Allopregnanolone suppresses mechanical allodynia and internalization of neurokinin-1 receptors at the spinal dorsal horn in a rat postoperative pain model

BackgroundTo identify a new strategy for postoperative pain management, we investigated the analgesic effects of allopregnanolone (Allo) in an incisional pain model, and also assessed its effects on the activities of the primary afferent fibers at the dorsal horn.MethodsIn experiment 1, 45 rats were assigned to Control, Allo small-dose (0.16 mg/kg), and Allo large-dose (1.6 mg/kg) groups (n = 15 in each). The weight bearing and mechanical withdrawal thresholds of the hind limb were measured before and at 2, 24, 48, and 168 h after Brennan\u27s surgery. In experiment 2, 16 rats were assigned to Control and Allo (0.16 mg/kg) groups (n = 8 in each). The degree of spontaneous pain was measured using the grimace scale after the surgery. Activities of the primary afferent fibers in the spinal cord (L6) were evaluated using immunohistochemical staining.ResultsIn experiment 1, the withdrawal threshold of the Allo small-dose group was significantly higher than that of the Control group at 2 h after surgery. Intergroup differences in weight bearing were not significant. In experiment 2, intergroup differences in the grimace scale scores were not significant. Substance P release in the Allo (0.16 mg/kg) group was significantly lower than that in the Control group.ConclusionsSystemic administration of Allo inhibited mechanical allodynia and activities of the primary afferent fibers at the dorsal horn in a rat postoperative pain model. Allo was proposed as a candidate for postoperative pain management

Postoperative daily living activities of geriatric patients administered general or spinal anesthesia for hip fracture surgery: A retrospective cohort study

Purpose:Maintaining independence after hip fracture repair is important for geriatric patients and general welfare. We investigated the effects of anesthetic methods on postoperative activities of daily living (ADLs) following hip fracture surgery in elderly patients.Methods:The medical records of 12,342 patients aged ≥65 years who underwent typical surgeries for hip fracture using either general anesthesia or spinal anesthesia were reviewed. To adjust for baseline differences and minimize selection bias for the chosen method of anesthesia, patients were matched by propensity scores. Factors affecting the deterioration in ADLs during hospital stay were also investigated in all subjects using a multivariate logistic regression analysis. Eating, grooming, toileting, bathing, and walking were selected as the ADL parameters, as they are considered important for an independent life.Results:Of the 12,342 patients, 6918 (56.1%) received general anesthesia and 5424 (43.9%) received spinal anesthesia. After the propensity score matching, the anesthesia types were not associated with ADL scores except toileting at discharge. Results from the multivariate logistic regression analysis showed that the types of anesthesia were not associated with deterioration in ADL scores. Advanced age, male sex, high Charlson Comorbidity Index scores, psychiatric disease, no administration of nonsteroidal anti-inflammatory drugs, and short length of hospital stay were associated with deterioration in ADL scores.Conclusion:The anesthesia types were not associated with ADL dependency except toileting at discharge. Spinal anesthesia adversely affected toilet use at hospital discharge. However, anesthesia types were not factors that affected deterioration in ADL during hospital stay in elderly patients who underwent hip fracture surgery

免疫組織化学法を用いた一側内耳破壊ラットの前庭代償の新しい評価法の開発

Background: Unilateral labyrinthectomy (UL) causes the disappearance of ipsilateral medial vestibular nuclear (ipsi-MVe) activity and induces spontaneous nystagmus (SN), which disappears during the initial process of vestibular compensation (VC). Ipsi-MVe-activity restores in the late process of VC. Objective: We evaluated the late process of VC after UL in rats and examined the effects of thioperamide (H3 antagonist) on VC. Materials and methods: MK801 (NMDA antagonist)-induced Fos-like immunoreactive (-LIR) neurons in contra-MVe, which had been suppressed by NMDA-mediated cerebellar inhibition in UL-rats was used as an index. Results: The number of MK801-induced Fos-LIR neurons in contra-MVe gradually decreased to the same level as that of sham-operated rats 14 days after UL. Thioperamide moved the disappearance of the MK801-induced Fos-LIR neurons 2 days earlier. The number of MK801-induced Fos-LIR neurons in thioperamide-treated rats was significantly decreased, compared with that of vehicle-rats on days 7 and 12 after UL. But, thioperamide did not influence the decline of SN frequency in UL-rats. Conclusion: There findings suggested that the number of MK801-induced Fos-LIR neurons in contra-MVe was decreased in concordance with the restoration of ipsi-MVe-activity during the late process of VC after UL and that thioperamide accelerated the late, but not the initial process of VC

Genome-Wide Haplotype Changes Produced by Artificial Selection during Modern Rice Breeding in Japan

During the last 90 years, the breeding of rice has delivered cultivars with improved agronomic and economic characteristics. Crossing of different lines and successive artificial selection of progeny based on their phenotypes have changed the chromosomal constitution of the ancestors of modern rice; however, the nature of these changes is unclear. The recent accumulation of data for genome-wide single-nucleotide polymorphisms (SNPs) in rice has allowed us to investigate the change in haplotype structure and composition. To assess the impact of these changes during modern breeding, we studied 177 Japanese rice accessions, which were categorized into three groups: landraces, improved cultivars developed from 1931 to 1974 (the early breeding phase), and improved cultivars developed from 1975 to 2005 (the late breeding phase). Phylogenetic tree and structure analysis indicated genetic differentiation between non-irrigated (upland) and irrigated (lowland) rice groups as well as genetic structuring within the irrigated rice group that corresponded to the existence of three subgroups. Pedigree analysis revealed that a limited number of landraces and cultivars was used for breeding at the beginning of the period of systematic breeding and that 11 landraces accounted for 70% of the ancestors of the modern improved cultivars. The values for linkage disequilibrium estimated from SNP alleles and the haplotype diversity determined from consecutive alleles in five-SNP windows indicated that haplotype blocks became less diverse over time as a result of the breeding process. A decrease in haplotype diversity, caused by a reduced number of polymorphisms in the haplotype blocks, was observed in several chromosomal regions. However, our results also indicate that new haplotype polymorphisms have been generated across the genome during the breeding process. These findings will facilitate our understanding of the association between particular haplotypes and desirable phenotypes in modern Japanese rice cultivars

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Prevalence of Human Papillomavirus Types 16/18 and Effect of Vaccination among Japanese Female General Citizens in the Vaccine Crisis Era

The Japanese government withdrew its recommendation for human papillomavirus (HPV) vaccination in June 2013 and resumed it in April 2022. This period is known as the vaccine crisis in Japan. This study aimed to elucidate the prevalence and genotype distribution of HPV among Japanese female citizens, and the effect of vaccination against HPV-16/18 in the era of the vaccine crisis. We recruited Japanese female citizens and asked them to provide self-collected samples from the vaginal wall using cotton swabs for HPV genotyping. Furthermore, we collected the participants’ characteristics, including lifestyle and experience of vaccination against HPV, to determine the significant association with HPV infection. HPV-16/18 positivity was found in 5.6% (115/2044) of participants. The highest vaccination rate was observed in the age group of 20–24 years (60.6%), whereas the lowest HPV-16/18 positivity was observed in the age group of 45–49 years (2.8%), followed by the age group of 20–24 years (4.0%). Experience with HPV vaccination significantly reduced the risk of HPV-16/18 infection (adjusted odds ratio, 0.047; 95% confidence interval, 0.011–0.196). Vaccinated women were much less likely to be infected by HPV-16/18, regardless of the HPV vaccine type or the vaccination dose