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pubmed_374_20488
|
Risk perception has been largely examined in studies that have aimed to explain and predict preparedness behavior in the context of natural hazards. Findings from studies on the relationship between previous experience, preparedness, and risk perception in disaster situations have been inconsistent. Hence, the main goal of this work was to explore the influence of physical and emotional experience on risk perception regarding natural hazards. This study was conducted in a statistically representative sample of the city of Iquique, in northern Chile (n = 701), who completed a survey one month after the occurrence of an earthquake and tsunami (8.2 Mw). The survey assessed the experience and preparation actions of survivors in relation to this event. Using a structural equation model, we examined nine proposed relationships, six of which were significant. The final model had an adequate fit (χ² = 752.23, df = 283, comparative fit index [CFI] = 0.90, root mean square error of approximation [RMSEA] = 0.049). Direct experience showed the greatest influence on risk perception: while direct physical experience (i.e., the physical and material consequences associated with the earthquake) maintained a direct positive effect on risk perception, direct emotional experience (i.e., the fear of experiencing an earthquake) produced an indirect positive effect (through worry). Emotional experience, however, did not directly influence current preparedness and risk perception. Implications for understanding the relationship between risk perception and direct experience are discussed.
|
10.1111/risa.13526
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pubmed_768_8513
|
Antiedema therapy with mannitol and furosemide is widely used for prevention and management of cerebral edema, elevated intracranial pressure, and cerebral hernia. There are some reports about mannitol and furosemide as risk factors of acute kidney injury (AKI). We investigated the risk factors for AKI including antiedema therapy in acute ischemic stroke patients. The subjects were 129 patients with acute ischemic stroke including 56 females and 73 males with a mean age 68.16±12.29 years. Patients were divided into two groups: patients with AKI and without AKI according to Acute Kidney Injury Network criteria. All patients had undergone cranial, carotid, and vertebral artery evaluation with magnetic resonance imaging. The number of patients with AKI was 14 (10.9%). Subjects experiencing atrial fibrillation (P=0.043) and higher diastolic blood pressure (DBP) (P=0.032) treated with mannitol (P=0.019) and furosemide (P=0.019) disclosed significant association with AKI. Regression analysis revealed that higher DBP (P=0.029) and management with mannitol (P=0.044) were the risk factors for AKI. Higher DBP at admission is the most important risk factor for AKI. However antiedema therapy should be used carefully in patients with acute ischemic stroke. Serum creatinine levels or estimated glomerular filtration rate should be watched frequently to prevent AKI.
|
10.2147/IJNRD.S59443
|
pubmed_19_16634
|
The antioxidant properties of the water and ethanol leaf extracts of kinkeliba (Combretum micranthum) were investigated, including scavenging of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (IC₅₀ values: 8.02 ± 0.34 for the ethanol extract [KE] and 9.1 ± 0.28 for the water extract [KW]), the 2,2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical (IC(50) values: 7.4 ± 0.14 for KE and 11.8 ± 0.01 for KW) and the hydroxyl radical (58.1% for KE and 61.1% for KW). The ferric thiocyanate method, reducing power, metal chelating activity, an assay of protein oxidation and the β-carotene-linoleic bleaching assay were also used. Butylated hydroxytoluene and ascorbic acid were used as the reference antioxidant compounds. At 20 mg mL⁻¹ concentration, KW and KE provided 36.8% and 75.1% inhibition of lipid peroxidation of linoleic acid emulsion, respectively. The IC₅₀ values of the ethanol extract in ABTS and DPPH tests were significantly lower than those from the water extract. Furthermore, crude polyphenols were extracted from kinkeliba leaf with 90% ethanol solution using a water bath treatment and then purified by a macroporous resin, AB-8. The polyphenols from kinkeliba leaf were subjected to analyses by RP-HPLC and ESI-MS. The dominant polyphenols in kinkeliba leaf were identified as gallic acid, rutin trihydrate, (+)-catechin and benzoic acid.
|
10.1080/14786419.2010.482048
|
pubmed_415_15134
|
AIMS
There have been few evaluations of the quality of computerized decision support tools in medical oncology despite their widespread use in clinical practice. In this article, we provide an in-depth quality assessment of eviQ, an Australian web-based protocol system.
METHODS
We used the Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument to examine the quality of eviQ chemotherapy protocols across six domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, editorial independence and overall quality rating. Domain scores were categorized as high quality (scores of >70%), moderate quality (30-70%), and low quality (<30%).
RESULTS
eviQ was rated highly with respect to articulating its scope and purpose, clarity of presentation, applicability and on the overall rating item (scores of 72-80%). Domains addressing the involvement of stakeholders in the development process and the rigor with which protocols were developed were of moderate quality (scores of 34-37%) and the management of editorial independence and conflict of interest issues were rated in the low quality range (22%).
CONCLUSION
Our evaluation demonstrated the eviQ protocol system is generally of high quality. However, we identified a number of areas in which eviQ could improve either its development processes or the means by which these processes are communicated to end-users. This research represents the first comprehensive evaluation of oncology protocols and paves the way for continued quality assurance research to ensure that these tools meet their objective of facilitating evidence-based medicine, standardizing treatment and, ultimately, improving patient outcomes.
|
10.1111/j.1743-7563.2011.01431.x
|
pubmed_587_20555
|
Nitric oxide (NO) activates corpus cavernosum smooth muscle soluble guanylate cyclase (sGC) and increases the synthesis of cGMP that results in smooth muscle relaxation and ultimately, penile erection. To characterize sGC and define the potential synergy between NO and the allosteric activator YC-1 in corpus cavernosum, rat sGC was activated by either sodium nitroprusside (SNP) or YC-1, and YC-1 potentiated the effects of SNP with a 200-fold activation of sGC. Both SNP and YC-1 decreased the Km and increased the Vmax. ODQ significantly inhibited sGC activated by SNP with IC50 of 0.5 nM, but did not affect the sGC activated by YC-1 as well as basal sGC activity. SNP and YC-1 synergistically increased intracellular cGMP levels in rabbit corpus cavernosum smooth muscle cell cultures. YC-1 significantly relaxed rabbit cavernosum tissue strips in organ baths with an EC50 of 8.4 microM. In the presence of L-nitroarginine methyl ester to block endogenous NO production, co-administration of SNP shifted the dose response of YC-1 to the left, showing the synergism of SNP and YC-1 in tissue strips. In view of the clinical efficacy of phosphodiesterase-5 inhibitors, activation of sGC may provide an alternative means for enhancing the activity of neurally derived NO during sexual stimulation in the corpus cavernosum, representing a novel approach for the treatment of erectile dysfunction.
|
10.1038/sj.ijir.3900843
|
pubmed_19_19029
|
We present first-principles density functional calculations and downfolding studies of the electronic and magnetic properties of the oxide-fluoride quantum spin system V(2)GeO(4)F(2). We discuss explicitly the nature of the exchange paths and provide quantitative estimates of magnetic exchange couplings. A microscopic modelling based on analysis of the electronic structure of this systems puts it in the interesting class of weakly coupled alternating chain S = 1 systems. Based on the microscopic model, we make inferrences about its spin excitation spectra, which needs to be tested by rigorous experimental study.
