhibitor HC067046 significantly attenuated obesity-induced ROS overproduction in aortic endothelial cells, and reversed the abnormal endothelial cytoskeletal structure. In order to discover small molecules disrupting the over-coupling of TPRV4 and Nox2 in obesity, we performed molecular docking analysis and found that compound M12 modulated TRPV4–Nox2 association, reduced ROS production, and finally reversed disruption of the vascular barrier in obesity. Together, this study, for the first time, provides evidence for the TRPV4 physically interacting with Nox2. TRPV4–Nox2 complex is a potential drug target in improving oxidative stress and disruption of the vascular barrier in obesity. Compound M12 targeting TRPV4–Nox2 complex can improve vascular barrier function in obesity.

Case report of patient with bradycardia as a complication of VNS therapy and psychiatric worsening after turning VNS off.

OBJECTIVE Some individuals with panic disorder (PD) display reduced heart rate variability, which may result in an increased risk of cardiovascular mortality. Heart rate variability-biofeedback (HRV-BF) training has been shown to improve the modulation of the autonomic activity. Therefore, this randomized controlled trial was conducted to investigate the effect of a four-week HRV-BF intervention in individuals with PD. Heart rate variability-biofeedback (HRV-BF) training improved the modulation of the autonomic activity. Therefore, with this randomized controlled trial we aimed to investigate the effect of a four-week HRV-BF intervention in people with PD. METHODS Thirty-six women and sixteen men with PD (mean age: 35.85 ± 15.60 years) were randomly allocated either to HRV-BF with 0.1 Hz breathing as intervention group or to HRV-Sham-BF as active control group. HRV-BF was performed over four weeks while HRV was measured both during a short-term resting condition as well as during a paced breathing condition before and after intervention. RESULTS HRV-BF with 0.1 Hz breathing increased HRV and reduced panic symptoms in individuals with PD. HRV-BF with 0.1 Hz breathing demonstrated an increase in the time and frequency domain parameters of HRV during the short-term resting condition (ΔPost-Pre RMSSD: 5.87 ± 14.03 ms; ΔPost-Pre SDNN: 11.63 ± 17.06 ms; ΔPost-Pre Total Power: 464.88 ± 1825.47 ms2; ΔPost-Pre LF: 312.73 ± 592.71 ms2), a decrease in the heart rate during the paced breathing condition (ΔPost-Pre: -5.87 ± 9.14 b/min), and a decrease in the Panic & Agoraphobia Scale (ΔPost-Pre: -3.64 ± 6.30). There was no intervention effect in the HRV-Sham-BF group. CONCLUSIONS HRV-BF as a non-invasive and non-pharmacological treatment seems to be an important intervention option to improve reduced HRV and decrease panic symptoms in individuals with PD. Future studies are needed to establish whether these effects translate to reductions in the risk of cardiovascular disease in PD.

OBJECTIVE The pathways underlying the early life adversity and cardiovascular reactivity association remain unclear. The current study examined the role of current depressive symptoms on this relationship. METHODS Mediation analyses were conducted using data from 639 participants drawn from the Midlife Development in the United States (MIDUS II) Biomarker Project. Responses were derived from the Childhood Trauma Questionnaire [CTQ] and Center for Epidemiologic Studies Depression Scale [CES-D]). Participants had their systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) monitored throughout a standardized stress testing protocol. RESULTS The association between early life adversity and reactivity was mediated by current depressive symptoms; all adversity factors were linked to higher levels of current depressive symptoms, which in turn, were associated with lower cardiovascular reactivity. For emotional abuse, this was noted for SBP (β = -.06, 95% CI [-.13,-.01]; and DBP: β = - .04, [-.07,-.01]), physical abuse (SBP: β = -.05, [-.11,-.01]; DBP: β = -.03, [-.06,-.01]), sexual abuse (SBP: β = -.04, [-.09,-.01]; DBP: β = -.02, [-.05,-.01]), emotional neglect (SBP: β = -.04, [-.09,-.01]; DBP: β = -.02, [-.05,-.01]), physical neglect (SBP: β = -.09, [-.17,-.02]; DBP: β = -.05, [-.09,-.02]) and total CTQ (SBP: β = -.02, [-.03,-.00]; DBP: β = -.01, [-.02,-.00]). CONCLUSIONS The present findings extend research and demonstrate that depression is an underlying mechanism linking early life adversity and blunted cardiovascular reactivity.

