Exercise hyperpnea and hypercapnic ventilatory responses in women

SummaryWe studied the relationship between exercise hyperpnea (i.e., ventilatory dynamics) at the onset of exercise and hypercapnic ventilatory response (HCVR), and their differences between the follicular (FP) and luteal (LP) phases of the menstrual cycle in six healthy females. HCVR was tested under three O2 conditions: hyperoxia (FiO2=1.0), normoxia (0.21), and hypoxia (0.12). HCVR was defined as the relationship between the end-tidal PCO2 and minute ventilation (V˙E) using the regression line of the CO2 slope and a mimetically apneic threshold of CO2. HCVR provocation and measurements were conducted using an inspired CO2 concentration of up to approximately 8mmHg higher than the end-tidal PCO2 level of basal isocapnic the end-tidal PCO2 at each menstrual both the slope and threshold in HCVR showed no statistically significant difference between LP and FP under any inspired FiO2 conditions. In the case of exercise hyperpnea during the onset of submaximal exercise, the mean response time (MRT) in V˙E dynamics showed no significant difference between LP and FP. Consequently, MRT in V˙E response was not related to the slope in HCVR. During steady-state exercise, even though the V˙E/V˙CO2 showed no significance between LP and FP, V˙E/V˙CO2 was significantly related to the slope in HCVR (r=0.59, P<0.05). Exercise ventilation (i.e., V˙E/V˙CO2) would partly be adjusted by the enhancement of the chemoreflex drive to CO2 only during the steady-state exercise

The Proportion of Female Physician Links With Advanced Educational Opportunity for Female and by Female

Background: The overall proportion of female physician is increasing worldwide. However, its ratio exhibits a substantial diversity among each member country of Organisation for Economic Co-operation and Development (OECD). This study aimed to reveal the social factors of countries associated with the percentage of female physicians.Methods: We retrieved the percentage of female physicians and social characteristic which may affect the ratio of female physicians of 36 OECD countries in 2016 or nearest year from the World Bank Open Data. Multivariate regression analysis was performed after univariate evaluations with Spearman’s coefficient to explore correlation of social variables with the proportion of female physicians.Results: The percentages of female adolescents who dropped out of school before lower secondary school, female population that attained or completed Master’s or equivalent degree, female labour force, and female academic staff in tertiary education showed statistically significant correlation with proportion of female physicians (Spearman coefficient = -0.527, 0.585, 0.501, and 0.499; P = .01, .001, .002, and .008). Female’s educational attainment at least Master’s or equivalent and that of female academic staff at tertiary education were selected after multivariate analysis.Conclusion: Our study revealed the relationships between advanced education opportunity and female participation in academic positions with the percentage of female physicians. Our research is limited in the difficulty to evaluate physicians’ working hours in spite of its possible effect. Further studies with qualitative assessment are warranted to explore the detail reasons to cause gender gap in physician

Adenosine triphosphate induces amorphous aggregation of amyloid β by increasing Aβ dynamics

アルツハイマー病に関係するアミロイドβ1分子の凝集動態を観察. 京都大学プレスリリース. 2024-04-23.Amyloid β (Aβ) aggregates into two distinct fibril and amorphous forms in the brains of patients with Alzheimer’s disease. Adenosine triphosphate (ATP) is a biological hydrotrope that causes Aβ to form amorphous aggregates and inhibit fibril formation at physiological concentrations. Based on diffracted X-ray blinking (DXB) analysis, the dynamics of Aβ significantly increased immediately after ATP was added compared to those in the absence and presence of ADP and AMP, and the effect diminished after 30 min as the aggregates formed. In the presence of ATP, the β-sheet content of Aβ gradually increased from the beginning, and in the absence of ATP, the content increased rapidly after 180 min incubation, as revealed by a time-dependent thioflavin T fluorescence assay. Images of an atomic force microscope revealed that ATP induces the formation of amorphous aggregates with an average diameter of less than 100 nm, preventing fibrillar formation during 4 days of incubation at 37℃. ATP may induce amorphous aggregation by increasing the dynamics of Aβ, and as a result, the other aggregation pathway is omitted. Our results also suggest that DXB analysis is a useful method to evaluate the inhibitory effect of fibrillar formation

Mixed germ cell tumor infiltrating the pineal gland without elevated tumor markers: illustrative case

BACKGROUND: Tumors in the pineal region consist of various histological types, and correct diagnosis from biopsy specimens is sometimes difficult. The authors report the case of a patient with a mixed germ cell tumor infiltrating into the pineal gland despite showing no elevation of tumor markers. OBSERVATIONS: An 18-year-old man complained of headache and nausea and showed disturbance of consciousness. Magnetic resonance imaging showed hydrocephalus associated with a cystic pineal tumor. The patient underwent tumor biopsy followed by endoscopic third ventriculostomy for hydrocephalus in a local hospital. A pineocytoma was diagnosed, and the patient was referred to the authors' hospital for treatment. Concentrations of placental alkaline phosphatase, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin in cerebrospinal fluid were not elevated. However, the authors' review of the tumor specimen revealed some immature cells infiltrating the pineal gland. These cells were positive for AFP, Sal-like protein 4, and octamer-binding transcription factor 3/4; and the diagnosis was changed to mixed germ cell tumor. Chemoradiotherapy was initiated, followed by surgical removal of the residual tumor. LESSONS: Careful examination of all tumor specimens and immunohistochemical analyses are important for accurate diagnosis of pineal tumors