|
10.1088/0953-8984/19/29/296206
|
pubmed_343_16463
|
In this paper, the problem of optimal system identification in nonlinear model predictive control (NMPC) for highly nonlinear dynamic processes is presented. Due to the short term changes in the operating point, the process may escape from its frequent operating points (FOP) to some infrequent operating points (IOP) for a short period. On the other hand, because the nonlinear model is identified using the operating data, it is mainly accurate for the FOP. Therefore, the NMPC causes tracking error or even instability in the IOP. To handle this problem, in this paper, we present a novel optimal identification algorithm, which is highly depended on the nonlinearity of the understudy plant, to train the nonlinear model of the NMPC. The nonlinear model is selected as a multi-layer perceptron neural network (MLP) which is trained to describe the nonlinear behaviour of the nonlinear dynamic system accurately in the FOP and while it has acceptable performance in the IOP. To validate the proposed algorithm, the well-known nonlinear dynamic pH neutralization process is chosen in both simulation and implementation parts. Finally, the simulation and implementation results prove the effectiveness of the proposed algorithm.
|
10.1016/j.isatra.2019.08.001
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pubmed_768_10813
|
The spatial congruence of chemical and biological recovery along an 18-km acid mine impaired stream was examined to evaluate the efficacy of treatment with an alkaline doser. Two methods were used to evaluate biological recovery: the biological structure of the benthic macroinvertebrate community and several ecosystem processing measures (leaf litter breakdown, microbial respiration rates) along the gradient of improved water chemistry. We found that the doser successfully reduced the acidity and lowered dissolved metals (Al, Fe, and Mn), but downstream improvements were not linear. Water chemistry was more variable, and precipitated metals were elevated in a 3-5-km "mixing zone" immediately downstream of the doser, then stabilized into a "recovery zone" 10-18 km below the doser. Macroinvertebrate communities exhibited a longitudinal pattern of recovery, but it did not exactly match the water chemistry gradient Taxonomic richness (number of families) recovered about 6.5 km downstream of the doser, while total abundance and % EPT taxa recovery were incomplete except at the most downstream site, 18 km away. The functional measures of ecosystem processes (leaf litter breakdown, microbial respiration of conditioned leaves, and shredder biomass) closely matched the measures of community structure and also showed a more modest longitudinal trend of biological recovery than expected based on pH and alkalinity. The measures of microbial respiration had added diagnostic value and indicated that biological recovery downstream of the doser is limited by factors other than habitat and acidity/alkalinity, perhaps episodes of AMD and/or impaired energy/nutrient inputs. A better understanding of the factors that govern spatial and temporal variations in acid mine contaminants, especially episodic events, will improve our ability to predict biological recovery after remediation.
|
10.1007/s10661-014-3684-y
|
pubmed_268_18254
|
The method of bacterial leaching of non precious dental alloys represents a useful completion of the method arsenal of biological investigations. In contrast to other well known methods it allows to point out small differences in corrosion resistance between alloys of the same type in a biologic system.
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pubmed_268_18254
|
pubmed_808_24128
|
At the 2016 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), we presented the case for quantitatively assessing the extent of both psoriasis and psoriatic arthritis in the clinical setting, with a particular focus on the validation and expanded novel use of the PGAxBSA (static physician's global assessment × body surface area of involvement) in the era of targeted metrics. Herein, we summarize our presentation.
|
10.3899/jrheum.170147
|
pubmed_92_18702
|
Although radiotherapy is recognized as an established risk factor for second malignant neoplasms (SMNs), the dose response of SMNs following radiotherapy has not been well characterized. In our previous meta-analysis of the risks of SMNs occurring among children who have received radiotherapy, the small number of eligible studies precluded a detailed evaluation. Therefore, to increase the number of eligible studies, we developed a method of calculating excess relative risk (ERR) per Gy estimates from studies for which the relative risk estimates for several dose categories were available. Comparing the calculated ERR with that described in several original papers validated the proposed method. This enabled us to increase the number of studies, which we used to conduct a meta-analysis. The overall ERR per Gy estimate of radiotherapy over 26 relevant studies was 0.60 (95%CI: 0.30-1.20), which is smaller than the corresponding estimate for atomic bomb survivors exposed to radiation as young children (1.7; 95% CI: 1.1-2.5). A significant decrease in ERR per Gy with increase in age at exposure (0.85 times per annual increase) was observed in the meta-regression. Heterogeneity was suggested by Cochran's Q statistic (P < 0.001), which may be partly accounted for by age at exposure.
|
10.1093/jrr/rru045
|
pubmed_753_13849
|
CD25+ regulatory T cells develop in the thymus (nTregs), but may also be generated in the periphery upon stimulation of naive CD4 T cells under appropriate conditions (iTregs). To gain insight into the mechanisms governing iTreg development, we performed longitudinal transcriptional profiling of CD25+ T cells during their differentiation from uncommitted naive CD4 T cells. Microarray analysis of mRNA from CD25+ iTregs early after stimulation revealed expression of genes involved in cell cycle progression and T cell activation, which largely overlapped with genes expressed in CD25+ effector T cells (Teffs) used as a control. Whereas expression of these genes remained elevated in Teffs, it declined gradually in developing iTregs, resulting in a more quiescent phenotype in mature iTregs. A similar pattern of kinetics was observed for biological processes and for intracellular pathways over-represented within the expressed genes. A maximum dichotomy of transcriptional activity between iTregs and Teffs was reached at late stages of their maturation. Of interest, members of the FoxO and FoxM1 transcription factor family pathways exhibited a reciprocal expression pattern in iTregs and Teffs, suggesting a role of these transcription factors in determining T cell fate.
|
10.1371/journal.pone.0016913
|
pubmed_405_24428
|
The phosphorylation of plant retinoblastoma-related (RBR) proteins by cyclin-dependent kinases (CDKs) is well documented, but the counteracting phosphatases have not been identified yet. We report here that rice retinoblastoma-related protein-1 (OsRBR1) interacted with the B″ subunit of rice protein phosphatase 2A (OsPP2A B″) and underwent reversible phosphorylation during the cell division cycle. The OsRBR1-OsPP2A B" association required B domain in OsRBR1 and the C-terminal region of OsPP2A B″. We found by immunoprecipitation that OsPP2A B″, OsPP2A catalytic subunit subtype II, PSTAIRE-type CDK and OsRBR1 were in the same protein complex, indicating a physical association between the phosphatase, the kinase and their common substrate. OsPP2A B″ contains three predicted CDK phosphorylation sites: Ser95, Ser102 and Ser119. The in vitro phosphorylation of Ser95 and Ser119 with PSTAIRE-kinases was verified by mass spectrometry. We generated a series of phosphorylation site mutants to mimic the dephosphorylated or phosphorylated states of OsPP2A B″, and confirmed that all of the three predicted sites can be phosphorylated. Yeast two-hybrid experiments suggested that the phosphorylation of OsPP2A B″ promoted the formation of the OsPP2A holoenzyme. A triple phosphorylation mimicking OsPP2A B″ mutant containing holoenzyme showed higher activity in phosphatase assays. Our data collectively show that the phosphatase activity of OsPP2A against OsRBR1 is regulated by the phosphorylation of its B″ regulatory subunit. However, the analysis of the effect of okadaic acid, a phosphatase inhibitor, in rice cell suspension cultures revealed that the dephosphorylation of OsRBR1 was completely inhibited only by high dose (300 nM) of the okadaic acid during the cell cycle progression. Therefore the role of the protein phosphatase 1 should be considered as an additional post translational regulatory component of RBR protein function in higher plants.
