iPSC screening for drug repurposing identifies anti‐RNA virus agents modulating host cell susceptibility

RNAウイルスの感染を阻害する既存薬の同定 --複数の異なるRNAウイルスに対して宿主細胞の感受性を下げることにより感染を抑制する薬剤--. 京都大学プレスリリース. 2021-04-07.iPS cells in drug screenings for COVID-19. 京都大学プレスリリース. 2021-04-07.Human pathogenic RNA viruses are threats to public health because they are prone to escaping the human immune system through mutations of genomic RNA, thereby causing local outbreaks and global pandemics of emerging or re‐emerging viral diseases. While specific therapeutics and vaccines are being developed, a broad‐spectrum therapeutic agent for RNA viruses would be beneficial for targeting newly emerging and mutated RNA viruses. In this study, we conducted a screen of repurposed drugs using Sendai virus (an RNA virus of the family Paramyxoviridae), with human‐induced pluripotent stem cells (iPSCs) to explore existing drugs that may present anti‐RNA viral activity. Selected hit compounds were evaluated for their efficacy against two important human pathogens: Ebola virus (EBOV) using Huh7 cells and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) using Vero E6 cells. Selective estrogen receptor modulators (SERMs), including raloxifene, exhibited antiviral activities against EBOV and SARS‐CoV‐2. Pioglitazone, a PPARγ agonist, also exhibited antiviral activities against SARS‐CoV‐2, and both raloxifene and pioglitazone presented a synergistic antiviral effect. Finally, we demonstrated that SERMs blocked entry steps of SARS‐CoV‐2 into host cells. These findings suggest that the identified FDA‐approved drugs can modulate host cell susceptibility against RNA viruses

A Case Report of Matrix-Producing Carcinoma of the Breast during Lactation : A secondary publication

Matrix-producing carcinoma (MPC) of the breast is relatively rare. We report on a case of MPC of the breast during lactation. A female in her 30s noticed a lump in the upper inner and outer quadrants of her left breast 9 months into her pregnancy. She came hospital at one month after delivery. Ultrasonography revealed a hypoechoic tumor with an unclear border region. An MRI revealed a breast tumor approximately 19 mm in size, with dynamic studies demonstrating early contrast and ring enhancement. A core needle biopsy was performed, resulting in an histopathological diagnosis of invasive carcinoma ［Estrogen receptor-, Progesterone receptor-, Human epidermal growth factor receptor 2(HER2)-; stage I, T1cN0M0］. Breast-conserving surgery and a sentinel lymph node biopsy (SLNB) were performed. The SLNB was negative for cancer. Chemotherapy (FEC100, DTX75) and radiotherapy were performed as adjuvant therapies. Seventeen months after surgery, the patient is recurrence-free

A retrospective analysis of antimicrobial resistance in pathogenic Escherichia coli and Salmonella spp. isolates from poultry in Uganda

There are increasing reports of antimicrobial treatment failures for bacterial diseases of poultry in Uganda. The paucity of data on antimicrobial resistance (AMR) of pathogenic bacteria in Uganda is a major setback to AMR control. This study investigated the occurrence of fowl typhoid, colibacillosis, and AMR in associated pathogens from 2012 to 2018. Laboratory records from the Central Diagnostic Laboratory (CDL), a National Veterinary Diagnostic Facility located at Makerere University, were reviewed. Archived isolates of the causative bacteria for the two diseases were also evaluated for AMR. The frequencies of the two disease conditions, their clinical and necropsy presentations and the demographic data of the diagnostic samples were summarized from the records. Archived bacterial isolates were revived before antimicrobial susceptibility testing. This was done on Mueller Hinton agar using the disk diffusion method, against 16 antimicrobials of medical and veterinary importance according to the Clinical Laboratory Standards Institute guidelines. A total of 697 poultry cases were presented for bacteriological investigations in the review period. Colibacillosis and salmonellosis had prevalence rates of 39.7% (277/697) and 16.2% (113/697), respectively. A total of 63 and 92 isolates of Escherichia coli and Salmonella spp., respectively, were archived but 43 (68.3%) E. coli and 47 (51.1%) Salmonella spp. isolates were recovered and evaluated for AMR. Multidrug resistance was more frequent in E. coli (38; 88.4%) than salmonellae (25; 53.2%), (p < 0.001). The high prevalence of colibacillosis, salmonellosis and the AMR of associated pathogens warrants immediate institution of appropriate disease control measures

