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We report a rare case of chronic myelomonocytic leukemia (CMML) with pericardial effusion. After receving the diagnosis of CMML, she had been successfully treated with hydroxycarbamide (HU). However, she was admitted to our hospital due to pericardial effusion. The majority of the cells in the pericardial fluid were monocytes. We made the diagnosis of pericardial involvement with CMML cells and intravenously administered etoposide (100 mg/body daily for 5 days). Although CMML cells disappeared from the peripheral blood, the pericardial effusion still persisted. This case indicates that pericardial effusion is a possible and life-threatening complication in CMML patients despite stably controlled leukocytes."
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Myelodysplastic-Myeloproliferative Diseases
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Zika virus (ZIKV) belongs to the positive-sense single-stranded RNA-containing Flaviviridae family. Its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns, and an urgency to develop a therapeutic strategy against ZIKV infection. However, there is no currently approved antiviral against ZIKV. Here we present a comprehensive overview on recent progress in structure-function investigation of ZIKV NS5 protein, the largest non-structural protein of ZIKV, which is responsible for replication of the viral genome, RNA capping and suppression of host interferon responses. Structural comparison of the N-terminal methyltransferase domain and C-terminal RNA-dependent RNA polymerase domain of ZIKV NS5 with their counterparts from related viruses provides mechanistic insights into ZIKV NS5-mediated RNA replication, and identifies residues critical for its enzymatic activities. Finally, a collection of recently identified small molecule inhibitors against ZIKV NS5 or its closely related flavivirus homologues are also discussed.
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Viral Nonstructural Proteins
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Plasmids and bacteriophage represent the classical vectors for gene transfer within the horizontal gene pool. However, the more recent discovery of an increasing array of other mobile genetic elements (MGE) including genomic islands (GIs), conjugative transposons (CTns), and mobilizable transposons (MTns) which each integrate within the chromosome, offer an increasingly diverse assemblage contributing to bacterial adaptation and evolution. Molecular characterisation of these elements has revealed that they are comprised of functional modules derived from phage, plasmids, and transposons, and further that these modules are combined to generate a continuum of mosaic MGE. In particular, they are comprised of any one of three distinct types of recombinase, together with plasmid-derived transfer and mobilisation gene functions. This review highlights both the similarities and distinctions between these integrating transferable elements resulting from combination of the MGE toolbox.
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Transposon Resolvases
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The bioconversion of chitin into N-acetyl-d-glucosamine (GlcNAc) using chitinolytic enzymes is one of the important avenues for chitin valorization. However, industrial applications of chitinolytic enzymes have been limited by their poor thermostability. Therefore, it is necessary to discover thermostable chitinolytic enzymes for GlcNAc production from chitin. In this study, two chitinolytic enzyme-encoding genes CaChiT and CaHex from Caldicellulosiruptor acetigenus were identified and heterologously expressed in Escherichia coli. The purified recombinant CaChiT and CaHex showed optimal activities at 70 degrees C and 90 degrees C respectively, and exhibited good thermostability over a range of temperature below 70 degrees C and broad pH stability at pH range of 3.0-8.0. CaChiT and CaHex were active on colloidal chitin, pNP-(GlcNAc)(2), pNP-(GlcNAc)(3), and pNP-GlcNAc, pNP-(GlcNAc)(2), pNP-(GlcNAc)(3), pNP-Glc respectively. Besides, the chitin oligosaccharides and colloidal chitin hydrolysis profiles revealed that CaChiT degraded chitin chains through exo-mode of action. Furthermore, CaChiT and CaHex exhibited a synergistic effect in the degradation of colloidal chitin, reaching 0.60 mg/mL of GlcNAc production after 1 h incubation. These results suggested that a combination of CaChiT and CaHex have great potential for industrial applications in the enzymatic production of GlcNAc from chitin-containing biowastes.
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beta-N-Acetylhexosaminidases
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Emmonsia crescens, an agent of adiaspiromycosis, Blastomyces dermatitidis, the agent of blastomycosis, and Histoplasma capsulatum, the agent of histoplasmosis, are known to form meiotic (sexual) stages in the ascomycete genus Ajellomyces (Onygenaceae, Onygenales), but no sexual stage is known for E. parva, the type species of the genus Emmonsia. To evaluate relationships among members of the putative Ajellomyces clade, large-subunit ribosomal and internal transcribed spacer region DNA sequences were determined from PCR-amplified DNA fragments. Sequences were analyzed phylogenetically to evaluate the genetic variation within the genus Emmonsia and evolutionary relationships to other taxa. E. crescens and E. parva are distinct species. E. crescens isolates are placed into two groups that correlate with their continents of origin. Considerable variation occurred among isolates previously classified as E. parva. Most isolates are placed into two closely related groups, but the remaining isolates, including some from human sources, are phylogenetically distinct and represent undescribed species. Strains of B. dermatitidis are a sister species of E. parva. Paracoccidioides brasiliensis and Histoplasma capsulatum are ancestral to most Emmonsia isolates, and P. brasiliensis, which has no known teleomorph, falls within the Ajellomyces clade.
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Chrysosporium
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This review summarizes our current understanding of lymphocytic esophagitis (LE), a novel form of chronic esophagitis that incorporates distinctive histologic, clinical, and endoscopic features. First described as a histologic entity, a diagnosis of LE requires intraepithelial lymphocytosis without significant granulocytic inflammation and some evidence of epithelial damage; the rationale for and studies supportive of these histologic criteria are discussed within. Clinically, the majority of patients who present with histologically confirmed LE are older women or patients with underlying immunologic abnormalities, such as Crohn disease, rheumatologic disorders, or common variable immunodeficiency. The most common presenting symptom of LE is dysphagia, and the endoscopic findings can vary from normal mucosa to mucosal changes that resemble eosinophilic esophagitis: edema, rings, furrows, and plaques. The incidence of luminal strictures and the persistent dysphagia and/or lymphocytosis present in some patients provide evidence that LE is a chronic inflammatory disorder, at least within a subset of individuals. Several histologic mimics of LE are examined, as are disagreements surrounding the LE diagnosis.
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Esophageal Mucosa
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Global rollout of the new antituberculosis drug bedaquiline has been slow, in part reflecting concerns about spread of bedaquiline resistance. Acquired resistance to bedaquiline is especially likely in patients with extensively drug-resistant (XDR) tuberculosis. However, the very high mortality rates of patients with XDR not receiving bedaquiline, and promising cohort study results, suggest these patients also have greatest need for the drug. In this Personal View, we argue that resistance concerns should not forestall use of bedaquiline in patients with XDR tuberculosis. Our position in favour of increased access to bedaquiline for these patients is based on three arguments. First, the use of drug combinations that include bedaquiline might prevent spread of XDR disease to others in the community. Second, until new combination regimens of novel drugs for XDR tuberculosis become available, patients with XDR disease and their infected contacts will face equivalent outcomes if bedaquiline is either not provided because of policy, or not effective because of resistance. Finally, because resistance to bedaquiline and other antituberculosis drugs is caused by mutations within a single bacterial chromosome, use of bedaquiline in patients with XDR tuberculosis will not substantially increase the risk of bedaquiline resistance in patients with drug-susceptible or multidrug-resistant (nonâÂÂXDR) tuberculosis strains.
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Diarylquinolines
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Receptor activator of NF-kappaB ligand (RANKL) induces generation of intracellular reactive oxygen species (ROS), which act as second messengers in RANKL-mediated osteoclastogenesis. Dual oxidase maturation factor 1 (Duoxa1) has been associated with the maturation of ROS-generating enzymes including dual oxidases (Duox1 and Duox2). In the progression of osteoclast differentiation, we identified that only Duoxa1 showed an effective change upon RANKL stimulation, but not Duox1, Duox2, and Duoxa2. Therefore, we hypothesized that Duoxa1 could independently act as a second messenger for RANKL stimulation and regulate ROS production during osteoclastogenesis. Duoxa1 gradually increased during RANKL-induced osteoclastogenesis. Using siRNA or retrovirus transduction, we found that Duoxa1 regulated RANKL-stimulated osteoclast formation and bone resorption positively. Furthermore, knockdown of Duoxa1 decreased the RANKL-induced ROS production. During Duoxa1-related control of osteoclastogenesis, activation of tumor necrosis factor receptor-associated factor 6 (TRAF6)-mediated early signaling molecules including MAPKs, Akt, IkappaB, Btk, Src and PLCgamma2 was affected, which sequentially modified the mRNA or protein expression levels of key transcription factors in osteoclast differentiation, such as c-Fos and NFATc1, as well as mRNA expression of osteoclast-specific markers. Overall, our data indicate that Duoxa1 plays a crucial role in osteoclastogenesis via regulating RANKL-induced intracellular ROS production and activating TRAF6-mediated signaling.
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Dual Oxidases
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BACKGROUND: With the development of left ventricular pacing for cardiac resynchronization, there is an interest in the possibility of improving ventricular antitachycardia pacing (ATP) efficacy by pacing from the LV electrode(s). OBJECTIVE: This study assessed the efficacy of pacing delivered from the left coronary vein (LCV) compared to that delivered from the right ventricular apex (RVA) upon ventricular tachycardia (VT) induction and termination. METHODS: Sixty patients undergoing provocative ventricular electrophysiology (EP) studies in three centers were enrolled. Multipolar EP catheters were placed in the atrium, the RVA, and LCV. VT induction was attempted from the RVA and LCV in random order. Upon detection of monomorphic VT, burst ATP for up to 10 pulses at 88% VT cycle length was delivered from the RVA or LCV, in a random order, and crossed over when possible. Identical VT morphologies were reinduced to allow paired comparison of RVA versus LCV ATP. RESULTS: Data from 55 patients were analyzed. Thirty-four morphologically distinct monomorphic VT types were induced in 22 patients. ATP succeeded in 18 (55%) and VTs in 13 patients. RVA ATP terminated 15 of 23 (65%) VTs, and LCV ATP terminated 10 of 23 (43%) VTs (P = 0.14). ATP delivered ipsilateral to the earliest activation site required 5.0 + or - 2.6 pulses to terminate compared to 4.8 + or - 1.7 pulses when delivered from the contralateral site (P = 0.90). Paired comparison was possible for 13 VT morphologies in 11 patients. Paired RVA and LCV ATP efficacy was identical (54%vs 54%, P = 1.0). CONCLUSION: ATP delivered from a LCV lead offers no efficacy advantage over pacing from the RVA.
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Tachycardia, Ventricular
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Although monosodium glutamate (MSG) is classified as a causative substance of headache in the International Classification of Headache Disorders 3rd edition (ICHD-III beta), there is no literature in which causal relationship between MSG and headache was comprehensively reviewed. We performed systematic review of human studies which include the incidence of headache after an oral administration of MSG. An analysis was made by separating the human studies with MSG administration with or without food, because of the significant difference of kinetics of glutamate between those conditions (Am J Clin Nutr 37:194-200, 1983; J Nutr 130:1002S-1004S, 2000) and there are some papers which report the difference of the manifestation of symptoms after MSG ingestion with or without food (Food Chem Toxicol 31:1019-1035, 1993; J Nutr 125:2891S-2906S, 1995). Of five papers including six studies with food, none showed a significant difference in the incidence of headache except for the female group in one study. Of five papers including seven studies without food, four studies showed a significant difference. Many of the studies involved administration of MSG in solution at high concentrations (>2 %). Since the distinctive MSG is readily identified at such concentrations, these studies were thought not to be properly blinded. Because of the absence of proper blinding, and the inconsistency of the findings, we conclude that further studies are required to evaluate whether or not a causal relationship exists between MSG ingestion and headache.
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Sodium Glutamate
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Disturbed vaginal microbiota have a role in the persistence of high-oncogenic-risk human papillomavirus (hrHPV) and Gardnerella spp. is closely related with this condition. Such bacteria are the major source of cervicovaginal sialidases, important for microbiota alterations. The sialidase-encoding gene nanH3 is account for their sialidase activity. Thus, a subset of 212 women positive for hrHPV at the first visit were included in the analysis of the current study aiming to compare the loads of nanH3 in cervicovaginal fluid (CFV) of women with persistent hrHPV infection and with those cleared the infection after a year. Participants were assigned to two study groups named persistence" (n = 124, 53.22%) or "clearance" (n = 88, 37.77%), according to the HPV status upon enrollment and follow-up. Absolute quantification of nanH3 gene was performed using quantitative real-time PCR (qPCR). Persistence and clearance group did not show statistical difference in the load of nanH3 gene (p = 0.19). When considering the subset of women with HPV16, differences in number of copies of nanh3 gene was observed between the persistent (7.39E+08 copies/muL) and clearance group (2.85E+07 copies/muL) (p = 0.007). Therefore, baseline loads of nanH3 gene is increased in women that persist with cervical HPV16 infection after 12 months."
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Human Papillomavirus Viruses
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We report the use of nivazol in a patient with Nelson's syndrome. Nivazol was highly effective in reducing ACTH secretion but, contrary to reports of its use in other primates, in our patient nivazol did have systemic glucocorticoid effects.
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Nelson Syndrome
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The World Health Organisation first identified, in 1975, the need for health professionals to be educated in the area of sexuality. Since then, studies exploring aspects of educational preparation of general nurses in relation to sexuality, found that there was an 'absence' of education in this area of practice. This paper reports findings on the educational discourses that shape mental health nurses' understandings of sexuality. Unstructured interviews were conducted with 27 consenting mental health nurses working in the Republic of Ireland. Data were analysed using the principles of Grounded Theory. Findings suggest that participants were exposed to a subtle network of legitimised sexual discourses during primary, secondary, and professional socialisation. These discourses provided participants with a view of sexuality that emphasised taboo, privatisation, pathology, and control. Social, political, or rights-based discourses that could have provided participants with the knowledge and clinical competence necessary to include sexuality in an open and confident manner within the horizons of nursing practice were absent. These findings challenge educators involved in curriculum development to rethink the fundamental philosophy that is shaping mental health nursing curricula. They also challenge educators to rethink their ideas around the meaning of 'absence' in relation to education.
