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26989121
Epigenetic variation in the FWA gene within the genus Arabidopsis. fwa is a late flowering epi-mutant in Arabidopsis thaliana. FWA is silenced by DNA methylation in vegetative tissue but is demethylated in the central cell of the female ovule and continues to be expressed in the endosperm from the maternal copy. FWA is stably silenced in A. thaliana, but in related Arabidopsis species, FWA expression and DNA methylation levels vary in vegetative tissue. In this study, we show that variation in FWA expression in field isolates having identical DNA sequences is associated with changes in DNA methylation and may change over time. Vegetative FWA expression is correlated with decreased methylation at non-CG sites in the region upstream of the transcription start site in species related to A. thaliana and we conclude that methylation of this region is critical for FWA silencing in these species. In A. thaliana, FWA expression is affected by methylation in regions both upstream and downstream of the transcription start site. Ectopic A. thaliana FWA expression causes a late flowering phenotype, but over-expression of Arabidopsis lyrata FWA does not. In A. thaliana, stable silencing of FWA to prevent late flowering may have evolved through the selection of large tandem repeats and spread of the critical methylated region to include these repeats.
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PubMed Abstracts
26989132
Metabolism of the hypolipidemic agent tiadenol in man and in the rat. The metabolism of the hypolipidemic agent 1,10-bis(hydroxyethylthio)decane (tiadenol, Eulip) has been studied in vivo in man and in the rat and in vitro in the rat. Following oral administration, in both species tiadenol was completely absorbed, extensively metabolized by the liver and more than 95% of the dose was eliminated in this form via kidneys within 48 h. Insignificant was the excretion of the unchanged drug in urine (approximately 1%) as well as that of its metabolites in the feces. 8 metabolites were isolated from human or rat urine and their structures were elucidated by means of electron impact, field desorption and positive and negative fast atom bombardment mass spectrometry. Both in man and in the rat the main metabolic pathway was the oxidation of the thioether sulfur, followed by oxidation or conjugation of the primary alcohol group(s). The urinary excretion of S-oxidized metabolites and sulfoxidized carboxylic metabolites accounted for 75% of the dose and that of S-oxidized conjugated metabolites for 20%. Rat in vitro studies showed that hepatic microsomal cytochrome P-450-dependent monooxygenase catalyzes the S-oxidative pathway, which governs the in vivo elimination of the drug in both species. Thus cytochrome P-450 is the key enzyme in the hepatic detoxification of tiadenol.
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PubMed Abstracts
26989141
Cardiac fibroblasts recruit Th17 cells infiltration into myocardium by secreting CCL20 in CVB3-induced acute viral myocarditis. Th17 cells contributed to myocardial inflammatory injury in acute viral myocarditis (AVMC), and the migration of these cells were mainly mediated by CCL20-secreting inflammatory cells. However, whether and how the resident cells such as cardiomyocytes and cardiac fibroblasts could mediate Th17 cell migration into the heart remains unclear in AVMC. The effect of CCL20 on the dynamic alterations of intracardiac Th17 cells and disease severity were investigated through the neutralization of CCL20 in AVMC mice. The key cells releasing CCL20 in the heart and the effects of CCL20-secreting cells on Th17 cell arrest, migration and differentiation were detected in vitro. Neutralization of CCL20 efficiently repressed the myocardial inflammation along with the reduction of Th17 cell infiltrations in the course of AVMC. In vitro, after stimulations of TNF-α, IL-1β and IL-17, cardiac fibroblasts rather than cardiomyocytes could be dominantly induced for CCL20 production. CCL20-secreting cardiac fibroblasts boosted Th17 cell arrest on endothelium, and induce Th17 cell migration. However, CCL20 produced by cardiac fibroblasts had no effect on Th17 cell differentiation and IL-17 production. It firstly suggested that cardiac fibroblasts could recruit Th17 cells infiltration into myocardium by secreting CCL20 in AVMC.
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PubMed Abstracts
26989149
[Efficiency of preventive dental care in school dentistry system]. Ways of development of Russian school dentistry are defined and justified based on the analysis according to logistics, personnel, legal, financial and economic basis for the reorientation of the service for preventive direction, which should be a priority in the current conditions. The implemented model of school dental care based on team work of the dentist and dental hygienist proved to be highly efficient and may be recommended for wide introduction in practice.
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PubMed Abstracts
26989159
Evaluation and treatment of acute psychosis in children with Systemic Lupus Erythematosus (SLE): consultation-liaison service experiences at a tertiary-care pediatric institution. Neurological and psychiatric manifestations of systemic lupus erythematosus (SLE) are prevalent in children with SLE. There are few data on the evaluation and management of psychotic features in children with this systemic autoimmune disorder. The authors describe contemporary Child and Adolescent Psychiatry Consultation and Liaison service management of acute psychosis in children with lupus. The authors reviewed the records (2003-2008) of all pediatric SLE inpatients who were administered a traditional or atypical antipsychotic agent. They describe clinical features, initial and discharge mental status examinations, and inpatient psychotropic medication usage. Ten pediatric SLE patients (age 10-19 years) required psychiatric management for psychosis during the review period. Paranoid delusions (70%), visual hallucinations (60%), and auditory hallucinations (60%) were the most common psychotic symptoms documented. All children were initially treated with an antipsychotic medication. Seven children were maintained on an atypical antipsychotic during their hospitalization. Two children had extrapyramidal signs, but no other adverse events were documented. All children were improved at discharge, and 40% had complete resolution of psychosis; 8 of the 10 patients were discharged on a psychotropic medication. Psychotic manifestations associated with severe disease presentations were successfully treated by child psychiatrists. Atypical antipsychotics were well-tolerated and used as an adjunct to immunosuppressive regimens in these patients. Prospective studies are necessary to improve the care of children and adolescents with SLE and severe psychiatric manifestations.
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PubMed Abstracts
26989161
Protein engineering of carboxyl esterases by rational design and directed evolution. In the past few years a considerable number of mutagenesis methods and high-throughput screening (HTS) systems have been developed and improved. In parallel, computer programs or software packages for molecular modeling have been further investigated. Thus, the number of examples for successful directed evolution and rational design is increasing constantly. In this review the essential mutagenesis methods and HTS systems, especially for esterases, are described and various examples for the application of these protein engineering tools are provided.
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PubMed Abstracts
26989166
A new approach to an influenza life vaccine: haemagglutinin cleavage site mutants generated by reverse genetics. A promising approach to reduce the impact of influenza is the use of an attenuated life virus as a vaccine. Using reverse genetics, a mutant of strain A/WSN/33 with a modified cleavage site within its haemagglutinin was generated which depends on proteolytic activation by elastase. Unlike the wild-type requiring trypsin, this mutant is strictly dependent on elastase. Both viruses grow equally well in cell culture in the presence of the respective protease. In contrast to the lethal wild-type, the mutant is entirely attenuated in mice at a virus dose of 10(6) pfu. At a dose of 10(5) pfu it induced complete protection against lethal challenge. This approach allows the conversion of any epidemic strain into a genetically homologous attenuated virus.
