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We aimed to analyze the characteristics of serious adverse events following immunizations (AEFIs) to identify potential safety information and prediction features. We screened the individual case safety reports (ICSRs) in adults who received mRNA-based COVID-19 vaccines using the Vaccine Adverse Event Reporting System until December 2021. We identified the demographic and clinical characteristics of ICSRs and performed signal detection. We developed prediction models for serious AEFIs and identified the prognostic features using logistic regression. Serious ICSRs and serious AEFIs were 51,498 and 271,444, respectively. Hypertension was the most common comorbidity (22%). Signal detection indicated that the reporting odds ratio of acute myocardial infarction (AMI) was more than 10 times. Those who had experienced myocardial infarction (MI) were 5.7 times more likely to suffer from MI as an AEFI (95% CI 5.28–6.71). Moreover, patients who had atrial fibrillation (AF), acute kidney injury (AKI), cardiovascular accident (CVA), or pulmonary embolism (PE) were 7.02 times, 39.09 times, 6.03 times, or 3.97 times more likely to suffer from each AEFI, respectively. Our study suggests that vaccine recipients who had experienced MI, AF, AKI, CVA, or PE could require further evaluation and careful monitoring to prevent those serious AEFIs.

Fibromuscular dysplasia is a nonatheromatous, noninflammatory arterial disorder that results in stenosis and/or aneurysm formation and rarely involves the mesenteric arteries. Herein, we report a case of fibromuscular dysplasia limited to the inferior mesenteric artery, which manifested with arterial aneurysms and ischemic colitis.

Serous cystic neoplasms of the pancreas are usually benign, with a low malignant potential. Herein, we report a case of malignant serous cystic neoplasm of the pancreas treated with subtotal pancreatectomy, which progressed to local recurrence and metachronous hepatic metastasis during the regular follow-up period.

Introduction MegaShield® is a newly developed temperature-sensitive anti-adhesive containing micronized acellular dermal matrix. The aim of this study was to investigate the efficacy and safety of MegaShield® compared with Guardix-SG® in the prevention of adhesions in patients undergoing bilateral total thyroidectomy. Method We conducted a multicenter trial between October 2018 and March 2020 in patients undergoing total thyroidectomy. The patients were randomly assigned to either the MegaShield® group or the Guardix-SG® group. The primary outcome was the esophageal movement using marshmallow six weeks after the surgery and the secondary outcome was the assessed adhesion score. The safety assessment was also evaluated. Results The study included 70 patients each in the MegaShield® and control (Guardix-SG®) groups. Baseline clinical characteristics, the mean score of marshmallow esophagography, and the sum of adhesion scores were not statistically different between the two groups. Inferiority test demonstrated that the efficacy of MegaShield® is not inferior to that of Guardix-SG®. There were no device-related complications in both groups. Conclusion The efficacy and safety of MegaShield® were not inferior than those of Guardix-SG®. MegaShield® demonstrated the potential of ADM as a potential future anti-adhesive agent. Trial registration The name of trial registry CRIS (Clinical Research Information Service) https://cris.nih.go.kr/cris/index.jsp. (The full trial protocol can be accessed) Registration number: KCT0003204.

Sarcomatoid mesothelioma is not very common, mesothelioma is directly attributable to occupational asbestos exposure, with 90% of cases showing a history of exposure. A 66-year-old male was admitted with an abdominal pain that persisted for 3 weeks. He had no abdominal mass. Computed tomography showed soft tissue thickening in perihepatic space and nodularities in omentum and peritoneum with ascites. There was no absolute diagnosis evidence in ascites analysis. Although the pathology of ascites was free for malignancy, the patient underwent omentum biopsy for definitive diagnosis. In laproscopic exploration, there was omental cake, peritoneal nodular seeding. It was suspected cancer carcinomatosis. Immunohistochemical findings suggested that it was sarcomatoid masothelioma. This is the rare case of a peritoneal sarcomatoid mesothelioma, without any exposure to asbestos.