OBJECTIVE Neurodevelopmental delays and frontal lobe cortical dysmaturation are widespread among children with congenital heart disease (CHD). The subventricular zone (SVZ) is the largest pool of neural stem/progenitor cells in the postnatal brain. Our aim is to determine the effects of cardiopulmonary bypass (CPB) on neurogenesis and cortical maturation in piglets whose SVZ development is similar to human infants. METHODS Three-week-old piglets (n = 29) were randomly assigned to control (no surgery), mild-CPB (34°C full flow for 60 minutes) and severe-CPB groups (25°C circulatory-arrest for 60 minutes). The SVZ and frontal lobe were analyzed with immunohistochemistry 3 days and 4 weeks postoperatively. MRI of the frontal lobe was used to assess cortical development. RESULTS SVZ neurogenic activity was reduced up to 4 weeks after both mild and severe CPB-induced insults. CPB also induced decreased migration of young neurons to the frontal lobe, demonstrating that CPB impairs postnatal neurogenesis. MRI 4 weeks after CPB displayed a decrease in gyrification index and cortical volume of the frontal lobe. Cortical fractional anisotropy was increased after severe CPB injury, indicating a prolonged deleterious impact of CPB on cortical maturation. Both CPB-induced insults displayed a significant change in densities of three major inhibitory neurons, suggesting excitatory-inhibitory imbalance in the frontal cortex. In addition, different CPB insults altered different subpopulations of inhibitory neurons. INTERPRETATION Our results provide novel insights into cellular mechanisms contributing to CHD-induced neurological impairments. Further refinement of CPB hardware and techniques is necessary to improve long-term frontal cortical dysmaturation observed in children with CHD. ANN NEUROL 2021;90:913-926.

The transformer oil jet fire accidents caused by the failure in the substation may cause significant economic losses. In this study, the geometric characteristics of transformer oil jet fire are st...

Background The number of patients with chronic heart failure is increasing in Japan. However, the annual number of patients with heart failure who receive cardiac resynchronization therapy (CRT) has been constant in the last few years. In this study, we evaluated patients who did not receive CRT despite being eligible for this treatment to elucidate the clinical impact of CRT administration. Methods We assessed 214 patients with a left ventricular ejection fraction (LVEF) ≤ 50% (excluding patients treated with CRT) who underwent transthoracic echocardiography between January and May 2020 at our institution. The patients were stratified into two groups: Group A (n = 26; patients eligible for CRT) and Group B (n = 188; patients ineligible for CRT); however, all patients only received pharmacological therapy. We retrospectively analyzed the prognosis of these patients with respect to the cumulative number of hospitalizations for heart failure and cardiogenic deaths. Results We observed no significant between‐group differences in age, sex, and severity/diagnosis of organic heart disease. Group A had a significantly higher number of hospitalizations for heart failure and cardiogenic deaths than Group B (log‐rank test, P, This study evaluates the underutilization of cardiac resynchronization therapy in eligible patients with heart failure with a left ventricular ejection fraction less than 50%.

Cell-based therapeutics bring great hope in areas of unmet medical needs. Mesenchymal stem cells (MSCs) have been suggested to facilitate neovascularization mainly by paracrine action. Endothelial progenitor cells (EPCs) can migrate to ischemic sites and participate in angiogenesis. The combination cell therapy that includes MSCs and EPCs has a favorable effect on ischemic limbs. However, the mechanism of combination cell therapy remains unclear. Herein, we investigate whether stromal cell-derived factor (SDF)-1 secreted by MSCs contributes to EPC migration to ischemic sites via CXCR4/Phosphoinositide 3-Kinases (PI3K)/protein kinase B (termed as AKT) signaling pathway. First, by a “dual-administration” approach, intramuscular MSC injections were supplemented with intravenous Qdot® 525 labeled-EPC injections in the mouse model of hind limb ischemia. Then, the mechanism of MSC effect on EPC migration was detected by the transwell system, tube-like structure formation assays, western blot assays in vitro. Results showed that the combination delivery of MSCs and EPCs enhanced the incorporation of EPCs into the vasculature and increased the capillary density in mouse ischemic hind limb. The numbers of CXCR4-positive EPCs increased after incubation with MSC-conditioned medium (CM). MSCs contributed to EPC migration and tube-like structure formation, both of which were suppressed by AMD3100 and wortmannin. Phospho-AKT induced by MSC-CM was attenuated when EPCs were pretreated with AMD3100 and wortmannin. In conclusion, we confirmed that MSCs contributes to EPC migration, which is mediated via CXCR4/PI3K/AKT signaling pathway.