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Psychiatric Nursing
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Fifty-nine nursing home patients (average age, 79.9 +/- .9 years) receiving chlorpropamide were screened with a serum sodium determination. Nine patients (15.3 percent) had a serum sodium concentration less than 135 mEq/L; six of these patients (10.2 percent) had a serum sodium equal to or less than 130 mEq/L; none of the patients had a serum sodium less than 125 mEq/L. Five hyponatremic patients (Na less than or equal to 130 mEq/L) and nine normonatremic patients (Na greater than or equal to 135 mEq/L) were screened with a standardized mental status examination and additional laboratory studies. The hyponatremic patients were switched to tolazamide after a one-week wash-out period, and the mental status examination and laboratory studies were repeated in both groups four weeks later. One patient in the hyponatremic group died during the course of the study; the other four became normonatremic on tolazamide. Mental status scores increased significantly in the hyponatremic group, 16.0 +/- 3.6 to 20 +/- 4.6 (a 37.3 +/- 21.5 percent increase), compared with the normonatremic group, 14.5 +/- 2.6 to 15.8 +/- 2.9 (a 7.8 +/- 3.2 percent increase). There were no significant differences in serum glucose, creatinine, chlorpropamide, or antidiuretic hormone concentrations between the two groups. It is recommended that periodic serum sodium determinations be obtained in geriatric patients receiving chlorpropamide.
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Chlorpropamide
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Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by the presence of multiple lipoprotein phenotypes that increase the risk of premature coronary heart disease. In a previous study, we identified an intragenic microsatellite marker within the protocadherin 15 (PCDH15) gene to be associated with high triglycerides (TGs) in Finnish dyslipidemic families. In this study we analyzed all four known nonsynonymous SNPs within PCDH15 in 1,268 individuals from Finnish and Dutch multigenerational families with FCHL. Association analyses of quantitative traits for SNPs were performed using the QTDT test. The nonsynonymous SNP rs10825269 resulted in a P = 0.0006 for the quantitative TG trait. Additional evidence for association was observed with the same SNP for apolipoprotein B levels (apo-B) (P = 0.0001) and total cholesterol (TC) levels (P = 0.001). None of the other three SNPs tested showed a significant association with any lipid-related trait. We investigated the expression of PCDH15 in different human tissues and observed that PCDH15 is expressed in several tissues including liver and pancreas. In addition, we measured the plasma lipid levels in mice with loss-of-function mutations in Pcdh15 (Pcdh15(av-Tg) and Pcdh15(av-3J)) to investigate possible abnormalities in their lipid profile. We observed a significant difference in plasma TG and TC concentrations for the Pcdh15(av-3J) carriers when compared with the wild type (P = 0.013 and P = 0.044, respectively). Our study suggests that PCDH15 is associated with lipid abnormalities."
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Hyperlipidemia, Familial Combined
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The murine peritoneal cavity contains factors that inhibit the in vitro growth and colony formation of macrophages. The inhibition of macrophage growth is not due to cell death. In the presence of inhibitors, the growth of colony-forming macrophages is suppressed, and small clusters are formed as a result of limited proliferation. The more mature mononuclear phagocytes (blood monocytes and peritoneal exudate macrophages) are more sensitive to the overall inhibitory effect of the peritoneal inhibitors than the less mature bone marrow mononuclear phagocytes. Furthermore, using dialysis and Amicon ultrafiltration, at least two inhibitors with differential inhibitory effects can be demonstrated. The colony formation of bone marrow mononuclear phagocytes is suppressed mainly by a protease-resistant, small molecular weight (less than 1,000) dialyzable inhibitor. In contrast, peritoneal exudate macrophages are sensitive to both the small molecular weight inhibitor and a protease-sensitive, large molecular weight (greater than 12,000), nondialyzable inhibitor. The data suggest a possible existence of a dual inhibitor control on the proliferation of mononuclear phagocytes in vivo. In addition, the in vitro cultured peritoneal exudate cells are capable of producing inhibitors that mimic the activity of the in vivo inhibitors.
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Growth Inhibitors
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BACKGROUND: Sleep abnormalities frequently occur in intensive care unit (ICU) patients, and the consequences of sleep abnormalities in patients who undergo off-pump coronary artery bypass graft (OPCABG) surgery are particularly significant. Although many interventions have been reported to improve sleep, few sleep promotion protocols have been designed specifically for patients in cardiac ICUs. AIMS AND OBJECTIVES: This study aimed to explore the effects of an evidence-based sleep promotion protocol on patients who underwent OPCABG in a cardiac ICU. DESIGN: A quasi-experimental study was conducted in a comprehensive hospital in Shandong province of China. METHODS: Overall, 67 participants were recruited (37 in the control group and 30 in the intervention group). An evidence-based sleep promotion protocol was developed by a 10-member interprofessional collaborative team and then applied. Sound levels, light intensity, and the number of nocturnal interventions were compared between groups. The Chinese version of the Richards-Campbell Sleep Questionnaire (RCSQ) was used to compare intergroup sleep status on two consecutive postoperative nights. RESULTS: No significant differences were found for demographics or disease severity between the groups. In the intervention group, sound levels and light intensity were significantly lower at various times, and nocturnal interventions were significantly less frequent over the two consecutive nights. RCSQ scores were significantly higher in the intervention group for both nights. CONCLUSIONS: The sleep promotion protocol reduced sound levels, night-time light intensity, the number of nocturnal interventions, and improved sleep among OPCABG patients in a cardiac ICU. RELEVANCE TO CLINICAL PRACTICE: Evidence-based practice can help to promote good quality of care, improve patient outcomes, and advance nursing in clinical settings."
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Coronary Artery Bypass, Off-Pump
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The size of the incisions for free muscle flaps is often very large, and a source of deep adhesions and unaesthetic scars. But it is justified by performing the microsurgical step comfortably. In the hopes of shortening the size of incisions, the goal of this work was to study the feasibility of vascular microanastomoses through an endoscopic approach. The material consisted of two cadavers, a telemanipulator, and a vascular clamp. The antebrachial skin was detached then distended by gas insufflation. Four incisions, 1cm each, allowed the insertion of four trocarts connected to the telemanipulator. The artery was dissected (radial or ulnar) and the vascular clamp was introduced under the skin through one of the trocarts, and then installed on the dissected artery. The vascular anastomosis was performed with the use of a 10/0 nylon suture. The anastomosis lasted 2 hours under insufflation without any leak. The two arteries were identified then dissected without difficulty. The anastomosis was performed in good conditions. The assembling and disassembling of the clamp were time consuming. The main difficulties were caused by a long suture and a very fragile needle. Our results demonstrate the feasibility of vascular microanastomosis through an endoscopic approach. The next step is to perform the first clinical case for example on a latissimus dorsi free muscle flap.
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Angioscopes
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Non-pharmacologic interventional techniques for treatment and management of almost all cardiac arrhythmias have greatly expanded over the past decade. These newer interventional electrophysiologic techniques continue to demonstrate increasing success at achieving their targeted goals, and enhancing the patient's quality of life. However, like all interventional procedures, complications may result. In this article we provide the reader with an overview of the more common and significant adverse events that may follow electrophysiologic and pacing procedures, and how best to recognize and manage these complications. After providing the reader with an overview of the complications inherent to all electrophysiologic procedures, we will detail the adverse events intrinsic to specific therapeutic electrophysiologic interventions (DC cardioversion, pharmacologic-based cardioversion, antitachycardia pacing, and ablation of specific arrhythmias). In the last part of the review, we will delineate complications associated with pacing procedures (pacemaker and defibrillator implantation, biventricular pacing and pacing lead extraction)."
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Electrophysiologic Techniques, Cardiac
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Skrjabinodon castillensis n. sp. is described and illustrated here, based on specimens found in the large intestines of Homonota horrida (province San Juan) and Homonota darwinii (province Neuquen) (Squamata: Phyllodactylidae) from Argentina. The new species is assigned to Skrjabinodon based lateral alae present in males, absent in females. Lateral alae beginning midway between lips and nerve ring and ending just posterior to first pair of caudal papillae. Females with vulva near esophageal bulb. In males, caudal alae absent, paired caudal papillae present. Skrjabinodon castillensis n. sp. represents the 9th species from the Neotropical realm. The new species differs from all other species assigned to Skrjabinodon by morphology of tail filament and number of tail filament spines. Skrjabinodon castillensis n. sp. is the only species of this genus known from Argentina. A key to the species of Skrjabinodon in the Neotropical realm is provided.
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Oxyurida
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During the past decade there have been significant advances in understanding the basic science of musculoskeletal injury and healing. These new concepts alter the approach to injury management and rehabilitation for clinicians managing musculoskeletal conditions. This article examines the most recent advances in the treatment of regional musculoskeletal pain, and muscle and tendon sports injury. Specifically, developments in understanding the pathogenesis of muscle and tendon sports injuries, newer imaging modalities, and updated treatment paradigms and their rationale are reviewed. The purpose of this review is to provide the clinician with new approaches for treating nonsurgical muscle and tendon injuries.
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Sprains and Strains
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The current studies examine the presence of the Na+-HCO3(-) cotransporter in chicken enterocytes and its role in cytosolic pH (pHi) regulation. The pH-sensitive dye 2',7'-bis(carboxyethyl)-5,6-carboxy-fluorescein (BCECF) was used to monitor pHi. Under resting conditions, pHi was 7.25 in solutions buffered with bis(2-hydroxyethyl)-1-piperazine ethanesulphonic acid (HEPES) and 7.17 in those buffered with HCO3(-). Removal of external Na+ decreased pHi and readdition of Na+ rapidly increased pHi towards the control values. These Na+-dependent changes were greater in HCO3(-)- than in HEPES-buffered solutions. In HCO3- - free solutions the Na+-dependent changes in pHi were prevented by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) and unaffected by 4,4'-diisothiocyanatostilbene disulphonic acid (H2-DIDS). In the presence of HCO3-, the Na+-induced changes in pHi were sensitive to both EIPA and H2-DIDS. In the presence of EIPA, cells partially recovered from a moderate acid load only when both Na+ and HCO3- were present. This pHi recovery, which was EIPA resistant, and dependent on Na+ and HCO3-, was inhibited by H2-DIDS and occurred at equal rates in both Cl--containing and Cl--free solutions. Kinetic analysis of the rate of HCO3- and Na+-dependent pHi recovery from an acid load as a function of the Na+ concentration revealed first-order kinetics with a Michaelis constant, Km, of 11 mmol/l Na+. It is concluded that in HCO3(-) buffered solutions both the Na+/H+ exchanger and the Na+-HCO3(-) cotransporter participate in setting the resting pHi in isolated chicken enterocytes and help the recovery from acid loads."
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
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Devriesea agamarum causes dermatitis and septicaemia in a variety of lizards, notably those belonging to the genus Uromastyx, whereas other species such as bearded dragons (Pogona vitticeps) seem to be asymptomatic carriers. Using amplified fragment length polymorphism (AFLP), the relatedness between 69 D. agamarum isolates was examined. The isolates derived from 44 diseased lizards, of which 31 belonged to the genus Uromastyx, and from 25 healthy lizards, of which 21 were bearded dragons. Eight AFLP genotypes were obtained, four of which comprised 93% of the isolates. These four genotypes were each present in 2, 2, 8 and 13 different captive colonies. Up to three genotypes were isolated from a single infected colony simultaneously. On two occasions, the same genotype was found in healthy bearded dragons and diseased Uromastyx lizards from the same colony, confirming the role of the former as an asymptomatic source of infection for the latter. Two genotypes, comprising 12 isolates, were exclusively associated with diseased Uromastyx lizards, suggesting strain dependent host adaptation. Finally, D. agamarum was shown to be able to persist for at least seven years in a lizard colony, persistently causing severe disease in several lizard species.
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Actinomycetales Infections
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Cubital tunnel syndrome is the second most common nerve compression syndrome observed in the upper extremity. Mechanical irritation of the ulnar nerve is also found in the upper and the lower arm even though cubital tunnel syndrome is documented most of the time. Apart from clinical examination electrophysiological testing is the most important contributor to the therapy decision. Depending on the clinical manifestation conservative treatment with elbow splinting may be appropriate. In the event of persistent or advanced nerve irritation surgical decompression may be the sensible intervention. Open or endoscopically assisted in situ decompression is currently recommended as the primary intervention while anterior transposition of the ulnar nerve is recommended for revision surgery.
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Cubital Tunnel Syndrome
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BACKGROUND: Evidence supports phenomenological, clinical, epidemiological and biological links between problem/pathological gambling and tobacco use. An improved understanding of the relationship would be helpful in treating individuals with co-occurring pathological gambling and nicotine dependence. METHODS: This study investigates the tobacco use behaviors of 225 adults (mean age +/- SD = 47.3 +/- 11.0 years; number of women = 120 [53.3%]) who were recruited for pharmacological treatment of pathological gambling. All subjects met criteria for pathological gambling based upon the Structured Clinical Interview for Pathological Gambling (SCI-PG), a DSM-IV-based diagnostic interview, and were assessed at baseline with multiple reliable and valid measures of gambling severity. RESULTS: 159 (70.7%) subjects were either current (n = 110; 48.9%) or prior daily smokers (n = 49; 21.8%). Compared with the group of never smokers, the group of current and prior daily smokers was more likely to be older (F = 3.55; df = 2, 222; p = 0.030), be female (chi square = 10.85; df = 2; p = 0.004), and have stronger urges to gamble (F = 128.15; df = 2,222; p < 0.001). CONCLUSIONS: Daily tobacco use in treatment-seeking pathological gamblers is common and associated with more severe urges to gamble. Treatments targeting urges in individuals with pathological gambling and current or prior daily tobacco use should be examined.
