Intradomain Allosteric Regulation of Soluble Epoxide Hydrolase by Its Substrates.

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with epoxide hydrolase activity in the C-terminal domain (C-EH) and lipid phosphate phosphatase activity in the N-terminal domain (N-phos). The C-EH hydrolyzes bioactive epoxy fatty acids such as epoxyeicosatrienoic acid (EET). The N-phos hydrolyzes lipid phosphomonesters, including the signaling molecules of lysophosphatidic acid (LPA).

Computational design of serine hydrolases.

Enzymes that proceed through multistep reaction mechanisms often utilize complex, polar active sites positioned with sub-angstrom precision to mediate distinct chemical steps, which makes their de novo construction extremely challenging. We sought to overcome this challenge using the classic catalytic triad and oxyanion hole of serine hydrolases as a model system. We used RFdiffusion to generate proteins housing catalytic sites of increasing complexity and varying geometry, and a newly developed ensemble generation method called ChemNet to assess active site geometry and preorganization at each step of the reaction.

Treatment of Rectovaginal Fistula.

[This corrects the article DOI: 10.23922/jarc.2023-007.

Treatment of Rectovaginal Fistula.

Rectovaginal fistula (RVF) is a challenging complication with unsatisfactory success and a significant burden for the patients. With insufficient clinical data due to the rare entity, the present state of treatments for RVFs was reviewed especially form the point of factors to determine management, classifications, principle of treatment, conservative and surgical treatments with outcomes. Size, fistula localization and etiology, type of fistula; "simple" or "complex," status of anal sphincter complex and surrounding tissue, presence or absence of inflammation, presence of diverting stoma, previous attempted repair and radiation therapy, patient's condition with co-morbidities, and surgeon's experience are important factors to determine the management of RVF.

Significant Acceleration of Regional Brain Aging and Atrophy After Mild Traumatic Brain Injury.

Brain regions' rates of age-related volumetric change after traumatic brain injury (TBI) are unknown. Here, we quantify these rates cross-sectionally in 113 persons with recent mild TBI (mTBI), whom we compare against 3 418 healthy controls (HCs). Regional gray matter (GM) volumes were extracted from magnetic resonance images.

Immunosuppressive therapy before and during pregnancy may improve obstetric outcomes in pregnancy complicated by dermatomyositis with anti-MDA-5 antibody positivity: A case report.

Dermatomyositis (DM) is one of the most common autoimmune rheumatic diseases affecting women of childbearing age. Pregnancy may lead to exacerbation of DM, especially of DM with anti-melanoma differentiation-associated gene (MDA) 5 antibody positivity, leading to a poor obstetric outcome. Here, we report consecutive pregnancies complicated by DM with anti-MDA-5 antibodies.

Acute abdominal disease with nonspecific symptoms in the elderly: A case series.

Acute stomach disease in elderly patients often lacks characteristic clinical manifestations. Presentations may differ from those in younger patients and are often complicated by concomitant diseases, delayed presentation, and misdiagnosis. Incorrect diagnosis and treatment can lead to medical-related death claims.

Morphological and biochemical changes in the pancreas associated with acute systemic hypoxia.

This study aimed to investigate the changes associated with acute systemic hypoxia in the endocrine system, particularly in pancreatic tissues. The investigation was based on macroscopic, pathohistological, biochemical, and molecular biological findings in cell lines and human cadavers. The results showed that cases of death due to asphyxia more frequently showed severe subcapsular/interstitial hemorrhage versus the other causes of death.

Preoperative underweight is associated with adverse postoperative events in patients undergoing microvascular reconstruction surgery for oral and maxillofacial cancer.

We aimed to describe the prevalence of postoperative complications and evaluate its relationship with underweight, obesity, preoperative nutritional status, and systemic inflammation status in patients undergoing microvascular reconstruction for oral and maxillofacial cancer. Patients who were ≥20 years old and underwent microvascular reconstruction surgery between January 2009 to June 2019 were investigated. Patient demographics including body mass index, prognostic nutritional status, and neutrophil-lymphocyte ratio were collected.

Inferior mesenteric artery laceration associated with blunt abdominal trauma with Casper's sign in a physically abused child: An autopsy case and literature review.

There have been few studies of the death of children secondary to child abuse-related abdominal compression, and the detailed pathophysiology of such deaths is therefore unknown. The autopsy findings of a 3-year-old boy who died of hemorrhagic shock due to non-accidental severe blunt abdominal trauma were compared to those of children who died of other non-accidental abdominal injuries. Old and acute subcutaneous hemorrhages, abrasions, and scars were present all over the subject's body.

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation.

We previously showed that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly higher in cases of hypothermia (cold exposure) than other causes of death. This study examined how the human hypothalamic-pituitary-adrenal axis, and specifically cortisol, responds to hypothermia. Human samples: Autopsies on 205 subjects (147 men and 58 women; age 15-98 years, median 60 years) were performed within 3 days of death.

Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers.

Background: The ABCD stratification [(combination of serum pepsinogen (PG) levels and titers of antibody (immunoglobulin G, IgG) against ()] is effective for the classification of individuals at risk of developing gastric cancer (GC). The Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a Cancer/Testis antigen frequently expressed in GC.

