Differential Diagnosis of an Elderly Manic-Depressive Patient with Depersonalization and Other Symptoms

The case study of an elderly man having persecutory delusions and bizarre complaints at the first psychiatric interview is reported. The patient complained: “I have no sense of time” and “I have no sense of money.” He refused nursing care. He had delusions centered on himself including that of his own death, which were difficult to diagnose but suggested the possibility of Cotard’s syndrome. We assumed that the man was depressed and treated him for depression. However, as a result of this treatment he became temporarily manic but finally recovered completely. After his recovery, we learnt the patient’s past history of hospitalization for psychiatric problems, and based on that history he was diagnosed as suffering from a bipolar I disorder. The lack of typical symptoms of depression and the remarkable depersonalization and derealization in this patient made it difficult to infer a depressive state. Nevertheless, being attentive to his strange feelings related to the flow of time would have helped us to make an accurate diagnosis earlier

Medical Treatment of Echinococcus multilocularis and New Horizons for Drug Discovery: Characterization of Mitochondrial Complex II as a Potential Drug Target

As an efficient drug for alveolar echinococcosis (AE) is still not available, new chemotherapy targets are necessary. The mitochondrial respiratory chain may be a good drug candidate because parasite respiratory chains are quite different from those of mammalian hosts. For example, Ascaris suum possesses an NADH‐fumarate reductase system (fumarate respiration) that is highly adapted to anaerobic environments such as the small intestine. It is composed of mitochondrial complex I (NADH‐ubiquinone reductase), complex II (succinate‐ubiquinone reductase), and rhodoquinone. We previously demonstrated that fumarate respiration is also essential in E. multilocularis. Quinazoline, a complex I inhibitor, inhibited growth of E. multilocularis larvae in vitro. These results indicate that fumarate respiration could be a target for E. multilocularis therapy. In the current chapter, we focused on complex II, which is another component of this system, because quinazoline exhibited strong toxicity to mammalian mitochondria. We evaluated the molecular and biochemical characterization of E. multilocularis complex II as a potential drug target. In addition, we found that ascofuranone, a trypanosome cyanide‐insensitive alternative oxidase inhibitor, inhibited E. multilocularis complex II at the nanomolar order. Our findings demonstrate the potential development of targeted therapy against Echinococcus complex II

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

Strangulated transmesosigmoid hernia as a late complication of a fall from a height: A case report

Introduction: A transmesosigmoid hernia is defined as small bowel herniation through a complete defect involving both layers of the sigmoid mesentery. Blunt trauma injury to the sigmoid mesocolon has been reported only rarely. We herein report a case of a strangulated transmesosigmoid hernia associated with a history of a fall from a height. Presentation of case: A 43-year-old woman presented to our hospital for evaluation of vomiting. She had no history of abdominal surgery but had sustained a complete spinal cord injury and pelvic fracture secondary to a fall from a height 25 years earlier. A computed tomography scan of her abdomen and pelvis demonstrated a closed loop of small bowel in the pelvis, with a zone of transition in the left lower abdomen. Although the cause of the obstruction was difficult to establish, ischemia was strongly suspected; therefore, the decision was made to perform emergency exploratory laparoscopy. During laparoscopy, a loop of ileum was observed to have herniated through a full-thickness defect in the sigmoid mesocolon, consistent with a transmesosigmoid hernia. The herniated loop was strangulated but not gangrenous and was successfully reduced using laparoscopic graspers. The incarcerated small bowel appeared viable and was therefore not resected. The defect was closed with a running suture. The patient had an uneventful postoperative course with no recurrence. Discussion and conclusion: Abdominal blunt trauma can cause sigmoid mesenteric rupture resulting in a transmesosigmoid hernia. In the management of transmesosigmoid hernias, laparoscopic herniorrhaphy has the advantage of facilitating simultaneous diagnosis and surgical intervention

Metachronous rectal metastasis from primary transverse colon cancer: a case report

Abstract Background Colorectal metastases from primary colorectal cancers are very rare, and little is known about their epidemiological aspects or the best diagnostic and therapeutic strategies. Herein, we report a case of a 65-year-old woman with suspected metachronous metastasis to the rectum from primary transverse colon cancer. Case presentation The patient underwent a laparoscopic extended right hemicolectomy for primary transverse colon cancer. Histopathological examination showed moderately differentiated adenocarcinoma, and the tumor was diagnosed as stage IIA (T3, N0, M0). Fifteen months after her colectomy, a computed tomography scan demonstrated a rectal tumor and a right ovarian tumor. Colonoscopy revealed a superficial elevated lesion in the middle rectum, and histological analysis showed moderately differentiated adenocarcinoma. Laparoscopic low anterior resection preserving the left colic artery and bilateral adnexectomy were performed. Histological examination of the rectal tumor showed that adenocarcinoma was mainly present in the submucosa and muscularis propria, while the carcinoma-involved region of the mucosal layer had mucosal colonization representing the spread of metastatic tumor cells along the basement membrane of preexisting crypts and/or villi. The right ovarian tumor proved to be moderately differentiated adenocarcinoma that was positive for cytokeratin 20 and negative for cytokeratin 7 staining, indicating metastasis from the colorectal cancer. The rectal and ovarian tumors were similar to transverse colon cancer in architectural and cytological atypia. Both adenocarcinomas of the transverse colon and rectum were negative for p53 in immunohistochemical staining and RAS wild type in genetic assessment. These findings support a possible diagnosis of rectal and ovarian metastasis from the primary transverse colon cancer. The patient recovered well after surgery, and neither relapse nor metastasis was observed 18 months after surgery. Conclusion Distinguishing primary from metastatic colorectal cancer can be challenging, but a comprehensive evaluation of histological features, clinical history, and tumor distribution can enable making a correct diagnosis and implementing optimal treatment