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Tobacco Use Disorder
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Coumarin, o-coumaric, and kaurenoic acid are bioactive compounds usually found in the leaves of Mikania laevigata. Genetic and environmental variations in the secondary metabolites of plants may have implications for their biological effects. Three different accessions of M. laevigata cultivated in four sites between the Equator and the Tropic of Capricorn in Brazil were evaluated aiming to present potential raw materials and discuss relationships among these three bioactive compounds. The results revealed effects of plant accessions and environmental factors and suggested two contrasting chemical phenotypes of M. laevigata. The first phenotype presented the highest levels of kaurenoic acid (2283 +/- 316 mg/100 g) besides lower levels of coumarin (716 +/- 61 mg/100 g), which was also stimulated by the environment and mild climate at the site nearest to the Tropic of Capricorn. The other phenotype presented the lowest levels of kaurenoic acid (137 +/- 17 mg/100 g) besides higher levels of coumarin (1362 +/- 108 mg/100 g), which was also stimulated by the environment and tropical climate at the site nearest to the Equatorial beach.
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Mikania
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The link between cancer metabolism and immunosuppression, inflammation and immune escape has generated major interest in investigating the effects of low pH on tumor immunity. Indeed, microenvironmental acidity may differentially impact on diverse components of tumor immune surveillance, eventually contributing to immune escape and cancer progression. Although the molecular pathways underlying acidity-related immune dysfunctions are just emerging, initial evidence indicates that antitumor effectors such as T and NK cells tend to lose their function and undergo a state of mostly reversible anergy followed by apoptosis, when exposed to low pH environment. At opposite, immunosuppressive components such as myeloid cells and regulatory T cells are engaged by tumor acidity to sustain tumor growth while blocking antitumor immune responses. Local acidity could also profoundly influence bioactivity and distribution of antibodies, thus potentially interfering with the clinical efficacy of therapeutic antibodies including immune checkpoint inhibitors. Hence tumor acidity is a central regulator of cancer immunity that orchestrates both local and systemic immunosuppression and that may offer a broad panel of therapeutic targets. This review outlines the fundamental pathways of acidity-driven immune dysfunctions and sheds light on the potential strategies that could be envisaged to potentiate immune-mediated tumor control in cancer patients.
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Tumor Escape
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Social learning facilitates informed decision making about foraging, mating and anti-predatory tactics among animals. We investigated the occurrence of social learning through performance in a spatial task among wild-caught zebrafish. Individual fish (demonstrators) were trained through a novel food finding task in a maze for 8days. Demonstrators were paired with naive individuals (observers) and subjected to trials through maze for 4days followed by removal of the demonstrators and further training of observers for 4 more days. Paired naive individuals were subjected to trials through the maze in similar fashion separately and the performance of observers were compared with theirs. Our results showed that observers associated with knowledgeable conspecifics did not perform the task better than naive-paired individuals. Performances across trials improved for both sets while number of mistakes committed increased indicating no learning. The presence of a demonstrator could have increased the observer's activity, increasing the chances for the observer to come in contact with the stimulus. Performance of observers and naive-paired fish were probably affected by social distraction. Sex and body-size of the dyads (demonstrator-observer pairs and naive pairs) could also have interfered with information transfer among individuals.
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Maze Learning
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Serum IgG subclasses were studied in 19 mothers of infants with serious infections caused by group B streptococci (GBS) and compared with a control group of 20 mothers of healthy infants. 13 of 19 mothers showed decreased subclass levels: 10 of 19 low IgG2, 9 of 19 low IgG1 and 4 of 19 low IgG3. The levels of IgG1, IgG2 and IgG3 were significantly lower among mothers of GBS-infected infants than among the controls. Thus, there is indirect evidence that the infants were immunodeficient at birth.
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Dysgammaglobulinemia
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The family Paramyxoviridae consists of a group of large, enveloped, negative-sense, single-stranded RNA viruses and contains many important human and animal pathogens. Molecular and biochemical characterization over the past decade has revealed an extraordinary breadth of biological diversity among this family of viruses. Like all enveloped viruses, paramyxoviruses must fuse their membrane with that of a receptive host cell as a prerequisite for viral entry and infection. Unlike most other enveloped viruses, the vast majority of paramyxoviruses contain two distinct membrane-anchored glycoproteins to mediate the attachment, membrane fusion and particle entry stages of host cell infection. The attachment glycoprotein is required for virion attachment and the fusion glycoprotein is directly involved in facilitating the merger of the viral and host cell membranes. Here we detail important functional, biochemical and structural features of the attachment and fusion glycoproteins from a variety of family members. Specifically, the three different classes of attachment glycoproteins are discussed, including receptor binding preference, their overall structure and fusion promotion activities. Recently solved atomic structures of certain attachment glycoproteins are summarized, and how they relate to both receptor binding and fusion mechanisms are described. For the fusion glycoprotein, specific structural domains and their proposed role in mediating membrane merger are illustrated, highlighting the important features of protease cleavage and associated tropism and virulence. The crystal structure solutions of both an uncleaved and a cleavage-activated metastable F are also described with emphasis on how small conformational changes can provide the necessary energy to mediate membrane fusion. Finally, the different proposed fusion models are reviewed, featuring recent experimental findings that speculate how the attachment and fusion glycoproteins work in concert to mediate virus entry."
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Hemagglutinin Glycoproteins, Influenza Virus
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The sinoatrial nodes (SAN) were observed, dissected, and measured on 95 adults and 30 child hearts under a dissection microscope. The majority of the SANs in adults are characterized by their pale color, firm consistency, and the location in relation to the penetration of the SAN artery, and they can be located in the superior part of the terminal sulcus. The SANs in children, however, are not easily discerned. The variation of the apex of the right auricular crest and the notch in the superior part of the terminal sulcus have been described, and the present authors suggested that the trigone of the SAN could be used as an important landmark to identify the SAN. The surface features on the SAN, its relationship to the surrounding myocardium and its surgical significance during operation are further discussed.
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Cardiovascular System
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OBJECTIVES: The purpose of the present study was to investigate differences in neck muscle stiffness between patients with chronic neck pain and asymptomatic control group. METHODS: Thirty-five patients with chronic neck pain and 35 age-matched asymptomatic participants enrolled in the study. Shear wave velocity (SWV) of upper trapezius, levator scapulae, splenius capitis, and sternocleidomastoid muscles were obtained using an ACUSON S3000 Ultrasonography Device (Siemens Medical Solutions, Mountain View, California). In patients with chronic neck pain, pain intensity was measured by Numerical Rating Scale and disability level was measured by Neck Disability Index. RESULTS: The SWV of splenius capitis was similar in both groups (P = .985); however, SWV of upper trapezius (P = .001), levator scapulae (P = .038), and sternocleidomastoid (P = .001) of the patients with chronic neck pain were higher compared with the asymptomatic controls groups. Numerical Rating Scale and Neck Disability Index scores did not correlate with the SWV of the selected muscles (P > .05). CONCLUSIONS: Stiffness of upper trapezius, levator scapulae, and sternocleidomastoid muscles in patients with neck pain were higher compared to asymptomatic participants. In addition, severity of pain and disability did not correlate to stiffness of these muscles in patient with chronic neck pain.
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Neck Muscles
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Thermoplastic masks made of polyester resin are used to immobilize patients receiving radiation therapy. We describe a case of allergic contact dermatitis (ACD) to a thermoplastic mask worn by a child receiving proton beam therapy for treatment of medulloblastoma. ACD to a thermoplastic mask in an adult was first reported in 2018. (J Med Case Rep. 2018;12:181) To our knowledge, ACD to a thermoplastic mask has not been reported previously in the pediatric population.
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Dermatitis, Allergic Contact
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Methylprednisolone acetate (MPA) has a long history of use in the treatment of sciatic pain and other neuropathic pain syndromes. In several of these syndromes, MPA is administered in the epidural space. On a limited basis, MPA has also been injected intrathecally in patients suffering from postherpetic neuralgia and complex regional pain syndrome. The reports on efficacy of intrathecal administration of MPA in neuropathic pain patients are contradictory, and safety is debated. In this review, we broadly consider mechanisms whereby glucocorticoids exert their action on spinal cascades relevant to the pain arising after nerve injury and inflammation. We then focus on the characteristics of the actions of MPA in pharmacokinetics, efficacy, and safety when administered in the intrathecal space.
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Methylprednisolone
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We describe a tool, Spatio-Temporal Association Mapping of Proteins (STAMP), for identifying protein interactomes via proximity labeling. For a proof-of-principle study, we use cytidine 5'-triphosphate synthase (CTPS) as an example. CTPS, a metabolic enzyme, forms filamentous structures termed cytoophidia in various tissues. We apply STAMP to a variety of developmental stages and tissues in Drosophila including adult ovaries. Using a cell-specific GAL4 driver, we verify that TurboID can biotinylate the bait protein CTPS, making possible the identification of protein-protein interactions (PPIs) in individual cells. Using the wild-type and mutant CTPS as bait proteins, STAMP results in two distinct sets of proximate proteomes. Our results suggest that STAMP is a feasible tool to catch in vivo PPIs in situ at a defined spatiotemporal resolution.
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Carbon-Nitrogen Ligases
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BACKGROUND: Dental case notes record clinical diagnoses and treatments, as well as providing continuity of patient care. They are also used for dento-legal litigation and forensic purposes. Maintaining accurate and comprehensive dental patient records is a dental worker's ethical and legal obligation. METHODS: Australian registered specialist forensic odontologists were surveyed to determine the relevance of recorded case note items for dental identification. A dental case notes sample was assessed for adherence with odontologist nominated forensic value and compiled professional record keeping guidelines of forensic relevance. Frequency of item recording, confidence interval, examiner agreement and statistical significance were determined. RESULTS: Broad agreement existed between forensic odontologists as to which recorded dental items have most forensic relevance. Inclusion frequency of these items in sampled case notes varied widely (e.g. single area radiographic view present in 75%, CI = 65.65-82.50; completed odontogram in 56%, CI = 46.23-65.33). Recording of information specified by professional record keeping guidelines also varied, although overall inclusion was higher than for forensically desired items (e.g. patient's full name in 99%, CI = 94.01 - >99.99; named treating practitioner in 23%, CI = 15.78-32.31). CONCLUSIONS: Many sampled dental case notes lacked details identified as being valuable by forensic specialists and as specified by professional record keeping guidelines.
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Dental Records
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Two floc-forming, nitrogen-fixing bacteria, strains EMB43(T) and EMB61, obtained from activated sludge of a domestic wastewater treatment plant in Korea, were characterized. The two strains were very closely related, sharing 99.7 % 16S rRNA gene sequence similarity and showing a level of DNA-DNA relatedness of 93 %, which suggests that they represent members of a single species. Phylogenetic analysis based on 16S rRNA gene sequences showed that the two novel isolates formed a distinct phyletic lineage within the genus Zoogloea and were related most closely to Zoogloea resiniphila DhA-35(T) and Zoogloea oryzae A-7(T), with sequence similarities of 97.2 %. Levels of DNA-DNA relatedness between strain EMB43(T) and Z. resiniphila DhA-35(T) and Z. oryzae A-7(T) were 12.8 and 7.4 %, respectively. Cells of strains EMB43(T) and EMB61 were facultatively aerobic, rod-shaped, Gram-negative and motile by means of a polar flagellum. The strains grew at temperatures of 15-40 degrees C (optimum: 25-30 degrees C) and at pH 6.0-9.0 (optimum: pH 6.5-7.5). The predominant fatty acids were C(16 : 0), C(10 : 0) 3-OH and summed feature 3 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH), and the predominant polar lipid was phosphatidylethanolamine. The genomic DNA G+C content was 64.9-65.0 mol% and the major isoprenoid quinone was ubiquinone-8 (Q-8). On the basis of phenotypic, chemotaxonomic and molecular data, the isolates are considered to represent a novel species of the genus Zoogloea, for which the name Zoogloea caeni sp. nov. is proposed. The type strain is EMB43(T) (=KCTC 22084(T)=DSM 19389(T)).
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Zoogloea
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In this study, pot and field experiments were conducted to study the enrichment of soil cadmium by Kochia scoparia. Further, rotations in pot experiments were carried out with four varieties of Brassica rapa to verify the remediation effect of Kochia scoparia on cadmium contamination in soil. The enrichment capacity of Kochia scoparia was leaf > root > stem with bioconcentration factors (BCFCd) of 15.07, 5.44 and 2.96, respectively. The total cadmium in soil decreased by 6.02% to 13.60% after planting Kochia scoparia, and the activities of soil urease and acid phosphatase also increased. The results of pot cultivation shows that the above-ground cadmium content of Brassica rapa in Kochia scoparia-Brassica rapa rotation system decreased by 17.21% on average compared with the control group without rotation, whereas the biomass increased slightly, and the above-ground translocation factors (TFCd) did not change significantly. These results suggest that the rotation of Brassica rapa with Kochia scoparia could increase the yield of Brassica rapa, and effectively reduce the cadmium content in edible parts of Brassica rapa, toward the purpose of realizing the green agricultural concept of harnessing while producing"."
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Bassia scoparia
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AIM: The aim was to evaluate the association of polymorphisms in the Toll-like receptor (TLR) 2 subfamily encoding genes with lung function by spirometry at 10-13 years of age in children who had been hospitalised for bronchiolitis at <6 months of age. METHODS: In a prospective cohort of 166 former bronchiolitis patients, 138 returned a structured questionnaire and 89 attended a clinical follow-up visit including spirometry before and after bronchodilation at 10-13 years of age. Data on polymorphisms of the TLR1, TLR2, TLR6 and TLR10 genes were available from 81-82 children. RESULTS: In the TLR10 rs4129009, the wild (AA) genotype was associated with lower FEV1/FVC before (92.4 vs 97.4, P = .002) and after (95.5 vs 98.6, P = .011) bronchodilator administration, compared to those with the variant genotype. When the TLR10 rs4129009 and TLR2 rs5743708 genotypes, and the TLR10 rs4129009 and TLR1 rs5743618 genotypes, respectively, were analysed as combined, both baseline and post-bronchodilator FEV1/FVC were lowest in the subjects with the wild (AA) genotype of the TLR10 rs4129009. CONCLUSION: In this post-bronchiolitis follow-up, lung function in children with the variant TLR10 rs4129009 genotype with potentially altered TLR10 function was superior to lung function in those with the wild genotype.
