[A CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS WITH RHINOSINUSITIS CONTROLLED WITH ENDOSCOPIC SINUS SURGERY].

Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease with marked elevation of blood eosinophil associated with various symptoms in the respiratory tract, gastrointestinal tract, peripheral nerves, and skin due to systemic vasculitis. Here, we report a case of EGPA in which rhinosinusitis was treated with endoscopic sinus surgery (ESS) with good results. A 49-year-old man who developed bronchial asthma at age 48 was diagnosed with EGPA in our hospital.

First-in-human study evaluating safety, pharmacokinetics, and pharmacodynamics of lorundrostat, a novel and highly selective aldosterone synthase inhibitor.

Dysregulation of the mineralocorticoid hormone aldosterone is an increasingly prevalent cause of hypertension. Aldosterone synthase (CYP11B2) shares 93% homology to 11β-hydroxylase (CYP11B1), which produces cortisol. Lorundrostat, a highly selective inhibitor of CYP11B2, is a potential safe and effective treatment for aldosterone-dependent, uncontrolled hypertension, including treatment-resistant hypertension.

Absorption, metabolism, and excretion of [ C]dersimelagon, an investigational oral selective melanocortin 1 receptor agonist, in preclinical species and healthy volunteers.

Dersimelagon (formerly MT-7117) is a novel, orally administered nonpeptide small molecule selective agonist for melanocortin 1 receptor currently being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis (dcSSc). Findings of studies evaluating the absorption, distribution, metabolism, and excretion (ADME) of dersimelagon following a single dose of [ C]dersimelagon in healthy adult volunteers (N = 6) who participated in phase 1, single-center, open-label, mass balance study (NCT03503266), and in preclinical animal models are presented. Rapid absorption and elimination were observed following oral administration of [ C]dersimelagon in clinical and nonclinical studies, with a mean T of 30 min in rats and 1.

Results from a first-in-human study of dersimelagon, an investigational oral selective MC1R agonist.

Purpose: To describe outcomes from the first-in-human study of dersimelagon, an investigational oral selective MC1R agonist, under development for the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP).

Methods: In this double-blind, placebo-controlled phase 1 study, the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of dersimelagon in healthy participants were evaluated.

Results: Dersimelagon was generally well tolerated in healthy participants, with the most common TEAEs being lentigo (52.

The Oral Bioavailability and Effect of Various Gastric Conditions on the Pharmacokinetics of Dersimelagon in Healthy Adult Volunteers.

Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis. In this open-label, multicenter, randomized, two-cohort, sequential crossover study, the relative oral bioavailability of two tablet formulations of dersimelagon was evaluated, and the effect of various gastric conditions (from a high-fat meal, a proton-pump inhibitor, and an acidic carbonated beverage) on the pharmacokinetics of dersimelagon were assessed in healthy participants (N = 50). Both tablet formulations demonstrated rapid absorption, and the 100-mg tablets showed a 97% relative oral bioavailability versus 50-mg tablets.

Development of a Machine Learning Model to Predict Cardiac Arrest during Transport of Trauma Patients.

Background: Trauma is a serious medical and economic burden worldwide, and patients with traumatic injuries have a poor survival rate after cardiac arrest. The authors developed a prediction model specific to prehospital trauma care and used machine learning techniques to increase its accuracy.

Methods: This retrospective observational study analyzed data from patients with blunt trauma injuries due to traffic accidents and falls from January 1, 2018, to December 31, 2019.

Machine learning for predicting successful extubation in patients receiving mechanical ventilation.

Ventilator liberation is one of the most critical decisions in the intensive care unit; however, prediction of extubation failure is difficult, and the proportion thereof remains high. Machine learning can potentially provide a breakthrough in the prediction of extubation success. A total of seven studies on the prediction of extubation success using machine learning have been published.

Wearing a face mask during controlled-intensity exercise is not a risk factor for exertional heatstroke: A pilot study.

