Radiotherapy quality assurance review in a multi-center randomized trial of limited-disease small cell lung cancer: the Japan Clinical Oncology Group (JCOG) trial 0202

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to analyze the radiotherapy (RT) quality assurance (QA) assessment in Japan Clinical Oncology Group (JCOG) 0202, which was the first trial that required on-going RT QA review in the JCOG.</p> <p>Methods</p> <p>JCOG 0202 was a multi-center phase III trial comparing two types of consolidation chemotherapy after concurrent chemoradiotherapy for limited-disease small cell lung cancer. RT requirements included a total dose of 45 Gy/30 fx (bis in die, BID/twice a day) without heterogeneity correction; elective nodal irradiation (ENI) of 30 Gy; at least 1 cm margin around the clinical target volume (CTV); and interfraction interval of 6 hours or longer. Dose constraints were defined in regards to the spinal cord and the lung. The QA assessment was classed as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable (I/NE).</p> <p>Results</p> <p>A total of 283 cases were accrued, of which 204 were fully evaluable, excluding 79 I/NE cases. There were 18 VU in gross tumor volume (GTV) coverage (8% of 238 evaluated); 4 VU and 23 DA in elective nodal irradiation (ENI) (2% and 9% of 243 evaluated, respectively). Some VU were observed in organs at risk (1 VU in the lung and 5 VU in the spinal cord). Overall RT compliance (PP + DA) was 92% (187 of 204 fully evaluable). Comparison between the former and latter halves of the accrued cases revealed that the number of VU and DA had decreased.</p> <p>Conclusion</p> <p>The results of the RT QA assessment in JCOG 0202 seemed to be acceptable, providing reliable results.</p

ESI-MS Analysis of Effluents from Medical Silicon Rubber

The catheter tubes of medical silicon rubber were dipped in ethanol. The effluents were fractionated by thin-layer chromatography (TLC), and their fractions were analyzed by ion trap electrospray ionization mass spectrometry (ESI-MS). The ESI mass spectra resulting from the main TLC fraction, R1=0.5 showed that the effluents were determined to be poly(dimethyl siloxane) (8 to 20 mer) that is a main part of a silicon rubber. The spectra for the origin in TLC showed that poly(ethylene glycol) (4 to 10 mer and 14 to 18 mer) and poly- (propylene glycol) (19 to 36 mer) as an antistatic agent were identified

Decreased ADP-Ribosyl Cyclase Activity in Peripheral Blood Mononuclear Cells from Diabetic Patients with Nephropathy

Aims/hypothesis. ADP-ribosyl-cyclase activity (ADPRCA) of CD38 and other ectoenzymes mainly generate cyclic adenosine 5’diphosphate-(ADP-) ribose (cADPR) as a second messenger in various mammalian cells, including pancreatic beta cells and peripheral blood mononuclear cells (PBMCs). Since PBMCs contribute to the pathogenesis of diabetic nephropathy, ADPRCA of PBMCs could serve as a clinical prognostic marker for diabetic nephropathy. This study aimed to investigate the connection between ADPRCA in PBMCs and diabetic complications. Methods. PBMCs from 60 diabetic patients (10 for type 1 and 50 for type 2) and 15 nondiabetic controls were fluorometrically measured for ADPRCA based on the conversion of nicotinamide guanine dinucleotide (NGD+) into cyclic GDP-ribose. Results. ADPRCA negatively correlated with the level of HbA1c (P = .040, R2 = .073), although ADPRCA showed no significant correlation with gender, age, BMI, blood pressure, level of fasting plasma glucose and lipid levels, as well as type, duration, or medication of diabetes. Interestingly, patients with nephropathy, but not other complications, presented significantly lower ADPRCA than those without nephropathy (P = .0198) and diabetes (P = .0332). ANCOVA analysis adjusted for HbA1c showed no significant correlation between ADPRCA and nephropathy. However, logistic regression analyses revealed that determinants for nephropathy were systolic blood pressure and ADPRCA, not HbA1c. Conclusion/interpretation. Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy

PAX5 alterations in an infant case of KMT2A-rearranged leukemia with lineage switch

Lineage switch is a rare event at leukemic relapse. While mostly known to occur in KMT2A-rearranged infant leukemia, the underlying mechanism is yet to be depicted. This case report describes a female infant who achieved remission of KMT2A-MLLT3-rearranged acute monocytic leukemia, but 6 months thereafter, relapsed as KMT2A-MLLT3-rearranged acute lymphocytic leukemia. Whole exome sequencing of the bone marrow obtained pre-post lineage switch revealed two somatic mutations of PAX5 in the relapse sample. These two PAX5 alterations were suggested to be loss of function, thus to have played the driver role in the lineage switch from acute monocytic leukemia to acute lymphocytic leukemia

Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate

Background We aimed to demonstrate the biochemical characteristics of vitamin B6–dependent epilepsy, with a particular focus on pyridoxal 5′-phosphate and pyridoxal in the cerebrospinal fluid. Methods Using our laboratory database, we identified patients with vitamin B6–dependent epilepsy and extracted their data on the concentrations of pyridoxal 5′-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5′-phosphate concentrations. Results We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5′-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5′-phosphate concentrations were low in patients with vitamin B6–dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6–dependent epilepsy, suggestive of pyridoxal 5′-phosphate deficiency in the brain. Conclusions Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5′-phosphate deficiency in the brain in vitamin B6–dependent epilepsy than low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5′-phosphate homeostasis protein deficiency, which does not have known biomarkers

IL-12 and IL-18 Induction and Subsequent NKT Activation Effects of the Japanese Botanical Medicine Juzentaihoto