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PubMed Abstracts
26989183
Cardiovascular adjustments to pulmonary vascular injury in dogs. The hemodynamic effects of blood volume augmentation and mechanical ventilation (MV) with positive end-expiratory pressure (PEEP) were studied in nine Beagles anesthetized with halothane before and after thrombin-induced pulmonary hypertension. The effect of therapy with dopamine, norepinephrine with and without nitroglycerin (NTG), and intraaortic balloon pumping (IABP) were studied in a second series of six Beagles. Before thrombin, dextran (35 ml.kg-1) caused a significant increase in right and left ventricular end-diastolic and end-systolic volumes (RV and LVEDV, and RV and LVESV). However, RV and LV performance, as estimated by ejection fraction, was unchanged during volume loading and MV with PEEP when the pulmonary vasculature was intact. The response to volume loading and MV with PEEP was altered significantly once PVR had been increased with the administration of thrombin. Stroke volumes were decreased, and remained so, despite volume loading and MV with PEEP. LVEDV decreased without a decrease in LVEDP, indicating a decreased LV compliance. Dopamine and norepinephrine with and without NTG increased stroke volumes and RV ejection fraction in contrast to IABP. Assessment of LV performance, according to the Frank-Starling mechanism, requires a measure of end-diastolic volume when diffuse pulmonary vasoconstriction leads to RV distension and LV hypovolemia secondary to septal shift. Measurement of LV filling pressures can provide misleading values to estimate changes in LV volume in this setting. Measurement of ventricular volumes is required for optimal management of patients with severe acute respiratory failure and pulmonary hypertension.
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PubMed Abstracts
26989185
[Clinical epidemiology and treatment of tuberculosis in elderly patients]. In developed countries the incidence of tuberculosis is higher in patients aged 65 and over than in any other age group, with the exception of HIV positive subjects. This high incidence is a consequence of the very high rate of infection in our countries in the first part of the century, and of the diminished efficiency of the aging immune system. In this age group, most cases of tuberculosis are reactivations of dormant mycobacteria. However, the possibility of a newly acquired infection must be kept in mind, especially in institutionalized patients. The clinical presentation is often insidious and non-specific, as is the radiological presentation (i.e. infiltrates in middle or lower lobes); the large number of cases discovered at autopsy illustrates the difficulty of clinical diagnosis. Extra-thoracic involvement is less frequent than in younger adults (15% of cases). Mortality is high, even in treated patients, and increases with age. The frequency of drug-induced hepatitis under tuberculostatic treatment increases with age: signs of hepatic toxicity should be monitored regularly; furthermore, compliance with treatment may be jeopardized by cognitive impairment: directly observed treatment should be set up when there is the slightest doubt as to compliance. Prophylactic treatment with isoniazid is indicated in recent tuberculin converters (after exclusion of active disease), in patients with diabetes or on immunosuppressive therapy, and in patients with radiological fibrotic lesions without serious co-morbidities. In institutionalized subjects regular tuberculin testing is warranted to detect nosocomial infection.
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PubMed Abstracts
26989210
The donor, the father, and the imaginary constitution of the family: parents' constructions in the case of donor insemination. Current international policy trends in the field of medically assisted conception are moving towards increased openness of information regarding the nature of conception where donated gametes are involved. In the case of donor insemination this means that the donor is no longer anonymous, offspring have the right to access information about the donor's identity, and parents are encouraged to tell children the nature of their donor-assisted conception. Until recently, however, the practice of donor insemination has tended to create the conditions for ignoring, or erasing, the existence of the donor as the provider of the gametes. Changing policy creates numerous challenges to this erasure, and to traditional conceptualisations of the father. This research is based on analysis of the narratives of a group of 41 New Zealand couples who conceived children with the assistance of donor insemination 15-18 years prior. This article focuses on their talk about the donor. The parents' negation of the donor supports the normative formation of 'family', and is in turn supported by an instrumental and de-personalising discourse in relation to the donor. A tension is created within the parents' talk whereby donors are negated and yet simultaneously appear as persons. We explore this discursive construction, suggesting that a new framework for thinking about donated gametes and the role of the donor is influencing parents' narrations and understandings of family. We discuss these influences and examine their implications, particularly with respect to a separation of the bio-genetic from the social-environmental.
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PubMed Abstracts
26989214
Radio-frequency clock delivery via free-space frequency comb transmission. We characterize the instability of an rf clock signal caused by free-space transmission of a frequency comb (FC) under typical laboratory conditions. The phase-noise spectra show the involvement of multiple random processes. For a 10 m transmission, the rms timing jitter integrated over 1-10(5) Hz is 95 fs, and the root Allan variance over 1 s is 4x10(-13). The measured Allan variance has a tau(-1) behavior and an excellent agreement with the phase noise measurement. These results indicate the feasibility of FC-based free-space rf clock distribution over short distances.
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PubMed Abstracts
26989218
Stability, persistence, and evolution of plasmid-encoded VanA glycopeptide resistance in enterococci in the absence of antibiotic selection in vitro and in gnotobiotic mice. Long-term persistence of VanA glycopeptide-resistant enterococci (GRE) has been observed in the absence of antibiotic selection. In the present study, we examined fitness parameters of a glycopeptide-susceptible Enterococcus faecium parent strain and its plasmid-mediated, VanA-resistant derivative before and after 1,000 generations in serial transfer broth cultures with or without antibiotic selection. With the exception of the vanA-containing plasmid, the strains were otherwise isogenic. The stability of the plasmid-encoded vanA resistance determinant was also investigated in vitro and in gnotobiotic mice. Competition experiments revealed that GRE with newly acquired VanA resistance had a 4% reduction in fitness relative to their susceptible parental counterpart. The relative difference in competitive fitness between resistant and susceptible strains was not significantly changed after 1,000 generations. Environmental adaptation was observed in all strains and exceeded the biological cost of resistance. Thus, the evolved VanA-resistant E. faecium populations out-numbered their unevolved ancestral susceptible E. faecium strain in mixed cultures, but remained less competitive than the evolved parent. The glycopeptide resistance determinant was similarly stably maintained during long-term colonization in gnotobiotic mice without antibiotic selection. In vivo vanA plasmid transfer was observed. The results suggest that environmental adaptation, in vivo gene transfer, and plasmid maintenance system(s) favor long-term VanA GRE persistence without antibiotic selection and compensate for the biological costs of possessing the resistance genes.
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PubMed Abstracts
26989221
Xylem-phloem hydraulic coupling explains multiple osmoregulatory responses to salt stress. Salinity is known to affect plant productivity by limiting leaf-level carbon exchange, root water uptake, and carbohydrates transport in the phloem. However, the mechanisms through which plants respond to salt exposure by adjusting leaf gas exchange and xylem-phloem flow are still mostly unexplored. A physically based model coupling xylem, leaf, and phloem flows is here developed to explain different osmoregulation patterns across species. Hydraulic coupling is controlled by leaf water potential, ψl , and determined under four different maximization hypotheses: water uptake (1), carbon assimilation (2), sucrose transport (3), or (4) profit function - i.e. carbon gain minus hydraulic risk. All four hypotheses assume that finite transpiration occurs, providing a further constraint on ψl . With increasing salinity, the model captures different transpiration patterns observed in halophytes (nonmonotonic) and glycophytes (monotonically decreasing) by reproducing the species-specific strength of xylem-leaf-phloem coupling. Salt tolerance thus emerges as plant's capability of differentiating between salt- and drought-induced hydraulic risk, and to regulate internal flows and osmolytes accordingly. Results are shown to be consistent across optimization schemes (1-3) for both halophytes and glycophytes. In halophytes, however, profit-maximization (4) predicts systematically higher ψl than (1-3), pointing to the need of an updated definition of hydraulic cost for halophytes under saline conditions.
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PubMed Abstracts
26989224
Efficacy and safety of aztreonam in the treatment of serious gram-negative bacterial infections. Aztreonam was used in the initial treatment of infection of the urinary tract (23 cases), respiratory tract (17 cases), skin and soft tissue (12 cases), abdominal cavity (three cases), endocarditis (two cases), septicemia (eight cases), and osteomyelitis (two cases). In 26 of 60 evaluable infectious episodes, aztreonam was used alone. Clinical cure was observed in 35 of 60, improvement in 24 of 60, and failure in one of 60 cases. Ten patients developed subsequent superinfection. Aztreonam was well tolerated, although one case of exfoliative dermatitis and one of pseudomembranous colitis occurred. However, these cases were complicated by proximal administration of other antibiotics.
