Cyclic Undrained Behavior of Saturated Sand Under Monotonic Loading

In order to investigate undrained behavior of saturated sand, three types of undrained triaxial tests were performed for saturated Toyoura sand, i.e., cyclic loading test with (DTU-test) and without (DU-test) constant initial shear stress and tests in which constant rate axial strain and cyclic axial stress were applied to a specimen simultaneously (DCU-test). In DCU-tests, three types of failure were observed, i.e.; 1) perfectly liquefied in the case of relatively loose sand, 2) initially liquefied, but shear failure was induced after strength recovery for succeeding loading in the case of relatively dense sand, and 3) shear failure was induced without liquefaction. Furthermore, constitutive equations taking account of strain history of materials were derived and applied to the above test conditions. Calculated stress-strain-pore water pressure behaviors showed good agreements with experimental results

Hemodynamic and autonomic response to acute hemorrhage in streptozotocin-induced diabetic rats

<p>Abstract</p> <p>Background</p> <p>The various autonomic control systems lead to characteristic changes in heart rate (HR) and blood pressure (BP) during acute hemorrhage. However, cardiovascular autonomic neuropathy due to diabetes mellitus may interfere with the normal compensation for hemorrhage.</p> <p>Materials and methods</p> <p>A controlled graded bleeding (6 - 36% loss of estimated total blood volume: ETBV) was performed in streptozotocin-induced diabetic rats (STZ rats) under a conscious state. Hemodynamic and autonomic responses to acute hemorrhage were examined using analysis of BP-HR variability. The effects of dextran treatment after hemorrhage were also examined.</p> <p>Results</p> <p>A significant reduction in mean arterial pressure began at 12% ETBV loss in STZ rats and 18% in the control rats, respectively. When blood loss reached 18% of TEBV, the decrease in HR was prominent in STD rats due to the activation of a parasympathetic drive, as indicated by the increase in high frequency (HF; 0.75~3.0 Hz) power in HR variability, while in the control rats this response was not observed. The administration of dextran prevented the activation of the parasympathetic drive in STZ rats during hemorrhaging. In the control rats, the dextran treatment sustained the initial increase in HR with reduced HF power in HR variability.</p> <p>Conclusion</p> <p>STZ rats showed different hemodynamic and autonomic responses to acute hemorrhage from the control rats. STZ rats were prone to develop bradycardiac hypotension characterized by marked parasympathetic activation during hemorrhaging. This finding suggests enhancement of the Bezold-Jarisch reflex in STZ rats. Dextran treatment to maintain a normovolemic hemorrhage state inhibits this reflex.</p

Premedication with midazolam in intellectually disabled dental patients: intramuscular or oral administration? A retrospective study

Background: The use of midazolam for dental care in patients with intellectual disability is poorly documented. The purpose of this study was to determine which method of premedication is more effective for these patients, 0.15 mg/kg of intramuscular midazolam or 0.3 mg/kg of oral midazolam. Material and Methods: This study was designed and implemented as a non-randomized retrospective study. The study population was composed of patients with intellectual disability who required dental treatment under ambulatory general anesthesia from August 2009 through April 2013. Patients were administered 0.15 mg/kg of midazolam intramuscularly (Group IM) or 0.3 mg/kg orally (Group PO). The predictor variable was the method of midazolam administration. The outcome variables measured were Observer’s Assessment of Alertness/ Sedation (OAA/S) Scale scores, the level of cooperation when entering the operation room and for venous cannulation, post-anesthetic agitation and recovery time. Results: Midazolam was administered intramuscularly in 23 patients and orally in 21 patients. More patients were successfully sedated with no resistance behavior during venous cannulation in Group PO than in Group IM ( p =0.034). There were no differences in demographic data and other variables between the groups. Conclusions: The results of this study suggest that oral premedication with 0.3 mg/kg of midazolam is more effective than 0.15 mg/kg of midazolam administered intramuscularly, in terms of patient resistance to venous cannulation. If both oral and intramuscular routes of midazolam are acceptable in intellectually disabled patients, the oral route is recommended

PARP-1 ensures regulation of replication fork progression by homologous recombination on damaged DNA

Poly-ADP ribose polymerase 1 (PARP-1) is activated by DNA damage and has been implicated in the repair of single-strand breaks (SSBs). Involvement of PARP-1 in other DNA damage responses remains controversial. In this study, we show that PARP-1 is required for replication fork slowing on damaged DNA. Fork progression in PARP-1−/− DT40 cells is not slowed down even in the presence of DNA damage induced by the topoisomerase I inhibitor camptothecin (CPT). Mammalian cells treated with a PARP inhibitor or PARP-1–specific small interfering RNAs show similar results. The expression of human PARP-1 restores fork slowing in PARP-1−/− DT40 cells. PARP-1 affects SSB repair, homologous recombination (HR), and nonhomologous end joining; therefore, we analyzed the effect of CPT on DT40 clones deficient in these pathways. We find that fork slowing is correlated with the proficiency of HR-mediated repair. Our data support the presence of a novel checkpoint pathway in which the initiation of HR but not DNA damage delays the fork progression