In this study, we first measured some cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT). Of the cytokines measured interleukin (IL) -18 was the most prominently up-regulated cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in mice, focusing especially on natural killer T (NKT) cell induction. Mice fed JTT were compared to control group ones. After sacrifice, the liver was fixed, embedded and stained. Transmission electron microscope (TEM) observations were performed. Although the mice receiving the herbal medicine had same appearance, their livers were infiltrated with massive mononuclear cells, some of which were aggregated to form clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of IL-12 and IL-18 in the liver of JTT treated mice. To clarify what the key molecules that induce immunological restoration with JTT might be, we next examined in vitro lymphocyte cultures. Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours) induction of interferon (IFN)-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their activation, following immunological restoration could contribute to anti-tumor effects

Structural difference due to intramolecular stacking interactions in dinuclear rhodium(III) complexes [{Rh(η5-C5Me5)(L)}2]n+containing pyrimidine-2-thionate and related ligands

Self-assembling reactions between [Rh(η5-C5Me5)(H2O)3]2+and pyrimidine-2-thionate(pymt) or related ligands[L; mpymt = 4-methyl-pyrimidine-2-thionate(1-), dmpymt = 4,6-dimethylpyrimidine-2-thionate(1-), apymt = 4-aminopyrimidine-2-thionate(1-), dapymt = 4,6-diaminopyrimidine-2-thionate(1-), or mpol = 2-sulfanyl-3-pyridinolate(2-)] were carried out and the products characterized by UV/vis, NMR spectroscopy, electrospray ionization mass spectrometry, and crystal structure analysis. All products are dinuclear rhodium(III) complexes of [{Rh(η5-C5Me5)(L)}2]n+: three crystal structures with mpymt, dmpymt and mpol were determined. The mpymt and dmpymt ligands co-ordinate through a 1κ2N,S:2κS mode and the two pyrimidine rings are located in cis position,whereas mpol adopts a five-membered chelating mode with 1κ2S,O:2κS and the two pyrimidine rings are located in trans position. Such structural difference can reasonably be explained by the　intramolecular stacking interaction between the two bridging ligands

Cooking characteristics of volume cooking and weight post-cooking according to the Standard Tables of Food Composition in Japan for nutritional management

給食施設では、利用者の適正な栄養管理を行うために提供する食事の栄養量が計算されるが、実際の摂取栄養量に近づけるために調理後の成分変化を考慮した栄養価計算が求められている。本研究は食品成分表の加熱調理後の重量変化率と加熱調理食品に着目し、大量調理における調理特性を分析した。2022 年10-12 月に実施した本学の給食経営管理論実習の予定献立を対象に、食品ごとの加熱調理法をゆで、蒸し、焼き、炒め、ホイル焼きに分類し、加熱調理後の成分値収載の有無を区分した。結果は、加熱調理食品数の累計167 回、食品成分表に加熱調理後の成分値の収載がないものは約４割と高かった。食品成分表の調理法は「ゆで」が多く、大量調理に対応する調理法の種類が少ない。さらに、大量調理は食材使用量が多く調理工程が長い特徴があるため、その仕上がり重量が少量調理と異なる。調理後の栄養成分値を算出する際には、食品成分表の食品の読み替えや、重量変化率の利用を慎重に行う必要がある。In food service facilities, nutritional values of the meals are calculated to ensure proper　nutritional management of consumers. Furthermore, it is recommended that nutrient values after cooking should be considered to calculate values closer to actual nutrient intake. The purpose of this study was to examine the rate of change in weight post-cooking and characteristics of volume cooking according to the Standard Tables of Food Composition in Japan 2020. We examined meals cooked by students in two classes. The study period was from October to December 2022. We classified each food into five cooking methods, viz., boiled, steamed, baked, stir-fried, and foil-baked, and determined whether the ingredient value was listed after cooking. The results showed that the total number of cooked foods was 167, and ingredients of approximately 40% of the foods were not listed after cooking. The most used cooking method according to the Standard Tables of Food Composition is “boiled”, and few other cooking methods are mentioned for volume cooking. Furthermore, volume cooking, which uses more ingredients and is a time-consuming process, yields finished weight that differs from that of low-volume cooking. To calculate nutrient values after cooking, several factors must be considered, such as whether another similar food can be substituted if that food is not on the ingredient list and whether the percentage change in weight should be considered.departmental bulletin pape

Specific Enrichment of miRNAs in Arabidopsis thaliana Infected with Tobacco mosaic virus

RNA silencing is a broadly conserved machinery and is involved in many biological events. Small RNAs are key molecules in RNA silencing pathway that guide sequence-specific gene regulations and chromatin modifications. The silencing machinery works as an anti-viral defense in virus-infected plants. It is generally accepted that virus-specific small interfering (si) RNAs bind to the viral genome and trigger its cleavage. Previously, we have cloned and obtained sequences of small RNAs from Arabidopsis thaliana infected or uninfected with crucifer Tobacco mosaic virus. MicroRNAs (miRNAs) accumulated to a higher percentage of total small RNAs in the virus-infected plants. This was partly because the viral replication protein binds to the miRNA/miRNA* duplexes. In the present study, we mapped the sequences of small RNAs other than virus-derived siRNAs to the Arabidopsis genome and assigned each small RNA. It was demonstrated that only miRNAs increased as a result of viral infection. Furthermore, some newly identified miRNAs and miRNA candidates were found from the virus-infected plants despite a limited number of examined sequences. We propose that it is advantageous to use virus-infected plants as a source for cloning and identifying new miRNAs