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Toll-Like Receptor 10
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Cranial neural crest cells populate the future facial region and produce ectomesenchyme-derived tissues, such as cartilage, bone, dermis, smooth muscle, adipocytes, and many others. However, the contribution of individual neural crest cells to certain facial locations and the general spatial clonal organization of the ectomesenchyme have not been determined. We investigated how neural crest cells give rise to clonally organized ectomesenchyme and how this early ectomesenchyme behaves during the developmental processes that shape the face. Using a combination of mouse and zebrafish models, we analyzed individual migration, cell crowd movement, oriented cell division, clonal spatial overlapping, and multilineage differentiation. The early face appears to be built from multiple spatially defined overlapping ectomesenchymal clones. During early face development, these clones remain oligopotent and generate various tissues in a given location. By combining clonal analysis, computer simulations, mouse mutants, and live imaging, we show that facial shaping results from an array of local cellular activities in the ectomesenchyme. These activities mostly involve oriented divisions and crowd movements of cells during morphogenetic events. Cellular behavior that can be recognized as individual cell migration is very limited and short-ranged and likely results from cellular mixing due to the proliferation activity of the tissue. These cellular mechanisms resemble the strategy behind limb bud morphogenesis, suggesting the possibility of common principles and deep homology between facial and limb outgrowth.
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Ectoderm
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A haemadsorption microtest for African swine fever (ASF) virus is described. This assay is as sensitive and its response is faster than the conventional assay which uses buffy coat cultures in Leighton tubes. The method can also process a larger number of samples by using smaller amounts of swine blood and laboratory space. A plaque assay for ASF virus adapted to grow in VERO cells gives a titre similar to that obtained using the haemadsorption microtest. In both the micromethod and the plaque assay infection may be produced by a single infective particle.
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Hemadsorption
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Plasma exchange (PEX) is a therapeutic procedure used to treat diseases caused by pathogenic antibodies or immune-complexes through the removal and the replacement of plasma. The frequency of complications and reactions associated with PEX are mild and of limited duration. In systemic autoimmune diseases and in a variety of other conditions, PEX might be use in association with intravenous immunoglobulin (IVIg) or therapeutic monoclonal antibodies for the management of acute or refractory patients to achieve a durable remission.
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Plasma Exchange
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Barriers to access are one reason for inconsistent or nonuse of contraception. The requirement for a prescription can be an obstacle for some contraceptive users. Several studies have demonstrated that women are capable of using self-screening tools to determine their eligibility for hormonal contraceptive use. Pelvic and breast examinations, cervical cancer screening, and sexually transmitted infection screening are not required before initiating hormonal contraception and should not be used as reasons to deny access to hormonal contraception. Also, a plan to improve access to hormonal contraception should address cost issues. Pharmacist-provided contraception may be a necessary intermediate step to increase access to contraception, but over-the-counter access to hormonal contraception should be the ultimate goal. The American College of Obstetricians and Gynecologists supports over-the-counter access to hormonal contraception without age restrictions. This Committee Opinion has been updated to expand the focus of over-the-counter contraception to include oral contraceptive pills, vaginal rings, the contraceptive patch, and depot medroxyprogesterone acetate, to address the role of pharmacist-provided contraception, and to provide recommendations for individuals younger than 18 years.
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Hormonal Contraception
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Percutaneous Endoscopic Gastrostomy is simply a plastic tube, placed in the stomach and passed through both the wall of the stomach and abdomen with the aid of a gastroscope, therefore avoiding the need for a laparotomy to form a gastrostomy. Egeberg proposed surgical gastrostomy in 1837. This was not carried out successfully until 1876 by Verneuil. The procedure, however, requires laparotomy and anaesthesia with its associated risks. The first gastrostomy without the need for a laparotomy is reported to have been performed in 1979 by Gauderer and Ponsky at Case Western Reserve University School of Medicine, Cleveland, USA. In 1980 they described the technique. Since then a variety of kits with which to perform the procedure have become available. PEG can be used for long term enteral nutrition or as an intermediate stage between Total Parentral Nutrition (TPN) and normal feeding. An important requirement is a successfully accomplished gastroscopy.
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Gastrostomy
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There is much debate between neonatologists and paediatricians about appropriate oxygen saturation targets for babies with chronic neonatal lung disease (CNLD). Overnight oximetry is used to guide the fraction of inspired oxygen to use. We did this literature review to examine the current literature on the use of overnight oximetry in term infants, preterm infants and babies with CNLD (especially relevant to ex-preterm babies with CNLD going home on oxygen). We reviewed the literature from January 1990 to October 2017 by searching the following databases: Cochrane Central Register of Controlled Trials, The Joanna Briggs Institute, CINAHL, MEDLINE, Scopus, EMBASE, ProQuest and Science Direct. Sixteen articles were included in the review. The literature available on overnight oximetry in neonates is limited, it is not contemporary, and it reports studies that did not use oximeters with modern software for data collection and analysis. It is imperative that reference ranges be defined for overnight oximetry parameters so that babies are not inadvertently administered inappropriate amounts of oxygen.
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Night Care
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alpha 2-HS-glycoprotein (AHSG) phenotypes were determined in 506 unrelated autochthonous individuals from the Galician population (NW Spain) by means of isoelectric focusing followed by silver stain immunofixation. The phenotype frequency distribution fitted with the Hardy-Weinberg law. No evidence of intrapopulation heterogeneity was observed. The allele frequencies obtained were: AHSG*1 = 0.7559 +/- 0.013 and AHSG*2 = 0.2441 +/- 0.013. Our findings lend support to the hypothesis of an AHSG gene frequency cline in European populations. Other population genetics' considerations have also been discussed.
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alpha-2-HS-Glycoprotein
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BACKGROUND: Seasonal patterns are assumed in many fields of medicine. However, biological processes are full of variations and the possibility of chance findings can often not be ruled out. METHODS: Using simulated data we assess whether auto correlation is helpful to minimize chance findings and test to support the presence of seasonality. RESULTS: Autocorrelation required to cut time curves into pieces. These pieces were compared with one another using linear regression analysis. Four examples with imperfect data are given. In spite of substantial differences in the data between the first and second year of observation, and in spite of otherwise inconsistent patterns, significant positive autocorrelations were constantly demonstrated with correlation coefficients around 0.40 (SE 0.14). CONCLUSIONS: Our data suggest that autocorrelation is helpful to support the presence of seasonality of disease, and that it does so even with imperfect data.
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Seasons
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BACKGROUND: The role of tumor-associated macrophages (TAMs) in determining the outcome between the antitumor effects of the adaptive immune system and the tumor's anti-immunity stratagems, is controversial. Macrophages modulate their activities and phenotypes by integration of signals in the tumor microenvironment. Depending on how macrophages are activated, they may adopt so-called M1-like, antitumor or M2-like, protumor profiles. In many solid tumors, a dominance of M2-like macrophages is associated with poor outcomes but in some tumor types, strong M1-like profiles are linked to better outcomes. We aimed to investigate the interrelationship of these TAM populations to establish how they modulate the efficacy of the adaptive immune system in early lung cancer. METHODS: Macrophages from matched lung (non-tumor-associated macrophages (NTAMs)) and tumor samples (TAMs) from resected lung cancers were assessed by bulk and single-cell transcriptomic analysis. Protein expression of genes characteristic of M1-like (chemokine (C-X-C motif) ligand 9) or M2-like (matrix metallopeptidase 12) functions was confirmed by confocal microscopy. Immunohistochemistry related the distribution of TAM transcriptomic signatures to density of CD8(+) tissue-resident memory T cells (T(RM)) in tumors and survival data from an independent cohort of 393 patients with lung cancer. RESULTS: TAMs have significantly different transcriptomic profiles from NTAMs with >1000 differentially expressed genes. TAMs displayed a strong M2-like signature with no significant variation between patients. However, single-cell RNA-sequencing supported by immuno-stained cells revealed that additionally, in 25% of patients the M2-like TAMs also co-expressed a strong/hot M1-like signature (M1(hot)). Importantly, there was a strong association between the density of M1(hot) TAMs and T(RM) cells in tumors that was in turn linked to better survival. Our data suggest a mechanism by which M1(hot) TAMs may recruit T(RM) cells via CXCL9 expression and sustain them by making available more of the essential fatty acids on which T(RM) depend. CONCLUSIONS: We showed that in early lung cancer, expression of M1-like and M2-like gene signatures are not mutually exclusive since the same TAMs can simultaneously display both gene-expression profiles. The presence of M1(hot) TAMs was associated with a strong T(RM) tumor-infiltrate and better outcomes. Thus, therapeutic approaches to re-program TAMs to an M1(hot) phenotype are likely to augment the adaptive antitumor responses.
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Tumor-Associated Macrophages
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Fifty-four patients with oculomotor nerve palsy who presented over a 21-year period at our institution were reviewed retrospectively. There were 38 isolated third nerve lesions, and 16 with additional cranial nerve involvement. Eleven cases were congenital in origin, and 43 were acquired. Of the acquired group, 31 were traumatic, 7 infection-related, 3 attributed to migraine or other vascular causes, and 2 neoplastic. Average follow up was 36 months. The congenital lesions were predominantly right-sided; amblyopia, although common, responded well to treatment. Trauma and bacterial meningitis accounted for more cases of isolated oculomotor nerve palsy than seen in the previous literature. In distinct contrast to the adult population, no cases of diabetes, posterior communicating artery aneurysms, metastatic tumors, or pituitary lesions were found.
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Oculomotor Nerve Injuries
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Using 85 sera collected from horses that had been experimentally infected with equine infectious anemia virus (EIAV) and 200 field sera collected from racehorses in Japan, we compared 4 agar gel immunodiffusion (AGID) kits for serologic detection of EIAV antibodies from Idexx, VMRD, IDvet, and the National Engineering Research Center of Veterinary Biologics, China (NECVB). The positive control lines were sufficiently clear in all kits for evaluation to be made, with slight differences in sharpness: NECVB was the sharpest, followed by VMRD, IDvet, and Idexx. The test results for all 285 samples agreed among the 4 kits, with 62 positives and 223 negatives. The sensitivities and specificities of VMRD, IDvet, and NECVB compared with the Idexx kit were 100%, and the kappa coefficient values between the kits were 1.0 for all combinations. We concluded that the testing capacity of these 4 kits was virtually identical.
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Immunodiffusion
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MED1 (mediator subunit 1) co-amplifies with HER2, but its role in HER2-driven mammary tumorigenesis is still unknown. Here, we generate MED1 mammary-specific overexpression mice and cross them with mouse mammary tumor virus (MMTV)-HER2 mice. We observe significantly promoted onset, growth, metastasis, and multiplicity of HER2 tumors by MED1 overexpression. Further studies reveal critical roles for MED1 in epithelial-mesenchymal transition, cancer stem cell formation, and response to anti-HER2 therapy. Mechanistically, RNA sequencing (RNA-seq) transcriptome analyses and clinical sample correlation studies identify Jab1, a component of the COP9 signalosome complex, as the key direct target gene of MED1 contributing to these processes. Further studies reveal that Jab1 can also reciprocally regulate the stability and transcriptional activity of MED1. Together, our findings support a functional cooperation between these co-amplified genes in HER2(+) mammary tumorigenesis and their potential usage as therapeutic targets for the treatment of HER2(+) breast cancers.
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Mediator Complex Subunit 1
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PURPOSE OF REVIEW: The purpose of this review is to summarize new literature regarding the description, diagnosis, and treatment of pediatric deep neck abscesses. RECENT FINDINGS: Providers should include multi-inflammatory syndrome in children (MIS-C) in a differential diagnosis in children suspected of having a retropharyngeal abscess. MRI may guide the proper management of children with deep neck abscesses by more accurately detecting free fluid compared to computed tomography imaging. Factors that may predict the need for surgical management include elevations in white blood cell counts and abscess size more than 3 cm. However, future investigation is necessary to establish consistent guidelines. Medical management is effective in many children, with a new study indicating success using a combination of cefotaxime and rifampicin. SUMMARY: Anatomical and age-related risk factors predispose children to the development of deep neck abscesses. Findings from recent studies may aid providers in making an accurate diagnosis and providing proper medical or surgical management of children with these infections.
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Retropharyngeal Abscess
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Brachial plexus injury in adults is commonly caused by motorcycle accidents. Surgical management consists of nerve repair and nerve grafting for extraforaminal nerve root or trunk injury, and of neurotization or nerve transfer for nerve roots avulsion. In general, the results regarding restoration of shoulder and elbow function are good but reinnervation of the forearm muscles is less than safisfactory in respect to restoration of hand function. Functioning free muscle transfer in combination with selective nerve transfer is a reasonable alternative surgical procedure. Key words: Brachial plexus injury; nerve repair; nerve graft; neurotization; functioning free muscle transfer.
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Intercostal Nerves
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Poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 are DNA-dependent poly(ADP-ribose)transferases localized in nucleus. They have a significant homology in the C-terminal catalytic domain structure but differ in their N-terminal DNA-binding parts. The structural difference has an impact on the interaction of PARP1 and PARP2 with DNA and their DNA-dependent activation. Here, we compare the interaction of PARP1 and PARP2 with free 147 bp nucleosomal DNA and its nucleosome-associated variant (NCP) that contain in one strand a 1-nucleotide gap with 5'-dRP (imitating the intermediate of Base Excision Repair) or no specific damage. The affinity of PARP2 for the DNA strongly depends on the gap presence and to a lesser extent on the association with nucleosomes, while PARP1 interacts primarily with blunt ends of all DNAs and with a lower affinity with the single-strand break. The activities of PARP1 and PARP2 in the autoPARylation reaction and heteromodification of histones are distinctly stimulated by HPF1, depending on the gap presence in activating DNA. The most significant HPF1-induced stimulation of the histone modification in the presence of gapped NCP is a peculiar feature of PARP2. We propose a specific regulatory role of PARP2 in the process of DNA repair in the context of chromatin.
