More Efficient Approach: Independent Diagnostic Value of Audiovisual Sexual Stimulation for Psychogenic Erectile Dysfunction.

The diagnostic value of audiovisual sexual stimulation (AVSS) for psychogenic erectile dysfunction (ED) is still unclear. We investigated the independent diagnostic value and optimal cut-off parameter of AVSS for psychogenic ED. All participants had received the AVSS test and nocturnal penile tumescence and rigidity (NPTR) monitoring at least twice. ED patients were divided into psychogenic ED and organic ED according to NPTR examination. The diagnostic accuracy of AVSS parameters was evaluated with the receiver operating characteristic (ROC) curve, and the Youden index was employed to determine the optimal diagnostic cut-off values. A total of 346 patients with ED and 60 healthy men were included in this study, among which 162 and 184 cases of psychogenic and organic ED were identified based on NPTR, respectively. When comparing the two ED groups, the area under the curve (AUC) of AVSS parameters was 0.85-0.89. Six-selected AVSS parameters could precisely diagnose psychogenic ED, exhibiting increased diagnostic specificity compared with corresponding sensitivity. When comparing psychogenic ED with the control group, the AUC of the tumescence of the tip was superior to the AUC other parameters (0.81 vs. 0.58, 0.66, 0.59, 0.53, 0.68), and the best determined diagnostic cut-off value was the tumescence of the tip < 29.87%. Independent AVSS could diagnose psychogenic ED objectively and effectively, and its diagnostic value was highest when 1.50% ≤ tumescence of the tip < 29.87%.

Mitigating Cross-Species Viral Infections in Xenotransplantation: Progress, Strategies, and Clinical Outlook.

Xenotransplantation holds great promise as a solution to address the critical shortage of organs, but it raises concerns regarding the potential transmission of porcine viruses to recipients, leading to infections and even zoonotic diseases. Data used in this review were mainly from literature of Pubmed database. Keywords included xenotransplantation, infection, virus, and epidemiology. The original articles and critical reviews selected were relevant to this review's theme. We review the major viral infections of concern in xenotransplantation, their risk of transmission, diagnosis, treatment, and ways to prevent infection. Then, we pivot to a comprehensive overview of the current status of xenotransplantation. In addition, we offer our own insights and recommendations for propelling xenotransplantation forward, transitioning from preclinical experiments to the critical phase of clinical trials. Viral infections pose considerable safety concerns within xenotransplantation, particularly with the possibility of emerging or currently unidentified viruses. Clinical trials serve as a crucial platform to progress the safety standards of xenotransplantation. However, further studies and dedicated efforts are required to effectively translate findings into practical applications that can improve safety measures in this field.

Forkhead box O6 (FoxO6) promotes cardiac pathological remodeling and dysfunction by activating Kif15-TGF-ß1 under aggravated afterload.

Pathological cardiac hypertrophy exhibits complex and abnormal gene expression patterns and progresses to heart failure. Forkhead box protein O6 (FoxO6) is a key transcription factor involved in many biological processes. This study aimed to explore the role of FoxO6 in cardiac hypertrophy. Three groups of mice were established: wild-type, FoxO6 knockout, and FoxO6-overexpressing. The mice received daily administration of angiotensin-II (Ang-II) or saline for 4 weeks, after which they were examined for cardiac hypertrophy, fibrosis, and function. Elevated cardiac expression of FoxO6 was observed in Ang-II-treated mice. FoxO6 deficiency attenuated contractile dysfunction and cardiac remodeling, including cardiomyocyte hypertrophy and fibroblast proliferation and differentiation. Conversely, FoxO6 overexpression aggravated the cardiomyopathy and heart dysfunction. Further studies identified kinesin family member 15 (Kif15) as downstream molecule of FoxO6. Kif15 inhibition attenuated the aggravating effect of FoxO6 overexpression. In vitro, FoxO6 overexpression increased Kif15 expression in cardiomyocytes and elevated the concentration of transforming growth factor-ß1 (TGF-ß1) in the medium where fibroblasts were grown, exhibiting increased proliferation and differentiation, while FoxO6 knockdown attenuated this effect. Cardiac-derived FoxO6 promoted pathological cardiac remodeling induced by aggravated afterload largely by activating the Kif15/TGF-ß1 axis. This result further complements the mechanisms of communication among different cells in the heart, providing novel therapeutic targets for heart failure.