Guideline-based Treatment of Glucocorticoid-induced Osteoporosis in Patients with Rheumatoid Arthritis: A Retrospective Study with the AORA Registry

Glucocorticoid-induced osteoporosis (GIOP) is one of the side effects associated with glucocorticoid (GC) therapy. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) provided new guidelines for the management and treatment of GIOP. The aim of the present study was to clarify the prevalence of patients with rheumatoid arthritis (RA) requiring treatment according to the new guidelines and to identify risk factors associated with lack of treatment in these patients. Patients in the 2018 Akita Orthopedic group on Rheumatoid Arthritis (AORA) database were enrolled. Of 2,234 patients with RA in the database, 683 (30.6%) met the 2014 JSBMR guideline treatment criteria, and 480 (70.3%) had been treated. The untreated group included a larger number of males, younger patients, and patients treated in clinics rather than hospital (p<0.001, p=0.015, and p<0.001, respectively). Multivariate analyses found that male sex, younger age, and clinic-based RA care were significant risk factors associated with lack of treatment (p<0.001, p=0.013, and p<0.001, respectively). Thus, male sex, younger age, and clinic-based care were identified as risk factor

Loss of Parp-1 affects gene expression profile in a genome-wide manner in ES cells and liver cells

BACKGROUND: Many lines of evidence suggest that poly(ADP-ribose) polymerase-1 (Parp-1) is involved in transcriptional regulation of various genes as a coactivator or a corepressor by modulating chromatin structure. However, the impact of Parp-1-deficiency on the regulation of genome-wide gene expression has not been fully studied yet. RESULTS: We employed a microarray analysis covering 12,488 genes and ESTs using mouse Parp-1-deficient (Parp-1(-/-)) embryonic stem (ES) cell lines and the livers of Parp-1(-/- )mice and their wild-type (Parp-1(+/+)) counterparts. Here, we demonstrate that of the 9,907 genes analyzed, in Parp-1(-/- )ES cells, 9.6% showed altered gene expression. Of these, 6.3% and 3.3% of the genes were down- or up-regulated by 2-fold or greater, respectively, compared with Parp-1(+/+ )ES cells (p < 0.05). In the livers of Parp-1(-/- )mice, of the 12,353 genes that were analyzed, 2.0% or 1.3% were down- and up-regulated, respectively (p < 0.05). Notably, the number of down-regulated genes was higher in both ES cells and livers, than that of the up-regulated genes. The genes that showed altered expression in ES cells or in the livers are ascribed to various cellular processes, including metabolism, signal transduction, cell cycle control and transcription. We also observed expression of the genes involved in the pathway of extraembryonic tissue development is augmented in Parp-1(-/- )ES cells, including H19. After withdrawal of leukemia inhibitory factor, expression of H19 as well as other trophoblast marker genes were further up-regulated in Parp-1(-/- )ES cells compared to Parp-1(+/+ )ES cells. CONCLUSION: These results suggest that Parp-1 is required to maintain transcriptional regulation of a wide variety of genes on a genome-wide scale. The gene expression profiles in Parp-1-deficient cells may be useful to delineate the functional role of Parp-1 in epigenetic regulation of the genomes involved in various biological phenomena

Prognostic Significance of C-reactive Protein-to-prealbumin Ratio in Patients with Esophageal Cancer

Background: The prognostic value of combination of C-reactive protein and prealbumin (CRP/PAlb) in esophageal cancer remains unclear. Methods: We enrolled 167 esophageal cancer patients who underwent curative esophagectomy. Univariate and multivariate analyses were performed to determine the prognostic significance of various markers, including CRP-to-albumin (CRP/Alb) ratio, modified Glasgow prognostic score, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index. Results: Receiver operating characteristic analysis revealed the optimal cut-off value of each inflammatory factor, and CRP/PAlb ratio had the greatest discriminative power in predicting recurrence-free survival (RFS) among the examined measures (AUC 0.668). The 5-year overall survival and RFS rates were significantly lower in patients with high CRP/PAlb ratio than in those with low CRP/PAlb ratio (P < 0.001, P = 0.001, respectively). In the univariate analysis, RFS was significantly worse in patients with low BMI, T2 or deeper tumor invasion, positive lymph node metastasis, positive venous invasion, high CRP/PAlb ratio, high CRP/Alb ratio, high NLR, and high LMR. Multivariate analysis revealed that CRP/PAlb, but not CRP/Alb, was an independent prognostic factor along with lymph node metastasis. Conclusion: CRP/PAlb ratio was useful for predicting the prognosis of esophageal cancer patients

Long-term results of a randomized controlled trial comparing neoadjuvant Adriamycin, cisplatin, and 5-fluorouracil vs docetaxel, cisplatin, and 5-fluorouracil followed by surgery for esophageal cancer (OGSG1003)

Sugimura, K, Yamasaki, M, Yasuda, T, et al. Long‐term results of a randomized controlled trial comparing neoadjuvant Adriamycin, cisplatin, and 5‐fluorouracil vs docetaxel, cisplatin, and 5‐fluorouracil followed by surgery for esophageal cancer (OGSG1003). Ann. Gastroenterol. Surg. 2020; 00: 1– 8. https://doi.org/10.1002/ags3.12388