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Poly ADP Ribosylation
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Early events of the human immunodeficiency virus 1 (HIV-1) lifecycle, such as post-entry virus trafficking, uncoating and nuclear import, are poorly characterized because of limited understanding of virus-host interactions. Here, we used mass spectrometry-based proteomics to delineate cellular binding partners of curved HIV-1 capsid lattices and identified Sec24C as an HIV-1 host dependency factor. Gene deletion and complementation in Jurkat cells revealed that Sec24C facilitates infection and markedly enhances HIV-1 spreading infection. Downregulation of Sec24C in HeLa cells substantially reduced HIV-1 core stability and adversely affected reverse transcription, nuclear import and infectivity. Live-cell microscopy showed that Sec24C co-trafficked with HIV-1 cores in the cytoplasm during virus ingress. Biochemical assays demonstrated that Sec24C directly and specifically interacted with hexameric capsid lattices. A 2.3-A resolution crystal structure of Sec24C(228-242) in the complex with a capsid hexamer revealed that the Sec24C FG-motif bound to a pocket comprised of two adjoining capsid subunits. Combined with previous data(1-4), our findings indicate that a capsid-binding FG-motif is conserved in unrelated proteins present in the cytoplasm (Sec24C), the nuclear pore (Nup153; refs. (3,4)) and the nucleus (CPSF6; refs. (1,2)). We propose that these virus-host interactions during HIV-1 trafficking across different cellular compartments are crucial for productive infection of target cells.
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Lentiviruses, Primate
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The release from a matrix compressed from a physical mixture of procaine hydrochloride, chlorinated poly(propylene), lactose, and a surfactant was investigated. With nonionic and cationic surfactants incorporated in the matrix, the release of procaine hydrochloride was linearly related to the square root of time, and as the concentration of the surfactants increased, the release was faster. When an anionic surfactant (sodium lauryl sulfate) was incorporated in the matrix, the release of procaine hydrochloride was linearly related to the square root of time; however, the release pattern depended on the concentration of the anionic surfactant. As the concentration of sodium lauryl sulfate increased to 4%, the release progressively slowed to a minimum because of the formation of a poorly soluble complex between the cationic procaine and the anionic surfactant. As the concentration of anionic surfactant increased further, the release increased as the complex was micellarly solubilized.
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Procaine
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The murine local lymph node assay (LLNA) is widely used to test chemicals to induce skin sensitization. Exposure of mouse auricle skin to a sensitizer results in proliferation of local lymph node T cells, which has been measured by in vivo incorporation of H(3)-methyl thymidine or 5-bromo-2'-deoxyuridine (BrdU). The stimulation index (SI), the ratio of the mean proliferation in each treated group to that in the concurrent vehicle control group, is frequently used as a regulatory-authorized endpoint for LLNA. However, some non-sensitizing irritants, such as sodium dodecyl sulfate (SDS) or methyl salicylate (MS), have been reported as false-positives by this endpoint. In search of a potential endpoint to enhance the specificity of existing endpoints, we evaluated 3 contact sensitizers; (hexyl cinnamic aldehyde [HCA], oxazolone [OXA], and 2,4-dinitrochlorobenzene [DNCB]), 1 respiratory sensitizer (toluene 2,4-diisocyanate [TDI]), and 2 non-sensitizing irritants (MS and SDS) by several endpoints in LLNA. Each test substance was applied to both ears of female CBA/Ca mice daily for 3 consecutive days. The ears and auricle lymph node cells were analyzed on day 5 for endpoints including the SI value, lymph node cell count, cytokine release from lymph node cells, and histopathological changes and gene expression profiles in auricle skin. The SI values indicated that all the test substances induced significant proliferation of lymph node cells. The lymph node cell counts showed no significant changes by the non-sensitizers assessed. The inflammatory findings of histopathology were similar among the auricle skins treated by sensitizers and irritants. Gene expression profiles of cytokines IFN-gamma, IL-4, and IL-17 in auricle skin were similar to the cytokine release profiles in draining lymph node cells. In addition, the gene expression of the chemokine CXCL1 and/or CXCL2 showed that it has the potential to discriminate sensitizers and non-sensitizing irritants. Our results suggest that multi-endpoint analysis in the LLNA leads to a better determination of the sensitizing potential of test substances. We also show that the gene expression of CXCL1 and/or CXCL2, which is involved in elicitation of contact hypersensitivity (CHS), can be a possible additional endpoint for discrimination of sensitizing compounds in LLNA.
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Local Lymph Node Assay
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BACKGROUND: Members of the Polyomaviridae family, BK virus (BKV), and John Cunningham virus (JCV) are linked to polyomavirus-associated nephropathy-associated transplant rejection in immunodeficient patients. OBJECTIVE: The aim of the study was to evaluate the prevalence of BKV and JCV in immunocompetent individuals in the north of Iran. METHODS: Ninety-one urine samples were obtained from renal transplant recipients with a mean age of 39.78 +/- 11.19 years. A healthy control group of 65 volunteers with an average age of 40.32 +/- 10.7 years also contributed. After DNA extraction, positive cases were detected through PCR. Genotyping was done by alignment and phylogenetic tree construction of the VP1 region against all known JCV and BKV genotypes. RESULTS: The prevalence of BKV and JCV was 15.38 and 19.78%, respectively. JCV was detected in 7.69% of the control group. The prevalence of the BKV between the case and control groups was significant (p < 0.0001). There was no significant association between BKV and JCV and duration of dialysis (p > 0.05). Overall, 62.16% of JCV cases were genotype I. Besides, genotype II was dominant within patients with BKV-positive patients. DISCUSSION: The results obtained here show a relatively lower prevalence of BKV and JCV in immunocompromised renal transplant receivers and healthy control than those reported from other areas in Iran. JCV genotyping was evaluated for the first time in Iran. Genotype I for JCV and genotype II for BKV were dominant genotypes in the north of Iran.
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Caspian Sea
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Secretory proteins are subjected to stringent quality control systems in the endoplasmic reticulum (ER) which include the targeting of misfolded proteins for proteasomal destruction via the ER-associated degradation (ERAD) pathway. Since deletion of ERAD genes in the filamentous fungus Aspergillus niger had hardly any effect on growth, this study investigates whether autophagy might function as an alternative process to eliminate misfolded proteins from the ER. We generated A. niger double mutants by deleting genes essential for ERAD (derA) and autophagy (atg1 or atg8), and assessed their growth both under normal and ER stress conditions. Sensitivity toward ER stress was examined by treatment with dithiothreitol (DTT) and by expressing a mutant form of glucoamylase (mtGlaA::GFP) in which disulfide bond sites in GlaA were mutated. Misfolding of mtGlaA::GFP was confirmed, as mtGlaA::GFP accumulated in the ER. Expression of mtGlaA::GFP in ERAD and autophagy mutants resulted in a twofold higher accumulation in DeltaderA and DeltaderADeltaatg1 strains compared to Deltaatg1 and wild type. As DeltaderADeltaatg1 mutants did not show increased sensitivity toward DTT, not even when mtGlaA::GFP was expressed, the results indicate that autophagy does not act as an alternative pathway in addition to ERAD for removing misfolded proteins from the ER in A. niger."
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Autophagy-Related Protein-1 Homolog
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Magnetic nanoparticles have been studied extensively for biomedical applications over the past decades. One of the promising applications of magnetic nanoparticles is hyperthermia, which refers to thermal treatment for cancer. To achieve adequate heat at target sites, it is essential to develop magnetic nanoparticles with high heating efficiency and to optimize external magnetic fields. Here, we discuss the heating mechanism of magnetic nanoparticles, the influence of the intracellular environment on magnetic behavior and heat generation, and recent advances in methods of heating efficiency assessment.
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Body Fluid Compartments
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STATEMENT OF PROBLEM: Denture stomatitis is a chronic inflammatory condition caused by the formation of Candida albicans biofilm on denture bases. It is associated with aggravating intraoral pain, itching, and burning sensations. It can also potentiate cardiovascular diseases and aspiration pneumonia. The problem has thus far eluded efficient, toxic-free, and cost-effective solutions. PURPOSE: The purpose of this in vitro study was to investigate the effectiveness of organoselenium to inhibit the formation of C. albicans biofilm on the surface of acrylic resin denture base materials when it is either incorporated into the acrylic resin material or coated on the denture surface as a light-polymerized surface sealant. MATERIAL AND METHODS: Sixty heat-polymerized polymethyl methacrylate disks were fabricated and assigned to 4 groups (n=15): disks coated with a light-polymerized organoselenium-containing enamel surface sealant (DenteShield), disks impregnated with 0.5% organoselenium (0.5% selenium), disks impregnated with 1% organoselenium (1% selenium), and disks without organoselenium (control). C. albicans biofilm was grown on each disk which had been placed in a well of the microtiter plate containing 1-mL brain heart infusion broth inoculated with C. albicans. The plates were incubated aerobically at 37 degrees C for 48 hours. A confocal laser scanning microscope was used to determine the biofilm thickness, biomass, and live/dead cell ratio. Biofilm morphology was examined with scanning electron microscopy, whereas microbial viability was quantified by the spread plate method. The data were analyzed by using ANOVA and Tukey-Kramer multiple comparisons (alpha=.05). RESULTS: The microbial viability, biofilm thickness, biofilm biomass, and live/dead cell ratio were lower (P<.001) on disks in the test groups (DenteShield, 0.5% selenium, 1% selenium) when compared with the control group, with these variables being lowest in the 0.5% selenium and 1% selenium groups. The 0.5% selenium and 1% selenium groups did not differ significantly from each other in any of the variables (P>.05). Scanning electron microscope images showed inhibition of both biofilm growth and yeast to hyphae transition in the DenteShield, 0.5% selenium, and 1% selenium groups, with visible disruption of the biofilm morphology. CONCLUSIONS: The present study demonstrated that organoselenium, whether incorporated into or coated on the surface of an acrylic resin denture base material, has the potential to inhibit Candida albicans biofilm growth on denture surfaces and as such can be clinically useful for the prevention of denture stomatitis.
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Acrylic Resins
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Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2, which encode polycystin-1 and polycystin-2, respectively. Rodent models are available to study the pathogenesis of polycystic kidney disease (PKD) and for preclinical testing of potential therapies-either genetically engineered models carrying mutations in Pkd1 or Pkd2 or models of renal cystic disease that do not have mutations in these genes. The models are characterized by age at onset of disease, rate of disease progression, the affected nephron segment, the number of affected nephrons, synchronized or unsynchronized cyst formation and the extent of fibrosis and inflammation. Mouse models have provided valuable mechanistic insights into the pathogenesis of PKD; for example, mutated Pkd1 or Pkd2 cause renal cysts but additional factors are also required, and the rate of cyst formation is increased in the presence of renal injury. Animal studies have also revealed complex genetic and functional interactions among various genes and proteins associated with PKD. Here, we provide an update on the preclinical models commonly used to study the molecular pathogenesis of ADPKD and test potential therapeutic strategies. Progress made in understanding the pathophysiology of human ADPKD through these animal models is also discussed.
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TRPP Cation Channels
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Emery-Dreifuss muscular dystrophy (EDMD) is a rare disease characterized by early contractures, progressive muscle weakness, and cardiac abnormalities. Different subtypes of EDMD have been described, with the two most common forms represented by the X-linked EDMD1, caused by mutations in the EMD gene encoding emerin, and the autosomal EDMD2, due to mutations in the LMNA gene encoding lamin A/C. A clear definition of the magnetic resonance imaging (MRI) pattern in the two forms, and especially in the rarer EDMD1, is still lacking, although a preferential involvement of the medial head of the gastrocnemius has been suggested in EDMD2. We report a 13-year-old boy with mild limb girdle muscle weakness, elbow and ankle contractures, with absence of emerin at muscle biopsy, carrying a hemizygous frameshift mutation on the EMD gene (c.153dupC/p.Ser52Glufs*9) of maternal inheritance. Minor cardiac rhythm abnormalities were detected at 24-hour Holter electrocardiogram and required beta-blocker therapy. MRI scan of the thighs showed a mild diffuse involvement, while tibialis anterior, extensor digitorum longus, peroneus longus, and medial gastrocnemius were the most affected muscles in the leg. We also provide a review of the muscular MRI data in EDMD patients and highlight the relative heterogeneity of the MRI patterns found in EDMDs, suggesting that muscle MRI should be studied in larger EDMD cohorts to better define disease patterns and to cover the wide disease spectrum."
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X-Linked Emery-Dreifuss Muscular Dystrophy
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The therapeutic relationship is an essential part of effective therapy. Therapists facing a rupture in this alliance are challenged to mend the discord in a forward moving and effective treatment service. In acceptance and commitment therapy (ACT) the alliance is characterized by client and therapist working together, using the core processes of ACT, creating a vital and moment-by-moment collaborative experience. As a transdiagnostic, behavioral intervention, acceptance, and mindfulness processes and commitment and behavioral change processes are used to create meaningful and engaged lives. ACT's core methods promote psychological flexibility in response to problems in living, psychopathology, and enhancement of general well-being. However, flexibility in session can be lost to therapeutic ruptures. In ACT, processes such as defusion, perspective-taking, choice, and values play a role in restoring a cooperative, engaged alliance repair. We will explore the therapeutic relationship within the ACT model and present its perspective on rupture and repair in psychotherapy."
