Pediatric Neurogenic Pulmonary Edema After Brain Tumor Removal Complicated with Severe Myocardial Injury: A Case Report.

BACKGROUND Neurogenic pulmonary edema (NPE) is a rare complication of neurological insults, such as traumatic brain injury and intracranial hemorrhage, in children. NPE frequently accompanies left ventricular (LV) dysfunction mediated via central catecholamine surge and inflammation. A high serum natriuretic (BNP) level was prolonged even after the LV contraction was improved in this case with severe myocardial injury. The overloading stress to the LV wall can last several days over the acute phase of NPE. CASE REPORT A 6-year-old boy developed NPE after the removal of a brain tumor in the cerebellar vermis, which was complicated by hydrocephalus. Simultaneously, he experienced LV dysfunction involving reduced global contraction with severe myocardial injury diagnosed by abnormally elevated cardiac troponin I level (1611.6 pg/ml) combined with a high serum BNP level (2106 pg/ml). He received mechanical ventilation for 4 days until the improvement of his pulmonary edema in the Intensive Care Unit (ICU). On the next day, after the withdrawal of mechanical ventilation, he was discharged from the ICU to the pediatric unit. Although the LV contraction was restored to an almost normal range in the early period, it took a total of 16 days for the serum BNP level to reach an approximate standard range (36.9 pg/ml). CONCLUSIONS Even in a pediatric patient with NPE, we recommend careful monitoring of the variation of cardiac biomarkers such as BNP until confirmation of return to an approximate normal value because of the possible sustained overloading stress to the LV wall.

Structural Assignment of the Product Ion Generated from a Natural Ciguatoxin-3C Congener, 51-Hydroxyciguatoxin-3C, and Discovery of Distinguishable Signals in Congeners Bearing the 51-Hydroxy Group.

Ciguatoxins (CTXs) stand as the primary toxins causing ciguatera fish poisoning (CFP) and are essential compounds distinguished by their characteristic polycyclic ether structure. In a previous report, we identified the structures of product ions generated via homolytic fragmentation by assuming three charge sites in the mass spectrometry (MS)/MS spectrum of ciguatoxin-3C (CTX3C) using LC-MS. This study aims to elucidate the homolytic fragmentation of a ciguatoxin-3C congener. We assigned detailed structures of the product ions in the MS/MS spectrum of a naturally occurring ciguatoxin-3C congener, 51-hydroxyciguatoxin-3C (51-hydoxyCTX3C), employing liquid chromatography/quadrupole time-of-flight mass spectrometry with an atmospheric pressure chemical ionization (APCI) source. The introduction of a hydroxy substituent on C51 induced different fragmentation pathways, including a novel cleavage mechanism of the M ring involving the elimination of 51-OH and the formation of enol ether. Consequently, new cleavage patterns generated product ions at m/z 979 (C55H79O15), 439 (C24H39O7), 149 (C10H13O), 135 (C9H11O), and 115 (C6H11O2). Additionally, characteristic product ions were observed at m/z 509 (C28H45O8), 491 (C28H43O7), 481 (C26H41O8), 463 (C26H39O7), 439 (C24H39O7), 421 (C24H37O6), 171 (C9H15O3), 153 (C9H13O2), 141 (C8H13O2), and 123 (C8H11O).

Regularized multi-trait multi-locus linear mixed models for genome-wide association studies and genomic selection in crops.