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PubMed Abstracts
26989227
CD86 polymorphism affects pneumonia-induced sepsis by decreasing gene expression in monocytes. Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of morbidity and mortality worldwide. CD86 (B7-2) is a costimulatory molecule on antigen-presenting cells and plays critical roles in immune responses. In the current study, we investigated the association of two CD86 polymorphisms, rs1129055G/A and rs17281995G/C, with susceptibility to pneumonia-induced sepsis and examined the effects of these two polymorphisms on gene expression in monocytes. CD86 rs1129055G/A and rs17281995G/C were identified in 192 pneumonia-induced septic patients and 201 healthy controls. Data showed that frequencies of the rs1129055GA and AA genotypes were significantly lower in patients than in controls (odds ratio [OR]=0.57, 95 % confidence interval [CI], 0.35-0.93, p=0.023, and OR=0.40, 95 % CI, 0.23-0.71, p=0.002). Interestingly, the other polymorphism, rs17281995G/C, revealed significantly increased numbers in pneumonia-induced sepsis compared to controls (OR=1.85, 95 % CI, 1.07-3.20, p=0.025). Further analyses about CD86 gene expression revealed that both messenger RNA (mRNA) and protein levels of CD86 were downregulated in monocytes from controls carrying rs17281995GC genotype than those carrying wild-type rs17281995GG genotype (p=0.022 and p=0013). These results suggest that polymorphisms in CD86 gene have diverse effects on the pathogenesis of pneumonia-induced sepsis, in which rs17281995G/C may increase the risk of the disease by interfering gene expression of CD86 in monocytes.
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PubMed Abstracts
26989251
Hypercholesterolemia. The evidence supports use of statins. Using statins to treat older men and women with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, Intermittent claudication, and congestive heart failure. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg in older patients with CAD, prior stroke, peripheral arterial disease, extracranial carotid arterial disease, abdominal aortic aneurysm, diabetes meilitus, and the metabolic syndrome. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia without cardiovascular disease. Consider using statins in older persons without cardiovascular disease but with a serum LDL cholesterol > or = 130 mg/dL, or a serum high-density lipoprotein cholesterol < 50 mg/dL. Data from the Heart Protection Study favor treating patients at high risk for vascular events with statins regardless of age or initial serum lipids.
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PubMed Abstracts
26989264
New Therapeutic Strategies for Primary Sclerosing Cholangitis. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, which in the majority of patients progresses to liver transplantation or death. To date, no medical treatment has been proven to be of benefit, although ursodeoxycholic acid is widely used. The etiopathogenesis of PSC is unclear, although it is associated with inflammatory bowel disease. Various hypotheses have been suggested, which have led to different therapeutic strategies. Recent studies have suggested that the microbiome may play a role in PSC, raising the possibility of efficacy of antibiotics and fecal microbiota transplantation. Gut-homing T cells may be important in the pathogenesis of PSC, and several agents are in development, targeting various receptors, integrins, and ligands on this pathway, including VAP-1, MAdCAM-1, α4β7, and CCR9. Nuclear receptor agonists such as obeticholic acid and fibrates hold promise, as do other therapies that alter bile acid composition such as norUDCA. Antifibrotic agents such as Loxl2 inhibitors are also being assessed. In conclusion, it is likely that an effective drug therapy for PSC will become available over the next decade.
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PubMed Abstracts
26989272
Pitucamycin: structural merger of a phenoxazinone with an epoxyquinone antibiotic. Chemical profiling of a Streptomyces griseus strain isolated from an old building with moisture damage led to the discovery of two novel phenoxazinones, chandrananimycin D and pitucamycin , along with the known grixazone B. Pitucamycin represents an unprecedented hybrid molecule composed of a phenoxazinone and an enaminomycin-like epoxyquinone moiety.
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PubMed Abstracts
26989274
Cholinergic changes during conditioned suppression in rats. Levels of acetylcholine were significantly elevated in the telencephalon and diencephalon + mesencephalon of rats killed by near-freezing during conditioned suppression of food-reinforced lever pressing, whereas levels of serotonin, dopamine, and norepinephrine were not altered. These neurochemical changes were not seen in rats serving as controls for conditioning experience, activity levels, or stimulus presentation.
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PubMed Abstracts
26989276
Anisotropy of ultrasonic propagation and scattering properties in fresh rat skeletal muscle in vitro. The anisotropy of frequency-dependent backscatter coefficient, attenuation, and speed of sound is assessed in fresh rat skeletal muscle within 5 h post-mortem. Excised rat semimembranosus and soleus muscles are measured in 37 degrees C Tyrode solution, with the muscle fibers at 90 degrees and 45 degrees orientations to the incident sound beam. Reflected and through transmission signals from either a 6- or 10-MHz focused transducer give frequency dependent information in the 4-14 MHz range. The attenuation coefficient in each muscle is consistently a factor of 2.0 +/- 0.4 lower for propagation perpendicular to the fibers than at 45 degrees, whereas speed of sound shows a much milder anisotropy, and is slightly faster for the 90 degrees orientation. The largest anisotropy is seen in the backscatter coefficient, most notably in the semimembranosus where the magnitude at 90 degrees is over an order of magnitude greater than at 45 degrees, with the frequency dependence in both cases giving a power law between 1.5 and 2.0.
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PubMed Abstracts
26989296
Genetic features of the X chromosome affect pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome. To investigate how genetic features of the X chromosome influence growth, pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome (KS). Previous studies have suggested that genetic features of the X chromosome may contribute to the wide phenotypic variation in KS. A prospective clinical study. Fourteen nonmosaic 47,XXY boys, aged 10-13.9 years. The relationship of genetic features of the X chromosome, including parental origin of X chromosomes, the CAG repeat length of the androgen receptor (AR) gene, and X inactivation with progression of pubertal development, growth and testicular function in KS boys. Paternal (47,XmXpY, n = 3) as compared to maternal (47,XmXmY, n = 11) origin of the supernumerary X chromosome was associated with a later onset of puberty. In 47,XmXpY patients, serum LH concentrations increased above 1.0 IU/l at 12.5 +/- 0.6 years (mean +/- SD), Tanner stage P2 occurred at 12.5 +/- 0.7 years, and pubertal acceleration of growth was noted at 13.9 +/- 1.4 years and peak velocity at 14.5 +/- 0.8 years. All of these occurred 1.3-1.9 years later than in 47,XmXmY patients (P = 0.01-0.09). In 47,XmXmY subjects, CAG repeat length (range 17-26) correlated with age at which serum LH level first exceeded 1.0 IU/l (rs = 0.63, P = 0.06, n = 10) and testosterone 1.0 nmol/l (28.8 ng/dl) (rs = 0.78, P = 0.02, n = 10). Paternal origin of the supernumerary X chromosome is associated with later onset of puberty and longer CAG repeats of the AR with later pubertal reactivation of the pituitary-testicular axis in KS boys. Identifying genetic factors that affect the phenotype may lead to a better understanding of the pathogenesis of KS.
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PubMed Abstracts
26989302
Subdural haematoma in neonates following forceps-assisted delivery: case series and review of the literature. Subdural haematoma (SDH) is a recognised complication of forceps-assisted delivery (FAD). There are no guidelines regarding its management. This study aims to provide a better insight into the management and outcomes of neonatal SDH post-FAD. Retrospective review of our neonatal database and systematic review of the literature for neonatal cases that presented with SDH after FAD. Retrospective neurosurgical database search for cases of neonatal SDH post-FAD managed in our unit between January 2007 and January 2017. Systematic review of the literature was performed using PRISMA guidelines. The inclusion criteria are as follows: (1) neonates; (2) forceps-assisted delivery; (3) evidence of SDH on imaging, with or without other traumatic lesions. A literature search yielded nine studies with 30 patients meeting our inclusion criteria. In addition, four cases were identified from our institutional database. Forty-two percent (n = 14) had their SDH managed surgically, with subsequent full neurological recovery in 57%. In comparison, 95% (n = 18) of the conservatively managed patients made a full recovery. Hydrocephalus was present in 1/19 and 11/14 of the conservatively managed and surgically managed patients respectively. Conservative management can lead to a full neurological recovery in SDH following FAD in neonates. However, a significant minority may still need neurosurgical intervention for the SDH or subsequent hydrocephalus; therefore, we advocate early transfer to a specialist neuroscience centre.