Intraoperative use of cell saver devices decreases the rate of hyperlactatemia in patients undergoing cardiac surgery.

Objective: This study was aimed to elucidate the effect of the intraoperative cell saver (CS) on hyperlactatemia of patients who underwent cardiac surgery. Design: A sub-analysis of the CS was performed, which is a historial control trial of patients undergoing cardiac surgery. Setting: This was a retrospective single-center and not blinded study. Participants: We examined the occurrence of hyperlactatemia retrospectively in patients of CS group (n = 78) who were included in prospective trial and received valvular surgery, where CS was used during the procedure. Patients subjected to valvular surgery before February 2021 were adopted in control group (n = 79). Interventions: Arterial blood was sampled (1) before cardiopulmonary bypass, (2) during bypass (3) immediately after bypass, (4) on ICU admission and (5) every 4 h up to 24 h postoperatively. Measurements and main results: A lower incidence of hyperlactatemia (32.1% vs. 57.0%; P = 0.001) was observed in patients from the CS group. Furthermore, the blood lactate concentration was higher in control group than in CS group during CPB, post CPB, on ICU admission and lasted until 20 h after the operation. Multivariable analysis revealed that intraoperative use of CS was expected to be a protective factor against hyperlactatemia in this study (OR = 0.31, 95% CI 0.15-0.63, P = 0.001). Conclusion: Intraoperative use of a CS device was associated with a lower incidence of hyperlactatemia. Whether such device use is valuable to limiting hyperlactatemia in cardiac patients after surgery requires further evaluation in larger prospective studies.

Risk factors associated with positive bacterial culture in salvaged red blood cells during cardiac surgery and postoperative infection incidence: A prospective cohort study.

Background: This study was designed to explore factors associated with the incidence of positive bacterial culture of salvaged red blood cells (sRBCs) recovered with a Cell Saver instrument during cardiac surgery and the impact of such positive outcomes on postoperative infection-related morbidity. Methods: The cohort study enrolled 204 patients scheduled for cardiac surgery with intraoperative blood cell salvage and retransfusion from July 2021 to July 2022. These patients were stratified into two groups based on intraoperative sRBCs bacterial culture results: culture (+) and culture (-) groups. Preoperative and intraoperative variables were compared between these groups aim to detect possible predictors of positive culture in sRBCs. In addition, differences in postoperative infection-related morbidity and other clinical outcomes were compared between these groups. Results: Of these patients, 49% were sRBCs culture (+), with Staphylococcus epidermidis as the most commonly identified pathogen. Risk factors independently associated with the risk of positive culture in sRBCs included BMI ≥25 kg/m2, a history of smoking, an operative duration ≥277.5 min, the higher number of staff in the operating room and higher surgical case order. Patients in the sRBCs culture (+) group exhibited a longer average ICU stay [3.5 days (2.0-6.0) vs. 2 days (1.0-4.0), P < 0.01], a longer duration of ventilation [20.45 h (12.0-17.8) vs. 13 h (11.0-17.0, P = 0.02)], underwent more allogeneic blood transfusions, exhibited higher transfusion-related costs [2,962 (1,683.0-5,608.8) vs. 2,525 (1,532.3-3,595.0), P = 0.01], and had higher rates of postoperative infections (22 vs. 9.6%, P = 0.02) as compared to patients in the sRBCs culture (-) group. In addition, culture (+) in sRBCs was an independent risk factor for postoperative infection (OR 2.62, 95% CI 1.16-5.90, P = 0.02). Conclusion: Staphylococcus epidermidis was the most common pathogen detected in sRBCs in the culture (+) group in this study, identifying it as a potential driver of postoperative infection. Positive sRBCs culture may contribute to postoperative infection and its incidence was significantly associated with patient BMI, history of smoking, operative duration, the number of staff in the operating room and surgical case order.

