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We conducted a phase II trial to evaluate the efficacy and toxicity of radiotherapy immediately after hyperbaric oxygenation (HBO) with chemotherapy in adults with high-grade gliomas. Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO with the period of time from completion of decompression to irradiation being less than 15 min. Chemotherapy consisted of procarbazine, nimustine (ACNU) and vincristine and was administered during and after radiotherapy. A total of 41 patients (31 patients with glioblastoma and 10 patients with grade 3 gliomas) were enrolled. All 41 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. Of 30 assessable patients, 17 (57%) had an objective response including four CR and 13 PR. The median time to progression and the median survival time in glioblastoma patients were 12.3 months and 17.3 months, respectively. On univariate analysis, histologic grade (P=0.0001) and Karnofsky performance status (P=0.036) had a significant impact on survival, and on multivariate analysis, histologic grade alone was a significant prognostic factor for survival (P=0.001). Although grade 4 leukopenia and grade 4 thrombocytopenia occurred in 10 and 7% of all patients, respectively, these were transient with no patients developing neutropenic fever or intracranial haemorrhage. No serious nonhaematological or late toxicities were seen. These results indicated that radiotherapy delivered immediately after HBO with chemotherapy was safe with virtually no late toxicity in patients with high-grade gliomas. Further studies are required to strictly evaluate the effectiveness of radiotherapy after HBO for these tumours.British Journal of Cancer (2006) 95, 862–868. doi:10.1038/sj.bjc.6603342 www.bjcancer.com Published online 5 September 2006 [ABSTRACT FROM AUTHOR]

Summary. The effect of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE4) and elevating cyclic AMP (cAMP), on in vivo and in vitro 3H-N-methylpiperidyl benzilate (3H-NMPB) binding to muscarinic acetylcholine receptors in the mouse brain was examined. Rolipram significantly decreased in vivo 3H-NMPB binding in the cerebral cortex, hippocampus and striatum, whereas in vitro 3H-NMPB binding in these regions was not altered. Saturation experiments on in vivo binding in conjunction with the kinetic analysis revealed that the apparent association rate constant (kon) of 3H-NMPB binding in vivo was significantly decreased by rolipram. A similar decrease in the apparent association rate constant (kon) by rolipram was reported for dopamine D1 and D2 receptor binding in vivo. These results indicate that rolipram plays an important role in the global modulation of apparent rates of ligand-receptor interactions in the intact brain. [ABSTRACT FROM AUTHOR]

Therapeutic angiogenesis using mesenchymal stem/stromal cell grafts have shown modest and controversial effects in preventing amputation for patients with critical limb ischemia. Through single-cell transcriptomic analysis of human tissues, we identify CD271 + progenitors specifically from subcutaneous adipose tissue (AT) as having the most prominent pro-angiogenic gene profile distinct from other stem cell populations. AT-CD271 + progenitors demonstrate robust in vivo angiogenic capacity over conventional adipose stromal cell grafts, characterized by long-term engraftment, augmented tissue regeneration, and significant recovery of blood flow in a xenograft model of limb ischemia. Mechanistically, the angiogenic capacity of CD271 + progenitors is dependent on functional CD271 and mTOR signaling. Notably, the number and angiogenic capacity of CD271 + progenitors are strikingly reduced in insulin-resistant donors. Our study highlights the identification of AT-CD271 + progenitors with in vivo superior efficacy for limb ischemia. Furthermore, we showcase comprehensive single-cell transcriptomics strategies for identification of suitable grafts for cell therapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Pulmonary arterial hypertension (PAH) remains a disease with poor prognosis; thus, a new mechanism for PAH treatment is necessary. Circulating nerve growth factor receptor (Ngfr)-positive cells in peripheral blood mononuclear cells are associated with disease severity and the prognosis of PAH patients; however, the role of Ngfr in PAH is unknown. In this study, we evaluated the function of Ngfr using Ngfr gene-deletion (Ngfr -/- ) mice. To elucidate the role of Ngfr in pulmonary hypertension (PH), we used Ngfr -/- mice that were exposed to chronic hypoxic conditions (10% O 2 ) for 3 weeks. The development of hypoxia-induced PH was accelerated in Ngfr -/- mice compared to littermate controls. In contrast, the reconstitution of bone marrow (BM) in Ngfr -/- mice transplanted with wild-type BM cells improved PH. Notably, the exacerbation of PH in Ngfr -/- mice was accompanied by the upregulation of pulmonary vascular remodeling-related genes in lung tissue. In a hypoxia-induced PH model, Ngfr gene deletion resulted in PH exacerbation. This suggests that Ngfr may be a key molecule involved in the pathogenesis of PAH.

