Enlarged housing space and increased spatial complexity enhance hippocampal neurogenesis but do not increase physical activity in mice

IntroductionEnvironmental enrichment (EE) improves various health outcomes, such as hippocampal neurogenesis, in rodents, which is thought to be caused, in part, by increased physical activity. However, the specific effect of each enrichment component, such as enlarged housing spaces and increased spatial complexity with a variety of objects, on physical activity remains unclear because of methodological limitations in measuring physical activity. We aimed to examine whether enlarged housing spaces and increased spatial complexity increase physical activity in mice using a body-implantable actimeter.MethodsAdult male C57BL/6J mice were assigned to either standard housing or EE groups. The housing environment in the EE mice was gradually enriched by enlarging the housing space and the placement of a variety of objects. Physical activity was measured using a body-implanted actimeter. Hippocampal neurogenesis was immunohistochemically examined.ResultsEnlarged housing spaces and the placement of a variety of objects did not increase physical activity in mice. In contrast, hippocampal neurogenesis was enhanced in the EE mice, suggesting that environmental interventions successfully provided enriched housing conditions for these mice.ConclusionsThese results indicate that enlarged housing spaces and increased spatial complexity do not increase physical activity in mice. Furthermore, we found that EE enhanced hippocampal neurogenesis without increasing activity volume. Besides the current understanding that increasing the amount of physical activity is key to improving hippocampal function, our result suggests that the environment in which physical activity takes place is also a crucial contextual factor in determining the impact of physical activity on hippocampal function

Evaluation of vascular quality of life questionnaire in dialysis patients with peripheral arterial disease treated by low-density lipoprotein apheresis

Background: Peripheral arterial disease (PAD) is a common complication in dialysis patients. Early diagnosis and treatment are recommended. Low-density lipoprotein apheresis (LDL-A) is a potential therapy to improve PAD. However, the mechanism has yet to be fully clarified due to lack of established quantitative methods to assess the therapeutic effects of LDL-A treatment. Improvement of skin perfusion pressure (SPP) or ankle brachial index (ABI) is a representative therapy goal, but clinical symptoms were not always consistent with the values of SPP/ABI. Vascular quality of life questionnaire (VascuQOL) was proposed as a disease-specific QOL score, getting validated recently. The possibility of VascuQOL to reflect the severity of PAD in dialysis patients and evaluate the therapeutic effects of LDL-A has yet to be elucidated. Methods: This is an observational study. LDL-A treatment was performed in 32 dialysis patients with PAD. They were divided to critical limb ischemia (CLI) group (17 subjects) and non-CLI group (15 subjects) according to their clinical manifestations. We examined the relationship of PAD severity with SPP, ABI, VascuQOL, and lipid profile such as apoB/apoA-I ratio, malondialdehyde-modified LDL, and remnant-like particles cholesterol. Furthermore, we evaluated these parameters successively to find out a suitable therapeutic marker just after the first LDL-A, at tenth LDL-A, and 1 month after completion of LDL-A treatment. Results: All of the lipid markers were higher in CLI patients, but not significantly different from those in the non-CLI group. They decreased significantly just after LDL-A, although no changes were observed 1 month after completion of LDL-A treatment. ABI was significantly different between the CLI and non-CLI groups, but did not improve by LDL-A treatment. By contrast, SPP was ameliorated significantly and the peak was at tenth LDL-A. Among VascuQOL domains, “Symptom” and “Emotional” domains were significantly different between the CLI and non-CLI groups. The average score of VascuQOL increased successively until 1 month after completion of LDL-A treatment. Conclusions: Several domains of VascuQOL can reflect the severity of PAD in dialysis patients. VascuQOL was a useful marker to show the prolonged therapeutic effects of LDL-A treatment in dialysis patients with PAD, independent of SPP

Inverse electron demand asymmetric cycloadditions of cyclic carbonyl ylides catalyzed by chiral Lewis acids-Scope and limitations of diazo and olefinic substrates

High enantioselectivities (94–96% ee) were obtained for the inverse electron-demand 1,3-dipolar cycloadditions between cyclohexyl vinyl ether and 2-benzopyrylium-4-olate generated via Rh₂(OAc)₄-catalyzed decomposition of o-methoxycarbonyl-α-diazoacetophenone. The reactions were effectively catalyzed by Eu(OTf)₃, Ho(OTf)₃, or Gd(OTf)₃ complexes (10 mol %) of chiral 2,6-bis[(4S,5S)-4,5-diphenyl-2-oxazolinyl]pyridine. The reactions with the other electron-rich dipolarophiles such as allyl alcohol, 2,3-dihydrofuran, and butyl-tert-butyldimethylsilylketene acetal showed moderate enanantioselectivities (60–73% ee). Good to high enantioselectivities (73–97% ee) were also obtained for the cycloadditions between 3-acyl-2-benzopyrylium-4-olates, generated from methyl 2-(2-diazo-1,3-dioxoalkyl)benzoates and butyl or cyclohexyl vinyl ethers, in the presence of binaphthyldiimine (BINIM)–Ni(II) complexes (10 mol %). Under similar conditions, the reaction between methyl 2-(2-diazo-1,3-dioxohexyl)benzoate and 2,3-dihydrofuran was highly endo-selective, and moderately enantioselective (70% ee). For the BINIM–Ni(II)-catalyzed reactions of cyclohexyl vinyl ether, the use of an epoxyindanone as the 3-acyl-2-benzopyrylium-4-olate precursor revealed that the chiral Lewis acid can function as a catalyst for asymmetric induction. The scope of the cyclic carbonyl ylides was extended to those generated from 1-diazo-2,5-pentanedione derivatives, which were reacted with butyl or TBS vinyl ether and catalyzed using the (4S,5S)-Pybox-4,5-Ph₂–Lu(OTf)₃ complex to give good levels of asymmetric inductions (75–84% ee).ArticleTetrahedron. 66(16):3070-3089 (2010)journal articl