Periampullary diverticulum is commonly found during endoscopy and can occur at any age although its prevalence increases with age. Periampullary diverticular bleeding is a rare and difficult to diagnose during clinical practice because of its unique appearance and location. This often can lead to massive bleeding and interfere with adequate bleeding control. Endoscopic management on duodenal diverticular bleeding is limited compared to colonic diverticular bleeding due to lack of experience. Herein, we report a case of active bleeding from a periampullary diverticulum during bile duct stone extraction diagnosed by side-viewing endoscope and successfully controlled using hemoclips without any complications. (Korean J Gastroenterol 2016;67:146-149)

OBJECTIVES:We evaluated the utility of whole-body MRI (WB MRI) for cancer screening and other regular health evaluations. METHODS:This retrospective study included 229 patients who underwent whole-body MRI as part of a routine health examination and cancer screening. The WB MRIs and radiologic reports were evaluated by a musculoskeletal radiologist, a neuroradiologist, and an abdominal radiologist. The consensus of their findings was characterized into three categories, as follows: suspicion of malignancy (category I); need for follow-up (category II); and no need for follow-up (category III). Any correlations between the abnormal findings and each study group were evaluated using the Mann-Whitney U test and chi-square test. RESULTS:There were six category I lesions, among which two cases were found to involve malignancy. The most common category II findings were annular tears of the disc (14% of category II findings) and severe disc bulging or protrusion, followed by shoulder bursitis and uterine myoma. The most common category III finding was mild disc bulging or protrusion (47% of category III findings). CONCLUSIONS:WB MRI can be used in cancer screening and for regular health evaluations. WB MRI not only provides information about potential malignancy, but also provides information regarding nonmalignant abnormalities that require further evaluation.

Objective: To evaluate whether multidetector CT with low-dose radiation (low-dose CT) of joints can be useful when evaluating fractures. Methods: Our study included CT scans of 398 patients, 103 shoulder cases, 109 wrist cases, 98 pelvis cases and 88 ankle cases. There were 191 females and 207 males. The low-dose CTs were performed using identical voltage and parameters with the exception of decreased (half of standard dose) tube current. Low-dose and standard-dose images were compared with regards to objective image quality, subjective evaluation of image quality and diagnostic performance for the fractures. Results: There was no significant difference of image noise between standard-dose CT and low-dose CT in every joint (p > 0.05). Each mean value of subjective score did not show significant difference according to the dosage of the CT scan. There were no statistically significant differences in the sensitivity (96–100%), specificity (95.2–100%) or accuracy (97.9–100%) between standard-dose CT and low-dose CT (p values, 0.1336– 1.000). Conclusion: The evaluation of extremities for fractures using low-dose CT can reduce radiation exposure by about 50% compared with standard-dose CT without affecting image quality or diagnostic performance. [ABSTRACT FROM AUTHOR]

Obese, insulin-resistant states are characterized by a paradoxical pathogenic condition in which the liver appears to be selectively insulin resistant. Specifically, insulin fails to suppress glucose production, yet successfully stimulates de novo lipogenesis. The mechanisms underlying this dysregulation remain controversial. Here, we hypothesized that carbohydrate-responsive element-binding protein (ChREBP), a transcriptional activator of glycolytic and lipogenic genes, plays a central role in this paradox. Administration of fructose increased hepatic hexose-phosphate levels, activated ChREBP, and caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis in mice. Activation of ChREBP was required for the increased expression of glycolytic and lipogenic genes as well as glucose-6-phosphatase (G6pc) that was associated with the effects of fructose administration. We found that fructose-induced G6PC activity is a major determinant of hepatic glucose production and reduces hepatic glucose-6-phosphate levels to complete a homeostatic loop. Moreover, fructose activated ChREBP and induced G6pc in the absence of Foxo1a, indicating that carbohydrate-induced activation of ChREBP and G6PC dominates over the suppressive effects of insulin to enhance glucose production. This ChREBP/G6PC signaling axis is conserved in humans. Together, these findings support a carbohydrate-mediated, ChREBP-driven mechanism that contributes to hepatic insulin resistance. [ABSTRACT FROM AUTHOR]

Gardner syndrome is a familial disease consisting of colonic polyposis, osteomas, and soft tissue tumors. We describe unilateral chest wall anomaly in a 32-year-old man with Gardner syndrome. A chest radiograph showed asymmetric hypertrophy of the right seventh to tenth ribs. CT images showed increased size of the medullary portions of these lesions, but relatively normal thickness of the cortex. Intercostal muscles along the right seventh to tenth ribs were hypertrophied as compared with the contralateral ribs. Both lungs were clear but the volume of right lung showed slightly smaller than left one. [ABSTRACT FROM AUTHOR]