|
10.1007/s11103-014-0265-y
|
pubmed_715_14944
|
Concern of physicians about being disciplined for prescribing opioids for patients in pain is one cause for undertreatment of pain. This study was done to assess the actual risk of being disciplined by state medical boards. A review of records of actions by the New York State Board for Professional Medical Misconduct for 3 years and of all medical boards in the United States for 9 months was done to determine this risk. New York State, with 7.8% of U.S. physicians, had 10 physicians disciplined annually related to overprescribing opioids, while the total for the entire U.S. was 120 physicians annually. Most physicians disciplined had multiple violations in addition to overprescribing controlled substances. In the national sample, 43% were prescribing for themselves or for nonpatients, 12% prescribed for addicts without addressing the patients' problems of addiction, 42% had inadequate records, 19% prescribed without indication for opioids, 13% were incompetent in additional ways, and 8% were having sexual activity with patients. Not a single physician, for whom information was available, was disciplined solely for overprescribing opioids. The actual risk of an American physician being disciplined by a state medical board for treating a real patient with opioids for a painful medical condition is virtually nonexistent.
|
10.1016/j.jpainsymman.2004.05.009
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pubmed_842_959
|
The health of old monkeys usually begins to deteriorate by 20 years of age, coinciding with the onset of a slowly progressing immune senescence. Changes in lymphocyte subsets and responses to several antigens have been characterized in geriatric primates, but systematic research has not been conducted on vaccination against influenza virus, a topic of considerable clinical concern for elderly humans. Antibody responses were significantly reduced to primary immunizations in old monkeys, but by administering a second vaccine at 1 month, it was possible to boost antibody titers up to the level found in young adults during their primary phase. The immune competence of unusually long-lived animals (26-37 years) was also compared to more typical aged monkeys (19-25 years). Antibody responses were low overall, although some monkeys in both age groups did respond to immunization. Among the oldest animals, the leukocytes of the responders with higher antibody titers were found to release more interleukin-2 following in vitro stimulation with an anti-CD3/anti-CD28 cocktail relative to their cellular reactions to staphylococcal enterotoxin B. The general decline in immune vigor, and the marked individual variation in how old monkeys age, provides a useful animal model for investigating factors associated with immunosenescence.
|
10.1007/s11357-011-9356-8
|
pubmed_125_19975
|
PURPOSE
The purpose of this study was to compare the subjective ankle function within the first year following matrix-induced bone marrow stimulation (M-BMS) of patients with a solitary osteochondral lesion of the talus (OCLT) with and without concomitant chronic ankle instability (CAI).
METHODS
Data from the German Cartilage Registry (KnorpelRegister DGOU) for 78 patients with a solitary OCLT and a follow-up of at least 6 months were included. All patients received M-BMS for OCLT treatment. The cohort was subdivided into patients with OCLT without CAI treated with M-BMS alone (n = 40) and patients with OCLT and CAI treated with M-BMS and additional ankle stabilisation (n = 38). The Foot and Ankle Ability Measure (FAAM), the Foot and Ankle Outcome Score (FAOS), and the Numeric Rating Scale for Pain (NRS) were used to assess patient-reported outcomes (median (minimum-maximum)).
RESULTS
From preoperatively to 12 months postoperatively, patients with OCLT without CAI treated with M-BMS alone had a significant improvement of all subscales in the FAAM [activity of daily living 64.3 (10-100) to 88.1 (39-100); sports 34.4 (0-100) to 65.6 (13-94), functional activities of daily life 50 (0-90) to 80 (30-100), functional sports 30 (0-100) to 70 (5-100)] and FAOS [pain 61.1 (8-94) to 86.1 (50-100), symptoms 60.7 (18-96) to 76.8 (29-100), activities of daily living 72.1 (24-100) to 91.9 (68-100), sport/recreational activities 30.0 (0-70) to 62.5 (0-95), quality of life 31.3 (6-50) to 46.9 (19-100)]. Within the first year, patients with OCLT and CAI treated with M-BMS and ankle stabilisation also showed significant improvement in the FAAM [activity of daily living 68.8 (5-99) to 90.5 (45-100); sports 32.8 (0-87.5) to 64.1 (0-94), functional activities of daily life 62.5 (25-100) to 80 (60-90), functional sports 30 (0-100) to 67.5 (0.95)] and the FAOS [pain 66.7 (28-92) to 87.5 (47-100), symptoms 57.1 (29-96) to 78.6 (50-100), activities of daily living 80.1 (25-100) to 98.5 (59-100), sport/recreational activities 35.0 (0-100) to 70.0 (0-100), quality of life 25.0 (0-75) to 50.0 (19-94)]. The pain level decreased significantly in both groups. No significant difference was found between both groups regarding the subscales of FAAM, FAOS and the NRS 1 year postoperatively.
CONCLUSION
Improvements in subjective ankle function, daily life activities and sports activities were observed within the first year following M-BMS. Our results suggest that preexisting and treated ankle instability did not compromise subjective outcome in patients treated with M-BMS in the first postoperative year.
LEVEL OF EVIDENCE
Level IV.
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10.1007/s00167-020-06172-5
|
pubmed_909_8198
|
Retinoblastoma is the most frequent intraocular cancer, affecting almost exclusively children. We report prospective study results assessing the national protocol for retinoblastoma treatment in Morocco. Treatment included, depending on stage and laterality, primary chemotherapy either to facilitate enucleation or to make conservative treatment possible, postoperative chemotherapy, enucleation and conservative treatments such as transpupillary thermotherapy, thermochemotherapy and cryotherapy. Radiation was used in a few cases. Close supervision was performed until the age of 5. The incidence of retinoblastoma within the study period was 18 new cases per year in our department. Observations of 32 children were included in the study: 18 unilateral retinoblastomas (56%) and 14 bilateral retinoblastomas (44%), for a total of 46 eyes. Leucocoria was the most frequent presenting symptom (69%). Buphthalmia or proptosis were present in 47% of cases. The stage of retinoblastoma was V/D or E (Reese-Elsworth/ABC) in 69.5% of cases. Enucleation was necessary for 28 eyes. Transpupillary thermotherapy or thermochemotherapy were used for 13 eyes (11 children) and cryotherapy for 13 eyes (10 children). After an average follow-up period of 52 months, among 32 children, 4 died and 2 abandoned treatment. Ocular salvage rate was 85.7% (12 eyes out of 14, among which 11 without radiation). Retinoblastoma is a genetic tumor, which occurs in two forms: sporadic, always unilateral, and hereditary, often bilateral. The latter is the most challenging case. Current treatment protocols rely primarily on chemotherapy and local treatments. The future is oriented toward purely local treatments such as intra-arterial chemotherapy and intraocular chemotherapy.
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pubmed_909_8198
|
pubmed_368_1195
|
Rapid and selective ion transport is essential for the generation and regulation of electrical signaling pathways in living organisms. Here, we use molecular dynamics (MD) simulations with an applied membrane potential to investigate the ion flux of bacterial sodium channel NaVMs. 5.9 µs simulations with 500 mM NaCl suggest different mechanisms for inward and outward flux. The predicted inward conductance rate of ∼27±3 pS, agrees with experiment. The estimated outward conductance rate is 15±3 pS, which is considerably lower. Comparing inward and outward flux, the mean ion dwell time in the selectivity filter (SF) is prolonged from 13.5±0.6 ns to 20.1±1.1 ns. Analysis of the Na+ distribution revealed distinct patterns for influx and efflux events. In 32.0±5.9% of the simulation time, the E53 side chains adopted a flipped conformation during outward conduction, whereas this conformational change was rarely observed (2.7±0.5%) during influx. Further, simulations with dihedral restraints revealed that influx is less affected by the E53 conformational flexibility. In contrast, during outward conduction, our simulations indicate that the flipped E53 conformation provides direct coordination for Na+. The free energy profile (potential of mean force calculations) indicates that this conformational change lowers the putative barriers between sites SCEN and SHFS during outward conduction. We hypothesize that during an action potential, the increased Na+ outward transition propensities at depolarizing potentials might increase the probability of E53 conformational changes in the SF. Subsequently, this might be a first step towards initiating slow inactivation.