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PubMed Abstracts
26989306
The course of schizophrenia: progressive deterioration, amelioration or both? Schizophrenia may follow a course of amelioration, deterioration or stability. It is possible that deterioration at the aggregate level may be due to a sub-group of patients with a tendency to deteriorate. To examine the course of schizophrenia in a national population-based cohort. All first admissions for schizophrenia in Israel 1978-1986 were followed for readmissions in the Israeli psychiatric hospitalization registry for 10 years (n=6865). Readmission rates were examined using cluster analysis. This was followed by an examination of changes in readmission patterns. Cluster analysis identified a small cluster of patients who spent more days in the hospital over time and two clusters that improved. A priori classification of the patients into deteriorating, improving and stable (based on days hospitalized per year) revealed that approximately 75% of patients improved over time. Over time a majority of patients appear to improve and a minority appear to deteriorate.
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PubMed Abstracts
26989313
Transcriptional repressor HipB regulates the multiple promoters in Escherichia coli. HipB is a DNA-binding protein in Escherichia coli and negatively regulates its own promoter by binding to the palindromic sequences [TATCCN8GGATA (N represents any nucleotides)] on the hipBA promoter. For such sequences, bioinformatic analysis revealed that there are a total of 39 palindromic sequences (TATCCN(x)GGATA: N is any nucleotides and x is the number of nucleotides from 1 to 30) in the promoter regions of 33 genes on the E. coli genome. Notably, eutH and fadH have two and three TATCCN(x)GGATA palindromic sequences located in their promoters, respectively. Another significant finding was that a palindromic sequence was also identified in the promoter region of hipAB locus, known to be involved in the RelA-dependent persister cell formation in bacteria. Here, we demonstrated that HipB binds to the palindromic structures in the eutH, fadH, as well as the relA promoter regions and represses their expressions. We further demonstrated that HipA enhances the repression of the relA promoter activity by HipB. This effect was not observed with D291A HipA mutant which was previously shown to lack an ability to interact with HipB, indicating that HipA enhances the HipB's repressor activity through direct interaction with HipB.
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PubMed Abstracts
26989329
A giant peritoneal loose body: report of a case. Peritoneal loose bodies are usually small, 0.5 to 2.5 cm in diameter, and rarely cause symptoms. However, "giant" peritoneal loose bodies, larger than 5 cm in diameter, presenting with various symptoms have been also reported. We report here a case of a "giant" peritoneal loose body found in a 73-year-old man. In this case, the peritoneal loose body was 9.5 cm in diameter, comparable to the largest one reported in the literature. The patient refused any treatment at his first visit but accepted surgical removal of the peritoneal loose body 5 years later. The size of the peritoneal loose body has increased from 7.3 cm to 9.5 cm in diameter during this observation period.
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PubMed Abstracts
26989350
BRAFV600E mutation in the pathogenesis of a large series of papillary thyroid carcinoma in Czech Republic. Activating point mutation of the BRAF gene, the most common genetic alteration reported in papillary thyroid carcinomas (PTC), has been associated with poor prognostic characteristics. Our objective was to determine the frequency of BRAFV600E mutation in PTC tumor tissues from the period 1960-2007 and to correlate it with clinicopathological parameters. DNAs were extracted from 242 PTCs, 23 sporadic medullary carcinomas, one anaplastic carcinoma and 6 poorly differentiated carcinomas. The presence of BRAFV600E mutation was determined using single strand conformation polymorphism method and verified by direct sequencing. BRAFV600E mutation was detected in 81 of 242 PTCs (33.5%), in one of 6 poorly differentiated carcinomas (16.7%) and in anaplastic carcinoma. BRAFV600E mutation was much less frequent in the follicular variant compared to classical variant and mixed follicular- classical variant of PTCs (p=0.001). BRAFV600E mutation was significantly associated with presence of nodal metastasis (p=0.029), more advanced TNM stage (p=0.014) and recurrence of disease (p=0.008). The mutation correlated with a higher age at diagnosis (p=0.049) and with a greater tumor size (p=0.041). Multivariate analysis confirmed these findings. The prevalence of BRAFV600E mutation before 1986 was significantly lower than after it (p=0.008). Our data suggest that BRAFV600E mutation is associated with high-risk clinicopathological characteristics of PTC and worse prognosis of patients. The frequency of the mutation significantly varied during the observed period but rather because of the different age distribution of patients in particular periods than as a consequence of Chernobyl accident.
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PubMed Abstracts
26989356
Treatment of hepatic failure with artificial liver support system. To assess the effectiveness of artificial liver support system (ALSS) treatment in patients with hepatic failure. 235 cases of hepatic failure were treated with ALSS in our hospital. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared according to different stages (i.e., early, middle and end stages). 108 patients survived after therapy of ALSS. After each ALSS treatment, the liver function of these patients was greatly improved, the serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while the ratio of branched chain amino acids and aromatic amino acids (BCAA/AAA ratio) increased; patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease. ALSS is a reliable therapy for advanced liver diseases and treatment at early or middle stages is appropriate.
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PubMed Abstracts
26989359
The use of silicone oil following failed vitrectomy for retinal detachment with advanced proliferative vitreoretinopathy. We have used silicone oil injection in a consecutive series of 44 patients with retinal detachment and advanced proliferative vitreoretinopathy, all of whom had previously failed to reattach with vitrectomy, membrane peeling, and scleral buckling. After a minimal follow-up period of six months, complete anatomic retinal reattachment posterior to the encircling scleral buckle was obtained in 64% of these eyes, and visual acuity of 5/200 or better was achieved in 57% of the anatomically successful cases. Silicone oil removal was performed in 69% of the anatomically and visually successful eyes without recurrent retinal detachment.
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PubMed Abstracts
26989362
Corticotropin-releasing hormone: a biochemical predictor of preterm delivery in a pilot randomized trial of the treatment of preterm labor. We assessed the ability of maternal plasma corticotropin-releasing hormone measurements to predict preterm delivery in the setting of a pilot study comparing transdermal glyceryl trinitrate with standard beta-mimetic therapy for preterm labor and to determine the effect of these tocolytics on maternal plasma corticotropin-releasing hormone concentrations. Twenty-six consecutive patients with preterm labor were randomized to tocolytic treatment with transdermal glyceryl trinitrate (n=13) or intravenous albuterol (n=13). Plasma corticotropin-releasing hormone immunoreactivity levels were higher in women who were delivered within 7 days (41.4+/-13.5 pmol/L) than in those continuing to term (14.2+/-2.4 pmol/L, p=0.011) and were not altered by treatment. Two women in each of the treatment groups delivered within 7 days of the initiation of treatment, two women in the glyceryl trinitrate group were changed to albuterol because of persistence of contractions. Glyceryl trinitrate treatment was associated with significantly fewer maternal side effects. Neither treatment altered umbilical artery Doppler ultrasonographic findings. Transdermal glyceryl trinitrate is better tolerated than intravenous albuterol but may be no more efficacious than albuterol for the treatment of preterm labor. Biologic markers such as plasma corticotropin-releasing hormone levels may be an important method of identifying women at high risk of preterm delivery.
