Acute Pancreatitis Secondary to Duodenoduodenal Intussusception in Duodenal Adenoma

Duodenoduodenal intussusception is a rare condition that is in general caused by a tumor. We describe duodenoduodenal intussusception secondary to a tubulovillous adenoma that caused acute pancreatitis in a 31-year-old female. We resected a duodenal tumor from the submucosal layer and then simply closed the duodenal wall. To the best of our knowledge, this is the first description of acute pancreatitis secondary to duodenoduodenal intussusception by tubulovillous adenoma in the second part of the duodenum in an adult

Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites

The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism

Case Report Total Hip Arthroplasty for Rapidly Destructive Coxarthrosis in a Patient with Severe Platelet Deficiency due to Liver Cirrhosis and Immune Thrombocytopenic Purpura

Rapidly destructive coxarthrosis (RDC) causes rapid and extreme destruction of the hip joint, which was reported by Postel and Kerboull. RDC is commonly unilateral and occurs mostly in elderly women. Immune thrombocytopenic purpura (ITP) is characterized by a low platelet count that is the result of both immune-mediated platelet destruction and suppression of platelet production. In patients with ITP undergoing surgery, bleeding associated with a low preoperative platelet count can lead to unsuccessful outcomes. To the best of our knowledge, there has been only one report describing total hip arthroplasty (THA) for patients with ITP and there have been no reports of THA for RDC with a very low platelet count due to liver cirrhosis (LC) and ITP. We report the case of a patient who had right RDC and a very low platelet count due to LC and ITP in whom THA was successfully performed. Furthermore, this case was also unique in that her platelet count increased after THA. THA for right RDC might resolve ITP by relieving inflammation of the right hip since her platelet count recovered after THA

Reconstructive Osteotomy for Ankle Malunion Improves Patient Satisfaction and Function

Treatment of chronic symptoms caused by a malunion is a difficult problem in orthopedic surgery. We encountered a case of ankle malunion at our hospital about 1 year after the first operation. The patient had been unable to walk with weight-bearing but regained the ability to walk after reconstructive osteotomy of the fibula. Functional scores for the foot and ankle were significantly improved after intervention. Reconstructive osteotomy appears to represent a good option for ankle malunion

Osteonecrosis of Femoral Head Occurred after Stent Placement of Femoral Artery

We present a case of osteonecrosis of femoral head (ONFH) that occurred after stent angiography of femoral artery for the treatment of arteriosclerosis obliterans (ASO) of left inferior limb in a 76-year-old woman. No case of late collapse of femoral head as a complication of endovascular procedure such as stent placement has been previously documented. We considered that ONFH occurred after detaining stent at a junction of left deep femoral artery for the treatment of the ischemia of left lateral and medial femoral circumflex artery

A panel of nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants including Omicron

新型コロナウイルスを中和するアルパカ抗体 --オミクロンを含む全ての変異株に有効--. 京都大学プレスリリース. 2022-07-14.We are amid the historic coronavirus infectious disease 2019 (COVID-19) pandemic. Imbalances in the accessibility of vaccines, medicines, and diagnostics among countries, regions, and populations, and those in war crises, have been problematic. Nanobodies are small, stable, customizable, and inexpensive to produce. Herein, we present a panel of nanobodies that can detect the spike proteins of five SARS-CoV-2 variants of concern (VOCs) including Omicron. Here we show via ELISA, lateral flow, kinetic, flow cytometric, microscopy, and Western blotting assays that our nanobodies can quantify the spike variants. This panel of nanobodies broadly neutralizes viral infection caused by pseudotyped and authentic SARS-CoV-2 VOCs. Structural analyses show that the P86 clone targets epitopes that are conserved yet unclassified on the receptor-binding domain (RBD) and contacts the N-terminal domain (NTD). Human antibodies rarely access both regions; consequently, the clone buries hidden crevasses of SARS-CoV-2 spike proteins that go undetected by conventional antibodies

Longitudinal monitoring of KRAS-mutated circulating tumor DNA enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer.

BACKGROUND:Liquid biopsies enable the detection of circulating tumor DNA (ctDNA). However, the clinical significance of KRAS-mutated ctDNA for pancreatic cancer has been inconsistent with respect to its prognostic and predictive potential. METHODS AND FINDINGS:A total of 422 blood samples were collected from 78 patients undergoing treatments for localized and metastatic pancreatic ductal adenocarcinoma. KRAS mutation in tissues and KRAS ctDNA levels in plasma were determined by RASKET and droplet digital polymerase chain reaction. Longitudinal monitoring of KRAS ctDNA was performed to assess its significance for predicting recurrence and prognosis and for evaluating therapeutic responses to chemotherapy compared with carbohydrate antigen 19-9 (CA19-9). In 67 tumor tissues, discrepancies in point mutations of KRAS were rarely observed among individual patients, implying that one targeted point mutation of KRAS can be determined in tumor tissues prior to longitudinal blood monitoring. One-time blood assessment of KRAS-mutated ctDNA before surgery or chemotherapy was not clearly associated with recurrence and prognosis. Sequential blood monitoring was performed in 39 patients who underwent surgery for potentially resectable tumors. Increased CA19-9 levels were significantly associated with recurrence, but not prognosis (P<0.001, P = 1.0, respectively), whereas emergence of KRAS ctDNA was significantly associated with prognosis (P<0.001) regardless of recurrence. Furthermore, in 39 patients who did not undergo surgery, detection of KRAS ctDNA was a predictive factor for prognosis (P = 0.005). Multivariate analysis revealed that detection of KRAS ctDNA was the only independent prognostic factor regardless of tumor resection (hazard ratios = 54.5 for patients who underwent surgery and 10.1 for patients who did not undergo surgery; P<0.001 for both). Patients without emergence of KRAS ctDNA within 1 year after surgery showed significantly better prognosis irrespective of recurrence (P<0.001). No detection or disappearance of KRAS ctDNA within 6 months of treatment was significantly correlated with therapeutic responses to first-line chemotherapy (P<0.001). Changes in KRAS status provided critical information for the prediction of therapeutic responses. CONCLUSIONS:Our study showed for the first time that detection of KRAS ctDNA levels within a short period enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer