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The role of poroelasticity on the functional performance of articular cartilage has been established in the scientific literature since the 1960s. Despite the extensive knowledge on this topic there remain few attempts to design for poroelasticity and to our knowledge no demonstration of an engineered poroelastic material that approaches the physiological performance. In this paper, we report on the development of an engineered material that begins to approach physiological poroelasticity. We quantify poroelasticity using the fluid load fraction, apply mixture theory to model the material system, and determine cytocompatibility using primary human mesenchymal stem cells. The design approach is based on a fiber reinforced hydrated network and uses routine fabrication methods (electrohydrodynamic deposition) and materials (poly[ɛ-caprolactone] and gelatin) to develop the engineered poroelastic material. This composite material achieved a mean peak fluid load fraction of 68%, displayed consistency with mixture theory, and demonstrated cytocompatibility. This work creates a foundation for designing poroelastic cartilage implants and developing scaffold systems to study chondrocyte mechanobiology and tissue engineering. Poroelasticity drives the functional mechanics of articular cartilage (load bearing and lubrication). In this work we develop the design rationale and approach to produce a poroelastic material, known as a fiber reinforced hydrated network (FiHy™), that begins to approach the native performance of articular cartilage. This is the first engineered material system capable of exceeding isotropic linear poroelastic theory. The framework developed here enables fundamental studies of poroelasticity and the development of translational materials for cartilage repair. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The main objective of this study was to investigate the effects of myosin heavy chain (MHC) isoforms on meat and sensory quality in Berkshire pigs. A total of 85 pigs were evaluated, and muscle samples were taken for the analyses of MHC isoform, meat quality, fatty acid composition, and sensory evaluation. Content of the MHC slow isoform was significantly correlated with pH24h (r =0.26, P <0.05) and drip loss (r =−0.32, P <0.01), although the content of MHC isoforms showed limited relationships with individual fatty acids. In the case of sensory evaluation of meat by a trained panel test, the MHC fast/slow ratio was correlated with the juiciness (r =−0.33, P <0.01), off-flavor (r =0.34, P <0.01), tenderness attributes (r =−0.43 to −0.47). These results imply that the content of MHC isoforms can influence various aspects of quality including pork and sensory quality in Berkshire pigs. [Copyright &y& Elsevier]

Abstract: Aim: This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5-FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had undergone curative resection of gastric carcinoma. Methods: From Nov 1999 to Jan 2002, 291 consecutive patients with stage IB–IIIB gastric adenocarcinoma were given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600mg/m2 (days 1, 8, 29 and 36), doxorubicin 30mg/m2 (days 1 and 29) and mitomycin-C 10mg/m2 (day 1), every 8 weeks for 6 months. Results: The median follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1% for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB (p =0.002). The 5-year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage II, 53.3% for stage IIIA, and 39.2% for stage IIIB (p <0.001). A total of 769 cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was nausea/vomiting (11 patients), followed by stomatitis (3 patients). Conclusions: Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated comparable RFS and OS with an acceptable toxicity profile. [Copyright &y& Elsevier]

Despite the fact that cloned animals derived from somatic cells have been successfully generated in a variety of mammalian species, there are still many unsolved problems with current cloning technology. Somatic cell nuclear transfer has shown several developmental aberrancies, including a high rate of abortion during early gestation and increased perinatal death. One cause of these developmental failures of cloned embryos may reside in the epigenetic reprogramming of somatic donor genome. In mammals, DNA methylation is an essential process in the regulation of transcription during embryonic development and is generally associated with gene silencing. A genome-wide demethylation may be a prerequisite for the formation of pluripotent stem cells that are important for later development. We analyzed methylation patterns in cloned bovine embryos to monitor the epigenetic reprogramming process of donor genomic DNA. Aberrant methylation profiles of cloned bovine embryos were observed in various genomic regions, except in single-copy gene sequences. The overall genomic methylation status of cloned embryos was quite different from that of normal embryos produced in vitro or in vivo. These results suggest that the developmental failures of cloned embryos may be due to incomplete epigenetic reprogramming of donor genomic DNA. We expect that advances in understanding the molecular events for reprogramming of donor genome will contribute to clarify the developmental defects of cloned embryos. [Copyright &y& Elsevier]