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PubMed Abstracts
26989363
Study of the fetal kidney length growth during the second and third trimesters of gestation. The fetal kidney length growth was studied in 240 kidneys taken from 120 staged human fetuses (74 males and 46 females) ranging in age from 10 to 36 weeks postconception. Each kidney was quantitatively evaluated considering its greatest longitudinal length. The data were correlated to the gestational age by using the allometric method (Y = bXk). Equations and growth curves of right and left kidneys, males, females and the whole sample during the second and the third trimesters are presented. This study has practical utility in the quantitative determination of the renal anomalies and in the determination of the gestational age.
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PubMed Abstracts
26989371
High-Flow Nasal Cannula Oxygen Therapy in Adults: Physiological Benefits, Indication, Clinical Benefits, and Adverse Effects. High-flow nasal cannula (HFNC) oxygen therapy is carried out using an air/oxygen blender, active humidifier, single heated tube, and nasal cannula. Able to deliver adequately heated and humidified medical gas at flows up to 60 L/min, it is considered to have a number of physiological advantages compared with other standard oxygen therapies, including reduced anatomical dead space, PEEP, constant F(IO2), and good humidification. Although few large randomized clinical trials have been performed, HFNC has been gaining attention as an alternative respiratory support for critically ill patients. Published data are mostly available for neonates. For critically ill adults, however, evidence is uneven because the reports cover various subjects with diverse underlying conditions, such as hypoxemic respiratory failure, exacerbation of COPD, postextubation, preintubation oxygenation, sleep apnea, acute heart failure, and conditions entailing do-not-intubate orders. Even so, across the diversity, many published reports suggest that HFNC decreases breathing frequency and work of breathing and reduces the need for respiratory support escalation. Some important issues remain to be resolved, such as definitive indications for HFNC and criteria for timing the starting and stopping of HFNC and for escalating treatment. Despite these issues, HFNC has emerged as an innovative and effective modality for early treatment of adults with respiratory failure with diverse underlying diseases.
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PubMed Abstracts
26989388
Aminophylline and isoproterenol in the treatment of cerebral vasopasm. Eighteen patients with cerebral vasospasm following subarachnoid hemorrhage were treated with 21 trials of intravenous aminophylline and isoproterenol. After angiographic demonstration of spasm, all patients were started on a continuous intravenous infusion of aminophylline 125 mg/hr and isoproterenol 125 micrograms/hr, preferably for a period of at least five days before the medications were tapered. Of the 21 treatment trials, there were 11 definite beneficial responses and ten failures. This study emphasizes the importance of instituting this therapy as rapidly as possible following the confirmation of symptomatic cerebral vasospasm. In addition, if a response occurs it will be noted within 24 hours of institution of the medications. If no response is noted following this time period, the medications should be discontinued. The major complications of this therapy include hypotension, tachycardia and arrythmias. These complications may necessitate diminishing the dosage of the medications. However, if a response has been obtained, every effort should be made to avoid discontinuing therapy prematurely since cerebral vasospasm may recur. The use of isoproterenol and aminophylline is based on their demonstrated ability to increase cyclic adenosine monophosphate (cyclic AMP) levels in vascular smooth muscle, thus producing relaxation of vasospasm.
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PubMed Abstracts
26989400
Utilization and unexpected hospitalization rates of a pediatric emergency department 23-hour observation unit. The 23-hour observation units (OUs) may be used to avoid unnecessary hospital admissions. However, unexpected hospitalizations from the 23-hour OUs involve transfer of care and may decrease the efficiency and safety of care of the patient and the unit itself. The primary objective of this study was to determine the predictors of unexpected hospitalization for admissions to a pediatric 23-hour OU. This is an observational prospective cohort study of patients admitted to a pediatric 23-hour OU. Bivariate and multivariate regression analyses identify factors associated with unexpected hospitalization. There were 4453 patients admitted to the 23-hour OU during the study. The overall rate of unexpected hospitalization was 20.3%; the mean 23-hour OU stay was 15 hours. Age, sex, race/ethnicity, and insurance status were not associated with increased unexpected hospitalization rates. Multivariate regression modeling revealed that unexpected hospitalization was associated with subgroups of resources used (intravenous medications and fluids, cardiorespiratory monitoring, respiratory therapist use, and supplemental oxygen), of subspecialty consultation, and of diagnosis categories (including asthma, adenitis, cellulitis, bronchiolitis, and esophageal foreign body ingestions). Experience of the health care provider involved in the care of the patient was not associated with increased unexpected hospitalization. Most of the patients (80%) were successfully discharged from the 23-hour OU. Demographics of the patient and practitioner characteristics did not influence the risk of unexpected hospitalizations; however, certain patient diagnoses, use of resources,and subspecialty consultation did increase the risk of unexpected hospitalization and, therefore, may guide future admission criteria for pediatric 23-hour OU.
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PubMed Abstracts
26989413
[Paroxysmal nocturnal hemoglobinuria. Diagnosis aided by a monoclonal antibody directed against the decay accelerating factor glycoprotein]. The laboratory diagnosis of paroxysmal nocturnal haemoglobinuria (also called Marchiafava-Micheli disease) is based on the sensitivity of the patient's red cells to complement-induced lysis. In view of the clonal expression of the disease, haemolysis tests are difficult to interpret when the abnormal red cell population is small. The sensitivity of abnormal red cells to haemolysis is due to the absence of proteins attached to the cell membrane by a phosphatidyl-inositol link, which intervene in the regulation of the complement-induced lysis mechanism. Using a monoclonal antibody directed against one of these proteins, the decay accelerating factor (DAF, protein CD 55), makes it possible to diagnose paroxysmal nocturnal haemoglobinuria. DAF expression on patients' blood cells was measured by quantitative agglutination and by indirect flow cytometry. The agglutination test using polybren is a fast detection method, but it may be uninterpretable, notably in cases with positive antiglobulin (Coombs') test. In contrast, DAF expression measured by indirect flow cytometry correlates perfectly with measurement of red cell sensitivity by haemolysis tests. Using the monoclonal antibody by indirect flow cytometry is the method of choice to confirm the diagnosis of paroxysmal nocturnal haemoglobinuria and to measure the proportions of normal and abnormal red cells in case of haematological disorder.
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PubMed Abstracts
26989416
The scapula: coracoid, acromial, and avulsion fractures. Fractures of the coracoid and acromial processes and avulsion fractures of the scapula are uncommon with the vast majority being managed quite successfully nonoperatively. On occasion, however, these injuries may be significantly displaced and of functional importance, thus making surgical management a consideration. Diagnosis is radiographic. Due to the complex anatomy in the area, CT scanning is often necessary to detect and accurately define these injuries. The various fracture patterns that occur as well as mechanisms of injury are described. Surgical indications are detailed as are the various fixation techniques that may be employed or required. The postoperative rehabilitation program is as important as the surgical procedure.
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PubMed Abstracts
26989425
Chronic Ethanol Exposure Alters DNA Methylation in Neural Stem Cells: Role of Mouse Strain and Sex. Prenatal alcohol exposure (PAE) is considered as a risk factor for the development of fetal alcohol spectrum disorders (FASD). Evidence indicates that PAE affects epigenetic mechanisms (such as DNA methylation) and alters the normal differentiation and development of neural stem cells (NSC) in the fetal brain. However, PAE effects depend on several factors such as sex and strain of the studied subjects. Here, we investigated whether murine sex and strain contribute to the effects of chronic ethanol exposure on DNA methylation machinery of differentiating NSC. Further, the effects of PAE on glial lineage (including both astrocytes and oligodendrocytes) in a sex- and strain-dependent manner have not been studied yet. To examine the effects of chronic ethanol exposure on gliogenesis, we exposed differentiating NSC to glio-inductive culture conditions. Applying a standard in vitro model system, we treated male and female differentiating NSC (obtained from the forebrain of CD1 and C57BL/6 embryos at embryonic day 14.5) with chronic ethanol exposure (70 mM) for 8 days. We show that ethanol induces global DNA hypomethylation, while altering the expression of DNA methylation-related genes in a sex- and strain-specific manner. The observed change in cellular DNA methylation levels was associated with altered expression of glial markers CNPASE, GFAP, and OLIG2 in CD1 (but not C57BL/6) cells. We conclude that the impact of ethanol effect on DNA methylation is dependent on cellular sex and strain. Also, ethanol impact on neural stem cell fate commitment was only detected in cells isolated from CD1 mouse strain, but not in C57BL/6 cells. The results of the current study provide evidence that sex and strain of rodents (C57BL/6 and CD1) during gestation are important factors, which affect alcohol effects on NSC differentiation and DNA methylation. Results of this study may also help in interpreting data on the developmental toxicity of many compounds during the gestational period.