Skin Tube Reconstruction for Esophageal Defects due to Postoperative Complications: Applying a skin flap in esophageal resection and reconstruction

Numerous improvements and advances in operational methods and techniques have occurred in the area of reconstruction for esophageal cancer. Patients with thoracic esophageal cancer who have previously had a gastrectomy usually undergo reconstruction using the colon and small intestine. The incidence of organ necrosis is not necessarily low after reconstruction with those organs. Generally, the main types of skin flaps and musculocutaneous flaps used for cervical and other esophageal reconstructions are deltopectoral (DP) flaps, pedicled musculocutaneous latissimus dorsi flaps and free anteriolateral thigh flaps. This kind of reconstruction is low invasive, relatively simple, and also causes very few fatal post-operative complications. Therefore, it is considered to be an effective reconstruction choice for the following types of patients: poor risk patients, patients whose gastrointestinal (GI) tract cannot be used for their reconstruction for some reason, and patients having a second reconstruction due to complications caused by organ necrosis after their first GI tract reconstruction

A Case of Cholesterol Crystal Embolization with Hemorrhagic Intestinal Ulcer

Cholesterol crystal embolization (CCE) is a rare systemic embolism caused　by formation of cholesterol crystals from atherosclerotic plaques. CCE usually occurs during　vascular manipulation such as vascular surgery or endovascular catheter manipulation, or　due to anticoagulation or thrombolytic therapy. We report a rare case of localized intestinal　ulcer with active hemorrhage caused by spontaneous CCE. An 83-year-old man with a history　of hypertension and diabetes was treated with a percutaneous coronary intervention (PCI)　for myocardial infarction. Melena occurred eight days after PCI. An abdominal computed　tomography revealed small intestinal ulcer, extravasation of the gastrointestinal tract and　bleeding in the abdominal cavity. The patient was diagnosed as bleeding from the small　intestinal ulcer, so an emergency laparotomy was performed. Partial resection of the small　intestine was performed. A histopathological examination indicated that small intestine　obstruction was caused by CCE. A histopathological examination indicated that small intestinal　obstruction was caused by CCE. Therefore, in cases of intestinal obstruction after vascular　manipulation, CCE should also be considered

Evaluation of intra-ductal cancer spread using contrast superb micro-vascular imaging (SMI) : a case report

Currently, breast conserving surgery has been adopted to treat more than half of all breast cancer patients in Japan. When performing breast-conserving surgery, an appropriate margin needs to be determined for radical cure. The resection volume influences the esthetic outcome, but a cancer-positive resection stump is also important risk factor of local recurrence. Additionally, the degree of cancer progression influences the surgical method, so understanding the appropriate resection margin is necessary for the surgeons. We report here on a 50- year old patient whose intra-ductal cancer progression was shown, as predicted, by contrast SMI (superb micro-vascular imaging). A one-cm size tumor mass was palpable with a clear boundary. B-mode ultrasound confirmed the presence of a breast duct towards the nipple from the tumor mass. Using contrast SMI, an accelerated blood flow was detected around the duct, which suggested intra-ductal progression. The pathological results also showed intra-ductal progression to the nipple from the tumor. Around the progression area, a meandering vessel was found and the vessel was able to be visualized by contrast SMI

