Subcutaneous endoscopically assisted ligation using miniport for the treatment of girls with inguinal hernia

Background This report describes the first miniport method using  subcutaneous endoscopically assisted ligation (SEAL) for the treatment of girls with inguinal hernia. To validate its safety and efficacy, the  authors evaluated their early experiences.Methods Between April 2014 and December 2014, 19 SEALs using miniport were performed on 14 patients at the Fukaya Red-Cross Hospital, Saitama, Japan. Their mean age was 6 years (range, 11–128 months). This technique was performed using two ports (a 5mm port placed using the open technique and an additional 2mm miniport). A 5mm laparoscope was inserted via the umbilicus. The miniport was introduced percutaneously in the inguinal region under laparoscopic guidance and manipulated around the medial or lateral   hemicircumference of the internal ring extraperitoneally to place a purse-string around the internal ring. The hernia sac and patent processus vaginalis were closed at the level of the internal inguinal ring   extraperitoneally with circuit suturing using the 2mm miniport. Only the umbilical fascia was closed with an absorbable suture. No skin sutures were applied. We collected data regarding operative time, complications,and recurrence. Results The mean operative time was 20 ±6 min (unilateral, n =9) or 42± 8 min (bilateral, n= 5). The mean follow-up period was 12.8 ± 2.5 (range, 9–19) months. No intraoperative complications associated with theprocedure occurred and no hernial recurrences have been identified so far.Conclusion SEAL using miniport proved to be a successful operative procedure compared with other  laparoscopic percutaneous extraperitoneal closure procedures and produced excellent cosmetic results. SEAL using miniport for the treatment of girls with inguinal hernias appears to be safe, effective, and reliable.Keywords: inguinal hernia, miniport, SEA

Molecular imaging analysis of microvesicular and macrovesicular lipid droplets in non‑alcoholic fatty liver disease by Raman microscopy

Predominant evidence of non-alcoholic fatty liver disease (NAFLD) is the accumulation of excess lipids in the liver. A small group with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH). However, there is a lack of investigation of the accumulated lipids with spatial and molecular information. Raman microscopy has the potential to characterise molecular species and structures of lipids based on molecular vibration and can achieve high spatial resolution at the organelle level. In this study, we aim to demonstrate the feasibility of Raman microscopy for the investigation of NAFLD based on the molecular features of accumulated lipids. By applying the Raman microscopy to the liver of the NASH model mice, we succeeded in visualising the distribution of lipid droplets (LDs) in hepatocytes. The detailed analysis of Raman spectra revealed the difference of molecular structural features of the LDs, such as the degree of saturation of lipids in the LDs. We also found that the inhomogeneous distribution of cholesterol in the LDs depending on the histology of lipid accumulation. We visualised and characterised the lipids of NASH model mice by Raman microscopy at organelle level. Our findings demonstrated that the Raman imaging analysis was feasible to characterise the NAFLD in terms of the molecular species and structures of lipids

The Influence of Chronic Cerebral Hypoperfusion on Cognitive Function and Amyloid β Metabolism in APP Overexpressing Mice

Cognitive impairment resulting from cerebrovascular insufficiency has been termed vascular cognitive impairment, and is generally accepted to be distinct from Alzheimer's disease resulting from a neurodegenerative process. However, it is clear that this simple dichotomy may need revision in light of the apparent occurrence of several shared features between Alzheimer's disease and vascular cognitive impairment. Nevertheless, it still remains largely unknown whether the burden of vascular- and Alzheimer-type neuropathology are independent or interdependent. Therefore, we investigated whether chronic cerebral hypoperfusion influences cognitive ability or amyloid β deposition in amyloid precursor protein (APP) overexpressing transgenic mice

Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid

The predominant action of cilostazol on Aβ metabolism is likely to facilitate Aβ clearance due to the sustained cerebrovascular function in vivo. Our findings mechanistically demonstrate that cilostazol is a promising therapeutic approach for AD and CAA

Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts

Cortical microinfarcts (CMIs) observed in brains of patients with Alzheimer’s disease tend to be located close to vessels afflicted with cerebral amyloid angiopathy (CAA). CMIs in Alzheimer’s disease are preferentially distributed in the arterial borderzone, an area most vulnerable to hypoperfusion. However, the causal association between CAA and CMIs remains to be elucidated. This study consists of two parts: (1) an observational study using postmortem human brains (n = 31) to determine the association between CAA and CMIs, and (2) an experimental study to determine whether hypoperfusion worsens CAA and induces CMIs in a CAA mouse model. In postmortem human brains, the density of CMIs was 0.113/cm2 in mild, 0.584/cm2 in moderate, and 4.370/cm2 in severe CAA groups with a positive linear correlation (r = 0.6736, p < 0.0001). Multivariate analysis revealed that, among seven variables (age, disease, senile plaques, neurofibrillary tangles, CAA, atherosclerosis and white matter damage), only the severity of CAA was a significant multivariate predictor of CMIs (p = 0.0022). Consistent with the data from human brains, CAA model mice following chronic cerebral hypoperfusion due to bilateral common carotid artery stenosis induced with 0.18-mm diameter microcoils showed accelerated deposition of leptomeningeal amyloid β (Aβ) with a subset of them developing microinfarcts. In contrast, the CAA mice without hypoperfusion exhibited very few leptomeningeal Aβ depositions and no microinfarcts by 32 weeks of age. Following 12 weeks of hypoperfusion, cerebral blood flow decreased by 26% in CAA mice and by 15% in wild-type mice, suggesting impaired microvascular function due to perivascular Aβ accumulation after hypoperfusion. Our results suggest that cerebral hypoperfusion accelerates CAA, and thus promotes CMIs

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

Influence of Ambient Temperature on Autonomic Nerve Function and Peripheral Sensation from Moderate-Intensity Treadmill Exercise

International Journal of Exercise Science 17(2): 491-503, 2024. Objective: The main objective was to ascertain the acute responses in autonomic nervous activity and peripheral sensation induced by moderate-intensity treadmill exercise performed under different ambient temperatures. Methods: Twelve young healthy subjects underwent three sessions of moderate-intensity treadmill exercise (warming, 5 min and running, 25 min), on different days under 10°C, 20°C and 30°C room temperatures. Pre- and post-intervention, heart rate variability (HRV) and plantar vibrotactile perception threshold (VPT) were measured. Additionally, rate of perceived exertion (RPE) was recorded after intervention. Results: In comparison with the corresponding baseline values, after intervention, low frequency power (LF) and LF/high frequency power (HF) of HRV increased significantly and HF decreased significantly under the condition of 10°C only (p \u3c .005). Following intervention, VPT increased significantly at the hallux for 31.5 Hz test frequency under 30°C and at the heel for 31.5 Hz test frequency under 10°C (both p \u3c .05). In contrast, VPT decreased significantly at the hallux for 125 Hz test frequency under 10°C (p \u3c .005). Exposure under the temperature of 20°C did not result in any significant change in VPT. After intervention, RPE under 30°C showed significantly higher values than those under 20°C (p \u3c .01) and 10°C (p \u3c .005) conditions with no difference between the latter two conditions. Conclusions: Treadmill exercise under 20°C ambient temperature did not exert any negative impacts on autonomic and peripheral nerve function and resulted in a perceived exertion of moderate intensity among the study participants. Therefore, an ambient temperature around 20°C might be recommended for the mentioned purpose