BACKGROUND: We consider two key problems in genomics involving multiple traits: multi-trait genome wide association studies (GWAS), where the goal is to detect genetic variants associated with the traits; and multi-trait genomic selection (GS), where the emphasis is on accurately predicting trait values. Multi-trait linear mixed models build on the linear mixed model to jointly model multiple traits. Existing estimation methods, however, are limited to the joint analysis of a small number of genotypes; in fact, most approaches consider one SNP at a time. Estimating multi-dimensional genetic and environment effects also results in considerable computational burden. Efficient approaches that incorporate regularization into multi-trait linear models (no random effects) have been recently proposed to identify genomic loci associated with multiple traits (Yu et al. in Multitask learning using task clustering with applications to predictive modeling and GWAS of plant varieties. arXiv:1710.01788 , 2017; Yu et al in Front Big Data 2:27, 2019), but these ignore population structure and familial relatedness (Yu et al in Nat Genet 38:203-208, 2006). RESULTS: This work addresses this gap by proposing a novel class of regularized multi-trait linear mixed models along with scalable approaches for estimation in the presence of high-dimensional genotypes and a large number of traits. We evaluate the effectiveness of the proposed methods using datasets in maize and sorghum diversity panels, and demonstrate benefits in both achieving high prediction accuracy in GS and in identifying relevant marker-trait associations. CONCLUSIONS: The proposed regularized multivariate linear mixed models are relevant for both GWAS and GS. We hope that they will facilitate agronomy-related research in plant biology and crop breeding endeavors.

Assignment of product ions produced from ciguatoxin-3C provides a deep insight into the fragmentation mechanism of polycyclic ether compounds.

RATIONALE: Marine polycyclic ethers have drawn attention owing to their unique chemical structures and involvement in food poisoning and fish killing. To study structural diversity, we performed a structural assignment of product ions produced from a representative ladder-shaped polycyclic ether, ciguatoxin-3C, and elucidated the mechanism of generation. METHODS: The product ions used for the structural assignment were produced from a precursor ion [M + H]+ using liquid chromatography/quadrupole time-of-flight mass spectrometry, by employing an atmospheric pressure chemical ionization source. RESULTS: Three charged sites were considered at both terminals of a molecule. Typical charge-remote fragmentation was produced at the respective charge sites, yielding a hybrid spectrum. C-C bonds bordering two ethers could cleave and trigger the fission of two other bonds. Prominent ions indicating the serial loss of water molecules resulted from the simultaneous deprivation of ethereal oxygen and hydrogen atoms. The resultant double bonds formed long chains of conjugated polyenes, which stabilized charge via resonance. CONCLUSIONS: Three alternative charge sites produce a hybrid spectrum. The simultaneous fission of three bonds was explained. For the first time, intense ions due to serial dehydration were explained by the elimination of ether oxygen atoms and the subsequent conjugation of double bonds. All product ions were considered by the structural features of polycyclic ether that facilitates the formation of conjugated polyenes.

Risk factors for intolerance of oral 5-aminosalicylic acid preparations in pediatric ulcerative colitis.

BACKGROUND: No previous study of Japanese children with ulcerative colitis (UC) has reported the risk factors for intolerance of 5-aminosalicylic acid (5-ASA). We aimed to identify risk factors for intolerance of oral 5-ASA preparations in pediatric UC. METHODS: Patients with childhood-onset UC who were seen at our hospital between November 2003 and March 2020 were investigated. Intolerance of 5-ASA was defined as having clinical symptoms (pyrexia, abdominal pain, diarrhea, bloody stool) that worsened after starting oral administration of 5-ASA and improved after discontinuation of 5-ASA. Patient sex, age, body size, laboratory data, pediatric UC activity index scores, and colonoscopy-based determinations of the extent and severity of the affected lesion at initiation of 5-ASA of intolerant and tolerant groups were compared. RESULTS: Fifteen patients were in the intolerant group, and 37 were in the tolerant group. The leukocyte count, C-reactive protein level, and erythrocyte sedimentation rate were significantly higher in the intolerant group than the tolerant group; the albumin level in the intolerant group was significantly lower. All intolerant patients and 68% of tolerant patients had pancolitis (Paris classification E4). Patients with a large, affected area (Paris classifications E3 and E4) more frequently had intolerance to 5-ASA than patients with a small lesion. The cumulative Mayo endoscopic subscore (cMES), which is the sum of MES scores for six regions of the large intestine, was significantly higher in the intolerant group. CONCLUSIONS: Pediatric UC patients with more intense inflammation and a large lesion could have an increased risk of intolerance for 5-ASA.