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10.1371/journal.pcbi.1003746
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pubmed_527_342
|
DesK is a sensor histidine kinase (HK) that allows Bacillus subtilis to respond to cold shock, triggering the adaptation of membrane fluidity via transcriptional control of a fatty acid desaturase. It belongs to the HK family HPK7, which includes the nitrogen metabolism regulators NarX/Q and the antibiotic sensor LiaS among other important sensor kinases. Structural information on different HK families is still scarce and several questions remain, particularly concerning the molecular features that determine HK specificity during its catalytic autophosphorylation and subsequent response-regulator phosphotransfer reactions. To analyze the ATP-binding features of HPK7 HKs and dissect their mechanism of autophosphorylation at the molecular level, we have studied DesK in complex with ATP using high resolution structural approaches in combination with biochemical studies. We report the first crystal structure of an HK in complex with its natural nucleotidic substrate. The general fold of the ATP-binding domain of DesK is conserved, compared with well studied members of other families. Yet, DesK displays a far more compact structure at the ATP-binding pocket: the ATP lid loop is much shorter with no secondary structural organization and becomes ordered upon ATP loading. Sequence conservation mapping onto the molecular surface, semi-flexible protein-protein docking simulations, and structure-based point mutagenesis allow us to propose a specific domain-domain geometry during autophosphorylation catalysis. Supporting our hypotheses, we have been able to trap an autophosphorylating intermediate state, by protein engineering at the predicted domain-domain interaction surface.
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10.1074/jbc.M110.147843
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pubmed_667_12421
|
Apparent life-threatening event (ALTE) is a term used to characterize an event of unknown cause after an infant is found limp, cyanotic, bradycardic, and/or requiring resuscitation. Like sudden infant death syndrome (SIDS), ALTE is a general term used until a precise diagnosis can be established. The relationship between ALTE and SIDS has not been clearly defined, although 7 to 15 percent of children with ALTE die of SIDS. If children with ALTE are at greater risk for SIDS, morbidity and mortality may be prevented if the underlying pathology can be identified and corrected or closely monitored. The otolaryngologist is being consulted more frequently to evaluate children who have been through an ALTE to help elucidate any underlying pathology that may have caused the near-death experience. This retrospective chart review reports the evaluation of 30 infants with ALTE requiring consultation by the Division of Pediatric Otolaryngology at the Children's Memorial Hospital in Chicago during a 3-year period. We reviewed the literature and here compare our findings with current animal models. Of the 30 children evaluated, 53% had gastroesophageal reflux, 40% had laryngeal abnormalities, 13% had tracheal abnormalities, and 10% had pharyngeal abnormalities. Thirteen percent of the children had nonotolaryngic anomalies identified during evaluation. Surgical intervention was required in 10 patients and medical treatment was used in 18. When evaluating a child with ALTE, a complete history and physical examination, evaluation for gastroesophageal reflux, assessment for upper airway obstruction by radiographs and endoscopy, and a multidisciplinary approach are recommended.
|
10.1016/S0194-59989770230-4
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pubmed_21_6481
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Group B Streptococcus (GBS) was the main causative organism of invasive infections in newborns due to vertical transmission from the colonized mothers. The study was undertaken to determine colonization rate, serotype distribution, genotypic characterization, antibiotic susceptibility profiles and molecular characteristics of erythromycin-resistant strains of GBS in pregnant women in Beijing, China. Vaginal-rectal swabs were collected from a total of 2850 pregnant women at 35-37 weeks of gestation, in which 7.1% were GBS positive. Serotypes III, Ia and V predominated. All isolates were penicillin susceptible, whereas the resistance rates for erythromycin and clindamycin were strikingly high.
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10.1111/1469-0691.12416
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pubmed_133_16771
|
Catabolic proinflammatory cytokines play a key role in mediating biochemical changes associated with many pathophysiological states. The present review emphasizes the role of this type of cytokine in inflammation and cachexia. Additionally, it reviews the role of one of these mediators in the induction of insulin resistance by dealing with some of the most recent publications on this topic.
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10.1097/00075197-199805000-00002
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pubmed_486_12725
|
Hypothyroidism is associated with an increased risk of atherosclerosis. Pulse wave velocity (PWV) is an index of arterial wall stiffness widely used for noninvasive assessment of early atherosclerosis. We assessed PWV in Egyptian patients with hypothyroidism. The study included 100 Egyptian females aged 18 to 55 years. They were classified into three groups: group I, 40 women with overt hypothyroidism; group II, 40 women with subclinical hypothyroidism; and group III, 20 euthyroid women as a control group. The three groups were age matched. Doppler ultrasonography was used to calculate the heart-femoral PWV. PWV was significantly higher in women with overt and subclinical hypothyroidism as compared with the control group (9.55 ± 1.81 m/s and 9.30 ± 1.28 m/s, respectively vs. 7.82 ± 2.14 m/s; P<.001 and <.01, respectively). There was a positive correlation between thyroid-stimulating hormone (TSH) and PWV in women with overt hypothyroidism and in those with subclinical hypothyroidism (P<.05 for both). Multivariate regression analysis showed that age and diastolic blood pressure were independent determinants of PWV in women with overt and subclinical hypothyroidism (P<.01 for all). TSH was also an independent determinant of PWV in both groups (P<.05 for both). PWV is significantly higher in Egyptian women with overt and subclinical hypothyroidism as compared with normal control subjects. This denotes early increase in arterial wall stiffness in patients with hypothyroidism, even in the subclinical phase. The positive correlation between PWV and TSH in both groups of patients suggests that the risk of atherosclerosis is proportionate to the severity of hypothyroidism. Abbreviations: ABI = ankle/brachial index; baPWV = brachial-ankle pulse wave velocity; BP = blood pressure; CIMT = carotid intima-media thickness; ECG = electrocardiogram; FT4 = free thyroxine; HDL = high-density lipoprotein; hfPWV = heart-femoral pulse wave velocity; LDL = low-density lipoprotein; PTT = pulse transit time; PWV = pulse wave velocity; SCH = subclinical hypothyroidism; TSH = thyroid-stimulating hormone.
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10.4158/EP-2019-0322
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pubmed_583_2806
|
Total-liquid ventilation (TLV) is an innovative experimental method of mechanical-assisted ventilation in which lungs are totally filled and then ventilated with a tidal volume of perfluorochemical liquid by using a dedicated liquid ventilator. Such a novel medical device must resemble other conventional ventilators: it must be able to conduct controlled-pressure ventilation. The objective was to design a robust controller to perform pressure-regulated expiratory flow and to implement it on our latest liquid-ventilator prototype (Inolivent-4). Numerical simulations, in vitro experiments, and in vivo experiments in five healthy term newborn lambs have demonstrated that it was efficient to generate expiratory flows while avoiding collapses. Moreover, the in vivo results have demonstrated that our liquid ventilator can maintain adequate gas exchange, normal acid-base equilibrium, and achieve greater minute ventilation, better oxygenation and CO2 extraction, while nearing flow limits. Hence, it is our suggestion to perform pressure-controlled ventilation during expiration with minute ventilation equal or superior to 140 mL x min(-1) x kg(-1) in order to ensure PaCO2 below 55 mmHg. From a clinician's point of view, pressure-controlled ventilation greatly simplifies the use of the liquid ventilator, which will certainly facilitate its introduction in intensive care units for clinical applications.
