J.S. Bach's Well-tempered Clavier, book II : a study of its aim, historical significance and compiling process.

J. S. Bach's Well-tempered Clavier, Book II (WTC II) is one of his works whose authoritative text is yet to be established. For this kind of popular COrf1)Ositionone may find it particularly strange that no two editions give identical texts. Apart from the Interest of pubUshers, there has been no further exhaustive survey of this Issue since the work of Franz Kroll (1866) and Hans Bischoff (1884) in their respective editions. It appears that Bach's autograph In the British Ubrary, Add.35021 does not contain Bach's final authoritative text in every detail. From the evidence In some of Bach's students' copies. It has been generally assumed that Bach made a subsequent fair copy, which is now lost. My study of the manuscript copies, printed editions and other scholars' treatises in the past suggests that the lack of our understanding could be ascribed partly to the complexity In Bach's compiling and copying process, but especially to the lack of thorough and objective scholarship in manuscript study. This study focuses on Add. 35021. The aim was to reconstruct Bach's compositional activities and habits, how he drew his staves with a rastrum based on his plan of layout, how he repeatedly revised his original text, and how, when he found It Impossible to make further revisions on the same sheet, he prepared a new sheet and made out his revision on it. This process went on until he was satisfied or until he thought he would leave It for the time for future amendments. It is especially Important to distinguish Bach's initial entries from his later additions, because this is normally the only evidence of the previous state of the work. One way of doing this is to classify the types of Ink and pen used by Bach at the time. The other possible method is to note the calligraphic distinction between Bach's fair copies and his composing scores, and also the way Bach planned his layout With care from the beginning or he compressed his notations Into smaller spaces when he came towards the end. When compared with Add.35021, some of the non-autograph sources represent a unique reading of Add.35021 at a particular moment In time. By referring to such secondary sources, we can see clearly Bach's continuous revision activities on Add.35021. In other words, we can reconstruct a time-table of the order of compositions In the compilation and the multiple layers of later revisions. From the study, I have found that long before the presumed lost authoritative version would have been completed, Bach had already shown to his pupils his continually revised autograph as if it were the final revision

Firm insoles effectively reduce hemolysis in runners during long distance running - a comparative study

<p>Abstract</p> <p>Background</p> <p>Shock absorbing insoles are effective in reducing the magnitude and rate of loading of peak impact forces generated at foot strike during running, whereas the foot impact force during running has been considered to be an important cause of intravascular hemolysis in long distance runners. Objective of this study was to evaluate the intravascular hemolysis during running and compare the effect of two different types of insoles (Soft and Firm) on hemolysis.</p> <p>Methods</p> <p>Twenty male long and middle distance runners volunteered to participate in this study. We selected two insoles (Soft and Firm) according to their hardness level (SHORE 'A' scale). Participants were randomly assigned to the soft insole (group 1) and firm insole (group 2) group with ten athletes in each group. Each athlete completed one hour of running at the calculated target heart rate (60-70%). Venous blood samples were collected before and immediately after running. We measured unconjucated bilirubin (mg/dl), lactate dehydrogenase (μ/ml), hemoglobin (g/l) and serum ferritin (ng/ml) as indicators of hemolysis.</p> <p>Results</p> <p>Our study revealed a significant increase in the mean values of unconjucated bilirubin (P < 0.05) while running with soft insoles indicating the occurrence of hemolysis in this group of athletes. Graphical analysis revealed an inverse relationship between hardness of insoles and hemolysis for the observed values.</p> <p>Conclusion</p> <p>Our results indicate that intravascular hemolysis occurs in athletes during long distance running and we conclude that addition of firm insoles effectively reduces the amount of hemolysis in runners compared to soft insoles.</p

Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication

Phenotypic and functional heterogeneity is one of the most relevant features of cancer cells within different tumor types and is responsible for treatment failure. Cancer stem cells (CSCs) are a population of cells with stem cell-like properties that are considered to be the root cause of tumor heterogeneity, because of their ability to generate the full rep- ertoire of cancer cell types. Moreover, CSCs have been invoked as the main drivers of metastatic dissemination and therapeutic resistance. As such, targeting CSCs may be a useful strategy to improve the effectiveness of classical anticancer therapies. Recently, metabolism has been considered as a relevant player in CSC biology, and indeed, onco- genic alterations trigger the metabolite-driven dissemination of CSCs. More interestingly, the action of metabolic pathways in CSC maintenance might not be merely a conse- quence of genomic alterations. Indeed, certain metabotypic phenotypes may play a causative role in maintaining the stem traits, acting as an orchestrator of stemness. Here, we review the current studies on the metabolic features of CSCs, focusing on the bio- chemical energy pathways involved in CSC maintenance and propagation. We provide a detailed overview of the plastic metabolic behavior of CSCs in response to microenvironment changes, genetic aberrations, and pharmacological stressors. In addition, we describe the potential of comprehensive metabolic approaches to identify and selectively eradicate CSCs, together with the possibility to ‘force’ CSCs within certain metabolic dependences, in order to effectively target such metabolic biochemical inflexibilities. Finally, we focus on targeting mitochondria to halt CSC dissemination and effectively eradicate cancer