Solid pseudopapillary neoplasms (SPNs) are rare tumors of the pancreas characterized by poorly cohesive uniform cells with solid and pseudopapillary growth patterns. Nuclear pleomorphism is not a well-recognized feature of SPNs and may complicate differentiation from other pancreatic neoplasms. We compared histologic, immunohistochemical, and clinical features of 18 pleomorphic SPNs with 121 conventional SPNs. The prevalence of pleomorphic SPN was 12.9% (18/139). Pleomorphic SPNs arose in older patients (median, 45 years versus 32 years; P b .001), but no differences were found in sex, tumor location, recurrence, and metastasis when compared with conventional SPNs. Except for pleomorphic nuclei, other cytologic and histologic features of pleomorphic SPNs, such as growth pattern, tumor size, infiltrative pattern, tumor extension, mitosis, and Ki-67 labeling index, were not different from those of conventional SPNs. Pleomorphic SPNs showed a significantly higher p53 protein expression (64.7% [11/17 cases]) than that of conventional SPNs (1.8% [2/112 cases], P b .001). However, immunoreactivity for β-catenin and E-cadherin was not different between pleomorphic and conventional SPNs. A TP53 gene mutation was observed in 2 of 3 p53- immunoreactive pleomorphic SPNs. In summary, nuclear pleomorphism occurs in a subset of SPNs. They are more often p53 immunoreactive than SPNs without pleomorphism, and some harbor TP53 gene mutations. However, pleomorphic SPNs do not appear to be more aggressive than conventional SPNs. Low mitotic rate and Ki-67 labeling index may suggest nuclear pleomorphisms as degenerative changes. Recognition of typical poorly cohesive tumor cells and immunohistochemical features could establish the correct diagnosis of SPNs. [ABSTRACT FROM AUTHOR]

The article focuses on a statistical analysis performed for an exploratory qualitative research which aimed to understand the adoption adjustments made by both the adoptive parents and the adoptee. The study consisted of well-structured interviews of nine adoptive parents and eight adoptee's. The sampling for the study was a combination of convenience, purposeful and snowball sampling. The study gained practical understanding of adoptive adjustments.

Adult neurogenesis occurs throughout life in the mammalian hippocampus and is essential for memory and mood control. There is significant interest in identifying ways to promote neurogenesis and ensure maintenance of these hippocampal functions. Previous work with a synthetic small molecule, isoxazole 9 (Isx-9), highlighted its neuronal-differentiating properties in vitro. However, the ability of Isx-9 to drive neurogenesis in vivo or improve hippocampal function was unknown. Here we show that Isx-9 promotes neurogenesis in vivo, enhancing the proliferation and differentiation of hippocampal subgranular zone (SGZ) neuroblasts, and the dendritic arborization of adult-generated dentate gyrus neurons. Isx-9 also improves hippocampal function, enhancing memory in the Morris water maze. Notably, Isx-9 enhances neurogenesis and memory without detectable increases in cellular or animal activity or vascularization. Molecular exploration of Isx-9-induced regulation of neurogenesis (via FACS and microarray of SGZ stem and progenitor cells) suggested the involvement of the myocyte-enhancer family of proteins (Mef2). Indeed, transgenic-mediated inducible knockout of all brain-enriched Mef2 isoforms (Mef2a/c/d) specifically from neural stem cells and their progeny confirmed Mef2's requirement for Isx-9-induced increase in hippocampal neurogenesis. Thus, Isx-9 enhances hlppocampal neurogenesis and memory in vivo, and its effects are reliant on Mef2, revealing a novel cell-intrinsic molecular pathway regulating adult neurogenesis. [ABSTRACT FROM AUTHOR]

MEF2 (A-D) transcription factors govern development, differentiation and maintenance of various cell types including neurons. The role of MEF2 isoforms in the brain has been studied using in vitro manipulations with only MEF2C examined in vivo. In order to understand specific as well as redundant roles of the MEF2 isoforms, we generated brain-specific deletion of MEF2A and found that Mef2aKO mice show normal behavior in a range of paradigms including learning and memory. We next generated Mef2a and Mef2d brain-specific double KO (Mef2a/dDKO) mice and observed deficits in motor coordination and enhanced hippocampal short-term synaptic plasticity, however there were no alterations in learning and memory, Schaffer collateral pathway long-term potentiation, or the number of dendritic spines. Since previous work has established a critical role for MEF2C in hippocampal plasticity, we generated a Mef2a, Mef2c and Mef2d brain-specific triple KO (Mef2a/c/ dTKO). Mef2a/c/d TKO mice have early postnatal lethality with increased neuronal apoptosis, indicative of a redundant role for the MEF2 factors in neuronal survival. We examined synaptic plasticity in the intact neurons in the Mef2a/c/d TKO mice and found significant impairments in short-term synaptic plasticity suggesting that MEF2C is the major isoform involved in hippocampal synaptic function. Collectively, these data highlight the key in vivo role of MEF2C isoform in the brain and suggest that MEF2A and MEF2D have only subtle roles in regulating hippocampal synaptic function. [ABSTRACT FROM AUTHOR]