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10.1109/TBME.2009.2031096
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pubmed_468_1926
|
OBJECTIVE
We investigated the influence of obstructive sleep apnea -hypopnea syndrome (OSAHS) on hypertension and metabolism.
METHOD
There were two groups in this research; they were the research group including 115 patients who were diagnosed with polysomnography and the control group of 122 healthy persons. The blood pressure in the morning, plasmas glucose (GLU), total cholesterol (TC), triglyceride (TG), and uric acid (UA) were measured. There were 32 moderate or severe OSAHS patients and 20 healthy persons were selected to be measured the mitochondrial coupling factor 6 (CF6) with radio-immunity method. The results were analyzed with statistic method. The P < 0.05 means the significant difference.
RESULT
The patients' blood pressure in the morning was significantly higher than the control healthy persons. The plasmas glucose, total cholesterol, triglyceride, and uric acid of the OSAHS patients were all in a higher level than those of the control group healthy persons. There were significant differences between the two groups. The mitochondrial coupling factor 6 (CF6) of moderate OSAHS patients or severe OSAHS patients was more than that of the healthy persons (P < 0.05).
CONCLUSION
OSAHS is a potential risk factor on the cardiovascular diseases and the metabolism disorders. The mitochondrial coupling factor 6 (CF6) may play an important role in the procedure of X syndrome.
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pubmed_468_1926
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pubmed_580_961
|
PURPOSE
Survey questions are commonly used to assess sleep duration because of their low cost and convenience. Responses to these questions correlate moderately with objectively measured sleep duration in nonpregnant individuals, but little is known about the validity of self-reported sleep measures in pregnancy. The aim of the present study was to determine the extent to which self-reported gestational sleep duration assessed by questionnaire predicted objectively measured gestational sleep duration via actigraphy.
METHODS
We analyzed data from 80 mothers enrolled in an ancillary study of Project BABIES, a prospective cohort study of urban, pregnant women. Sleep measurements were collected in midpregnancy and included 7 days of wrist actigraphy, a sleep log, and survey questions about sleep time adapted from the Pittsburgh Sleep Quality Index.
RESULTS
Mean measured gestational sleep duration derived from actigraphy was 6.87 h [standard deviation (SD) 0.87], and questionnaire-assessed nocturnal sleep time averaged 7.29 h (SD 1.84). While the difference between measures did not reach statistical significance (p = 0.07 for paired samples t test), over half (62 %) of participants reported a habitual average nightly sleep time that differed more than 1 h from their average actigraphically measured sleep duration (39 % overestimated by more than an hour; 23 % underestimated by more than an hour). There was no correlation between measures (r = 0.007; 95 % confidence interval -0.21, 0.23).
CONCLUSION
Questionnaire-derived reports of usual sleep hours do not reflect objectively measured sleep time in urban, pregnant women. Actigraphy is preferable to accurately assess gestational sleep duration.
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10.1007/s11325-013-0835-2
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pubmed_17_923
|
BACKGROUND
It is of clinical importance to localize pathologic brain tissue in epilepsy. Noninvasive localization of cortical areas associated with interictal epileptiform spikes may provide important information to facilitate presurgical planning for intractable epilepsy patients.
METHODS
A cortical potential imaging (CPI) technique was used to deconvolve the smeared scalp potentials into the cortical potentials. A 3-spheres inhomogeneous head model was used to approximately represent the head volume conductor. Five pediatric epilepsy patients were studied. The estimated cortical potential distributions of interictal spikes were compared with the subsequent surgical resections of these same patients.
RESULTS
The areas of negativity in the reconstructed cortical potentials of interictal spikes in 5 patients were consistent with the areas of surgical resections for these patients.
CONCLUSIONS
The CPI technique may become a useful alternative for noninvasive mapping of cortical regions displaying epileptiform activity from scalp electroencephalogram recordings.
|
10.1016/s1388-2457(03)00194-9
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pubmed_1092_13663
|
The interplay between viral and host factors plays a major role in viral pathogenesis. Hepatitis B virus (HBV) infection is a global health problem that leads to liver cirrhosis and hepatocellular carcinoma (HCC). Although HBV proteins have been studied extensively about their implication in hepatocarcinogenesis, the molecular mechanisms of oncogenesis are still largely unknown. A recent concept in gene regulation, in which competitive endogenous RNAs compete for common microRNAs (miRNAs), suggests that mRNA targets are key elements in the regulation of miRNA availability. Here, we show that HBV mRNA in the preS2 region can be targeted by host miRNA let-7 g. This leads to the sequestration of let-7 g and inhibition of let-7 g function. The expression of HBV transcripts, including the preS2 region, de-repressed let-7 g targets, which may contribute to long-term oncogenesis. HBV transcript-expressing transgenic mice, but not non-targeted transcript-expressing mice, were more prone to chemically induced hepatoocarcinogenesis. Let-7 target protein expression was upregulated in human HCC tissues derived from HBV-infected patients. On the other hand, let-7 g inhibited HBV preS2 protein expression and viral products. These results suggest that the interplay between viral intermediate transcripts during HBV replication and host miRNAs is crucial to the pathogenesis of chronic viral infection.
|
10.1038/srep23237
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pubmed_1098_11420
|
Accumulated clinical and biomedical evidence indicates that the gut microbiota and their metabolites affect brain function and behavior in various central nervous system disorders. This study was performed to investigate the changes in brain metabolites and composition of the fecal microbial community following injection of amyloid β (Aβ) and donepezil treatment of Aβ-injected mice using metataxonomics and metabolomics. Aβ treatment caused cognitive dysfunction, while donepezil resulted in the successful recovery of memory impairment. The Aβ + donepezil group showed a significantly higher relative abundance of Verrucomicrobia than the Aβ group. The relative abundance of 12 taxa, including Blautia and Akkermansia, differed significantly between the groups. The Aβ + donepezil group had higher levels of oxalate, glycerol, xylose, and palmitoleate in feces and oxalate, pyroglutamic acid, hypoxanthine, and inosine in brain tissues than the Aβ group. The levels of pyroglutamic acid, glutamic acid, and phenylalanine showed similar changes in vivo and in vitro using HT-22 cells. The major metabolic pathways in the brain tissues and gut microbiota affected by Aβ or donepezil treatment of Aβ-injected mice were related to amino acid pathways and sugar metabolism, respectively. These findings suggest that alterations in the gut microbiota might influence the induction and amelioration of Aβ-induced cognitive dysfunction via the gut-brain axis. This study could provide basic data on the effects of Aβ and donepezil on gut microbiota and metabolites in an Aβ-induced cognitive impairment mouse model.
|
10.3390/molecules27196591
|
pubmed_247_24657
|
OBJECTIVE
To determine the prevalence of cardiac valvular involvement in patients with the primary antiphospholipid syndrome.
DESIGN
Cross-sectional study with evaluation of case patients and control patients by Doppler echocardiography. The mean follow-up for case patients was 22 months.
SETTING
University-based tertiary medical center.
PATIENTS
Twenty-eight consecutive patients who were diagnosed with the primary antiphospholipid syndrome during a 10-year period; 28 age- and sex-matched healthy controls.