This retrospective, observational cohort study investigated the economic impact of genotype by classifying methicillin-resistant Staphylococcus aureus (MRSA) by using the polymerase chain reaction-based open reading frame typing (POT) method. Using administrative claims and bacteriological data for April 2016 to March 2021 from the University of Yamanashi Hospital, we ascertained the POT1 numbers and classified MRSA as either "hospital-derived" or "community-derived". We defined MRSA-associated medical practices and estimated the associated medical costs. After applying inverse probability of treatment weighting (IPTW)-based adjustment for patient characteristics between the two groups, we estimated the differences in medical costs during the "total therapy period" (defined as the interval from specimen submission to Day 42 after the susceptibility report) and the "definitive therapy period" (defined as the interval from susceptibility reporting to Day 42). Among the 135 MRSA-infected patients, 54 and 81 were classified as having hospital-derived and community-derived MRSA infections, respectively. Significant differences in patient characteristics were observed with regard to age ( p = 0.0478), sex ( p = 0.0422), surgery ( p = 0.0349), chemotherapy ( p = 0.0457) and immunosuppressive drug use ( p = 0.0222). The median duration of the definitive therapy was 29 and 27 days, and the mortality rate during this period was 11% and 5% for the hospital-derived and community-derived types, respectively. After IPTW-based adjustment, the medical costs for the total therapy period were 324,480 and 296,462 Japanese yen (JPY) per patient for the hospital-derived and community-derived types, respectively, whereas the medical costs for the definitive therapy period were 279,635 and 256,542 JPY per patient for the hospital-derived and community-derived types, respectively. No statistically significant difference was detected ( p = 0.5813 and p = 0.6355, respectively). In this study, MRSA healthcare costs were compared according to the POT scores, and no statistically significant differences were observed between hospital-derived and community-derived MRSA infections., Competing Interests: Conflict of interest: M. A. consulted for Shionogi & Company and Astellas Pharma Inc. and received an honorarium for lectures from Takeda Pharmaceutical Company. F. K. received an honorarium for lectures from AstraZeneca. All other authors declare no conflict of interest regarding the publication of this paper., (© 2022 the Author(s), licensee AIMS Press.)

Background: Patients with critical limb ischemia (CLI) still have a high rate of lower limb amputation, which is associated with not only a decrease in quality of life but also poor life prognosis. Implantation of adipose-derived regenerative cells (ADRCs) has an angiogenic potential for patients with limb ischemia., Objectives: We investigated safety, feasibility, and efficacy of therapeutic angiogenesis by cell transplantation (TACT) of ADRCs for those patients in multicenter clinical trial in Japan., Methods: The TACT-ADRC multicenter trial is a prospective, interventional, open-labeled study. Patients with CLI (Fontaine class III-IV) who have no other option for standard revascularization therapy were enrolled in this study. Thirty-four target ischemic limbs of 29 patients were received freshly isolated autologous ADRCs implantation., Results: The overall survival rate at a post-operative period and at 6 months follow-up was 100% at any time points. As a primary endpoint for efficacy evaluation, 32 limbs out of 34 (94.1%) were free from major amputation for 6 months. Numerical rating scale (from 6 to 1) as QOL score, ulcer size (from 317 mm 2 at to 109 mm 2 ), and 6-min walking distance (from 255 to 369 m) improved in 90.6%, 83.3%, and 72.2% patients, respectively., Conclusions: Implantation of autologous ADRCs could be safe and effective for the achievement of therapeutic angiogenesis in the multicenter settings, as a result in no major adverse event, optimal survival rate, and limb salvage for patients with no-conventional option against critical limb ischemia. TRN: jRCTb040190118; Date: Nov. 24th, 2015., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To generate an effective embryo prediction model and identify a non-invasive evaluation method by analyzing microRNAs (miRNAs) in embryo culture medium., Design: Analysis of microRNA profiles from spent culture medium of blastocysts with good morphology that did or did not result in pregnancy., Setting: Clinical and experimental research., Patients: Sixty patients who underwent thawed embryo transfer of blastocysts after intracytoplasmic sperm injection., Intervention(s): None., Main Outcome Measure(s): The association of miRNA abundance levels secreted by blastocysts in culture medium and implantation success., Results: Our RNA sequencing analysis found a total of 53 differentially expressed miRNAs in the culture media of pregnancy and non-pregnancy groups. Twenty-one miRNAs were analyzed for their potential to predict implantation success. Eight miRNAs (hsa-miR-191-5p, hsa-miR-320a, hsa-miR-92a-3p, hsa-miR-509-3p, hsa-miR-378a-3p, hsa-miR-28-3p, hsa-miR-512-5p, and hsa-miR-181a-5p) were further extracted from the results of a logistic regression analysis of qPCR Ct values. A prediction model for high-quality blastocysts was generated using the eight miRNAs, with an average accuracy of 0.82 by 5-fold cross validation., Conclusion: We isolated blastocyst miRNAs that may predict implantation success and created a model to predict viable embryos. Increasing the number of investigated cases and further studying the effect of each miRNA on embryonic development is needed to refine the miRNA-based predictive model., (© 2022. The Author(s).)