Safety of SARS-CoV-2 BNT162b2 Vaccine in Elderly Patients from Japan - A Preliminary Assessment and A Call on Careful Pharmacovigilance

Vaccines are efficacious, effective and safe measures to control COVID-19. Despite phase 3 and 4 studies, some concerns should be addressed in certain populations regarding its specific vaccine safety. One of them is the safety of the elderly. The majority of enrollees in clinical studies on COVID-19 vaccines have been young to middle-aged individuals, with few exceptions

Safety of SARS-CoV-2 BNT162b2 Vaccine in Elderly Patients from Japan - A Preliminary Assessment and A Call on Careful Pharmacovigilance

Vaccines are efficacious, effective and safe measures to control COVID-19. Despite phase 3 and 4 studies, some concerns should be addressed in certain populations regarding its specific vaccine safety. One of them is the safety of the elderly. The majority of enrollees in clinical studies on COVID-19 vaccines have been young to middle-aged individuals, with few exceptions

RUNX inhibitor suppresses graft‐versus‐host disease through targeting RUNX‐NFATC2 axis

Patients with refractory graft-versus-host disease (GVHD) have a dismal prognosis. Therefore, novel therapeutic targets are still needed to be identified. Runt-related transcriptional factor (RUNX) family transcription factors are essential transcription factors that mediate the essential roles in effector T cells. However, whether RUNX targeting can suppress, and GVHD is yet unknown. Here, we showed that RUNX family members have a redundant role in directly transactivating NFATC2 expression in T cells. We also found that our novel RUNX inhibitor, Chb-M’, which is the inhibitor that switches off the entire RUNX family by alkylating agent–conjugated pyrrole-imidazole (PI) polyamides, inhibited T-cell receptor mediated T cell proliferation and allogenic T cell response. These were designed to specifically bind to consensus RUNX-binding sequences (TGTGGT). Chb-M’ also suppressed the expression of NFATC2 and pro-inflammatory cytokine genes in vitro. Using xenogeneic GVHD model, mice injected by Chb-M’ showed almost no sign of GVHD. Especially, the CD4 T cell was decreased and GVHD-associated cytokines including tissue necrosis factor-α and granulocyte-macrophage colony-stimulating factor were reduced in the peripheral blood of Chb-M’ injected mice. Taken together, our data demonstrates that RUNX family transcriptionally upregulates NFATC2 in T cells, and RUNX-NFATC2 axis can be a novel therapeutic target against GVHD

Immunological Microenvironment Predicts the Survival of the Patients with Hepatocellular Carcinoma Treated with Anti-PD-1 Antibody

Introduction: Although immune checkpoint inhibitors (ICIs) have been considered as promising agents for the treatment of advanced hepatocellular carcinoma (HCC), previous clinical trials revealed that the response to anti-programmed cell death protein 1 (anti-PD-1) monotherapy was as low as 20%. Identifying subgroups that respond well to ICIs is clinically important. Here, we studied the prognostic factors for anti-PD-1 antibody treatment based on the molecular and immunological features of HCC. Methods: Patients who were administered anti-PD1 antibody for advanced HCC at Kindai University Hospital were included. Clinicopathological backgrounds and antitumor responses were examined in 34 cases where tumor tissues before treatment were available. Transcriptome analysis was performed using 40 HCC samples obtained from surgical resection, and immune status was compared between 20 HCCs with activating mutations in β-catenin and those without the mutations using transcriptome-based immunogram. Results: Univariate analysis showed that the disease control rate was significantly better in patients with α-fetoprotein &#x3c; 400 ng/mL, negative for β-catenin/glutamate synthetase (GS) staining, high combined positive score (CPS) of programmed death-ligand 1 (PD-L1), and increased infiltration of CD8+ cells in tumor tissues. Among them, negative staining of β-catenin/GS, CPS of PD-L1 ≥ 1, and high degree of CD8+ tumor-infiltrating lymphocytes (TILs) were significantly associated with longer survival in both progression-free survival (PFS) and overall survival (OS). The combination of these factors well stratified the survival of the patients on anti-PD-1 antibody in both PFS and OS (p &#x3c; 0.0001 and p = 0.0048 for PFS and OS, respectively). In addition, the immunogram revealed that tumor-carrying mutations in β-catenin showed downregulation of immune-related genes, especially in those related to priming and activation by dendritic cells, interferon-γ response, inhibitory molecules, and regulatory T cells. Discussion/Conclusion: The combined score including Wnt/β-catenin activation, CPS of PD-L1, and degree of CD8+ TILs in HCC is informative for predicting the response to ICI in HCC cases. Constitutive activation of β-catenin can induce an immune cold phenotype with downregulation of immune-related genes, and immunohistochemistry-based evaluation is beneficial for identifying the subgroup that shows a good response to ICI