Measurement of melatonin in body fluids: Standards, protocols and procedures

Abstract: The circadian rhythm of melatonin in saliva or plasma, or of the melatonin metabolite 6‐ sulphatoxymelatonin in urine, is a defining feature of suprachiasmatic nucleus function, the endogenous oscillatory pacemaker. These measurements are useful to evaluate problems related to the onset or offset of sleep and for assessing phase delays or advances of rhythms in entrained individuals. Additionally, they have become an important tool for psychiatric diagnosis, its use being recommended for phase typing in patients suffering from sleep and mood disorders. Thus, the development of sensitive and selective methods for the precise detection of melatonin in tissues and fluids of animals emerges as necessary. Due to its low concentration and the co‐existence of many other endogenous compounds in blood, the determination of melatonin has been an analytical challenge. This review discusses current methodologies employed for detection and quantification of melatonin in biological fluids and tissues

含糖酸化鉄注射液の長期投与でFGF23関連低リン血症性骨軟化症を来たしたクローン病の１例

症例は50歳代，男性．クローン病で２年前に右半結腸切除術，小腸部分切除を施行．術後に他院にてアダリムマブを導入され，クローン病は臨床的寛解の状態であった．４か月前より下肢を中心とした疼痛が出現した．アダリムマブによる薬剤起因性ループスあるいは腸炎性関節炎を疑い，２か月前よりアダリムマブ投与を中止し，プレドニゾロンの内服を開始するも改善を認めなかった．血液検査にて，低リン血症と高アルカリフォスファターゼ血症を認め，精査治療目的で当院に紹介入院となった．骨塩定量検査にて骨密度の低下を，骨シンチグラフィーで疼痛を認める骨への多発取り込みを認め，骨軟化症と診断した．血清のfibroblast growth factor 23（FGF23）が175pg/ml と高値であり，入院前まで定期的に使用されていた含糖酸化鉄注射液による，FGF23関連低リン血症性骨軟化症と診断した．含糖酸化鉄注射液投与を中止し，リン製剤とビタミンD 製剤の投与を開始したところ，徐々に低リン血症と高アルカリフォスファターゼ血症の改善を認めた．その後の経過は良好で，FGF23値は徐々に低下を示し，下肢を中心とした疼痛は軽快し，退院した．長期的に含糖酸化鉄注射液を投与する場合は，FGF23関連低リン血症の早期発見のため，血中リン濃度を定期的に測定する必要がある．The case is a man in his 50s. He underwent operations of right half colon resection and small intestine segmental resection due to Crohn’s disease two years ago. After surgery, Adalimumab was introduced in other hospital, and he was a state of the clinical remission in Crohn’s disease. The sharp pain mainly on lower limbs develops from four months ago. We doubted drug origin-related lupus with Adalimumab or enteritis-related joint pain. Therefore, we stopped Adalimumab injection and started internal use of the prednisolone, however the symptoms did not improve and had continued for two months.Laboratory test showed hypophosphatemia and hyperphosphatasemia and then he was transported to our hospital. Bone mineral quantity showed bone salt decrease and bone scan showed increased uptakes in multiple bones. Fibroblast growth factor23 (FGF23) of the serum was high (175pg/ml), and we diagnosed him FGF23-mediated hypophosphatemic osteomalasia induced by prolonged administration of saccharated ferric acid.Saccharated ferric acid has regularly been used until hospitalization. After stopping the ferric acid injection, and taking phosphorus and vitamin D, hypophosphatemia and hyperphosphatasemia was gradually improved. FGF23 level gradually reduced, and the sharp pain mainly on lower limbs was relieved, and it became a discharge. Regular measurement of serum phosphorus concentration is necessary for early detection of the FGF23-related hypophosphatemia in patients with long term use of saccharated ferric acid

ICAR: endoscopic skull‐base surgery

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