Learning and memory depend on the activity-dependent structural plasticity of synapses and changes in neuronal gene expression. We show that deletion of the MEF2C transcription factor in the CNS of mice impairs hippocampal-dependent learning and memory. Unexpectedly, these behavioral changes were accompanied by a marked increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Conversely, neuronal expression of a superactivating form of MEF2C results in a reduction of excitatory postsynaptic sites without affecting learning and memory performance. We conclude that MEF2C limits excessive synapse formation during activity-dependent refinement of synaptic connectivity and thus facilitates hippocampal- dependent learning and memory. [ABSTRACT FROM AUTHOR]

The adult heart responds to biomechanical stress and neurohormonal signaling by hypertrophic growth, accompanied by fibrosis, diminished pump function, and activation of a fetal gene program. Class II histone deacetylases (HDACs) suppress stress-dependent remodeling of the heart via their association with the MEF2 transcription factor, an activator of heart disease. Protein kinase D (PKD) is a stress-responsive kinase that phosphorylates class II HDACs, resulting in their dissociation from MEF2 with consequent activation of MEF2 target genes. To test whether PKD1 is required for pathological cardiac remodeling in vivo, we generated mice with a conditional PKD1-null allele. Mice with cardiac-specific deletion of PKD1 were viable and showed diminished hypertrophy, fibrosis, and fetal gene activation as well as improved cardiac function in response to pressure overload or chronic adrenergic and angiotensin II signaling. We conclude that PKD1 functions as a key transducer of stress stimuli involved in pathological cardiac remodeling in vivo. [ABSTRACT FROM AUTHOR]

Atrial cardiomyocytes, neurons, and endocrine tissues secrete neurotransmitters and peptide hormones via large dense-core vesicles (LDCVs). We describe a new member of the Ras family of G-proteins, named RRP17, which is expressed specifically in cardiomyocytes, neurons, and the pancreas. RRP17 interacts with Ca2+-activated protein for secretion-1 (CAPS1), one of only a few proteins known to be associated exclusively with LDCV exocytosis. Ectopic expression of RRP17 in cardiomyocytes enhances secretion of atrial natriuretic peptide (ANP), a regulator of blood pressure and natriuresis. Conversely, genetic deletion of RRP17 in mice results in dysmorphic LDCVs, impaired ANP secretion, and hypertension. These findings identify RRP17 as a component of the cellular machinery involved in regulated secretion within the heart and potential mediator of the endocrine influence of the heart on other tissues. [ABSTRACT FROM AUTHOR]