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Acceptance and Commitment Therapy
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The objective of this study was to assess whether the positioning of the wrist joint in the cast in such a manner that it counteracts the direction of angulation of fragments is more important than the cast index in the prevention of secondary displacements in distal forearm fractures. A retrospective review of all pediatric patients (0-16 years of age) who were hospitalized in our institution with displaced fractures of the distal forearm (either isolated fractures of the distal radius or both bone fractures) who underwent subsequent closed reduction and splinting in the period from August 2018 to October 2020. Patients with physeal fractures and open fractures, and skeletally mature patients were excluded from the study. Patients were divided into two categories - the first one in which the cast index was below 0.9 and the second in which it was above 0.9. In each category, we have identified two groups of patients - the first one in whom the wrist joint was positioned in such a manner that it counteracts the direction of angulation of fracture fragments and the second one in whom the wrist joint was in a neutral position. The two groups in each category have been compared according to age, sex, initial angulation, fracture type (isolated radius or both bone fractures), displacement type (angulation or complete dislocation) and the rate of secondary displacement. In both categories, the two groups were comparable according to age, sex, initial angulation, fracture and displacement type. In both categories (cast index below 0.9 and cast index above 0.9), a statistically significant higher portion of patients with secondary displacement was identified in the group of patients who had the wrist joint in a neutral position ( Z = -2.1997; P = 0.0278 - for cast index <0.9 and Z = -2.1672; P = 0.030216 for cast index >0.9). Our research supports the notion that positioning of the wrist joint in the position that counteracts the force that leads to angulation of fracture fragments is more important than the cast index in the prevention of secondary displacements in pediatric distal forearm fractures.
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Wrist Fractures
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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anticancer agent due to its selectivity in killing transformed cells. However, TRAIL can also stimulate the proliferation and metastasis of TRAIL-resistant cancer cells. Thus, acquired TRAIL resistance during TRAIL therapy would shift the patient's treatment from beneficial to detrimental. In this study, we focused on the acquired TRAIL resistance mechanism and showed that the elevated expression of the antiapoptotic factor cellular FLICE-like inhibitory protein (c-FLIP) and the prosurvival Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) underlie the main mechanism of this type of TRAIL resistance in lung cancer cells. Chronic exposure to TRAIL resulted in lung cancer cell resistance to TRAIL-induced cytotoxicity, and this resistance was associated with the increase in the cellular levels of c-FLIP(L) and Mcl-1(L). Overexpresssion of c-FLIP(L) suppressed recruitment of caspase-8 to the death-inducing signaling complex, whereas increased Mcl-1(L) expression blunted the mitochondrial apoptosis pathway. The elevation of c-FLIP(L) and Mcl-1(L) expression was due to Akt-mediated stabilization of these proteins in TRAIL-resistant cells. Importantly, suppressing c-FLIP(L) and Mcl-1(L) expression by RNA interference collectively alleviated acquired TRAIL resistance. Taken together, these results identify c-FLIP(L) and Mcl-1(L) as the major determinants of acquired TRAIL resistance and could be molecular targets for improving the therapeutic value of TRAIL against lung cancer."
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Death Domain Receptor Signaling Adaptor Proteins
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The mathematical model proposed focuses on the description of the behavior of the interaction between thyrotropin (i.e. thyroid-stimulating hormone (TSH)) and thyroid hormones with the objective of providing a better understanding of the behavior of TSH-T4 relationship in health and in disease. The normal pituitary-thyroid axis is tightly coupled and regulated with a servomechanism. In the physiological situation, any elevation of thyroid hormones will inhibit TSH secretion by the thyrotrophs of the pituitary, which in turn lead to an appropriate reduction in stimulation of the thyroid, accompanied by a decline of thyroid hormones towards normal. Similarly, a decline in thyroid hormones represents a potent input signal that when sensed by the pituitary thyrotrophs, will result in an increase of TSH output by the latter to accelerate the synthesis and secretion of thyroid hormones to drive the state towards normal equilibrium. Using this model, the profound sensitivity of thyrotrophs to feedback by thyroid hormones can be appreciated and understood better in the context of diseases of thyroid hormone excess and deficiency.
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Thyrotrophs
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Twenty-nine clinical isolates of community acquired Klebsiella pneumoniae obtained from 17 children with malnutrition were characterized by antibiotic susceptibility, plasmid analysis, and random amplified polymorphic DNA (RAPD) techniques. Disc diffusion methodology was used to test the susceptibility of the isolates to 13 antibiotics: amoxycillin, cephapirin, ceftazidime, cefoxitin, cefotaxime, aztreonam, gentamicin, ciprofloxacin, chloramphenicol, erythromycin, nalidixic acid, trimethoprim and amoxycillin-clavulanic acid. All the isolates showed multiresistance patterns (15 patterns) ranging from resistance to two antibiotics to resistance to 10 antibiotics. All isolates were resistant to amoxycillin and erythromycin. Ten K. pneumoniae isolates producing extended-spectrum beta-lactamases (ESBLs) as evidenced by the double-disc diffusion synergy test were isolated sporadically from six patients. Six of these 10 isolates were hyperproducers of ESBL, which resulted in increased resistance to the beta-lactam-beta-lactamase inhibitor combination amoxycillin-clavulanic acid. Plasmid analysis showed plasmid ranging in size from 48 kilobases (kb) to 1.4 kb. All the 29 isolates shared the same plasmid 26 kb. There was a consistent relationship between antibiotype and plasmid profiles for each pair of isolates obtained from five individual patients. RAPD analysis using a single (10-mer) primer demonstrated that the isolates that have the same antibiotype and the same plasmid profile had different RAPD fingerprint patterns. These results demonstrate that the RAPD technique is better than antibiotype characterization and a plasmid analysis profile for typing K. pneumoniae as well as for revealing strain differences.
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Klebsiella pneumoniae
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We analyzed the structure of the N-linked oligosaccharides enzymatically liberated from the organic matrix (OM) component in the nacreous layer of Japanese pearl oyster: Pinctada fucata. The lectin-blot analysis of the soluble OM after separation by SDS-PAGE, four components, with sizes of approximately 55 kDa, 35 kDa, 25 kDa, and 21 kDa were detected with GNA lectin, which recognized terminal mannose of high mannose and hybrid types of N-glycan. The 55-kDa component of the soluble OM detected by lectin blotting was identified as nacrein by using liquid chromatography/mass spectrometry (LC/MS). LC/MS analysis of the N-glycan liberated from nacrein detected a hybrid-type N-glycan, which contained sulfite and sialic acid at its terminus. The data strongly imply that nacrein, a sulfated OM glycoprotein, participates in molluscan biomineralization by creating a favorable environment for calcium ion uptake through sulfonic acid and sialic acid.
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Pinctada
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Work undertaken using the embryonic carcinoma 2102Ep line, highlighted the requirement for robust, well-characterized and standardized protocols. A systematic approach utilizing 'quick hit' experiments demonstrated variability introduced into culture systems resulting from slight changes to culture conditions (route A). This formed the basis for longitudinal experiments investigating long-term effects of culture parameters including seeding density and feeding regime (route B).Results demonstrated that specific growth rates (SGR) of passage 59 (P59) cells seeded at 20,000 cells/cm(2) and subjected to medium exchange after 48h prior to reseeding at 72h (route B2) on average was marginally higher than, P55 cells cultured under equivalent conditions (route A1); whereby SGR values were (0.021+/-0.004) and (0.019+/-0.004). Viability was higher in route B2 over 10 passages with average viability reported as (86.3%+/-8.1) compared to route A1 (83.3+/-8.8). The metabolite data demonstrated both culture route B1 (P57 cells seeded at 66,667 cells/cm(2)) and B2 had consistent-specific metabolite rates (SMR) for glucose, but SMR values of route B1 was consistently lower than route B2 (0.00001 mmol, cell-1.d-1 and 0.000025).Results revealed interactions between phenotype, SMR and feeding regime that may not be accurately reflected by growth rate or observed morphology. This implies that current schemes of protocol control do not adequately account for variability, since key cell characteristics, including phenotype and SMR, change regardless of standardized seeding densities. This highlights the need to control culture parameters through defined protocols, for processes that involve culture for therapeutic use, biologics production, and reference lines.
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Cell Line
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PURPOSE OF REVIEW: The purpose of this review is to discuss the risk factors associated with laryngospasm and the techniques used for prevention and treatment. We also summarize the prevention and treatment modalities in organized algorithms. RECENT FINDINGS: According to recent endoscopic studies, laryngospasm is always complete, thus airway management and intravenous therapy are indicated. Parental history of children having upper respiratory infection is associated with increased risk of laryngospasm. Anesthesia administered by a pediatric anesthesiologist is associated with lower incidence of laryngospasm. Intravenous anesthesia is associated with lower incidence of laryngospasm than inhalational anesthesia. In tracheal intubation, the use of muscle relaxants decreases laryngospasm. Deep laryngeal mask airway removal is associated with lower incidence of laryngospasm in sevoflurane or isoflurane anesthesia. In no intravenous line situation, laryngospasm can be treated with succinylcholine administration by intramuscular, intraosseous and intralingual routes. SUMMARY: Identifying the risk factors and taking the necessary precautions are the key points in prevention of laryngospasm. An experienced anesthesiologist is associated with lower incidence of laryngospasm. Airway management is the most essential part of treatment of laryngospasm. Drugs can be used as an adjunct in treatment of laryngospasm, especially when anesthesia is administered by beginners.
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Intraoperative Complications
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Hispanics in the United States have worse cardiovascular disease (CVD) risk factor profiles than non-Hispanic Whites. Cardiovascular health literacy is important for health promotion but is not well characterized among monolingual Spanish-speaking Hispanics outside of health care settings. We recruited Hispanic participants (N=235) from a community-based health fair in Denver, Colorado. A total of 182 participants (77%) completed a subsequent language-congruent telephone survey to assess CVD risk-factor knowledge. Of these, 174 self-identified as monolingual Spanish-speaking, and constituted the analysis cohort. Cardiovascular disease risk knowledge score was defined as the number of established risk factors an individual participant could name (out of 10 pre-specified), and multivariable regression analyses were conducted to determine factors independently associated with knowledge. The mean knowledge score for the cohort was 2.2 +/- 1.1 out of 10. This suggests an unmet need for tailored educational interventions beyond simple screening events.
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Risk Factors
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STATEMENT OF PROBLEM: Advertisements of glass-ionomer-containing restorative materials recommend suitability as load-bearing permanent or semi-permanent restorations. Historically, unacceptably high wear rates limit clinical indications of glass-ionomer-containing restorations in this regard. OBJECTIVE: To compare the in vitro wear of contemporary glass-ionomer-containing dental materials commercially advertised for use in permanent dentition as load-bearing restorations in a chewing simulator. Resin composite was tested as a control. METHODS AND MATERIALS: A resin-modified glass ionomer (Ionolux, VOCO gmbH), a high viscosity glass-ionomer hybrid system (Equia Forte HT with Equia Coat, GC America), and a bioactive ionic resin with reactive glass filler (Activa Bioactive Restorative, Pulpdent) were evaluated. Filtek Supreme Ultra (3M ESPE) is a visible light-activated resin composite that served as a control. Standardized flat disk-shaped specimens (n=12/group) were submitted to 500,000 cycles with continuous thermal cycling against steatite antagonists. Volumetric wear was measured at 1000, 10,000, 200,000, and 500,000 cycles. RESULTS: There was a statistically significant difference in mean volumetric wear for Activa Bioactive Restorative (p=0.0081, 95% CI: 0.3973, 0.4982) and Equia Forte HT (p<0.001, 95% CI: 1.2495, 1.8493), but no statistically significant difference in mean volumetric wear for Ionolux (p=0.6653) compared to control. Activa Bioactive Restorative wore approximately 60% less than, and Equia Forte HT twice more than Filtek Supreme Ultra on average, respectively. CONCLUSIONS: Compared to a resin composite, contemporary glass-ionomer-containing restorative materials advertised for use as load-bearing restorations display measurably variable in vitro wear rates.
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Glass Ionomer Cements
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The extracellular matrix (ECM) is dynamically tuned to optimize physiological function. Its major properties, including composition and mechanics, profoundly influence cell biology. Cell-ECM interactions operate through an integrated set of sensor and effector circuits that use several classes of receptors and signal transduction pathways. At the single-cell level, the ECM governs differentiation, metabolism, motility, orientation, proliferation, and survival. At the cell population level, the ECM provides higher-order guidance that is essential for physiological function. When pathological changes in the ECM lead to impairment of organ function, we use the term fibrosis." In this Review, we differentiate fibrosis initiation from progression and focus primarily on progressive lung fibrosis impairing organ function. We present a working model to explain how the altered ECM is not only a consequence but also a driver of fibrosis. Additionally, we advance the concept that fibrosis progression occurs in a fibrogenic niche that is composed of a fibrogenic ECM that nurtures fibrogenic mesenchymal progenitor cells and their fibrogenic progeny."
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Extracellular Matrix
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The toxicity of receiving waters was evaluated by means of the young tadpoles assays. The sentinel organism was Bufo arenarum, an indigenous anuran species. The assayed water samples were taken from a highly polluted urban watercourse (Reconquista River, Buenos Aires, Argentina), characterized by high concentration of nitrites, phosphates and heavy metals. The toxicity of water samples was assessed performing the pass-fail test and by means of the NOEC and LC(50); TUs (toxic units) were also calculated. The effect of the addition of a positive control (Cd) on the toxicity of the river water samples was also examined. Water samples of three sites, characterised by their different degree of pollution, were assayed. The lethal response had a clear cut correspondence with the water quality of the sample evaluated by means of physicochemical parameters. In most cases, the dilution of the samples resulted in a significant reduction of their toxicity to TU values compatible to those stated by the USEPA for industrial effluents. It was concluded that (a) the used Bufo arenarum bioassay was an adequate method for assessing the toxicity of natural polluted water samples and (b) the three considered endpoints showed no important differences after 48 or 96 h of exposure, therefore we concluded that it may not be necessary to extend the assay for a longer period than 48 h.
