Histological Observation of the Development of Follicles and Follicular Atresia in Immature Rat Ovaries

To clarify the development of follicular growth and atresia in the immature ovary, rats. ovaries and blood were removed at fixed points during the period from 0 to 35 days after birth (Day 0 to Day 35). The ovaries were immunohistochemically examined, and blood concentrations of serum follicle-stimulating hormone (FSH) and estrogen (E) were measured. We investigated how time-course changes in follicular cell proliferation, estrogen receptor β (ERβ), apoptosis, and FSH and E concentrations are connected with follicular growth and atresia. Apoptosis was found in the ova from Day 0 to Day 3. On Day 15, apoptosis occurred in some granulosa cell nuclei in some follicles, but BrdU uptake and the presence of cyclin D2 and ER β could be observed in other granulosa cells. From Day 17, apoptosis increased in the follicular granulosa cells, and BrdU uptake and the presence of cyclin D2 and ERβ were decreased. Follicular atresia continued, reaching a peak on Day 30. Serum FSH and E concentrations increased until Day 15, then markedly decreased after Day 17. The mechanism of apoptosis in the ova from Day 0 to 3 has not been clarified. However, the onset of follicular atresia was caused by apoptotic degeneration from Days 15 to 17. These results showed that the oocytes were selected by apoptosis at 2 points in the time-course of the maturation of the ovary

Differential, histochemical and immunohistochemical changes in rat hepatocytes after isoflurane or sevoflurane exposure.

Differential, histochemical and immunohistochemical changes were observed in hepatocytes from immediately to 7 days after isoflurane or sevoflurane exposure (at H 0 to on Day 7) to study the process of development and recovery in anesthetic-induced hepatic injury. A total of 570 7-week-old male Sprague-Dawley rats with or without phenobarbital treatment were exposed to isoflurane or sevoflurane in 100%, 21%, or 10% oxygen, or to 10% oxygen alone for 2h. In phenobarbital-treated rats, hepatocytes both with and without anesthetic exposure markedly changed in 10% oxygen at H 0. Glycogen and ribosomal ribonucleic acid (rRNA) disappeared at H 0 and at H 6, respectively, and at H 6, AST levels in the blood rose. From H 6 to Day 1, necrosis developed more markedly and widely in zone 3 hepatocytes exposed to anesthetics in 10% oxygen than in those exposed to oxygen alone. All degenerated tissues had returned to normal levels by day 7. Recovery of the hepatolobular structure may be attributed to rearrangement of remaining hepatocytes in the portal vein area. Both the disappearance of glycogen and rRNA and the increase in blood AST levels after exposure to isoflurane or sevoflurane are considered to be factors contributing to the induction of necrosis around the central vein. The grade of isoflurane-induced hepatic injury was found to be significantly higher than that of sevoflurane.</p

Quantification of PERF 15 mRNA in Tissue Sections from Rat Testes

We previously conducted basic research to quantify in situ hybridization (ISH) signals in rat testes. In this experimental model, we selected ribosomal RNA (rRNA) as the hybridizable RNA in paraffin sections, since it allowed us to easily analyze ISH signals expressed with digoxygenin (DIG)-labeled probes quantitatively through “posterization” of the images. We applied this method to analyze the quantification of transcript, PERF 15 mRNA. PERF 15 is expressed specifically in the testes and localized in the rigid cytoskeletal structure of the sperm head, and has been considered to be involved in the apoptotic process of spermatogenic cells. Quantification of the signals may help to clarify the detailed function of PERF 15. We further analyzed the signals concomitant with a confocal laser scanning microscope. The peak of PERF 15 mRNA expression was found in diplotene spermatocytes, and the amount of PERF 15 mRNA was greatest in late pachytene and diplotene spermatocytes and early spermatids, followed by early pachytene spermatocytes, and then late spermatids. PERF 15 may be involved in the events leading to meiotic division, in which apoptosis is also involved. The present study may help to determine the concentration of mRNA in tissue sections

FoxO1 Gain of Function in the Pancreas Causes Glucose Intolerance, Polycystic Pancreas, and Islet Hypervascularization