Maintenance of skeletal and cardiac muscle structure and function requires precise control of the synthesis, assembly, and turnover of contractile proteins of the sarcomere. Abnormalities in accumulation of sarcomere proteins are responsible for a variety of myopathies. However, the mechanisms that mediate turnover of these long-lived proteins remain poorly defined. We show that muscle RING finger 1 (MuRF1) and MuRF3 act as E3 ubiquitin ligases that cooperate with the E2 ubiquitin-conjugating enzymes UbcH5a, -b, and -c to mediate the degradation of beta/slow myosin heavy chain (beta/slow MHC) and MHCIIa via the ubiquitin proteasome system (UPS) in vivo and in vitro. Accordingly, mice deficient for MuRF1 and MuRF3 develop a skeletal muscle myopathy and hypertrophic cardiomyopathy characterized by subsarcolemmal MHC accumulation, myofiber fragmentation, and diminished muscle performance. These findings identify MuRF1 and MuRF3 as key E3 ubiquitin ligases for the UPS-dependent turnover of sarcomeric proteins and reveal a potential basis for myosin storage myopathies. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine the usefulness of magnetic resonance (MR) imaging in the differentiation of various lesions causing an abnormality of the endometrial cavity by evaluating the imaging features on dynamic contrast-enhanced study and late contrast-enhanced T1-weighted images (T1WI). Contrast-enhanced MR imaging of 59 pathologically proven lesions that showed an abnormality of the endometrial cavity, including 32 endometrial cancers, five sarcomas, nine hyperplastic polyps, nine submucosal myomas, three hyperplasia, and one adenomyoma, were retrospectively reviewed. The enhancement degree and patterns on dynamic contrast-enhanced study and late contrast-enhanced T1WI were compared among different pathologies. On dynamic contrast-enhanced study, 72% (23/32) of endometrial cancers showed early peak enhancement to be reached within 1 min following intravenous administration of contrast material. On late-contrast-enhanced T1WI, lesions showed weak enhancement with gradual washout. Ninety-five percent (21/22) of benign lesions and 100% (5/5) of sarcomas showed late peak enhancement to be reached in 2–3 min following intravenous administration of contrast material. On late contrast-enhanced T1WI, both of these lesions showed persistent strong enhancement. Different enhancement patterns on dynamic contrast-enhanced MR imaging and late contrast-enhanced T1WI can provide a useful clue in the differentiation of various lesions causing an abnormality of the endometrial cavity. [ABSTRACT FROM AUTHOR]

Pancreatic panniculitis is an inflammation and necrosis of fat at distant foci in patients with pancreatic disorders, most frequently, pancreatitis and pancreatic carcinoma. Clinically, pancreatic panniculitis is manifested by painless or painful subcutaneous nodules on the legs, buttocks, or trunk. The usual sites are the distal parts of the lower extremities. To the best of our knowledge, there have not been many reports for the radiologic findings of pancreatic panniculitis. In this article, we report a case of pancreatic panniculitis, including radiologic findings of CT and ultrasonography. The patient was presented with painful subcutaneous nodules on the trunk, and had underlying acute pancreatitis and hemorrhagic pseudocysts. [ABSTRACT FROM AUTHOR]

An abstract of the article "Protein Kinase D1 Stimulates MEF2 Activity in Skeletal Muscle and Enhances Muscle Performance" by Mi-Sung Kim, Jens Fielitz, and John McAnally is presented.

Gα12 family participates in the regulation of diverse physiological processes. This study investigated the role of Gα12/Gα13 in the regulation of p53 and mdm4. Immunoblotting and immunocytochemistry revealed that Gα12 deficiency decreased p53 level and DNA binding activity, accompanying p21 repression with Bcl2 induction, whereas Gα13 deficiency exerted weak effects, p53 mRNA level was unchanged in Gα12 or Gα13 deficiency. ERK1/2 or Akt was not responsible for p53 repression by Gα12 deficiency. Mdm4 was repressed by Gα12 deficiency and to a lesser extent by Gα13 deficiency, whereas mdm2, PTEN and β-catenin were unaffected, p53 accumulation by proteasomal inhibition during Gα12 deficiency suggested the role of Gα12 in p53 stabilization. An activated mutant (QL) of Gα12 or Gα13 promoted p53 accumulation with mdm4 induction in MCF10A cells. Mdm4 overexpression enhanced p53 accumulation, but not vice versa, and knockdown verified the regulatory role of mdm4 for p53 downstream of Gα12/Gα13. Increasing the flow-cytometric pre-Gi phase, doxorubicin or etoposide treatment caused p53 accumulation and serine phosphorylations in the Gα12 or Gα12/13 knockout cells, but failed to induce mdm4. Gα12/13QL overexprcssion failed to phosphorylate p53. In conclusion, Gα12 family regulates p53 level via mdm4, which constitutes a cell signaling pathway distinct from the elicited by genotoxic stress. [ABSTRACT FROM AUTHOR]