MEASUREMENTS AND MAIN RESULTS
Ten patients (36%; 95% Cl, 19% to 56%) with the primary antiphospholipid syndrome had cardiac valvular involvement: Four patients had mitral valve involvement; four patients, aortic valve involvement; and two patients, both mitral and aortic valvular involvement; no patients had tricuspid or pulmonary valve disease. Eight of 10 patients had a regurgitant murmur. None of the control patients had valvular disease. The mean mitral valve thickness in patients with mitral valve involvement was 7.0 +/- 1.6 mm, compared with 2.7 +/- 0.8 mm in patients with normal valves and 3.2 +/- 0.9 mm in the control group. The mean aortic valve thickness in patients with aortic valve involvement was 3.8 +/- 0.5 mm compared with 1.4 +/- 0.3 mm in patients with normal valves and 1.4 +/- 0.5 mm in the control group. Stenotic lesions were not found. Regurgitation was severe in two patients (one required surgery), moderate in three patients, and mild in three patients.
CONCLUSIONS
Valvular involvement is frequently found in patients with the primary antiphospholipid syndrome. The lesions are left-sided, causing regurgitation that may be clinically important.
|
10.7326/0003-4819-116-4-293
|
pubmed_821_14589
|
Although many renal transplant recipients are protective of their grafts and often express concern about the possibility of traumatic injury, such injury has been reported only rarely. We describe a case report of a boy who sustained an injury to his renal allograft after a bicycle accident. Despite a dramatic anatomic abnormality seen on magnetic resonance imaging, he suffered only minor and self-limited symptomatic and clinical consequences. We reviewed the literature addressing traumatic injuries affecting renal allografts. The long-term consequences of such injuries on allograft function and survival are unknown.
|
10.1016/s0272-6386(01)90019-8
|
pubmed_798_17168
|
BACKGROUND AND AIMS
Neuropsychiatric symptoms may accompany mild cognitive impairment (MCI) and assist in identifying incipient dementia. The aim of this study was to evaluate the role of apathy and depression in the conversion to dementia among MCI subjects.
METHODS
124 MCI outpatients were investigated. Diagnosis of apathy and depression was based on clinical criteria. The main endpoint was the development of dementia within 2 years from the enrolment.
RESULTS
50 (40.3%) subjects were classified as MCI normal, 38 (30.7%) as MCI depressed, 21 (16.9%) as MCI depressed-apathetic and 15 (12.1%) as apathetic. The rates of conversion were 24% for MCI normal, 7.9% for MCI depressed, 19% for MCI depressed-apathetic and 60% for MCI apathetic. Diagnosis of apathy was a risk factor for conversion apart from age, functional and cognitive status at baseline (OR = 7.07; 95% CI 1.9-25.1; p = 0.003). In contrast, MCI depressed subjects had a reduced risk of conversion (OR = 0.10; 95% CI 0.02-0.4; p = 0.001).
CONCLUSION
These findings argue for a differential role of apathy and depression in the development of dementia, and suggest the need of dissecting in MCI patients apathy and depression symptoms in the reading of mood disorders.
|
10.1159/000210045
|
pubmed_351_6490
|
The activation of the nonselective cation channels in mouse pancreatic acinar cells has been assessed at low agonist concentrations using patch-clamp whole cell, cell-attached patch, and isolated inside-out patch recordings. Application of acetylcholine (ACh) (25-1,000 nM) and cholecystokinin (CCK) (2-10 pM) evoked oscillatory responses in both cation and chloride currents measured in whole cell experiments. In cell-attached patch experiments we demonstrate CCK and ACh evoked opening of single 25-pS cation channels in the basolateral membrane. Therefore, at least a component of the whole cell cation current is due to activation of cation channels in the basolateral acinar cell membrane. To further investigate the reported sensitivity of the cation channel to intracellular ATP and calcium we used excised inside-out patches. Micromolar Ca2+ concentrations were required for significant channel activation. Application of ATP and ADP to the intracellular surface of the patch blocked channel opening at concentrations between 0.2 and 4 mM. The nonmetabolizable ATP analogue, 5'-adenylylimidodiphosphate (AMP-PNP, 0.2-2 mM), also effectively blocked channel opening. The subsequent removal of ATP caused a transient increase in channel activity not seen with the removal of ADP or AMP-PNP. Patches isolated into solutions containing 2 mM ATP showed channel activation at micromolar Ca2+ concentrations. Our results show that ATP has two separate effects. The continuous presence of the nucleotide is required for operation of the cation channels and this action seems to depend on ATP hydrolysis. ATP can also close the channel and this effect can be demonstrated in excised inside-out patches when ATP is added to the bath after a period of exposure to an ATP-free solution. This action does not require ATP hydrolysis. Under physiological conditions hormonal stimulation can open the nonselective cation channels and this can be explained by the rise in the intracellular free Ca2+ concentration.
|
10.1085/jgp.100.1.11
|
pubmed_955_1412
|
PURPOSE
To assess the value of chemical shift gradient-echo (GRE) magnetic resonance (MR) imaging with the fast low-angle shot (FLASH) technique to detect fatty metamorphosis in hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
Sixty-three cirrhotic patients with 69 HCCs underwent MR imaging at 1.0 T with chemical shift GRE technique. Both opposed-phase and in-phase FLASH imaging with breath holding was performed, and the percentage variation in signal intensity of the nodules between the two images was calculated.
RESULTS
Chemical shift GRE imaging depicted fat in 10 HCCs (14%). In these cases, the percentage variation in signal intensity increased notably and was 88.6%-369.3% (mean, 174.7%), which indicated fatty content (sensitivity, 100%; specificity, 100% when compared with fine-needle aspiration cytology). In the remaining 59 nodules, the percentage of signal intensity variation ranged from 12.7% to -19.1% (mean, -4.0%).
CONCLUSION
Chemical shift GRE MR imaging can be used to detect fatty metamorphosis in HCC.
|
10.1148/radiology.195.1.7892452
|
pubmed_389_12799
|
BACKGROUND
IRAK1 has been repoted to play an essential role in the development of multiple cancers. However, the clinical significance of IRAK1 in hepatocellular carcinoma (HCC) and the underlying molecular mechanism remain unclear. Therefore, we aimed to investigate the role of IRAK1 in the pathogenesis of HCC in this study.
MATERIALS AND METHODS
HCC tissues and para-carcinoma tissues were collected for immunohistochemistry (IHC) analysis to evaluate IRAK1 expression. Data of IRAK1 expression were downloaded from the cancer genome atlas (TCGA) for analyzing the clinical significance of IRAK1. Receiver operating characteristic (ROC) curve and survival analyses were carried out to assess the diagnostic and prognostic significance of IRAK1 in IHC and TCGA data. Additionally, we investigated the alteration of IRAK1 gene in HCC from cBioPortal to generate a network of the interaction between IRAK1 and the neighboring genes. The influence of IRAK1 gene alteration on the prognosis of HCC patients was evaluated by survival analysis.
RESULTS
Analysis of both IHC and TCGA data revealed a significant upregulation of IRAK1 in HCC tissues. The IHC analysis revealed there was an increasing trend in IRAK1 expression among normal liver tissues, liver cirrhosis tissues, para-carcinoma tissues and HCC tissues. The ROC curves for IHC and TCGA data demonstrated that IRAK1 exhibited a significant diagnostic value for HCC. Moreover, IRAK1 expression was observed to be associated with tumor size, metastasis and T-stage. The survival analysis indicated that the upregulation of IRAK1 predicted a worse overall survival of HCC. Additionally, data from cBioPortal confirmed that 29% of HCC tissues possessed an alteration of the IRAK1 gene.