Utility of a rapid assay for prostaglandin E-major urinary metabolite as a biomarker in pediatric ulcerative colitis.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a urinary biomarker reflecting ulcerative colitis (UC) activity. This prospective observational study aimed to evaluate the usefulness of PGE-MUM via rapid chemiluminescent enzyme immunoassay in detecting endoscopic remission (ER) and histologic remission (HR) in pediatric UC (6-16 years) in comparison with fecal calprotectin (FCP). ER and HR were defined as Mayo endoscopic score (MES) of 0 and Matts' histological grades (Matts) of 1 or 2, respectively. A total of 104 UC and 39 functional gastrointestinal disorder (FGID) were analyzed. PGE-MUM levels were significantly higher in the UC group than in the FGID group (P < 0.001). FCP levels were significantly elevated in the group without ER and HR than in the group with ER and HR (P < 0.001 and P = 0.001), whereas PGE-MUM levels were significantly higher in the group without ER compared to the group with ER (P < 0.001). No significant differences were noted in the AUCs for PGE-MUM and FCP in detecting ER and HR. Although PGE-MUM was inferior to FCP for the detection of HR, it might have the potential for application as a biomarker of endoscopic activity in pediatric UC owing to its noninvasive and rapid method.

Serum leucine-rich alpha-2 glycoprotein and calprotectin in children with inflammatory bowel disease: A multicenter study in Japan.

BACKGROUND AND AIM: Serum leucine-rich alpha-2 glycoprotein (LRG) and calprotectin have been studied as disease activity markers in adults with inflammatory bowel disease (IBD). We evaluated them in pediatric IBD patients. METHODS: Subjects under 17 years old undergoing care at 11 Japanese pediatric centers were retrospectively assigned to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illness. Serum LRG and calprotectin were measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: We enrolled 173 subjects, including 74 with CD, 77 with UC, and 22 NC. Serum LRG concentrations in active CD (median, 200 µg/mL) were significantly greater than in remission (81 µg/mL; P < 0.001) or NC (69 µg/mL; P < 0.001). Serum calprotectin concentrations in active CD (2941 ng/mL) also were significantly greater than in remission (962 ng/mL; P < 0.05) or NC (872 ng/mL; P < 0.05). Serum LRG concentrations in active UC (134 µg/mL) were significantly greater than in remission (65 µg/mL; P < 0.01) but not significantly greater than in NC (69 µg/mL); serum calprotectin concentrations in active UC (1058 ng/mL) were not significantly different from those in remission (671 ng/mL) or NC (872 ng/mL). In receiver operating characteristic analyses of LRG, calprotectin, C-reactive protein, and erythrocyte sedimentation rate for ability to distinguish active IBD from remission, CD and UC showed areas under receiver operating characteristic curves for LRG (0.77 and 0.70, respectively), exceeding those for calprotectin, C-reactive protein, or erythrocyte sedimentation rate. CONCLUSIONS: In pediatric IBD, serum LRG may better reflect disease activity than serum calprotectin, particularly in CD.

Incidence and characteristics of early elevation of cardiac troponin I after intrathoracic surgery: A single-center retrospective observational study.

The early elevation of cardiac troponins within 24 hours after noncardiac surgery is reportedly associated with increased postoperative morbidities. Several predisposing factors, including the frequent occurrence of hypoxia and increased pulmonary arterial pressure, may likely contribute to this elevation, especially after intrathoracic surgery. Therefore, this retrospective study aimed to elucidate the incidence and characteristics of the early elevation of cardiac troponin I after intrathoracic surgery. This study included 320 patients who underwent intrathoracic surgery between January 1, 2018, and June 30, 2021. Specific perioperative variables were retrospectively collected from their electrical clinical records. The serum concentration of high-sensitivity cardiac troponin I (hs cTnI) was measured twice immediately after the intensive care unit arrival and on the following day. We grouped these patients into two: the early elevation of hs cTnI (EECT) group (hs cTnI value > 26.2 ng/L by at least 1 measurement) and the non-early elevation (non-EECT) group. Patient characteristics were then compared between these groups. The hs cTnI level elevated within 24 hours postoperatively in 103 patients (32.2%). In univariate analysis, intraoperative variables, including the duration of unilateral ventilation (199.2 minutes, P = .0025) and surgery (210.6 minutes, P = .0012), estimated blood loss volume (406.7 mL, P = .0022), percentage of stored red blood cell (RBC) transfusion (10.7%, P = .0059), and percentage of lobectomy or combination of other lung resection types (88.3%, P = .00188), were significantly higher in the EECT group than in the non-EECT group. In the log-rank test, prolonged hospitalization was more prevalent in the EECT group (P = .0485). Furthermore, multivariate analysis revealed 3 independent risk factors for the early elevation of hs cTnI: coexisting chronic renal failure (odds ratio [OR], 3.25), lobectomy or combined resections (OR, 2.65), and stored RBC transfusion (OR, 3.41). The early elevation of hs cTnI commonly occurs after intrathoracic surgery, with an incidence of 32.2%. Its 3 independent risk factors are coexisting chronic renal failure, lung resection type, and stored RBC transfusion.