In response to pathological stresses such as hypertension or myocardial infarction, the heart undergoes a remodeling process that is associated with myocyte hypertrophy, myocyte death, and fibrosis. Histone deacetylase 5 (HDAC5) is a transcriptional repressor of cardiac remodeling that is subject to phosphorylation-dependent neutralization in response to stress signaling. Recent studies have suggested a role for protein kinase C (PKC) and its downstream effector, protein kinase D1 (PKD1), in the control of HDAC5 phosphorylation. While PKCs are well-documented regulators of cardiac signaling, the function of PKD1 in heart muscle remains unclear. Here, we demonstrate that PKD1 catalytic activity is stimulated in cardiac myocytes by diverse hypertrophic agonists that signal through G protein-coupled receptors (GPCRs) and Rho GTPases. PKD1 activation in cardiomyocytes occurs through PKC-dependent and -independent mechanisms. In vivo, cardiac PKD1 is activated in multiple rodent models of pathological cardiac remodeling. PKD1 activation correlates with phosphorylation-dependent nuclear export of HDAC5, and reduction of endogenous PKD1 expression with small interfering RNA suppresses HDAC5 shuttling and associated cardiomyocyte growth. Conversely, ectopic overexpression of constitutively active PKD1 in mouse heart leads to dilated cardiomyopathy. These findings support a role for PKD1 in the control of pathological remodeling of the heart via its ability to phosphorylate and neutralize HDAC5. [ABSTRACT FROM AUTHOR]

Aims: To investigate the diagnostic performance of ultrasound-guided attenuation parameter (UGAP) for the detection of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD) cohorts using histopathology as the reference standard and comparing it with that of various imaging modalities. Materials and methods: A total of 87 subjects who underwent UGAP, controlled attenuation parameter (CAP), and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) between December, 2020 and January, 2022 were enrolled. Of these patients, 38 patients had NAFLD. The association between UGAP and clinical and imaging parameters was assessed using Pearson's or Spearman's correlations. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: The UGAP and MRI-logPDFF demonstrated strong positive correlations (correlation coefficient= 0.704, P <0.0001). UGAP showed excellent diagnostic performance for distinguishing steatosis grade ≥1 with an AUROC of 0.821 (95% confidence interval [CI], 0.729-- 0.913), which was comparable to that of MRI-PDFF (0.829, 95%CI, 0.723--0.936). The AUROCs of BUSG (B-mode ultrasonography) (0.766, 95% CI, 0.767--0.856) and CAP (0.788, 95% CI, 0.684--0.891) were slightly lower than those of UGAP. The AUROCs of UGAP, MRI-PDFF, CAP, and BUSG for detecting steatosis grade ≥2 were 0.796 (95% CI, 0.616--0.975), 0.971 (95% CI, 0.936--1.000), 0.726 (95% CI, 0.561--0.891) and 0.774 (95% CI, 0.612--0.936), respectively. Conclusion: UGAP may be a valuable potential screening tool as a first-line assessment of liver steatosis in patients with NAFLD. [ABSTRACT FROM AUTHOR]

In 2 separate longitudinal studies, infants and their mothers were seen in 3 longitudinal visits. At 2 months, they were observed in free play where mothers' contingency toward their infants was obtained. At 5 months, a goal blockage response was produced when a previously learned contingent response became ineffective in producing an interesting event. Infants' emotional responses, in particular anger and sad facial expressions, were observed. At 2 years, toddlers' persistence at play was assessed by measuring children's responses to an interruption of their play. In both studies, the amount of toddlers' persistence was positively related to their anger response to the blocked goal at 5 months. Maternal contingency was not related either to infants' response to the blocked goal or to their persistence at play. These findings provide evidence for the contribution to and the consequences of infants' response to a goal blockage and the role of anger as an approach emotion. [ABSTRACT FROM AUTHOR]

Summary: Senescent cells constantly experience stressful conditions and restrain their protein translation to cope with it. Here, we present a detailed protocol to measure the rate of global protein synthesis using L-azidohomoalanine (L-AHA)-based click chemistry in human senescent fibroblasts. We optimized several aspects of the procedure, including senescence induction, a flow cytometry analysis of senescent cells, and the duration of L-AHA incorporation. This protocol uses senescent human fibroblasts but can be applied to other types of cells or circumstances.For complete details on the use and execution of this protocol, please refer to Lee et al. (2021).

The metabolic syndrome (MetS), defined as the co-occurrence of disorders including obesity, dyslipidemia, insulin resistance, and hepatic steatosis, has become increasingly prevalent in the world over recent decades. Dietary and other environmental factors interacting with genetic predisposition are likely contributors to this epidemic. Among the involved dietary factors, excessive fructose consumption may be a key contributor. When fructose is consumed in large amounts, it can quickly produce many of the features of MetS both in humans and mice. The mechanisms by which fructose contributes to metabolic disease and its potential interactions with genetic factors in these processes remain uncertain. Here, we generated a small F2 genetic cohort of male mice derived from crossing fructose-sensitive and -resistant mouse strains to investigate the interrelationships between fructose-induced metabolic phenotypes and to identify hepatic transcriptional pathways that associate with these phenotypes. Our analysis indicates that the hepatic transcriptional pathways associated with fructose-induced hypertriglyceridemia and hyperinsulinemia are distinct from those that associate with fructose-mediated changes in body weight and liver triglyceride. These results suggest that multiple independent mechanisms and pathways may contribute to different aspects of fructose-induced metabolic disease.