CONCLUSION
IRAK1 may act as an oncogene in the development of HCC with its overexpression in HCC. Moreover, IRAK1 might serve as a promising diagnostic and therapeutic target for HCC.
|
10.2147/OTT.S132120
|
pubmed_534_19557
|
UNLABELLED
ESSENTIALS: Hemostasis biomarkers impact thrombosis occurrence and survival in cancer patients. We performed a longitudinal analysis of hemostatic parameters in 112 cancer patients. Hemostatic parameters are associated with disease state, patients' prognosis, and the risk of VTE. The procoagulant state exists not only at diagnosis, but also during the course of disease.
BACKGROUND
Hemostasis biomarkers are known to have an impact on venous thromboembolism (VTE) occurrence and survival in cancer patients.
OBJECTIVES
As there are almost no data on longitudinal changes, we aimed to evaluate those in the present prospective observational study during chemotherapy and the course of disease.
PATIENTS/METHODS
Patients with cancer of the brain (n = 39), lung (n = 41), colon (n = 15) or pancreas (n = 17) were included before initiation of antitumor therapy. Blood samples for determination of factor VIII, thrombin peak height, D-dimer, F1 + 2 , fibrinogen and soluble P-selectin (sP-selectin) were drawn on a monthly basis. The study endpoints were death, VTE occurrence, or completion of the study period.
RESULTS
Overall, 546 blood samples of 112 patients were analyzed. D-dimer and sP-selectin levels were significantly higher in patients with distant metastasis than in those without. Patients with complete remission had significantly lower levels of F1 + 2 , D-dimer and fibrinogen. Peak height thrombin levels showed a decrease over time in all tumor types. Levels of biomarkers behaved differently in the various tumor types. Patients who developed VTE (n = 14) showed increasing levels of FVIII, sP-selectin, and D-dimer. At the last blood sampling time-point before VTE occurrence, in 13 patients the D-dimer level was above the median, and in seven of these patients it was even above the 75th percentile; however, the individual course was highly variable. Regarding survival, steadily increased FVIII, sP-selectin and D-dimer levels were associated with higher mortality.
CONCLUSIONS
Hemostatic parameters show an association with disease state, prognosis, and the risk of VTE, not only at diagnosis, but also during the course of antineoplastic treatment.
|
10.1111/jth.13218
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pubmed_1039_5269
|
Two cases of the association of Fallot's tetralogy and coarctation of the aorta are reported. In both cases there was a right aortic arch. In addition, the second case had a cervical aorta and a left subclavian artery isolated from the aorta and vascularised by the left vertebral artery. The two children underwent complete repair: the first patient had a Waterston shunt followed by repair of the Fallot's tetralogy, followed by repair of the coarctation; the second patient first had a Gore-tex tube inserted from the ascending to the descending aorta and then underwent repair of the Fallot's tetralogy. The association of a coarctation with an obstructive lesion of the right heart is very rare; only two cases have previously been reported: one Fallot's tetralogy and one tricuspid atresia with pulmonary stenosis. Both cases also had a right aortic arch. This seems to go against the haemodynamic theory of coarctation: blood flow in the ascending aorta increases while flow in the pulmonary artery decreases. Coarctation could be caused by a partial involution of the terminal segment of the right primitive dorsal aorta as proposed in cases of coarctation with a right sided aortic arch. The second case also presented two uncommon features: a cervical aortic arch and a left subclavian artery isolated from the aorta.
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pubmed_1039_5269
|
pubmed_578_290
|
Molten methylboronic acid has been used as a reactive flux to prepare the first neptunium(V) borate, NpO(2)[B(3)O(4)(OH)(2)] (NpBO-1), and the first actinide boronate, UO(2)(CH(3)BO(2))(H(2)O) (UCBO-1). NpBO-1 contains cation-cation interactions between the neptunyl units. In contrast, the presence of the methyl groups in the uranyl boronate leads to a one-dimensional structure.
|
10.1021/ic101678d
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pubmed_1012_11746
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A 23-year-old woman developed biochemical signs of acute severe hepatitis together with confusion and flapping tremor after snorting a large dose of cocaine. Blood levels of cocaine were very high and liver biopsy performed few days later showed centrilobular necrosis. She recovered completely with conservative measures. Cocaine toxicity should be considered in similar cases of fulminant liver failure.
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pubmed_1012_11746
|
pubmed_1071_17912
|
FAT10 is an oncogene that is localized at 6q21.3, a region frequently amplified in hepatocellular carcinoma (HCC). Recently, growing attention has been paid to its effect in the initiation of various cancers. However, there has been little research into the influence of FAT10 on the progression and prognosis of HCC, especially in hepatitis B virus (HBV)-related HCC. Here, we aimed at investigating clincopathological significance of FAT10 in HBV-related HCC and its underlying mechanisms. Based on the analysis of FAT10 expression in a reliable and large number of cases with 5-year follow-up, we showed that FAT10 was significantly increased in 260 samples from HBV-related HCC patients, compared with 30 normal tissue, 50 cirrhosis and matched adjacent nontumor tissues. FAT10 expression is correlated with recurrence and poor prognosis in HBV-related HCC. In addition, ectopic expression of FAT10 enhanced cell proliferation, inhibited apoptosis and induced cell cycle progression, whereas silencing FAT10 expression suppressed cell proliferation and induced apoptosis. FAT10 also induced the epithelial-mesenchymal transition (EMT) and promoted invasion of HCC cells. Furthermore, we found Akt/GSK3β pathway contributed to the effects of FAT10 in HCC cells. Blocking the Akt pathway significantly inhibited the actions of FAT10. Taken together, the ubiquitin-like protein FAT10 has a central role in regulating diverse aspects of the pathogenesis of HCC, indicating that it might be a potential therapeutic target.
|
10.1038/onc.2013.236
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pubmed_115_3250
|
Multichannel imaging systems provide several observations of the same scene which are often corrupted by noise. In this paper, we are interested in multispectral image denoising in the wavelet domain. We adopt a multivariate statistical approach in order to exploit the correlations existing between the different spectral components. Our main contribution is the application of Stein's principle to build a new estimator for arbitrary multichannel images embedded in additive Gaussian noise. Simulation tests carried out on optical satellite images show that the proposed method outperforms conventional wavelet shrinkage techniques.
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10.1109/tip.2005.857247
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pubmed_1086_17369
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A man aged 80 and three women aged 66, 26, and 39 years respectively, underwent surgery for Graves' disease. The first woman had pneumonia and experienced thyrotoxic storm. Euthyroidism was restored with antithyroid drugs (ATD) and thyroidectomy was performed as ablative treatment for hyperthyroidism. The man presented with thyrotoxicosis and had severe Graves' ophthalmopathy. After euthyroidism was restored with ATD, he underwent subtotal thyroidectomy. The second woman presented with severe thyrotoxicosis but was allergic to ATD. She was treated with iodine and beta-blockers after which subtotal thyroidectomy was done as an ablative procedure. Medical treatment for hyperthyroidism failed in the last patient and, as she had experienced severe psychological disturbances during a previous relapse, she too chose surgery as a definitive treatment option. In two patients the postoperative course was complicated by early hypocalcaemia and one of these patients experienced temporary recurrent laryngeal nerve paralysis. Surgery has a limited role in the treatment of Graves' disease. In pregnant women with severe ATD-resistant thyrotoxicosis, surgery is the only treatment option, while in patients with Graves' orbitopathy surgery may be preferable because of its neutral and perhaps even beneficial effects on eye symptoms. Large goitre size and thyroid nodules are concomitant reasons for choosing surgery, as are allergy to ATD and patients' preference. Lastly, in patients who have suffered from severe thyrotoxicosis, surgery provides rapid and definitive treatment. Early morbidity following surgery is common and should be discussed with the patient.