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Bufo arenarum
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Gravid females of Philometroides were found under the scales of stock carp Cyprinus carpio L. imported from Lithuania to the Czech Republic in the spring of 1997 and kept in a quarantine pond. These specimens and those obtained from pond-cultured carp in Russia (Moscow district) were used for detailed morphological studies, including scanning electron microscopy. The results confirm that the valid name of this parasite is Philometroides cyprini (Ishii, 1931), whereas Philometra lusii Vismanis, 1962, Philometra schikhobalowae Belous, 1965, Philometra lusiana Vismanis, 1966 and Philometroides lusiana (Vismanis, 1966) Ivashkin et al., 1971 are its junior synonyms. P. cyprini, the agent of a serious disease of carp, seems to have been originally distributed in east Asia, from where it was introduced into Europe in the early 1960s.
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Camallanina
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Mycobacterium tuberculosis adenylyl cyclase (AC) Rv1625c/Cya is an evolutionary ancestor of the mammalian membrane ACs and a model system for studies of their structure and function. Although the vital role of ACs in cellular signalling is well established, the function of their transmembrane (TM) regions remains unknown. Here, we describe the cryo-EM structure of Cya bound to a stabilizing nanobody at 3.6 A resolution. The TM helices 1-5 form a structurally conserved domain that facilitates the assembly of the helical and catalytic domains. The TM region contains discrete pockets accessible from the extracellular and cytosolic side of the membrane. Neutralization of the negatively charged extracellular pocket Ex1 destabilizes the cytosolic helical domain and reduces the catalytic activity of the enzyme. The TM domain acts as a functional component of Cya, guiding the assembly of the catalytic domain and providing the means for direct regulation of catalytic activity in response to extracellular ligands.
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Adenylyl Cyclases
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1. Sparteine and mephenytoin phenotyping tests were carried out in 327 healthy Danish subjects. Two weeks later each subject took 25 mg imipramine followed by urine collection for 24 h. The urinary content of imipramine, desipramine, 2-hydroxy-imipramine and 2-hydroxy-desipramine was assayed by h.p.l.c. 2. The medians of the hydroxylation ratios (i.e. 2-hydroxy-metabolite over parent compound) were 6 to 14 times higher in 300 extensive metabolizers of sparteine (EMs) as compared with 27 poor metabolizers (PMs), but none of the ratios separated the two phenotypes completely. 3. There were 324 EM of mephenytoin (EMM) and three PM (PMM) in the sample. The demethylation ratios between desipramine, 2-hydroxy-desipramine and their corresponding tertiary amines showed statistically significant correlations with the mephenytoin S/R isomer ratio (Spearman's rs: -0.20 and -0.27, P < 0.05). 4. The demethylation ratios were higher in 80 smokers than in 245 non-smokers. This indicates that CYP1A2, which is induced by cigarette smoking, also catalyzes the N-demethylation of imipramine. 5. CYP2D6 genotyping was carried out by PCR in 325 of the subjects, and the D6-wt allele was amplified in 298 EMs, meaning that they were genotyped correctly. One PMs was D6-wt/D6-B, another PMs had the genotype D6-wt/ and hence both were misclassified as EMs. The remaining 25 PMs were D6-A/D6-B (n = 5), D6-B/ (n = 18) or D6-D/D6-D (no PCR amplification, n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)
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Mephenytoin
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The activation of stimulator of interferon genes (STING) and NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis signaling pathways represent two distinct central mechanisms in liver disease. However, the interconnections between these two pathways and the epigenetic regulation of the STING-NLRP3 axis in hepatocyte pyroptosis during liver fibrosis remain unknown. STING and NLRP3 inflammasome signaling pathways are activated in fibrotic livers but are suppressed by Sting knockout. Sting knockout ameliorated hepatic pyroptosis, inflammation, and fibrosis. In vitro, STING induces pyroptosis in primary murine hepatocytes by activating the NLRP3 inflammasome. H3K4-specific histone methyltransferase WD repeat-containing protein 5 (WDR5) and DOT1-like histone H3K79 methyltransferase (DOT1L) are identified to regulate NLRP3 expression in STING-overexpressing AML12 hepatocytes. WDR5/DOT1L-mediated histone methylation enhances interferon regulatory transcription factor 3 (IRF3) binding to the Nlrp3 promoter and promotes STING-induced Nlrp3 transcription in hepatocytes. Moreover, hepatocyte-specific Nlrp3 deletion and downstream Gasdermin D (Gsdmd) knockout attenuate hepatic pyroptosis, inflammation, and fibrosis. RNA-sequencing and metabolomics analysis in murine livers and primary hepatocytes show that oxidative stress and metabolic reprogramming might participate in NLRP3-mediated hepatocyte pyroptosis and liver fibrosis. The STING-NLRP3-GSDMD axis inhibition suppresses hepatic ROS generation. In conclusion, this study describes a novel epigenetic mechanism by which the STING-WDR5/DOT1L/IRF3-NLRP3 signaling pathway enhances hepatocyte pyroptosis and hepatic inflammation in liver fibrosis.
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NLR Proteins
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Multiple sclerosis (MS) represents a considerable challenge to experimentally model due to its twin pathologies of inflammatory demyelination and neurodegeneration along with its multifocal and multiphasic nature. Experimental autoimmune encephalomyelitis (EAE) in Biozzi ABH mice has previously been shown to reproduce many clinical features also found in secondary progressive MS. In this study we sought to characterise the pathology of chronic EAE in ABH mice. In addition to marked gliosis, we report substantial demyelination, remyelination and axonal and neuronal loss. Together with the clinical pattern, our findings identify chronic EAE as an excellent model of secondary progressive multiple sclerosis.
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Mice, Biozzi
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May-Thurner syndrome (MTS) is a known structural risk factor for deep vein thrombosis (DVT) and embolism. In patients with a patent foramen ovale (PFO), emboli originating from the deep veins are able to paradoxically reach the systemic circulation via the PFO, consequently resulting in transient ischemic attacks (TIA) or stroke.We report the case of a 31-year-old pregnant woman, with a recent history of TIA, who presented with chronic bilateral numbness, pain, and swelling in the lower extremities. On imaging, she was found to have a PFO and MTS. Her pregnancy was subsequently terminated. This decision was made independently by the patient. Her care team did not advise her to terminate her pregnancy as there was no specific medical reason to do so. However, the patient was in significant physical pain and distress and ultimately was not comfortable continuing with the pregnancy. This highlights the complex, multifactorial decision-making process that pregnant patients with comorbid health conditions undertake. The patient then underwent transcatheter PFO closure and stents were placed bilaterally in the left and right common iliac veins. Following the stent procedure, lower extremity symptoms swiftly resolved, allowing the patient to significantly improve her ability to ambulate. There have been no signs of TIA since her procedures, and her venous symptoms have been stable.In patients with TIA or stroke from a paradoxical embolism, MTS should be considered as a potential etiology. Endovascular intervention to treat the underlying MTS should also be considered to decrease the risk of recurrent DVT and embolism.
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Embolism, Paradoxical
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Ras proteins must localize to the plasma membrane (PM) for biological function. The membrane anchor of the K-Ras4B isoform comprises a farnesylated and methylated C-terminal cysteine together with an adjacent hexa-lysine polybasic domain (PBD). Traditionally, polybasic sequences have been thought to interact electrostatically with negatively charged membranes showing no specificity for anionic lipid head groups. By contrast we recently showed that the K-Ras membrane anchor actually exhibits a very high degree of specificity for phosphatidylserine (PtdSer). The selectivity for PtdSer is determined by a combinatorial code comprising the PBD sequence plus the prenyl anchor. Lipid binding specificity is therefore altered by PBD point mutations that in turn modulate signaling output. For example, mutating Lys177 or Lys178 to glutamine switches K-Ras4B lipid affinity from PtdSer to phosphoinositol 4,5-bisphosphate (PIP(2)). Changing the lipid anchor from farnesyl to geranylgeranyl or the PBD lysines to arginines also changes lipid binding specificity. All-atom molecular dynamics simulations reveal the structural basis for these K-Ras anchor lipid-binding preferences. Here we examine the PM interactions of a series of geranylgeranylated PBD mutants and provide further evidence that the precise PBD sequence and prenyl lipid determines lipid sorting specificity of the K-Ras anchor and hence biological function.
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Polylysine
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Potential of mean force (PMF) profiles and position-dependent diffusion coefficients of Na(+) and K(+) are calculated to elucidate the translocation of ions through a cyclic peptide nanotube, composed of 8 x cyclo[-(d-Leu-Trp)(4)-] rings, in water and in hydrated DMPC bilayers. The PMF profiles and PMF decomposition analysis for the monovalent cations show that favorable interactions of the cations with the CPN as well as the lipid bilayer and dehydration free energy penalties are two major competing factors which determine the free energy surface for ion transport through CPNs both in water and in lipid bilayers, and that the selectivity of CPNs to cations mainly arises from favorable interaction energies of cations with CPNs and lipid bilayers that are more dominant than the dehydration penalties. Calculations of the position-dependent diffusion coefficients and dynamic friction kernels of the cations indicate that the dehydration process along with the molecular rearrangements occurring outside the channel and the coupling of the ion motions with the chain-structured water movements inside the channel lead to a decrease of the diffusion coefficients far away from the channel entrance and also reduced coefficients inside the channel. The PMF and diffusivity profiles for Na(+) and K(+) reveal that the energetics of ion transport through the CPN are governed by global interactions of ions with all the components in the system, while the diffusivity of ions through the channel is mostly determined by local interactions of ions with the confined water molecules inside the channel. Comparison of Na(+) and K(+) ion distributions based on overdamped Brownian dynamics simulations based on the PMF and diffusivity profiles with the corresponding results from molecular dynamics shows good agreement, indicating accuracy of the Bayesian inference method for determining diffusion coefficients in this application. In addition, this work shows that position-dependent diffusion coefficients of ions are required to explain the dynamics and conductance of ions through the CPN properly.
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Nanotubes, Peptide
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BACKGROUND: The prevalence of obesity has risen in recent decades and reached epidemic proportions worldwide. The proportion of those living with obesity is also increasing in nursing homes. This could impact the nursing care required, equipment and facilities provided, and morbidity in these settings. Limited evidence exists on clinical consequences of obesity in nursing home residents and their care. OBJECTIVE: Therefore, the aim was to examine the rate and associated factors of obesity (BMI >/=30; class I (BMI 30.0-34.9 kg/m(2) ), class II (BMI 35.0-39.9 kg/m(2) ), and class III (BMI >40.0 kg/m(2) )) amongst older nursing home residents in European countries. METHODS: We analysed data from 21,836 people who reside in nursing homes in Austria, the Netherlands, and the United Kingdom. They participated in the International Prevalence Measurement of Care Quality", a cross sectional study between 2016 and 2019, where trained nurses interviewed the residents, reviewed care records, and conducted clinical examinations. A tested and standardised questionnaire comprised questions on demographic data, measured BMI, medical diagnosis according to ICD-10, and care dependency. Descriptive and logistic regression analyses were performed. RESULTS: Obesity rates were highest in Austria (17.1%) and lowest in the UK (13.0%) (p = .006). Residents with obesity were younger and less likely to be care dependent or living with dementia and had more often diabetes mellitus, endocrine, metabolic, and skin diseases compared to residents without obesity (p < .05). Most obese residents had obesity class I. Therefore, two subgroups were built (class I vs. class II + III). Residents with obesity class II + III were more frequently care dependent for mobility, getting dressed and undressed, and personal hygiene compared to residents with class I (p < .05). CONCLUSIONS: This study identified several factors that are associated with obesity amongst older nursing home residents in selected European countries. IMPLICATIONS FOR PRACTICE: The division into obesity classes is important for planning targeted care according to the individual needs of nursing home residents."
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Secondary Data Analysis
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The [3H]guanosine and [3H]guanine label is shown to be distributed unevenly in the purine components of chicken tissues. 60 min after isotope administration about 80% of radioactivity is localized in xanthine and uric acid in the liver and duodenum, that agrees with high activity of purine nucleoside phosphorylase (EC 2.4.2.1) and guanine deaminase (EC 3.5.4.3). At the same time over 50% of label is found in the spleen in adenine nucleotides of the pool, RNA as well as in hypoxanthine and only 20% in oxypurines. Such a distribution of the label is in direct correlation with the activity of GMP-reductase (EC 1.6.6.8) catalyzing the reduction deamination of GMP in IMP.
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GMP Reductase
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Members of the T-box family of transcription factors share an evolutionarily conserved DNA-binding domain and play significant roles in various processes of embryonic development. Vertebrate T-box genes are categorized into the following five major subfamilies (eight groups), depending on sequence similarities: Brachyury, Tbx1 (Tbx1/10, Tbx15/18/22, Tbx20), Tbx2/3/4/5 (Tbx2/3 and Tbx4/5), Tbx6, and Tbr/Eomes/TBX21. Ascidians are primitive chordates, and their tadpole larva are considered to represent the simplified and basic body plan of vertebrates. In addition, it has been revealed that the ascidian genome contains the basic ancestral complement of genes involved in development. The present characterization of cDNAs and survey of the Ciona intestinalis draft genome demonstrated that the Ciona genome contains a single copy gene for each of the Brachyury, Tbx1/10, Tbx15/18/22, Tbx20, Tbx2/3, and Tbr/Eomes/TBX21 groups, and at least three copies of the Tbx6 subfamily. Each of the Ciona T-box genes shows a characteristic expression pattern, although that of Tbx20 was not determined in the present study. These results provide basic information that will be useful for future studies of the function of each gene, genetic cascades of different T-box genes, and genome-wide surveys of evolutionary changes in the T-box gene structure and organization in this primitive chordate.
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Fetal Proteins
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The wishes of registered organ donors are regularly set aside when family members object to donation. This genuine overruling of the wishes of the deceased raises difficult ethical questions. A successful argument for providing the family with a veto must (a) provide reason to disregard the wishes of the dead, and (b) establish why the family should be allowed to decide. One branch of justification seeks to reconcile the family veto with important ideas about respecting property rights, preserving autonomy, and preventing harm. These arguments are ultimately unsuccessful. Another branch of arguments is consequentialist, pointing out the negative consequences of removing the veto. Whether construed as concerning family distress or as a potential drop in the organs available, these arguments are unsuccessful; the first fails to recognize the tremendous distress associated with waiting for an organ, while the second has little supporting evidence. A final section considers and rejects whether combining some of the arguments just examined could justify the family veto. We should thus remove the family veto in organ donation.