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PubMed Abstracts
26989433
Physical Activity, Physical Function, and Quadriceps Muscle Thickness in Male Patients with Sub-Acute Stroke during Hospitalization: A Pilot Study. Increasing physical activity (PA) is an important rehabilitation target for patients with sub-acute stroke during hospitalization in order to recover physical function and prevent stroke recurrence. However, the characteristics of low PA in stroke patients during hospitalization who were targets for increased intervention have not been reported. The purpose of this study was to investigate the relationship between the daily number of steps and physical function and quadriceps muscle thickness (QMT) in patients with sub-acute stroke during hospitalization for convalescence rehabilitation. Twenty-nine patients with ischemic or haemorrhagic stroke (mean age, 69 ± 11 years) hospitalized for inpatient convalescent rehabilitation were included. PA was measured using a three-dimensional accelerometer that calculates the daily number of steps taken. Physical function was measured by a short physical performance battery (SPPB; 0-12 points) and the leg motor selectivity score (6 motor stages defined by Brunnstrom), and the QMT of both legs was measured using ultrasonography. PA was significantly correlated with the SPPB score (r = 0.63, p = 0.0002), QMT on the paretic side (r = 0.41, p = 0.02), and QMT on non-paretic side (r = 0.56, p = 0.002). There were no significant effects of the leg motor selectivity score on daily PA (F = 1.37, p = 0.27). In the multiple regression analysis, only the SPPB score showed significant linear regression (β = 0.44, p = 0.02). PA in male patients with sub-acute stroke during hospitalization was related to physical function and QMT and not with the severity of paresis.
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PubMed Abstracts
26989437
Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids. Boronic acids are an increasingly important compound class for many applications, including C-C bond formation reactions, medicinal chemistry, and diagnostics. The deprotection of boronic ester intermediates is frequently a problematic and inefficient step in boronic acid syntheses. We describe an approach that highly facilitates this transformation by leveraging the volatility of methylboronic acid and its diol esters. The method is performed under mild conditions, provides high yields, and eliminates cumbersome and problematic purification steps.
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PubMed Abstracts
26989447
Imaging diagnosis-magnetic resonance imaging features of metastatic cerebral lymphoma in a dog. We describe histopathologically confirmed intracranial metastasis of cutaneous lymphoma. In magnetic resonance (MR) images there was a heterogeneous, contrast-enhancing, extraaxial mass in the right parietal and piriform lobes at the level of the optic chiasm. Our MR imaging findings are consistent with reports in humans in that lymphoma masses have indistinct borders that are iso- to hyperintense relative to adjacent gray matter on T2-weighted images. Our report varies from findings in humans in that the mass was extraaxial, whereas masses reported in humans are intraaxial. Contrast enhancement can be heterogeneous, as in our report, or homogeneous.
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PubMed Abstracts
26989449
Fatal liver necrosis following percutaneous ethanol injection for hepatocellular carcinoma. A 76-year-old man underwent an injection of 5 ml of ethanol for the treatment of a hepatocellular carcinoma 3 cm in diameter. Shortly after the procedure, he had an attack of abdominal pain. His condition soon deteriorated and he died 5 days later. Massive hepatic necroses distant from the injection site and a myocardial infarction were found at autopsy. To our knowledge, this is the first fatality associated with percutaneous ethanol injection therapy.
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PubMed Abstracts
26989453
[Surgical treatment of renovascular hypertension with special reference to the indications for reconstructive surgery]. Based on the retrospective analysis of 38 cases of renovascular hypertension treated by surgical intervention, the following indications are proposed for arterial reconstructive surgery: younger age of patient, short duration of hypertension, renin-mediated hypertension and extent and functional significance of the obstructing arterial lesion, favorable level of renal function in the affected side, and renal function threatened by advanced progressive vascular disease, surgically correctable lesion, and focal, unilateral renal arterial atherosclerosis without generalized atherosclerosis, good surgical risk, and hypertension not responding to medical treatment. Although the clinical use of the angiotensin I converting enzyme inhibitor and induction of percutaneous transluminal angioplasty can provide a new approach to non-surgical treatment for renovascular hypertension, the long-term use of antihypertensive drugs induces gradual decrease in renal function. Surgical treatment is best reserved for the patient on whom the available data meet the above criteria for vascular surgery.
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PubMed Abstracts
26989465
Characterization of bacterial pathogens in rural and urban irrigation water. The study aimed to compare the bacteriological quality of an urban and rural irrigation water source. Bacterial counts, characterization, identification and diversity of aerobic bacteria were determined. Escherichia coli isolated from both sites was subjected to antibiotic susceptibility testing, virulence gene (Stx1/Stx2 and eae) determination and (GTG)5 Rep-PCR fingerprinting. Low mean monthly counts for aerobic spore formers, anaerobic spore formers and Staphylococcus aureus were noted although occasional spikes were observed. The most prevalent bacterial species at both sites were Bacillus spp., E. coli and Enterobacter spp. In addition, E. coli and Bacillus spp. were most prevalent in winter and summer respectively. Resistance to at least one antibiotic was 84% (rural) and 83% (urban). Highest resistance at both sites was to cephalothin and ampicillin. Prevalence of E. coli possessing at least one virulence gene (Stx1/Stx2 and eae) was 15% (rural) and 42% (urban). All (rural) and 80% (urban) of E. coli possessing virulence genes showed antibiotic resistance. Complete genetic relatedness (100%) was shown by 47% of rural and 67% of urban E. coli isolates. Results from this study show that surface irrigation water sources regardless of geographical location and surrounding land-use practices can be reservoirs of similar bacterial pathogens.
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PubMed Abstracts
26989469
[Spontaneous rupture of mediastinal cystic teratoma (case report)]. Teratomas are rare tumors in the mediastinum. Benign cystic teratomas of anterior mediastinum are rarely complicated by rupture into an adjacent body cavity. Such rupture, however, is usually associated with life-threatening complications. We present a case with spontaneous rupture of mediastinal cystic teratoma. The patient was evaluated with chest radiograph, computed tomography (CT) and magnetic resonance imaging (MRI). A complex mass including predominantly cystic components was detected in the left anterior mediastinum. After surgery, pathologic diagnosis was reported as mature cystic teratoma. High levels of amylase and lipase were detected in both the cystic fluid and serum. This finding supported the hypothesis of autolysis for the explanation of rupture. In addition, carbohydrate antigen (CA) 19-9, CA 125 and carcinoembryonic antigen (CEA) levels were high in the cystic fluid.