Anti-inflammatory effects of dopamine on microglia and a D1 receptor agonist ameliorates neuroinflammation of the brain in a rat delirium model.

Microglia play a central role in neuroinflammatory processes by releasing proinflammatory mediators. This process is tightly regulated along with neuronal activities, and neurotransmitters may link neuronal activities to the microglia. In this study, we showed that primary cultured rat microglia express the dopamine (DA) D1 receptor (D1R) and D4R, but not D2R, D3R, or D5R. In response to a D1R-specific agonist SKF-81297 (SKF), the cultured microglia exhibited increased intracellular cAMP levels. DA and SKF suppressed lipopolysaccharide (LPS)-induced expression of interleukin-1ß (IL-1ß) and tumor necrosis α (TNFα) in cultured microglia. Microglia in the normal mature rat prefrontal cortex (PFC) were sorted and significant expression of D1R, D2R, and D4R was observed. A delirium model was established by administering LPS intraperitoneally to mature male Wistar rats. The model also displayed sleep-wake disturbances as revealed by electroencephalogram and electromyogram recordings as well as increased expression of IL-1ß and TNFα in the PFC. DA levels were increased in the PFC 21 h after LPS administration. Increased cytokine expression was observed in sorted microglia from the PFC of the delirium model; however, TNFα, but not IL-1ß expression, was abruptly decreased 21 h after LPS administration in the delirium model, whereas DA levels were increased. A D1R antagonist SCH23390 partially abolished the TNFα expression change. This suggests that endogenous DA may play a role in suppressing neuroinflammation. Administration of the DA precursor L-DOPA or SKF to the delirium model rats inhibited the expression of IL-1ß and TNFα. The simultaneous administration of clozapine, a D4R antagonist, strengthened the suppressive effects of L-DOPA. These results suggest that D1R mediates the suppressive effects of LPS-induced neuroinflammation, in which microglia may play an important role. Agonists for D1R may be effective for treating delirium.

Bilateral ovarian endometriomas after laparoscopic hysterectomy following adjuvant tamoxifen therapy for breast cancer: A case report.

Tamoxifen, a selective estrogen receptor modulator, is widely used as adjunctive therapy for women with breast cancer. However, tamoxifen has an agonistic effect on the endometrium and may be associated with endometrial proliferation, hyperplasia, polyp formation and carcinoma. The case report describes a 50-year-old woman who developed bilateral ovarian endometriomas while taking tamoxifen for breast cancer after total laparoscopic hysterectomy. She had undergone total laparoscopic hysterectomy for multiple uterine fibroids with no ovarian pathology at age 48 years, had been diagnosed with breast cancer and had commenced tamoxifen as post-mastectomy adjuvant therapy. One year after starting tamoxifen, she developed bilateral ovarian swelling accompanied by acute abdominal pain. At laparoscopic bilateral salpingo-oophorectomy, endometriomas were visible on both ovaries. Pathological examination confirmed endometriotic cysts with no evidence of malignancy. Postoperatively, anastrozole (an aromatase inhibiter) was substituted for tamoxifen as adjuvant therapy for her breast cancer.

Hemodynamic deterioration due to increased anterior and posterior cardiac compression during posterior spinal fusion for scoliosis with pectus excavatum.