Aim: This study aimed to measure the influence of wearing face masks on individuals' physical status in a hot and humid environment.

Methods: Each participant experienced different physical situations: (i) not wearing a mask (control), (ii) wearing a surgical mask, (iii) wearing a sport mask. An ingestible capsule thermometer was used to measure internal core body temperature during different exercises (standing, walking, and running, each for 20 min) in an artificial weather room with the internal wet-bulb globe temperature set at 28°C.

Machine Learning Prediction for Supplemental Oxygen Requirement in Patients with COVID-19.

Background: The coronavirus disease (COVID-19) poses an urgent threat to global public health and is characterized by rapid disease progression even in mild cases. In this study, we investigated whether machine learning can be used to predict which patients will have a deteriorated condition and require oxygenation in asymptomatic or mild cases of COVID-19.

Methods: This single-center, retrospective, observational study included COVID-19 patients admitted to the hospital from February 1, 2020, to May 31, 2020, and who were either asymptomatic or presented with mild symptoms and did not require oxygen support on admission.

Indicators of Acute Kidney Injury as Biomarkers to Differentiate Heatstroke from Coronavirus Disease 2019: A Retrospective Multicenter Analysis.

Background: Coronavirus disease 2019 (COVID-19) and heat-related illness are systemic febrile diseases. These illnesses must be differentiated during a COVID-19 pandemic in summer. However, no studies have compared and distinguished heat-related illness and COVID-19.

Frontline Science: Conversion of neutrophils into atypical Ly6G SiglecF immune cells with neurosupportive potential in olfactory neuroepithelium.

Neutrophils are generally considered as short-lived, homogenous, and terminally differentiated phagocytes that play crucial roles in conquering infection, although they occasionally cause severe collateral tissue damage or chronic inflammation. Recent reports have indicated that neutrophils also play a protective role in inflammation resolution and tissue repair. However, how terminally differentiated neutrophils have diverse functions remains unclear.

Relationship Between Pain Reduction and Improvement in Health-Related Quality of Life in Patients with Knee Pain Due to Osteoarthritis Receiving Duloxetine: Exploratory Post Hoc Analysis of a Japanese Phase 3 Randomized Study.

Purpose: This post hoc analysis of a Japanese phase 3 randomized study (ClinicalTrials.gov identifier: NCT02248480) investigated relationships between changes in pain severity and changes in health-related quality of life (HRQoL) in duloxetine-treated patients with knee osteoarthritis (OA).

Patients And Methods: Patients with knee OA and Brief Pain Inventory (BPI) average pain score ≥4 received duloxetine 60 mg/day or placebo for 14 weeks.

Duloxetine 60 mg for chronic low back pain: post hoc responder analysis of double-blind, placebo-controlled trials.

Introduction: Duloxetine has demonstrated efficacy in chronic low back pain (CLBP). We examined the predictors of response to duloxetine for CLBP.

Patients And Methods: This was a post hoc analysis of pooled data from 4 double-blind, ran-domized, placebo-controlled trials of duloxetine (60 mg/day for 12-14 weeks) in adult patients with CLBP.

The relationship between pain severity and patient-reported outcomes among patients with chronic low back pain in Japan.

Objective: The aim of this study was to quantify the impact of pain severity on patient-reported outcomes among individuals diagnosed with chronic low back pain in Japan.

Methods: Data were provided by the 2012 Japan National Health and Wellness Survey (N=29,997), a web-based survey of individuals in Japan aged ≥18 years. This analysis included respondents diagnosed with low back pain of ≥3-month duration.

Correlation between pain response and improvements in patient-reported outcomes and health-related quality of life in duloxetine-treated patients with diabetic peripheral neuropathic pain.

Objective: We assessed whether quality of life (QoL) improvement in duloxetine-treated patients with diabetic peripheral neuropathic pain (DPNP) correlates with the extent of pain relief.