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Third-Party Consent
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Diabetic human and murine retinas revealed pronounced microglial morphological activation and vascular abnormalities associated with inflammation. Pharmacological fibrinogen depletion using ancrod dampened microglial morphology alterations, resolved fibrinogen accumulation, rescued axonal integrity, and reduced inflammation in the diabetic murine retina.
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Ancrod
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Numerous techniques and tools can be used to access difficult areas of the cerebrum: skull base techniques, modern operating room equipment, and a unified team approach. Using these principles, challenging areas of the cerebrum can be approached with maximal success and minimal morbidity. These techniques are powerful tools in the armamentarium of neurosurgeons and can improve any neurosurgical approach. The basilar region remains one of the most difficult areas to approach. Despite its inherent complexity, lesions of the basilar region can be treated successfully. The far-lateral approach is used to access the lower two-fifths of the basilar region; the transcochlear approach is used to access the middle fifth of the basilar region; and the orbitozygomatic approach is used to access the upper two-fifths of the basilar region. Each approach beautifully exemplifies the principles of skull base surgery.
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Brain
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The ileal apical sodium-dependent bile acid transporter (ASBT) is crucial for the enterohepatic circulation of bile acids. ASBT function is rapidly regulated by several posttranslational modifications. One reversible posttranslational modification is S-acylation, involving the covalent attachment of fatty acids to cysteine residues in proteins. However, whether S-acylation affects ASBT function and membrane expression has not been determined. Using the acyl resin-assisted capture method, we found that the majority of ASBT ( approximately 80%) was S-acylated in ileal brush border membrane vesicles from human organ donors, as well as in HEK293 cells stably transfected with ASBT (2BT cells). Metabolic labeling with alkyne-palmitic acid (100 mum for 15 h) also showed that ASBT is S-acylated in 2BT cells. Incubation with the acyltransferase inhibitor 2-bromopalmitate (25 mum for 15 h) significantly reduced ASBT S-acylation, function, and levels on the plasma membrane. Treatment of 2BT cells with saturated palmitic acid (100 mum for 15 h) increased ASBT function, whereas treatment with unsaturated oleic acid significantly reduced ASBT function. Metabolic labeling with alkyne-oleic acid (100 mum for 15 h) revealed that oleic acid attaches to ASBT, suggesting that unsaturated fatty acids may decrease ASBT's function via a direct covalent interaction with ASBT. We also identified Cys-314 as a potential S-acylation site. In conclusion, these results provide evidence that S-acylation is involved in the modulation of ASBT function. These findings underscore the potential for unsaturated fatty acids to reduce ASBT function, which may be useful in disorders in which bile acid toxicity is implicated."
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Organic Anion Transporters, Sodium-Dependent
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Glioma is the most common primary malignant brain tumors in adults. Despite considerable advances in treatment, the clinical outcome remains dismal. Translocator protein 18 kDa (TSPO), an evolutionarily conserved transmembrane protein, has always been found to be elevated in glioma, which predicts a poor prognosis. However, studies on the regulatory network of TSPO in glioma are limited. The Cancer Genome Atlas (TCGA) and our research group cohorts demonstrated that TSPO expression was also highly expressed in glioma tissues and glioma cell lines. Inhibition of TSPO expression significantly reduced glioma cell proliferation and mobility in vitro. Suppression of TSPO decreased the expression of MAPK-activated protein kinase 3 (MAPKAPK3) and increased the degradation rate of its mRNA. TSPO directly interacts with ELAV1-like RNA-binding protein 1 (HUR) and promotes the nuclear-cytoplasmic shuttling of HUR. Inhibition of HUR decreased MAPKAPK3 expression and cell proliferation and mobility, whereas overexpression of MAPKAPK3 reversed the effects. Overexpression of HUR in TSPO-knockdown cells enhanced the mRNA stability of MAPKAPK3. Furthermore, rescue experiments show that the HUR/MAPKAPK3 axis accounts for the TSPO-mediated effects on glioma cell proliferation and mobility. Together, our present study indicated that TSPO may promote the nuclear-cytoplasmic shuttling of HUR, thus increasing the mRNA stability of MAPKAPK3 and promoting the proliferation and mobility of glioma cells. The HUR/MAPKAPK3 axis may be key targets for blocking the effects of TSPO and may contribute to glioma therapy.
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ELAV-Like Protein 1
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We present a 6-NHC-Cu(I) complex that provides alpha-substituted allylboronates using allylic aryl ether substrates. The method was discovered by comparison of the chemoselectivities exhibited by complexes 1a, 1b, 2, and 3. We observed that 1a preferentially reacts with electron-rich alkenes over electron-deficient alkenes. Development of an asymmetric method revealed that 1b reacts with both the E and Z isomers to provide the same absolute configuration without showing E-Z isomerization. This stereoconvergent reaction occurs with high yields (av 86%), high S(N)2' selectivity (>99:1), and high ee (av 94%) and exhibits wide functional-group tolerance using pure E or Z isomer or E/Z alkene mixtures. The stereoconvergent feature enables the use of many different olefination strategies for substrate production, including cross-metathesis. Chiral allylboronates could be purified by silica gel chromatography and stored in the freezer without decomposition.
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Allyl Compounds
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The B104 neuroblastoma cell line was investigated for use as an assay for predicting the patterning of primary neurons. B104 cells were grown on four uniform substrates with the result that the cells preferred, in descending order, poly-D-lysine (PDL), phenyltrichlorosilane (PTCS), coverslip glass, and silicon dioxide coated coverslips. B104 cells were then grown on micropatterned PDL grids on silicon dioxide coated substrates with excellent patterning. Compliance of somata to the pattern, defined as the percentage of cell bodies in a grid field located on the grid pattern, was 86% after 8 h. Neurites were not as compliant, since only 10% of background areas were free of neurites and connected cells. Compliance at longer time periods was greatly reduced. With the addition of the differentiating agent dibutyrylcyclicAMP (DBcAMP), the compliance of somata was maintained at high levels for up to 72 h. Also, the compliance of neurites greatly increased (70%) and showed positive improvement with longer pattern path lengths, contrary to B104 cells without DBcAMP. At longer times neurite compliance was reduced (12% at 28 h and 44% at 72 h). Although there are differences in substrate preferences, the B104 system with DBcAMP appears to be a useful tool in the investigation of the technology of patterned substrates.
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Bucladesine
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In general, primary amenorrhea is caused by gonadal dysgenesis, anomalies of internal or external genitalia with or without chromosomal anomalies, and sometimes by hormonal abnormalities that affect the hypothalamus, pituitary, ovaries, adrenals or thyroid, or by chronic or metabolic diseases. We report a rare case of a juvenile granulosa-cell tumor of the ovary that caused primary amenorrhea in a 16-year-old girl. Her hormonal profiles before the operation were characterized by an extremely low level of follicle-stimulating hormone (FSH), a relatively low level of estradiol and a high level of inhibin B. The patient had menarche after the removal of the tumor. Her elevated serum FSH after the operation was the result of a decreased serum level of inhibin that had been produced by the tumor. The present case highlights that a granulosa-cell tumor, known as an inhibin-secreting tumor, should be considered when treating primary amenorrheic girls.
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Neoplasms, Gonadal Tissue
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Intracellular bacteria of the genus Wolbachia (alpha Proteobacteria) induce cytoplasmic incompatibility (CI) in many arthropod species, including spider mites, but not all Wolbachia cause CI. In spider mites CI becomes apparent by a reduced egg hatchability and a lower daughter:son ratio: CI in haplodiploid organisms in general was expected to produce all-male offspring or a male-biased sex ratio without any death of eggs. In a previous study of Japanese populations of Tetranychus urticae, two out of three green-form populations tested were infected with non-CI Wolbachia strains, whereas none of six red-form populations harbored Wolbachia. As the survey of Wolbachia infection in T. urticae is still fragmentary in Japan, we checked Wolbachia infection in thirty green-form populations and 29 red-form populations collected from a wide range of Japanese islands. For Wolbachia-infected populations, we tested the effects of Wolbachia on the reproductive traits and determined the phylogenetic relationships of the different strains of Wolbachia. All but one green-form populations were infected with Wolbachia and all strains belonged to the subgroup Ori when the wsp gene was used to determine the phylogenetic relationships of different strains of Wolbachia. Six out of 29 red-form populations harbored Wolbachia and the infected strains belonged to the subgroups Ori and Bugs. Twenty-four of 29 infected green-form populations and five of six infected red-form populations induced CI among the hosts. Thus, CI-Wolbachia strains are widespread in Japan, and no geographical trend was observed in the CI-Wolbachia. Although three red-form populations harbored other intracellular bacteria Cardinium, they did not affect host reproduction.
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Tetranychidae
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One of the main difficulties in using body surface potential mapping (BSPM) techniques is the need of complicated multi-channel measuring system. In this paper practical portable ECG mapping system is introduced. The system consists of a notebook computer and a data acquisition system box connected to the computer by fast IEEE 1284 parallel interface working in ECP mode. Concept of the device enables to extend the basic 134-channel high-resolution multi-channel ECG amplifying unit up to 256 channels. Application software includes measurement and real time monitoring of ECG signals, computation and display of several types of body surface potential maps. System can be connected to hospital information networks and supply them with measured ECG data for advanced processing or central archiving."
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Body Surface Potential Mapping
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Angiotensin is a potent dipsogenic substance and causes elevated water intake in some pathological conditions but as yet no physiological role for angiotensin in normal thirst has been proven. If angiotensin is important in normal drinking, then it should contribute to the drinking which follows water deprivation. The rehydration of bilaterally nephrectomized rats, rats with bilateral ureteric ligation and control rats was compared after 21 hours of water deprivation. The total intake during the 6 hour rehydration was the same in the 3 groups despite the differences in the level of circulating angiotensin. Thus the renal renin-angiotensin system is not essential for deprivation-induced drinking. Another way to test any contribution to drinking by angiotensin is the administration of the competitive angiotensin inhibitor, saralasin acetate. In a control experiment saralasin acetate was found to block the dipsogenic effect of intravenous angiotensin. The infusion of saralasin acetate in a wide range of doses did not, however, affect the drinking following ligation of the inferior vena cava. Thus angiotensin is not essential for drinking following caval ligation. Two possible explanations for these results are that angiotensin is not normally involved in these types of thirst or that there is redundancy in the control of drinking with compensation for blocked mechanisms.
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Angiotensin II
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This study's aim was to uncover psychological and social motives for using untact services and to explore the relationships between identified motivations and attitudinal and continuous behavioral intention variables. We conducted a survey with 328 untact service users, and used exploratory and confirmatory factor analysis to find underlying motivations. The findings suggest that users of untact services have four primary motives. Individuals use untact services to protect their personal information (privacy), to increase their control over business transactions (control), to enjoy the process itself (fun), and to avoid uncomfortable interactions with employees (interaction avoidance). In addition, identified motivations and attitudes toward as well as continuing intention to use the services were all positively related. Among the motivations, control showed the strongest relationship with both attitude and continuance intention.
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Privacy
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Malacca (Phyllanthus emblica) is one of the plants that is often by the community in the Aceh Besar district of Indonesia as a traditional medicine for the treatment of various diseases such as antimicrobial, antibacterial, antifungals, antivirals, antimutagenic, antimalaria, and antiallergic. This research was conducted to analyze the content of chemical compounds in the ethanol extract of the Malacca leaf (EEDM) using a gas chromatography-mass spectrophotometer (GC-MS). Malacca leaves were extracted by the maceration method using n-hexane, ethyl acetate, and ethanol. The GC-MS analysis showed EEDM contained 22 chemical compounds. The highest chemical content of EEDM is octadecanoic acid reaching 22.93%, 9,12-octadecanoic acid 14.99%, octadecanoic acid 7.59%, 9-hexadecenoic acid 6.17%, octadecanoic acid 5.95%, octadecanal 5.59%, 9,12-octadecanoic acid 5.06%, 3-eicosyne 4.75%, 1-hexadecenoic acid 4.08%, 11-tetradecen-1-ol 2.92%, 2-furanmethanol 2.83%, delta-guaiene 2.43%, cyclohexane 2.13%, hexadecanoic acid 1.99%, sativen 1.87%, octadecanoic acid 1.52%, 1H-cyclopropaanaphthalene 1.40%, tetradecanoic acid 1.40%, 3,7,11-tridecatrienenitrile 1.20%, caryophellene 1.11%, 2H-pyran 1.07%, and trans-caryophellene 1.03%. This study clearly shows the presence of fatty acids which play a major role in the efficacy of these traditional medicines particularly as antioxidant and antimalarial.
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Phyllanthus emblica
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BACKGROUND: Mothers of twins have some difficulties to individualize their child-raising activities during the first year. This study was aimed to determine factors influencing such activities. POPULATION AND METHODS: Thirty-seven pairs of twins born after 36 weeks of gestation and weighing more than 2,000 g were included in the study. Relationships between the parents and their children were studied from questionnaires concerning activities during the first trimester and the end of the first year of age. Each item concerning organization of meals and sleeping was graded 1 to 3 according to the degree of individualization of the care. Items concerning support of the mother by the father or other people were graded 1 to 3 according to the degree of this assistance. The physical and psychological status of the mother was also graded according to the presence or not of asthenia and/or depression. Home activities of the mother were also observed. RESULTS: The state of the mother during the first few months had an impact on her mothering behavior: tired or depressed mothers tend to treat the twins collectively and simultaneously. No link was found between social, paternal or general familial support and the degree of individualization in the maternal behaviors. CONCLUSIONS: Several factors can interfere with the psychological repercussions of a twin birth on the mother and subsequent psychoemotional development of children. Further studies are necessary to understand how each parent contributes to the organization of the family system.
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Father-Child Relations
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