Hemodynamics may deteriorate during the perioperative period when performing posterior spinal fusion in patients with pectus excavatum and scoliosis. A 13-year-old teenager diagnosed with Marfan syndrome had thoracic scoliosis and pectus excavatum. Thoracic scoliosis was convex to the right, and a right ventricular inflow tract stenosis was observed due to compression induced by the depressed sternum. The patient underwent T3-L4 posterior spinal fusion surgery for scoliosis. Deterioration of hemodynamics was observed when the patient was placed in the prone position or when the thoracic spine was corrected to the left front. Postoperative computed tomography examination showed that the mediastinal space was narrowed due to the corrected thoracic spine. Special attention should be paid in the following cases: (1) severe pectus excavatum, (2) right ventricular inflow tract compression due to depressed sternum on the left side, (3) correction of the thoracic spine on the left front, (4) long-term surgery, and (5) risk of massive bleeding. In some cases, pectus excavatum surgery should be prioritized.

Evaluation of the European League Against Rheumatism/American College of Rheumatology-2019 classification criteria in patients with childhood-onset systemic lupus erythematosus: a single-center retrospective study.

This study aimed to compare the sensitivity and specificity of the European League Against Rheumatism/American College of Rheumatology-2019 (EULAR/ACR-2019) classification criteria with prior classification schemes for patients with childhood-onset systemic lupus erythematosus (cSLE). This single-center retrospective study examined 53 patients with cSLE and 53 patients having antinuclear antibody (ANA) titers ≥ 1:80 but not cSLE as controls. Sensitivity and specificity were calculated for the EULAR/ACR-2019 criteria, original criteria reported earlier in 2019, the ACR-1997 criteria, and the Systemic Lupus International Collaborating Clinics-2012 (SLICC-2012) criteria. The frequency of positivity in the cSLE group for each item of the EULAR/ACR-2019, ACR-1997, and SLICC-2012 criteria was determined. Characteristics of the misclassified patients were also investigated. All patients with cSLE had ANA titers ≥ 1:80. The non-SLE diagnoses included juvenile idiopathic inflammatory myopathies, primary Sjögren's syndrome (pSS), juvenile idiopathic arthritis, systemic sclerosis, mixed connective tissue disease (MCTD), and others. Sensitivities of the EULAR/ACR-2019 criteria, the original criteria, the ACR-1997 criteria, and the SLICC-2012 criteria were 100%, 100%, 86.8%, and 100%, respectively; the specificities were 84.9%, 92.5%, 98.1%, and 88.7%, respectively. In the cSLE group, the items of the SLE-specific antibody (100%), complement (98.1%), hematological (94.3%), and renal (84.9%) domains were frequently observed in the EULAR/ACR-2019 criteria. The EULAR/ACR-2019 criteria misclassified patient controls more frequently, especially those with MCTD or pSS, as having SLE than the previous criteria. The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity; the weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be more appropriate for the classification of SLE in a pediatric population. Key Points • The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity. • The EULAR/ACR-2019 criteria more frequently misclassified non-SLE patients who did not have SLE, especially those with MCTD or pSS, as having SLE than the previous criteria in patients with childhood onset. • The weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be a more appropriate classification of SLE for a pediatric population.

Serum Zinc and Selenium in Children with Inflammatory Bowel Disease: A Multicenter Study in Japan.

BACKGROUND: Reports of zinc and selenium deficiencies accompanying inflammatory bowel disease (IBD) mostly have originated from Western countries and concerned adult patients. Whether Japanese children with IBD have similar deficiencies remained unclear. AIM: We aimed to elucidate differences in serum zinc and selenium concentrations in Japanese children between types of IBD. METHODS: Children under 17 years old undergoing care at 12 Japanese pediatric centers were retrospectively enrolled between November 2016 and February 2018 to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illnesses. Serum zinc and selenium were measured by atomic absorption spectrophotometry. Zinc and selenium deficiencies were defined by serum concentrations < 70 µg/dL and < 9.5 µg/dL, respectively. RESULTS: Subjects included 98 patients with CD (median age, 13 years), 118 with UC (11 years), and 43 NC (11 years). Serum zinc and selenium were significantly lower in CD (median, 64 and 12.6 µg/dL respectively) than in UC (69 and 14.6; P < 0.05 and P < 0.001) or NC (77 and 15.7; P < 0.01 and P < 0.001). Zinc deficiency was significantly more prevalent in CD (60.2%) than in NC (37.2%; P < 0.05), but not than in UC (51.7%; P = 0.22). Selenium deficiency was significantly more prevalent in CD (15.3%) than in UC (5.9%; P < 0.05) or NC (0%; P < 0.01). CONCLUSIONS: In Japanese children under 17 years old, serum zinc and selenium were significantly lower in CD than in UC or NC. Zinc and selenium should be monitored, and supplemented when deficient, in children with IBD, especially CD.