Genetic studies revealed that the ablation of insulin/IGF-1 signaling in the pancreas causes diabetes. FoxO1 is a downstream transcription factor of insulin/IGF-1 signaling. We previously reported that FoxO1 haploinsufficiency restored β cell mass and rescued diabetes in IRS2 knockout mice. However, it is still unclear whether FoxO1 dysregulation in the pancreas could be the cause of diabetes. To test this hypothesis, we generated transgenic mice overexpressing constitutively active FoxO1 specifically in the pancreas (TG). TG mice had impaired glucose tolerance and some of them indeed developed diabetes due to the reduction of β cell mass, which is associated with decreased Pdx1 and MafA in β cells. We also observed increased proliferation of pancreatic duct epithelial cells in TG mice and some mice developed a polycystic pancreas as they aged. Furthermore, TG mice exhibited islet hypervascularities due to increased VEGF-A expression in β cells. We found FoxO1 binds to the VEGF-A promoter and regulates VEGF-A transcription in β cells. We propose that dysregulation of FoxO1 activity in the pancreas could account for the development of diabetes and pancreatic cysts

Body mass index and colorectal cancer risk : A Mendelian randomization study

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations

ボセイ カンゴガク ジッシュウ ニ オケル ガクセイ ノ ギジュツ ケイケン ジョウキョウ チョウサ : ガクセイ ノ ボセイ カンゴガク ジッシュウ ギジュツ チェックリスト カラ

　本研究は、母性看護学実習における学生の看護技術経験状況を把握し、母性看護学実習や演習および講義の効果的な方法を検討するための資料を得る事を目的とした。分析に用いたのは、本学科初の母性看護学実習を行った学生84名が自己記入した「母性看護学実習技術チェックリスト」である。技術経験項目は、外来実習6項目、分娩室実習3項目、褥室実習5項目、新生児室実習10項目の計24項目であった。94％以上が経験した技術は新生児の衣類の着脱、おむつ交換、沐浴等7項目、半数以上が未経験の項目は児心音の測定、レオポルド触診法、搾乳等5項目でいずれも対象者の経過やプライバシーの配慮の高い項目であった。男子学生の経験率が有意に低かった項目は外陰部や乳房に関する2項目で、プライバシーの配慮の観点からやむを得えないものであった。実習病院別で経験率に差が見られた項目は、外来実習の4項目、分娩実習の1項目で、外来・分娩室の実習形態の違いがその要因であった。以上の結果から、学内演習では経験率の高い項目の重点化を図り、実習病院には技術経験の均等化への調整を行うと同時に、技術経験項目の精選等の検討を行う必要性を確認した。　The objective of this study is to describe the actual skills experience that maternity nursing students’ get from the maternity nursing practice， and to obtain sources to examine effective methods for lecture. To this end， we conducted an analysis of the“ maternity nursing skills checklist”， which was filled in by 84 students who took the maternity nursing practice course which was offered for the first time in our college.There were 24 skills experienced in: the outpatient department（ 6）， the delivery room（ 3）， the puerperal room（ 5）， and the nursery （10）. There were 7 skills that 94% or more of the students had experience in， which included: changing a newborn infant\u27s clothes， changing diapers， and bathing. There were 5 skills that 50% or more of the students did not have experience in， which require privacy considerations and/or subjects to follow-up， including measurement of fetal heart rate， the Leopold maneuver， and expression of breast milk．There were 2 skills of which the malestudents\u27 experience rate was significantly low， these being procedures involving the female patient’s vulva and breasts， a lack of experience thought to be unavoidable in terms of consideration of privacy. There were skills in which differences of experience levels were found depending upon the hospitals in which the nursing practice was held. There were 4 of these skills related to the training in the outpatient department and one skill related to delivery room training due to the differences between training format in the outpatient department and the deliveryroom. The findings described above clearly show the necessity to enhance the items which show a high experience rate and conduct an investigation pertaining to the selection of items for technical experience， as well as to make efforts to provide uniform technical experience in the training hospitals

Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022