CAUSES OF FUNCTIONAL DECLINE IN ELDERLY HOSPITALIZED PATIENTS RECEIVING EITHER INDIVIDUAL OR EXCLUSIVE REHABILITATION THERAPY: A COHORT STUDY

Background: Recently, exclusive rehabilitation therapy was introduced to prevent functional decline due to hospital-associated deconditioning by managing older inpatients’ activities of daily living in Japan. However, this type of therapy does not provide one-on-one exercises similar to individual rehabilitation therapy. This study aimed to report the present ward conditions and the causes of the functional decline in elderly patients receiving individual or exclusive rehabilitation therapy. Methods: A total of 1,636 inpatients, aged 65 years or older, were included in the study. Barthel Index at admission and discharge was assessed prospectively to analyze functional decline. We further analyzed the causes of functional decline by investigating the inpatient’s medical records. Results: Forty-three inpatients (2.6%) had functional decline during hospitalization. There were no significant differences in age, Barthel Index at the time of admission, and the type of clinical department between inpatients with and without functional decline. The functional decline rate in individual rehabilitation therapy was 8.2%, which was significantly higher compared to exclusive rehabilitation therapy (0.8%). The most common causes of functional decline were a pain, low postoperative physical fitness, malignant neoplasm, and new-onset cerebral stroke. Conclusion: We report the present ward conditions in elderly patients receiving either individual or exclusive rehabilitation therapies. Functional decline was correlated to the inpatients’ disease and conditions. The causes of the functional decline can be classified based on whether rehabilitation was effective or ineffective. If the functional decline was caused by hospital-associated deconditioning, we should address the functional decline by providing appropriate rehabilitation methods

Oxaliplatin for Metastatic Colon Cancer in a Patient with Renal Failure

The efficacy, safety, pharmacokinetics, and dialysability of oxaliplatin were assessed in a hemodialysis patient with recurrent cecal cancer

Carcinosarcoma of the Sigmoid Colon: Report of a Case

Our case was a 65-year-old male, with the chief complaints of diarrhea and abdominal distention. Three years earlier, the patient had undergone transcatheter arterial embolization and radiofrequency treatment based on a diagnosis of hepatocellular carcinoma due to hepatitis B by another doctor. In October 2007, the patient developed diarrhea and increased abdominal distention. In December, CT examination conducted by the previous doctor revealed a 20-cm tumor within the pelvis. The patient was diagnosed with sigmoid colon cancer based on barium enema examination using gastrografin, and was introduced to our hospital for treatment. He was diagnosed with low-differentiated carcinoma by biopsy of the colon during endoscopy and underwent sigmoidectomy based on a diagnosis of sigmoid colon cancer. The tumor had infiltrated the bladder, and a tumorectomy was conducted through partially combined resection. The tumor was a huge lesion occupying the inside of the lumen, and histopathological findings revealed that the tumor, the main part of which lay beneath the mucous membrane, had a transitional image composed of both spindle-shaped atypical cells and sarcomatoid shape. The result of immunostaining was CK7(+), CK20(-), AFP(-), and the patient was diagnosed as having carcinosarcoma of the colon. Carcinosarcoma of the colon is a malignant tumor with poor prognosis, and the mean survival period in past reports was approximately 6 months. The patient was treated with FOLFIRI+Bevacizumab therapy according to chemotherapy for colon cancer, but he was refractory to the therapy

Ultra-High-Resolution Computed Tomography of the Lung: Image Quality of a Prototype Scanner

Purpose: The image noise and image quality of a prototype ultra-high-resolution computed tomography (U-HRCT) scanner was evaluated and compared with those of conventional high-resolution CT (C-HRCT) scanners. Materials and Methods: This study was approved by the institutional review board. A U-HRCT scanner prototype with 0.25 mm × 4 rows and operating at 120 mAs was used. The C-HRCT images were obtained using a 0.5 mm × 16 or 0.5 mm × 64 detector-row CT scanner operating at 150 mAs. Images from both scanners were reconstructed at 0.1-mm intervals; the slice thickness was 0.25 mm for the U-HRCT scanner and 0.5 mm for the C-HRCT scanners. For both scanners, the display field of view was 80 mm. The image noise of each scanner was evaluated using a phantom. U-HRCT and C-HRCT images of 53 images selected from 37 lung nodules were then observed and graded using a 5-point score by 10 board-certified thoracic radiologists. The images were presented to the observers randomly and in a blinded manner. Results: The image noise for U-HRCT (100.87 ± 0.51 Hounsfield units [HU]) was greater than that for C-HRCT (40.41 ± 0.52 HU; P <.0001). The image quality of U-HRCT was graded as superior to that of C-HRCT (P <.0001) for all of the following parameters that were examined: margins of subsolid and solid nodules, edges of solid components and pulmonary ves sels in subsolid nodules, air bronchograms, pleural indentations, margins of pulmonary vessels, edges of bronchi, and interlobar fissures. Conclusion: Despite a larger image noise, the prototype U-HRCT scanner had a significantly better image quality than the C-HRCT scanners

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target