Phenol, a monosubstituted aromatic hydrocarbon with various commercial uses, is a major organic constituent in industrial wastewaters. The ecotoxic action of phenol for aquatic environment is well known. In this study, rapid phenol toxicity tests (1 h) were developed based on chlorophyll a (Chl a) fluorescence and the movement parameters of the freshwater flagellate, Euglena agilis Carter. Phenol significantly reduced the maximum quantum yield (Fv/Fm) of photosystem II (PS II) and the maximum photosynthetic electron transport rate (rETRmax) with median effective concentration (EC50) values of 8.94 and 4.67 mM, respectively. Phenol reduced the motility and triggered change in the swimming velocity of the test organism. Among the parameters tested, velocity was the most sensitive biomarker with an EC50 of 3.17 mM. The EC50 values for Fv/Fm, motility, and velocity appear to overlap the permitted levels of phenol. In conclusion, the photosynthesis and movement of E. agilis can be fast and sensitive risk assessment parameters for the evaluation of phenol toxicity in municipal and industrial effluents. [ABSTRACT FROM AUTHOR]

MEF2 (A-D) transcription factors govern development, differentiation and maintenance of various cell types including neurons. The role of MEF2 isoforms in the brain has been studied using in vitro manipulations with only MEF2C examined in vivo. In order to understand specific as well as redundant roles of the MEF2 isoforms, we generated brain-specific deletion of MEF2A and found that Mef2aKO mice show normal behavior in a range of paradigms including learning and memory. We next generated Mef2a and Mef2d brain-specific double KO (Mef2a/dDKO) mice and observed deficits in motor coordination and enhanced hippocampal short-term synaptic plasticity, however there were no alterations in learning and memory, Schaffer collateral pathway long-term potentiation, or the number of dendritic spines. Since previous work has established a critical role for MEF2C in hippocampal plasticity, we generated a Mef2a, Mef2c and Mef2d brain-specific triple KO (Mef2a/c/dTKO). Mef2a/c/d TKO mice have early postnatal lethality with increased neuronal apoptosis, indicative of a redundant role for the MEF2 factors in neuronal survival. We examined synaptic plasticity in the intact neurons in the Mef2a/c/d TKO mice and found significant impairments in short-term synaptic plasticity suggesting that MEF2C is the major isoform involved in hippocampal synaptic function. Collectively, these data highlight the key in vivo role of MEF2C isoform in the brain and suggest that MEF2A and MEF2D have only subtle roles in regulating hippocampal synaptic function.

Little is known about the natural history of right colonic diverticulitis treated with conservative management. The purpose of this study was to, analyze the short-term outcome of a conservative approach to the treatment of patients with acute right colonic diverticulitis. A retrospective review of the clinical and radiological findings of 62 patients with acute right colonic diverticulitis was carried out. Conservative treatment was provided to 47 patients and surgical treatment to 15 patients with the diagnosis of acute right colonic diverticulitis. An initial ultrasound was performed in 45 of 62 patients (73%) and a CT was performed in 16 of 62 patients (26%). Diverticulitis was confirmed pretreatment diagnosis in 56 of 61 (91.8%) patients who had radiological evaluation. There were seven (11.3%) pericolic abscesses identified as a complication of the diverticulitis. All 47 patients who received conservative management were successfully treated and had improvement of symptoms with no sign of clinical deterioration. For the fifteen patients who had surgery: 5 had right hemicolectomies, 8 had appendectomies without diverticulectomy, 1 had an appendectomy with diverticulectomy, and I had diverticulectomy alone. During a median followup of 23.9 months, two of 55 (3.6%) patients who did not have surgical resection for inflamed diverticulum had recurrences one and ten months after the initial treatment; they were successfully treated again with bowel rest and antibiotics without complication. Conservative treatment should be considered as a safe and effective option for acute right colonic diverticulitis. In addition, a less aggressive approach may be more suitable for recurrent diverticulitis than extended surgical resection. [ABSTRACT FROM AUTHOR]