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PubMed Abstracts
26989471
Gap Junction Coupling Shapes the Encoding of Light in the Developing Retina. Detection of ambient illumination in the developing retina prior to maturation of conventional photoreceptors is mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) and is critical for driving several physiological processes, including light aversion, pupillary light reflexes, and photoentrainment of circadian rhythms. The strategies by which ipRGCs encode variations in ambient light intensity at these early ages are not known. Using unsupervised clustering of two-photon calcium responses followed by inspection of anatomical features, we found that the population activity of the neonatal retina could be modeled as six functional groups that were composed of mixtures of ipRGC subtypes and non-ipRGC cell types. By combining imaging, whole-cell recording, pharmacology, and anatomical techniques, we found that functional mixing of cell types is mediated in part by gap junction coupling. Together, these data show that both cell-autonomous intrinsic light responses and gap junction coupling among ipRGCs contribute to the proper encoding of light intensity in the developing retina.
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PubMed Abstracts
26989474
Perioperative outcomes and complications of open vs laparoscopic extraperitoneal inguinal hernia repair in a mature surgical practice. Although the laparoscopic totally extraperitoneal (TEP) approach to hernia repair has been associated with less pain and a faster postoperative recovery than traditional open repair, many practicing surgeons have been reluctant to adopt this technique because of the lengthy operative times and the learning curve for this procedure. Data from all patients undergoing TEP repair since 1997 and open mesh repair (OPEN) since 1999 were collected prospectively. Selection of surgical approach was based on local hernia factors, anesthetic risk, previous abdominal surgery, and patient preference. Statistical analyses were performed using unpaired t-tests and chi-squared tests. Data are mean +/- SD. TEP repairs were performed in 147 patients and open repairs in 198 patients. Patients in the OPEN group were significantly older (59 +/- 19 years OPEN vs 51 +/- 13 years TEP) and had a higher ASA (1.9 +/- 0.7 OPEN vs 1.5 +/- 0.6 TEP; p < 0.01). TEP repairs were more likely to be carried out for bilateral (33% TEP, 5% OPEN) or recurrent hernias (31% TEP, 11% OPEN) than were open repairs ( p < 0.01). Concurrent procedures accompanied 31% of TEP and 12% of OPEN repairs ( p < 0.01). Operative times (min) were significantly shorter in the TEP group for both unilateral (63 +/- 22 TEP, 70 +/- 20 OPEN; p = 0.02) and bilateral (78 +/- 27 TEP, 102 +/- 27 OPEN; p = 0.01) repairs. Mean operative times decreased over time in the TEP group for both unilateral and bilateral repairs ( p < 0.01). Patients undergoing TEP were more likely ( p < 0.01) to develop urinary retention (7.9% TEP, 1.1% OPEN), but were less likely ( p < 0.01) to have skin numbness (2.8% TEP, 35.8% OPEN) or prolonged groin discomfort (1.4% TEP, 5.3% OPEN). Despite a higher proportion of patients undergoing bilateral repairs, recurrent hernia repair, and concurrent procedures, operative times are shorter for laparoscopic TEP repair than for open mesh repair. TEP repairs can be performed efficiently and without major complications, even when the learning curve is included.
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PubMed Abstracts
26989498
New (RS)-benzoxazepin-purines with antitumour activity: The chiral switch from (RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine. Completing an SAR study, a series of (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H or 9H-purines has been prepared under microwave-assisted conditions. Their antiproliferative activities on MCF-7 and MDA-MB-231 cancerous cell lines are presented, being the majority of the IC(50) values below 1μM. The most active compound (RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine (14) presents an IC(50) of 0.166μM against the human cancerous cell line MDA-MB-231. Compound 14 was the most selective against the human breast adenocarcinoma MCF-7 and MDA-MB-231 cancer cell lines (Therapeutic Indexes, TIs=5.1 and 11.0, respectively) in relation to the normal one MCF-10A. (RS)-14 was resolved into its enantiomers. Both enantiomers are equally potent, but more potent than the corresponding racemic mixture. (R)-14 induces apoptosis against MCF-7 up to 52.50% of cell population after 48h, being more potent than the clinical-used drug paclitaxel (43%). (RS)-14 induces no acute toxicity in mice after two weeks of treatment.
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PubMed Abstracts
26989503
A history of Norwegian psychiatry. In Norway the building of asylums started in 1855 with the establishment of Gaustad State Asylum. Until the 1950s Norwegian psychiatry was mainly a hospital psychiatry, strongly influenced by the pre-war German tradition. After World War II, it was influenced by British social psychiatry and American psychoanalysis. Psychiatric units in general hospitals were established in the 1960s onwards and outpatient clinics from the 1970s. During the last twenty years Norwegian psychiatry has taken a more biological trend with stronger emphasis on diagnostics and drug treatment. The increase in the number of psychiatrists and especially psychologists has been formidable during the last fifty years.
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PubMed Abstracts
26989524
Candida aechmeae sp. nov. and Candida vrieseae sp. nov., novel yeast species isolated from the phylloplane of bromeliads in Southern Brazil. Two novel yeast species, Candida aechmeae sp. nov. and Candida vrieseae sp. nov., were isolated from bromeliads in Itapuã Park, Rio Grande do Sul, Brazil. These species are genetically isolated from all other currently recognized ascomycetous yeasts based on their sequence divergence in the D1/D2 domain of the LSU rRNA gene. C. aechmeae sp. nov. is phylogenetically close to Candida ubatubensis, a species also isolated from bromeliads in Brazil, but the novel species can be differentiated on the basis of differences in the D1/D2 domain and positive results for the assimilation of l-arabinose, raffinose, inulin and citrate. Candida vrieseae sp. nov. is phylogenetically placed in a clade near Candida membranifaciens that is composed of several species associated with insects, but the novel species can be differentiated from them by the D1/D2 and ITS gene sequences, positive results for the assimilation of nitrite and a negative result for the assimilation of ethylamine. The type strain for Candida aechmeae sp. nov. is BI153(T) (=CBS 10831(T)=NRRL Y-48456(T)) and the type strain for C. vrieseae sp. nov. is BI146(T) (=CBS 10829(T)=NRRL Y-48461(T)).
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PubMed Abstracts
26989528
Surface defect detection in tiling Industries using digital image processing methods: analysis and evaluation. Ceramic and tile industries should indispensably include a grading stage to quantify the quality of products. Actually, human control systems are often used for grading purposes. An automatic grading system is essential to enhance the quality control and marketing of the products. Since there generally exist six different types of defects originating from various stages of tile manufacturing lines with distinct textures and morphologies, many image processing techniques have been proposed for defect detection. In this paper, a survey has been made on the pattern recognition and image processing algorithms which have been used to detect surface defects. Each method appears to be limited for detecting some subgroup of defects. The detection techniques may be divided into three main groups: statistical pattern recognition, feature vector extraction and texture/image classification. The methods such as wavelet transform, filtering, morphology and contourlet transform are more effective for pre-processing tasks. Others including statistical methods, neural networks and model-based algorithms can be applied to extract the surface defects. Although, statistical methods are often appropriate for identification of large defects such as Spots, but techniques such as wavelet processing provide an acceptable response for detection of small defects such as Pinhole. A thorough survey is made in this paper on the existing algorithms in each subgroup. Also, the evaluation parameters are discussed including supervised and unsupervised parameters. Using various performance parameters, different defect detection algorithms are compared and evaluated.
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PubMed Abstracts
26989531
Copper extrusion after accumulation during growth of copper-tolerant yeast Yarrowia lipolytica. The Cu2+-tolerant yeast Yarrowia lipolytica accumulated Cu2+ until the late logarithmic phase. Thereafter, Cu2+ was temperature-dependently extruded into phosphate-limited culture medium containing high concentrations of heavy metal ions but not into 10 mM 2-(N-morpholino)ethane sulfonic acid (MES) buffer (pH 6.0). Peptone in the culture medium played an important role in the extrusion, which proceeded even when peptone was substituted with cysteine or histidine, but not with any other amino acid tested.