Safety and efficacy of the endoscopic delivery of capsule endoscopes in adult and pediatric patients: Multicenter Japanese study (AdvanCE-J study).

BACKGROUND AND AIM: We retrospectively determined the safety and efficacy of the endoscopic delivery (ED) of capsule endoscopes. METHODS: We enrolled 10,156 patients who underwent small bowel capsule endoscopy (SBCE), 3182 who underwent patency capsule (PC), and 1367 who underwent colon capsule endoscopy (CCE), at 11 gastroenterological and nine pediatric centers. RESULTS: Small bowel capsule endoscopies, PCs, and CCEs were endoscopically delivered to 546 (5.4%), 214 (6.7%), and 14 (1.0%) patients, respectively. Only mild complications occurred for 21.6% (167/774), including uneventful mucosal damage, bleeding, and abdominal pain. Successful ED of SBCE to the duodenum or jejunum occurred in 91.8% and 90.7% of patients aged <16 years and ≥16 years, respectively (P = 0.6661), but the total enteroscopy rate was higher in the first group (91.7%) than in the second (76.2%, P < 0.0001), for whom impossible ingestion (87.3%) was significantly more common than prolonged lodging in the stomach (64.2%, P = 0.0010). Successful PC and CCE delivery to the duodenum occurred in 84.1% and 28.6%, thereafter the patency confirmation rate and total colonoscopy rate was 100% and 61.5%, respectively. The height, weight, and age cutoff points in predicting spontaneous ingestion were 132 cm, 24.8 kg, and 9 years 2 months, respectively, in patients aged <16 years. Patients aged ≥16 years could not swallow the SBCEs mainly due to dysphagia (75.0%); those who retained it in the esophagus due to cardiac disease (28.6%), etc. and in the stomach due to diabetes mellitus (15.7%), etc. CONCLUSIONS: This large-scale study supports the safety and efficacy of ED in adult and pediatric patients. UMIN000042020.

Reconstruction of Completely Circumferentially Degloved Thumb Using Omental Flap and Tubular Split-thickness Skin Graft.

Various types of thin flaps have been used for reconstruction in cases of complete circumferential degloving injuries of digits (Urbaniak classification class III). The omental flap has extensive, pliable, and well-vascularized tissue and helps prevent bone resorption of the distal phalange that can result from avascular necrosis. A 31-year-old right-handed man with class III left thumb injury and compartment syndrome of the left forearm was treated successfully with a free omental flap wrapped around the thumb and then covered with a tubular split-thickness skin graft. The postoperative course was good, except that the distal third of the phalange of the thumb was resected because of insufficient omentum volume transplanted to the thumb tip resulting from omental volume bias in the distal part of the thumb. Bone scintigraphy 1 year after injury showed technetium-99m accumulation in the remaining two-thirds of the distal phalange, although there was no blood supply before the reconstruction. The advantages of our treatment method are that the thickness of the reconstructed digits can be adjusted by the amount of the omental flap. Skin grafting can be simplified; and with multiple digital injuries, separated fingers can be reconstructed in a single operation by wrapping each digit with a divided omental flap. Use of the free omental flap and tubular split-thickness skin graft is a therapeutic reconstruction option for Urbaniak class III injury.

Takotsubo Cardiomyopathy Induced by Very Low-Dose Epinephrine Contained in Local Anesthetics: A Case Report.