Nitric oxide is an endogenous thiol-reactive molecule that modulates the functions of many regulatory proteins by a thiol-redox mechanism. NO has now been shown to inhibit the activation of apoptosis signal-regulating kinase 1 (ASK1) in murine fibrosarcoma L929 cells through such a mechanism. Exposure of L929 cells to interferon-γ resulted in the endogenous production of NO and in inhibition of the activation of ASK1 by hydrogen peroxide. The interferon-γ-induced inhibition of ASK1 activity was blocked by NG-nitro-L-arginine, an inhibitor of NO synthase. Furthermore, the NO donor S-nitro-N-acetyl-DLpenicillamine (SNAP) inhibited ASK1 activity in vitro, and this inhibition was reversed by thiol-reducing agents such as dithiothreitol and β-mercaptoethanol. SNAP did not inhibit the kinase activities of MKK3, MKK6, or p38 in vitro. The inhibition of ASK1 by interferon-γ was not changed by 1H-(1,2,4)oxadiazolo[4,3-α]quinoxalin-1-one, an inhibitor of guanylyl cyclase nor was it mimicked by 8-bromo-cyclic GMP. Site-directed mutagenesis revealed that replacement of cysteine 869 of ASK1 by serine rendered this protein resistant to the inhibitory effects both of interferon-y in intact cells and of SNAP in vitro. Coimmunoprecipitation data showed that NO production inhibited a binding of ASK1, but not ASKl(C869S), to MKK3 or MKK6. Moreover, interferon-γ induced the Snitrosylation of endogenous ASK1 in L929 cells. Together, these results suggest that NO mediates the interferon-γinduced inhibition of ASK1 in L929 cells through a thiolredox mechanism. [ABSTRACT FROM AUTHOR]

Diverse stimuli initiate the activation of apoptotic signaling pathways that often causes nuclear DNA fragmentation. Here, we report a new antiapoptotic protein, a caspase-activated DNase (CAD) inhibitor that interacts with ASK1 (CIIA). CIIA, by binding to apoptosis signal-regulating kinase 1 (ASK1), inhibits oligomerization-induced ASK1 activation. CIIA also associates with CAD and inhibits the nuclease activity of CAD without affecting caspase-3-mediated ICAD cleavage. Overexpressed CIIA reduces H[sub2]O[sub2]- and tumor necrosis factor-α-induced apoptosis. CIIA antisense oligonucleotides, which abolish expression of endogenous CIIA in murine L929 cells, block the inhibitory effect of CIIA on ASK1 activation, deoxyribonucleic acid fragmentation, and apoptosis. These findings suggest that CIIA is an endogenous antagonist of both ASK1- and CAD-mediated signaling. [ABSTRACT FROM AUTHOR]

Aim: To determine the influence of anthropomorphic parameters on the relationship between patient centering, mean computed tomography (CT) numbers and quantitative image noise in abdominal CT., Methods: Our Institutional Review Board approved study included 395 patients (age range 21-108, years; male:female = 195:200) who underwent contrast-enhanced abdominal CT on a 16-section multi-detector row scanner (GE LightSpeed 16). Patient centering in the gantry isocenter was measured from the lateral localizer radiograph (off center S = patient off centered superior to isocenter; off center I = patient off centered inferior to isocenter). Mean CT numbers (Hounsfield Units: HU) and noise (standard deviation of CT numbers: SD) were measured in the anterior (aHU, aSD) and posterior (pHU, pSD) abdominal wall subcutaneous fat and liver parenchyma (LivHU, LivSD) at the level of the porta hepatis. Patients' age, gender, weight, body mass index and maximal anteroposterior diameter were recorded. The data were analyzed using linear regression analysis., Results: Most patients (81%; 320/395) were not correctly centered in the gantry isocenter for abdominal CT scanning. Mean CT numbers in the abdominal wall increased significantly with an increase in the off-centering distance, regardless of the direction of the off-center (P < 0.05). There was a substantial increase in pSD (P = 0.01) and LivSD (P = 0.017) with off-centering. Change in mean CT numbers and image noise along the off-center distance was influenced by the patient size (P < 0.01)., Conclusion: Inappropriate patient centering for CT scanning adversely affects the reliability of mean CT numbers and image noise.