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PubMed Abstracts
26989545
Pharmacokinetics of the new progestogens and influence of gestodene and desogestrel on ethinylestradiol metabolism. The purpose of the present report is to summarize the most important pharmacokinetic features of the new progestogens. In addition, the question of whether or not gestodene, in comparison to desogestrel, has an influence on the pharmacokinetics of ethinylestradiol (EE2) will be addressed.
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PubMed Abstracts
26989548
Construction and evaluation of Bordetella pertussis live attenuated vaccine strain BPZE1 producing Fim3. Pertussis or whooping cough is currently the most prevalent vaccine-preventable childhood disease despite >85% global vaccination coverage. In recent years incidence has greatly increased in several high-income countries that have switched from the first-generation, whole-cell vaccine to the newer acellular vaccines, calling for improved vaccination strategies with better vaccines. We have developed a live attenuated pertussis vaccine candidate, called BPZE1, which is currently in clinical development. Unlike other pertussis vaccines, BPZE1 has been shown to provide strong protection against infection by the causative agent of pertussis, Bordetella pertussis, in non-human primates. BPZE1 is a derivative of the B. pertussis strain Tohama I, which produces serotype 2 (Fim2) but not serotype 3 fimbriae (Fim3). As immune responses to fimbriae are likely to contribute to protection, we constructed a BPZE1 derivative, called BPZE1f3, that produces both serotypes of fimbriae. Whereas nasal vaccination of mice with BPZE1 induced antibodies to Fim2 but not to Fim3, vaccination with BPZE1f3 elicited antibodies to both Fim2 and Fim3 at approximately the same level. In mice, both BPZE1 and BPZE1f3 provided equal levels of protection against clinical isolates that either produce Fim2 alone, both Fim2 and Fim3, or no fimbriae. However, vaccination with BPZE1f3 provided significantly stronger protection against Fim3-only producing B. pertussis than vaccination with BPZE1, indicating that immune responses to fimbriae contribute to serotype-specific protection against B. pertussis infection.
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PubMed Abstracts
26989561
Modeling the reduction of hydrogen peroxide by glutathione peroxidase mimics. Theoretical calculations have been performed on three model reactions representing the reduction of hydrogen peroxide by ebselen, ebselen selenol, and ebselen diselenide. The reaction surfaces have been investigated at the B3PW91/6-311G(2df,p) level, and single-point energies were calculated using the 6-311++G(3df,3pd) basis set. Solvent effects were included implicitly with the conductor-like polarizable continuum model and in one case with explicit inclusion of three water molecules. Mechanistic information is gained from investigating the critical points using the quantum theory of atoms in molecules. The barriers for the reduction of hydrogen peroxide with the ebselen, ebselen selenol, and ebselen diselenide models are 56.7, 53.4, and 35.3 kcal/mol, respectively, suggesting that ebselen diselenide may be the most active antioxidant in the ebselen GPx redox pathway. Results are also compared to that of the sulfur analogues of the model compounds.
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PubMed Abstracts
26989569
Anxiety symptoms and generalized anxiety disorder in the elderly: a review. Anxiety is a common but underestimated, undertreated, and poorly studied problem in the elderly. Generalized anxiety disorder (GAD) and nonspecific anxiety symptoms that do not fall under a specific anxiety disorder are good examples. The current literature on the epidemiology, consequences, phenomenology, assessment, and treatment implications of these challenging problems is reviewed. A variety of limitations are observed. They include limited understanding of the expression of GAD in this age group, variable definitions of "elderly" (specifically with regard to the minimum age), limited ability of currently available diagnostic instruments to identify GAD in the elderly, and the availability of only a few trials addressing treatment of GAD specifically in this group. Despite these limitations there is enough evidence suggesting GAD in the elderly has a potential for negative consequences independent of the common comorbidity with major depressive disorder. The treatments reviewed are promising but need further research in order to document their safety and efficacy. The limitations of our current knowledge are discussed, with recommendations for future research.
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PubMed Abstracts
26989572
A clinical nurse specialist intervention to facilitate safe transfer from ICU. The purpose of this article was to describe an innovative quality initiative implemented by the clinical nurses specialist in medicine to facilitate the transition process between the intensive care unit and the medical wards. Safely transferring patients with complex health conditions from an area of high technology and increased monitoring, like the intensive care unit, to an area with lower nurse-to-patient ratio is an intricate process. The care of these patients, once transferred, also requires varying levels of expertise. As indicated in the nursing literature, this type of transition is often associated with high stress levels for the patient and family, as well as for the healthcare providers. To maximize patient safety and ensure optimal care for this patient population, well-defined mechanisms must be put in place. The introduction of a formal assessment, consultation, and follow-up process conducted by a clinical nurse specialist (CNS). On average, 150 patients are assessed each year by the CNS. Among these patients, 15% are considered at high risk for complications upon transfer to the unit. INTERPRETATION/CONCLUSION/IMPLICATIONS: A systematic evaluation of patients by the CNS, before their transfer from the ICU to a medical unit, has been proven beneficial in ensuring a comprehensive patient care plan. Patients and families have verbalized that this intervention is helpful. Staff members have indicated that this safety initiative is useful in planning patient transfers. The next step would be to formally measure patient, family, and staff satisfaction with this initiative.
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PubMed Abstracts
26989577
Tubular secretion and reabsorption of mercury compounds in mouse kidney. To determine whether Hg accumulated in renal cells is secreted into the lumen of proximal tubules with intracellular glutathione (GSH) and reabsorbed by tubular cells via a gamma-glutamyltranspeptidase (gamma-GTP)-dependent process as in the case of GSH itself, the effect of postadministration of acivicin (1 mmol/kg i.p.), a gamma-GTP inhibitor, on renal Hg accumulation was investigated in mice. Renal Hg content 4 hr after injection of CH3HgCl or HgCl2 (5 mumol/kg i.v.) was decreased to 35 or 44% of control, respectively, but urinary Hg excretion was increased by acivicin administration 2 hr after injection of the mercurials. When renal GSH was decreased to 19% of control by treatment with DL-buthionine-S,R-sulfoximine (4 mmol/kg s.c.) 2 hr before acivicin injection, the increase in urinary Hg excretion caused by acivicin was suppressed. Acivicin administration 24 hr after injection of the mercurials decreased renal methylmercury content determined 2 hr after acivicin injection and increased urinary Hg excretion. The postadministration of acivicin, however, did not affect the renal content of inorganic Hg which predominantly bound to metallothionein (MT) induced by HgCl2 itself. Pretreatment with Bi(NO3)3 as a renal MT inducer diminished the effect of acivicin administered 2 hr after HgCl2 injection on renal Hg content and urinary excretion. These results suggest that methylmercury and inorganic Hg bound to ligands other than MT in renal cytosol may be secreted into the lumen of proximal tubules with intracellular GSH and be reabsorbed via a gamma-GTP-dependent process.
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PubMed Abstracts
26989592
The DNA binding protein Tfx from Methanobacterium thermoautotrophicum: structure, DNA binding properties and transcriptional regulation. In Methanobacterium thermoautotrophicum, the fmdECB operon encoding the molybdenum formyl-methanofuran dehydrogenase is directly preceded by an open reading frame tfx predicted to encode a DNA binding protein. The 16.1 kDa protein has an N-terminal basic domain with a helix-turn-helix motif for DNA binding and a C-terminal acidic domain possibly for transcriptional activation. We report here on the DNA binding properties of the Tfx protein heterologously overproduced in Escherichia coli. Tfx was found to bind specifically to a DNA sequence downstream of the promoter of the fmdECB operon, as shown by electrophoretic mobility shift assays and DNase I footprint analysis. Northern blot hybridizations revealed that transcription of tfx is repressed during the growth of M. thermoautotrophicum in the presence of tung-state. Based on its structure and properties, the DNA binding protein Tfx is proposed to be a transcriptional regulator composed of a basic DNA binding domain and an acidic activation domain.
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PubMed Abstracts