Tetrahydrocurcumin improves lipopolysaccharide-induced myocardial dysfunction by inhibiting oxidative stress and inflammation via JNK/ERK signaling pathway regulation.

BACKGROUND: Acute myocardial dysfunction in patients with sepsis is attributed to oxidative stress, inflammation, and cardiomyocyte loss; however, specific drugs for its prevention are still lacking. Tetrahydrocurcumin (THC) has been proven to contribute to the prevention of various cardiovascular diseases by decreasing oxidative stress and inflammation. This study was performed to investigate the functions and mechanism of action of THC in septic cardiomyopathy. METHODS: After the oral administration of THC (120 mg/kg) for 5 consecutive days, a mouse model of sepsis was established via intraperitoneal lipopolysaccharide (LPS, 10 mg/kg) injection. Following this, cardiac function was assessed, pathological section staining was performed, and inflammatory markers were detected. RESULTS: Myocardial systolic function was severely compromised in parallel with the accumulation of reactive oxygen species and enhanced cardiomyocyte apoptosis in mice with sepsis. These adverse changes were markedly reversed in response to THC treatment in septic mice as well as in LPS-treated H9c2 cells. Mechanistically, THC inhibited the release of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)-1ß, and IL-6, by upregulating mitogen-activated protein kinase phosphatase 1, to block the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK). Additionally, THC enhanced the levels of antioxidant proteins, including nuclear factor-erythroid 2-related factor 2, superoxide dismutase 2, and NAD(P)H quinone oxidoreductase 1, while decreasing gp91phox expression. Furthermore, upon THC treatment, Bcl-2 expression was significantly increased, along with a decline in Bax and cleaved caspase-3 expression, which reduced cardiomyocyte loss. CONCLUSION: Our findings indicate that THC exhibited protective potential against septic cardiomyopathy by reducing oxidative stress and inflammation through the regulation of JNK/ERK signaling. The findings of this study provide a basis for the further evaluation of THC as a therapeutic agent against septic cardiomyopathy.

GDF11 Alleviates Pathological Myocardial Remodeling in Diabetic Cardiomyopathy Through SIRT1-Dependent Regulation of Oxidative Stress and Apoptosis.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor ß superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in diabetic cardiomyopathy (DCM) remain largely unknown. In this study, we sought to determine whether GDF11 could prevent DCM. After establishing a mouse model of diabetes by administering a high-fat diet and streptozotocin, intramyocardial injection of an adeno-associated virus was used to achieve myocardium-specific GDF11 overexpression. GDF11 remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression and activity were observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were eliminated by SIRT1 depletion. Our results demonstrate for the first time that GDF11 protects against DCM by regulating SIRT1 signaling pathway.

Lifetime increased cancer risk in mice following exposure to clinical proton beam-generated neutrons.

PURPOSE: To evaluate the life span and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical spread-out Bragg peak (SOBP) proton beam. METHODS AND MATERIALS: Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid-SOBP of a 165-MeV, clinical proton beam. The average distance from the edge of the mid-SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once-daily fractions of 25 Gy, 4 days per week, for 6 weeks. The age at death and cause of death (ie, cancer and type vs noncancer causes) were assessed over the life span of the mice. RESULTS: Exposure of mice to a dose of 600 Gy of proton beam-generated neutrons, reduced the median life span of the mice by 4.2% (Kaplan-Meier cumulative survival, P=.053). The relative risk of death from cancer in neutron exposed versus control mice was 1.40 for cancer of all types (P=.0006) and 1.22 for solid cancers (P=.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10. CONCLUSIONS: Exposure of mice to neutrons generated by a proton dose that exceeds a typical course of radiation therapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field second solid cancers from SOBP proton-generated neutrons and typical treatment schedules, is 6 to 10 times less than is suggested by current neutron risk estimates.