Introduction/Background What is rehabilitation medicine? What is its aims and goals? These fundamental questions were rarely asked in rehabilitation medicine, although it has been practiced every day for decades. Since the practice of rehabilitation medicine affects physical, mental, and social aspect of patient at the same time, an interdisciplinary research of human being is required to understand what practitioners of rehabilitation medicine really do and should do. As a preliminary result of such research, this article focuses on philosophical understandings of human being, functioning, and disability with regard to ICF and also endeavor to establish a theoretical framework for rehabilitation medicine. Material and method Pairs of concepts defining human being, living, life in general, and their relationships with rehabilitation medicine are discussed on the basis of French philosophy of medicine from the 18th century to the present, in particular that of Pierre-Jean-Georges Cabanis (1757–1808) and Georges Canguilhem (1904–1995). Results From the theoretical consideration of French philosophy of medicine and rehabilitation medicine, an analogical framework between philosophical concepts and ICF is found. Furthermore, new aims and goals of rehabilitation medicine can be established under the name of ‘REHAB SMART’ (Sustaining Movement And Restorative Thinking) as shown in the following. According to the chart, living human being consists of not only functioning, but also disability. Disability should thus be understood as diversity and not as criteria of discrimination. Eventually, rehabilitation medicine should aim to recover self-identity of patient by restoring patient's neural and social network. Conclusion In order to ensure more successful practice of rehabilitation medicine, it's basic concepts, underlying aims and goals should be examined with the help of philosophical understandings of patient as a holistic human being. Such broad and fundamental considerations will enforce the integrity of theory and practice in rehabilitation medicine. [ABSTRACT FROM AUTHOR]

In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally. • This updated analysis of the phase III HIMALAYA study in uHCC showed sustained OS benefit with STRIDE vs sorafenib. • Four-year OS rates were 25.2% with STRIDE vs 15.1% with sorafenib. • STRIDE improved OS vs sorafenib across subgroups and further improved 3- and 4-year OS rates in those with disease control. • Subsequent anticancer systemic therapy was more common in the sorafenib vs STRIDE arm. • No new serious treatment-related AEs occurred after the primary analysis for STRIDE. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of new 1β-methylcarbapenems 1a–d bearing aminopyrimidinylthioether moiety at C-5 position of pyrrolidine ring and their antibacterial activities are described. All the compounds exhibited potent antibacterial activity. Of these carbapenems, 1d showed the best combination of antibacterial activity and stability to dehydropeptidase-I (DHP-I). [Copyright &y& Elsevier]

Abstract: ATP acts as a neurotransmitter or co-neurotransmitter in many areas of the CNS and peripheral nervous systems; however, little is known about the expression and functional role of purinoceptors (P2) in midbrain dopaminergic neurons. Therefore, we investigated P2X receptor expression and regulation of spontaneous firing activity in dopaminergic neurons of the substantia nigra pars compacta (SNc) in rats using patch-clamp and Ca2+-imaging techniques. In most neurons, application of ATP (1 μM–1 mM) increased firing rate dose-dependently (EC50=1.26±0.26 μM, n=45). When the P2-receptor agonists such as 2-methylthio-adenosine 5′-triphosphate (2-MeSATP) or ATPγS were applied or pressure-applied to the neuron, the firing activity increased together with a rise in cytosolic Ca2+ concentration ([Ca2+]c), but application of beta,gamma-methylene ATP (P2X1, 3 agonist) or methylthio-adenosine 5′-diphosphate (P2Y1 agonist) had no effect. In many neurons, the effect of ATP was abolished by the application of the P2-receptor antagonists, suramin or pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS). When ATP was applied in a Ca2+-free solution, there was no detectable change in [Ca2+]c, suggesting that ATP does not release Ca2+ from intracellular stores. In the single-cell reverse transcription polymerase chain reaction (RT-PCR), we found that 65% of dopaminergic neurons expressed mRNAs for P2X receptors; positive amplifications of P2X6 (57.1%), P2X2/6 (25.0%), and P2X4 mRNA (17.9%), respectively. From the above results, we could conclude that ATP modulates firing activities in the rat SNc dopaminergic neurons, possibly via P2X2, P2X2/6, and/or P2X4 receptors. [Copyright &y& Elsevier]