BACKGROUND Takotsubo cardiomyopathy is a reversible left ventricular dysfunction triggered by emotional or physical stress. Perioperatively, takotsubo cardiomyopathy is sometimes induced by various psychological factors, such as stress from surgery, and non-psychological factors, such as epinephrine misinjection. This report describes a case of takotsubo cardiomyopathy induced by the administration of very low-dose epinephrine contained in a local anesthetic. CASE REPORT A 78-year-old woman with mycosis in the maxillary sinus was scheduled to undergo endoscopic sinus surgery. After the submucosal injection of 3 mL of local anesthetic (lidocaine, 0.5%; epinephrine, 1: 200 000) immediately before the incision, her heart rate and blood pressure reached 135 beats per min and 254/185 mmHg, respectively, inducing ventricular tachycardia. After receiving 50 mg of lidocaine, her cardiac rhythm resumed a normal sinus rhythm, without cardioversion. As her hemodynamics stabilized, the surgical procedure began as planned. Postoperative electrocardiography, echocardiography, and coronary arteriography demonstrated takotsubo cardiomyopathy. Subsequently, her cardiac movement gradually improved, and she was discharged from the hospital on postoperative day 9. CONCLUSIONS To the best of our knowledge, this is the first reported case in which a very small amount of epinephrine (0.015 mg) induced takotsubo cardiomyopathy. Therefore, epinephrine should be used cautiously, especially in the nasal mucosa, vaginal mucosa, and uterus, where blood flow is relatively high. If unexpected hemodynamic alterations and ST-segment abnormalities occur after epinephrine administration, asymptomatic takotsubo cardiomyopathy should be considered.

Disseminated intravascular coagulation as a complication of bursitis: angiogenesis and repetitive bleeding as potential factors for disseminated intravascular coagulation: a case report.

BACKGROUND: Malignant tumors, such as acute leukemia and solid cancers, frequently cause disseminated intravascular coagulation. However, cases of disseminated intravascular coagulation as a complication of bursitis were not reported previously. CASE PRESENTATION: A 72-year-old Japanese woman was scheduled to undergo resection of a rapidly growing subcutaneous tumor-like lesion on her left back. Preoperative blood tests suggested disseminated intravascular coagulation. The resected lesion was cystic tumor containing a hematoma. After the operation, the patient completely recovered from disseminated intravascular coagulation, indicating that disseminated intravascular coagulation in this case was caused by the tumor. Pathological examination of the resected tumor revealed considerable fibrin deposition and angiogenesis on the cyst wall, which was presumably a response to inflammation and indicated presence of repetitive intratumoral bleeding, subsequently leading to a diagnosis of chronic hemorrhagic bursitis. CONCLUSIONS: Clinicians should note that, despite being benign, soft-tissue tumors accompanied by inflammation with angiogenesis and repetitive intratumoral bleeding can cause disseminated intravascular coagulation, albeit rarely.

High cellulolytic potential of the Ktedonobacteria lineage revealed by genome-wide analysis of CAZymes.

Traditionally, filamentous fungi and actinomycetes are well-known cellulolytic microorganisms that have been utilized in the commercial production of cellulase enzyme cocktails for industrial-scale degradation of plant biomass. Noticeably, the Ktedonobacteria lineage (phylum Chloroflexi) with actinomycetes-like morphology was identified and exhibited diverse carbohydrate utilization or degradation abilities. In this study, we performed genome-wide profiling of carbohydrate-active enzymes (CAZymes) in the filamentous Ktedonobacteria lineage. Numerous CAZymes (153-290 CAZymes, representing 63-131 glycoside hydrolases (GHs) per genome), including complex mixtures of endo- and exo-cellulases, were predicted in 15 available Ktedonobacteria genomes. Of note, 4-28 CAZymes were predicted to be extracellular enzymes, whereas 3-29 CAZymes were appended with carbohydrate-binding modules (CBMs) that may promote their binding to insoluble carbohydrate substrates. This number far exceeded other Chloroflexi lineages and were comparable to the cellulolytic actinomycetes. Six multi-modular extracellular GHs were cloned from the thermophilic Thermosporothrix hazakensis SK20-1T strain and heterologously expressed. The putative endo-glucanases of ThazG5-1, ThazG9, and ThazG12 exhibited strong cellulolytic activity, whereas the putative exo-glucanases ThazG6 and ThazG48 formed weak but observable halos on carboxymethyl cellulose plates, indicating their potential biotechnological application. The purified recombinant ThazG12 had near-neutral pH (optimal 6.0), high thermostability (60°C), and broad specificity against soluble and insoluble polysaccharide substrates. It also represented described a novel thermostable bacterial ß-1,4-glucanase in the GH12 family. Together, this research revealed the underestimated cellulolytic potential of the Ktedonobacteria lineage and highlighted its potential biotechnological utility as a promising microbial resource for the discovery of industrially useful cellulases.