Degos 病の関与が疑われた腸管気腫症の一例

症例は70歳代男性．既往に脳梗塞，パーキンソン病があり抗凝固薬を内服していた．デイサービス利用中に倦怠感および血圧低下を認め近医を受診し入院加療となった．入院２日目に40℃の熱発があり，腹部造影CT を施行したところfree air を認め外科的治療目的に当院へ救急搬送された．造影CT では肝彎曲部から脾彎曲部にかけての横行結腸に腸間膜気腫および腸管壁内ガスを認めた．明らかな腸間膜虚血および壊死を示唆する所見はなかった．消化管穿孔または腸管気腫症が考えられ緊急手術が検討されたが，腹部症状に乏しく液体成分など腸管内容の流出を示唆する所見がないことから一旦保存的加療を行った．また，体幹部を中心に小豆大までの皮膚潰瘍が多発していた．皮膚病理所見，既往および今回の病態からDegos 病と診断された．入院６日目に注腸造影および腹部CT を施行したところ，free air はほぼ消失しており，造影剤の腸管外漏出は認めず８日目に退院となった．Degos 病は皮膚の萎縮性丘疹を呈し，消化管の多発性潰瘍や穿孔，中枢神経系の出血や梗塞を特徴とし，病態としては末梢の血栓性血管炎が主体と考えられている．今回我々は，Degos病の関連が疑われた腸管気腫症の一例を経験したので文献的考察を加えて報告する．The patient was a 70 year-old-male. His past medical history was significant for cerebral infarction and Parkinson’s disease. He presented with malaise and hypotension and had been admitted to a local hospital three days ago. After admission，he had a fever of 40℃ and a computed tomography (CT) showed free air in the upper abdomen，he was referred to our hospital for an operation. A contrast-enhanced computed tomography also showed free air and pneumatosis intestinalis in transverse colon, with no evidence of mesenteric ischemia such as superior mesenteric artery occlusion (SMA) or non-occulusive mesenteric ischemia. Due to no abdominal pain and intraperitoneal fluid, we assessed that pneumatosis cystoides intestinalis was more probable than intestinal perforation. It was observed that the patient had many skin ulcers the size of red beans which were located around the chest and abdomen. A skin biopsy was performed，indicating Degos’ disease by a pathological exam. On day 6 of admission，we performed a barium enema exam and plain abdomen computed tomography (CT), it was seen that the free air almost disappeared and there was no leakage of the contrast medium. He was discharged on day 8. Patients with Degos’ disease present atrophic papula with perforation of intestinal or cerebral vascular accidents such as hemorrhage or infarction. This is considered a cause for bythrombotic angiitis of the peripheral vessels. We present a report with reference to the relevant literature

Vacuum-assisted biopsy and steroid therapy for granulomatous lobular mastitis: report of three cases.

We report the cases of three patients with granulomatous lobular mastitis (GLM), who were treated successfully with low-dose steroid therapy. Furthermore, the findings of our review of 271 patients reported in the literature suggest that steroid therapy is the treatment of choice for GLM

The significance of a screening test for anemia in the elderly in the health check-up

本研究は, 地域で生活する高齢者の健康診査での貧血検査の必要性と高齢者の貧血の判断基準について検討を行った. 対象は老人保健法に基づく基本健康診査を受診した40歳以上男性362名, 女性621名である. 貧血検査の結果より, 造血機能は男女とも70歳代以降から有意に低下し, また加齢にともない個人差が大きくなっていた. 貧血は高齢者の活動性を維持した社会生活を送るための指標として重要な項目である. 貧血症状を鑑別しにくい高齢者にとっては血液学的検査が有効であり, 健康診査で高齢者に貧血検査を実施することは, 二次性の貧血の早期発見に加え, 加齢による経年的変化をふまえ個々にあった生活指導に活用することができ, 意義が大きいと考える. また, 地方の一地域で生活する住民を対象とした貧血検査から得られた結果ではあるが, 65歳以上の高齢者の貧血のスクリーニングの基準値の一例として, 性別のヘモグロビン濃度の(平均値-標準偏差)を正常範囲最小値とし, 男性13.1g/dl, 女性11.8g/dlを提案したい.The purpose of this study is to grasp the actual conditions of anemia in the elderly who live in the community, to examine the criteria for anemia in the elderly as a screening level in the health check-up, and to discuss the necessity of anemia screening in the elderly. The research subjects were 362 men and 621 women over 40 years of age, who took the annual health check-up prescribed in the law for welfare of the elderly. As the criteria for anemia, it is proposed that the reference values for hemoglobin should be 13.1 g/dl for men and 11.8 g/dl for women, according to the average values of hemoglobin for persons over 65 years of age with their standard deviations (14.4 ± 1.27 g/dl for men, 13.1 ± 1.23 g/dl for women). The early detection of anemia in the elderly is crucial, because the main cause of secondary anemia in the elderly is the bleeding in the gastrointestinal organs. However, it is difficult for the elderly to detect their own anemic condition, by either subjective symptoms or inspection. Blood testing is an effective means of screening anemia, and it is recommended that an anemia inspection is carried out every year in the annual health check-up