Methods: Pooled data from three multicountry, double-blind, 12-week, placebo-controlled trials of duloxetine-treated (duloxetine 60 mg once daily; total number =335) patients with DPNP were analyzed. Based on improvement in 24-hour average pain scores, patients were stratified into four groups.

Bilateral cervical fistulas from heterotopic salivary gland tissues.

A 24-year-old male was referred to our department with intermittent clear drainage in both sides of the middle neck that did not increase while eating. On physical examination, there were fistulas in both sides of the neck, anterior to the sternocleidomastoid muscles. Fistulography revealed a 9-mm-long sinus from the left fistula, extending in the medial-caudal direction.

Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a major cause of cancer-related death. Since significant upregulation of αvβ6 integrin has been reported in PDAC, this integrin is a promising target for PDAC detection. In this study, we aimed to develop a radioiodinated probe for the imaging of αvβ6 integrin-positive PDAC with single-photon emission computed tomography (SPECT).

Development of an oxygen-sensitive degradable peptide probe for the imaging of hypoxia-inducible factor-1-active regions in tumors.

Purpose: We aimed to develop a radiolabeled peptide probe for the imaging of hypoxia-inducible factor-1 (HIF-1)-active tumors.

Procedures: We synthesized the peptide probes that contain or lack an essential sequence of the oxygen-dependent degradation of HIF-1α in proteasomes ((123/125)I-DKOP30 or (125)I-mDKOP, respectively). The degradation of probes was evaluated in vitro using cell lysates containing proteasomes.

Evaluation of [125I]IPOS as a molecular imaging probe for hypoxia-inducible factor-1-active regions in a tumor: comparison among single-photon emission computed tomography/X-ray computed tomography imaging, autoradiography, and immunohistochemistry.

To image hypoxia-inducible factor-1 (HIF-1)-active tumors, we previously developed a chimeric protein probe ([(123/125) I]IPOS) that is degraded in the same manner as HIF-1α under normoxic conditions. In the present study, we aim to show that the accumulation of radioiodinated POS reflects the expression of HIF-1. In vivo single-photon emission computed tomography (SPECT)/X-ray CT (CT) imaging, autoradiography, and double-fluorescent immunostaining for HIF-1α and pimonidazole (PIMO) were carried out 24 h after the injection of [(125) I]IPOS.

Craniofacial and dental characteristics of Goldenhar syndrome: a report of two cases.

We describe the dental and craniofacial anomalies of 2 ethnically distinct patients with Goldenhar syndrome, which is characterized by hemifacial microsomia, facial asymmetry, and ear and dental abnormalities. A 7-year-old Japanese girl and 12-year-old Turkish boy with Goldenhar syndrome were examined clinically and radiographically; both had symptoms of hemifacial microsomia. Multiple organ involvement can limit surgical correction of deformities and affect patient management.

Distinct effects of folate and choline deficiency on plasma kinetics of methionine and homocysteine in rats.

Both folate and betaine, a choline metabolite, play essential roles in the remethylation of homocysteine to methionine. We have studied the effects of folate and choline deficiency on the plasma kinetics of methionine, especially remethylation of homocysteine to methionine, by means of stable isotope methodology. After a bolus intravenous administration of [(2)H(7)]methionine (5 mg/kg body weight) into the rats fed with folate-, choline-, folate + choline-deficient or control diets, the plasma concentrations of [(2)H(7)]methionine, demethylated [(2)H(4)]homocysteine, and remethylated [(2)H(4)]methionine were determined simultaneously with endogenous methionine and homocysteine by gas chromatography-mass spectrometry-selected ion monitoring.

Phytotoxic components produced by pathogenic Fusarium against morning glory.

A pathogenic isolate of Fusarium, F. oxysporum f. sp.

Morning glory systemically accumulates scopoletin and scopolin after interaction with Fusarium oxysporum.

An isolate of non-pathogenic Fusarium, Fusarium oxysporum 101-2 (NPF), induces resistance in the cuttings of morning glory against Fusarium wilt caused by F. oxysporum f. sp.