Neural precursor cells are decreased in the hippocampus of the delayed carbon monoxide encephalopathy rat model.

The pathophysiology of delayed carbon monoxide (CO) encephalopathy remains unclear. In this study, the effects of CO exposure on the dentate gyrus (DG) were investigated in a Wistar rat model by histochemical and molecular methods. Model rats showed significant cognitive impairment in the passive-avoidance test beginning 7 days after CO exposure. Immunohistochemistry showed that compared to the control, the cell number of SRY (sex-determining region Y)-box 2 (SOX2)+/brain lipid binding protein (BLBP)+/glial fibrillary acidic protein (GFAP)+ cells in the DG was significantly less, but the number of SOX2+/GFAP- cells was not, reflecting a decreased number of type 1 and type 2a neural precursor cells. Compared to the control, the numbers of CD11b+ cells and neuron glial antigen 2+ cells were significantly less, but the number of SOX2-/GFAP+ cells was not. Flow cytometry showed that the percent of live microglial cells isolated from the hippocampus in this CO rat model was significantly lower than in controls. Furthermore, mRNA expression of fibroblast growth factor 2 and glial cell-derived neurotrophic factor, which are neurogenic factors, was significantly decreased in that area. We conclude that, in this rat model, there is an association between delayed cognitive impairment with dysregulated adult hippocampal neurogenesis and glial changes in delayed CO encephalopathy.

Diagnostic accuracy of serum proteinase 3 antineutrophil cytoplasmic antibodies in children with ulcerative colitis.

BACKGROUND AND AIM: Serologic markers such as myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA) (MPO-ANCA) have been used to screen patients for ulcerative colitis (UC). However, MPO-ANCA shows limited accuracy in Asians. Proteinase 3 ANCA (PR3-ANCA) has performed better at UC diagnosis in Japanese adults than MPO-ANCA. The present study aimed to evaluate usefulness of PR3-ANCA for diagnosis of UC in Japanese pediatric practice. METHODS: Patients under 17 years old undergoing assessment at 12 Japanese pediatric centers between November 2016 and February 2018 were prospectively enrolled and divided into groups with UC, Crohn's disease (CD), intestinal disease control (IC), and healthy control (HC). Serum PR3-ANCA and MPO-ANCA were analyzed using chemiluminescence enzyme immunoassay kits. RESULTS: Sera from 367 patients (148 with UC at a median age of 12 years; 120 with CD, 13 years; 56 with IC, 10.5 years; and 43 with HC, 10 years) were examined. Median PR3-ANCA values in UC (1.6 U/mL) were greater than in CD (0.2; P < 0.001), IC (0.15; P < 0.001), and HC (0.1; P < 0.001). In receiver operating characteristic curve analyses, the area under the curve for PR3-ANCA was 0.79, significantly greater than for MPO-ANCA (0.58; P < 0.001). Using a cut-off value of 0.8 U/mL determined from the receiver operating characteristic analyses, PR3-ANCA showed significantly greater sensitivity (64.9%) than MPO-ANCA (cut-off, 0.2 U/mL; sensitivity, 19.6%; P < 0.001) and good specificity (83.6%). CONCLUSIONS: In Japanese children and adolescents, PR3-ANCA performed better as a serologic marker for diagnosis of UC than MPO-ANCA. To our knowledge, this is the first report of such a comparison.