Aim: To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.

Prognostic Significance of ZKSCAN3 (ZNF306) Expression in Gastric Carcinoma.

Background/aim: Zinc finger protein ZKSCAN3 (ZNF306) is a promising oncogene candidate in colon, bladder, breast, uterine cervical, and prostate cancers. The present study aimed to investigate ZKSCAN3 protein expression in gastric carcinoma patient tissues and to evaluate oncological outcomes in these patients.

Materials And Methods: ZKSCAN3 was detected using the anti-ZKSCAN3 rabbit polyclonal antibody.

Case Report of an Autopsy of a Child Who Died in a Drum-Type Washing Machine Tub: Pathophysiology Resulting in Death and Assessment of Previous Literature.

The patient was a 5-year-old boy who was found in a state of cardiorespiratory arrest in the tub of a washing machine without water with the door closed. The autopsy findings included severe facial congestion and petechiae of the facial skin and palpebral conjunctiva. Several organs exhibited congestion.

Safety profile and oncological outcomes of gastric gastrointestinal stromal tumors (GISTs) robotic resection: Single center experience.

Background: Although usefulness of robot assisted surgery has been largely reported and accepted, robot assisted gastrointestinal stromal tumor (GIST) treatment is rare. Hence, the aim of this study is to report a single center evaluation on gastric GIST's robotic resection.

Methods: Six patients were analyzed focusing on safe (conversion/complications rate, hospital stay), oncological (margin resection, recurrence rate), and feasible (operative time, technical tip, and tricks) profile of robotic-assisted GIST surgery.

Evaluation of screening for drug use using postmortem prolactin levels in serum and cerebrospinal fluid.

Prolactin (PRL) levels can usually be controlled by PRL-inhibiting psychiatric drugs that include anti-dopamine agents. However, the use of dopamine (DA) antagonists may lead to hyperprolactinemia under certain clinical conditions. The aim of this study was to investigate postmortem PRL levels as potential markers of drug abuse, especially that of DA antagonists, in autopsy cases.

Immunohistochemical detection of respiratory syncytial virus at autopsy.

Background: Respiratory syncytial virus (RSV) infection can be fatal in infants <1 year after birth. Morphological findings associated with infant death, however, are insufficient, and screening procedures are problematic. The aim of the present study was to establish a postmortem diagnosis of RSV pathogenicity.

Postmortem water contents of major organs with regard to the cause of death.

The water contents of individual organs are maintained in a narrow range, but altered in morbidity owing to a disturbance of water equilibrium. The present study investigated the tissue water contents of major organs with regard to the cause of death in serial autopsy cases within 3 days postmortem (n = 329; 223 males, 106 females; age range, 1-100 years). Individual tissue water contents differed markedly across organs, but no significant postmortem or survival-period dependence, gender-related difference, or age dependence was observed.

Evaluation of the distribution of nicotine intravenous injection: an adult autopsy case report with a review of literature.

We reported the first comprehensive autopsy case of death due to intravenous injection of nicotine. We examined the distribution of nicotine in the body tissues and fluid and exposed the pathophysiology of nicotine poisoning. A 19-year-old woman was rushed to the hospital in cardiorespiratory arrest and was confirmed dead upon arrival.

Pathophysiological significance of clock genes BMAL1 and PER2 as erythropoietin-controlling factors in acute blood hemorrhage.

This study aimed to characterize the pathophysiology, including possible correlations, of clock gene expression and erythropoietin (EPO) production in the acute stage of blood hemorrhage. Specimens of human cortical tissues (right and left kidneys) and cardiac blood were collected at autopsy from 52 cases following mortality due to acute-stage blood hemorrhage following sharp instrument injury. BMAL1 and PER2 mRNA levels were determined by reverse transcription-polymerase chain reaction; BMAL1 and PER2 protein levels were assessed using immunohistochemistry; BMAL1 protein levels were quantitatively measured by western blotting; and serum EPO levels were measured by chemiluminescent enzyme immunoassay.

Toxicological and Biochemical Analyses of an Autopsy Case Involving Oral Overdose of Multiple Antidiabetic and Antihypertensive Drugs.

Oral antidiabetics can cause fatal hypoglycemia; although they can be chemically identified and quantified, biochemical investigations are important for assessing the biological consequences of an overdose. Such cases of overdose involving oral antidiabetics may involve other drugs for treating lifestyle-related diseases, particularly antihypertensives. Here, we report a toxicological and biochemical investigation of drugs and biochemical profiles in a fatal overdose involving multiple oral antidiabetics and antihypertensives.

Lymph node metastasis and high serum CEA are important prognostic factors in hormone receptor positive and HER2 negative breast cancer.

In recent years, treatment options for breast cancer have increased, and prognosis has improved since the 1990s. The present study examined the prognosis for recurrence of breast cancer between 2006 and 2009, in comparison with the results of past treatments, and sought to guide future treatment strategies by elucidating present prognostic factors. A total of 662 patients with breast cancer stage 0-III who underwent surgery at Kitasato University Hospital between January 2006 and March 2009 were included.