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pubmed_1086_17369
|
pubmed_950_17995
|
BACKGROUND
An understanding of the cultural aspects of suicidal behavior is essential for the development of culturally appropriate suicide prevention and intervention strategies.
AIMS
This study explored the attitudes toward youth suicide in 686 Italian, Indian and Australian undergraduate students (18-24 years old).
METHOD
A 21-item suicide attitude inventory titled Attitude towards Youth Suicide (AtYS) scale, included in this paper, was used in the three samples.
RESULTS
Four factors were extracted, labeled negative attitudes toward suicide, belief that suicide was not preventable, suicide as acceptable and normal, and the existence of risk signs for suicide. Country differences were found for all four subscales, with Indian students having the most negative attitudes toward suicide. Sex differences were found in all three countries with women, on the whole, having less negative attitudes toward suicide, more belief in the preventability of suicide in India and more belief in risk signs for suicide in Italy.
CONCLUSION
Attitudes are linked to suicide in a complex manner. More quantitative and qualitative studies, including in lower-income and non-English speaking Western societies, are needed.
|
10.1177/0020764020926551
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pubmed_234_8893
|
The antimicrobial susceptibility of 239 coagulase-negative staphylococci (CNS) isolates consecutively collected from blood culture in patients admitted in a 600-bed teaching hospital was evaluated. The isolates were identified to the species level by conventional methods and the MicroScan Positive Combo Panel type 6 system, and their susceptibility to vancomycin, teicoplanin, and oxacillin were tested by agar dilution, disk diffusion, and MicroScan-WalkAway system. The species distribution was as follows: Staphylococcus epidermidis 120 (50.2%), S. hominis 29 (12.1%), S. haemolyticus 24 (10.0%), S. cohnii 14 (5.9%), and isolates from other CNS species 52 (21.8%). The percentage of resistance to oxacillin was 74.5% by agar dilution. The highest percentages of oxacillin resistance were found among S. haemolyticus (95.8%) and S. epidermidis (80.8%). Teicoplanin resistance (MIC > or = 32 micrograms/mL) was detected in five S. haemolyticus isolates, whereas intermediate resistance (MIC = 16 micrograms/mL) was detected in nine strains. These isolates with reduced susceptibility to teicoplanin were resistant to oxacillin, but remained susceptible to vancomycin (MIC < or = 4 micrograms/mL). Two isolates, one S. haemolyticus and one S. epidermidis, showed a vancomycin MIC of 8 micrograms/mL, and both MicroScan and disk diffusion methods classified these isolates as susceptible. Our results showed that glycopeptide resistance is emerging among CNS isolates in our institution and the disk diffusion method may not detect isolates with decreased susceptibility to these antimicrobial agents.
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10.1016/s0732-8893(99)00034-6
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pubmed_1138_20610
|
BACKGROUND
Age-related macular degeneration (ARMD) is a major cause of blindness in the elderly. Unfortunately, no proven form of treatment is currently available for the dry, atrophic form of ARMD seen in more than 90 percent of patients with this condition.
METHODS
A recent theory suggests that ARMD is associated with damage to the retina caused by free radicals. If this is correct, it is possible that the damage could be prevented or moderated by supplementing the diet with specific antioxidant vitamins and minerals that enhance the body's natural defenses against free radicals.
RESULTS AND CONCLUSION
This paper reviews the literature regarding the pathogenesis of ARMD and presents a rationale for its management or prevention by the use of supplemental vitamins and minerals.
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pubmed_1138_20610
|
pubmed_527_24256
|
BACKGROUND
Brain tumours and head trauma are two pathological entities that may involve the central nervous system to produce similar clinical neurologic signs and symptoms. There has been a long-term debate in the literature on association between these two clinical conditions following observations over time of development of intracranial tumours in individuals who previously sustained head injury. In this teaching centre, there were in succession, two cases of head injury which, at brain CT scanning, turned out to be brain tumours. These findings stimulated the need to review the literature.
OBJECTIVE
To examine the literature for evidence of the role of brain tumour as a factor in development of falls and subsequent head injury and thus raise awareness of their association.
METHODS
Related literature materials on brain tumours and head injury were reviewed.
RESULTS
Some reports in the medical literature established only weak evidence in support of head injury as an aetiologic agent for brain tumour occurrence; others found no association between them. CT and MRI are useful investigative modalities.
CONCLUSION
Head trauma may only have caused small and preexisting quiescent tumour to grow as a result of predisposition to fall by musculoskeletal incoordination caused by the tumour itself.
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pubmed_527_24256
|
pubmed_273_19436
|
Since 1999 we have developed three approaches to quantifying each amino acid in a protein as well as a protein in whole based on random mechanisms. With our approaches, we can reliably describe the evolution of a protein family, for example, the hemagglutinins from influenza A viruses along the time course in a 2-dimensional graph, and then we use the fast Fourier transform to find the mutation periodicity in order to time the mutation. In this study, we realize that the changes in quantified randomness in a hemagglutinin family over time is the difference between randomness associated with mutant amino acids and randomness associated with original amino acids. This is a standard mass-balance relationship, by which we can build a differential equation for a hemagglutinin family or a system of differential equations for all hemagglutinins in the family. In this context, the randomness defined by us actually is the entropy, thus we have a general model to describe the evolution, namely, the evolution is the exchange of entropy between protein family and environment through mutations quantified using our approaches.
|
10.2174/092986609788681751
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pubmed_396_14020
|
Using the path-integral Monte Carlo method, we calculate the energy to form single and pair vacancies and interstitials in a two-dimensional Wigner crystal of electrons. We confirm that the lowest energy point defects of a 2D electron Wigner crystal are interstitials, with a creation energy roughly 2/3 that of a vacancy. The formation energy of the defects goes to zero at melting, suggesting that point defects may be the melting mechanism and that the melting could be a continuous transition. In addition, we find that the interaction between defects is strongly attractive, so that most defects will exist as bound pairs.
|
10.1103/PhysRevLett.86.492
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pubmed_905_23832
|
Odoamide is a novel cyclic depsipeptide with highly potent cytotoxic activity isolated from the Okinawan marine cyanobacterium Okeania sp. It contains a 26-membered macrocycle composed of a fatty acid moiety, a peptide segment and isoleucic acid. Four possible stereoisomers of the odoamide polyketide substructure were synthesised using a chiral pool approach. The first total synthesis of odoamide was also successfully achieved. The structure of synthetic odoamide was verified by comparing its NMR spectra with those of the natural product.
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10.1039/c6ob01583b
|
pubmed_392_14999
|
INTRODUCTION
Ghrelin is an endogenous peptide with potential protective effects on ischemic heart.
METHODS
Synthetic ghrelin was administered (100 μg·kg-1 subcutaneous injection, twice daily) for 4 weeks in a rat model of myocardial infarction (MI) with coronary artery occlusion. At the 5th week, electrocardiogram, monophasic action potentials and autonomic nerve function were evaluated. Cardiac tyrosine hydroxylase (TH) was determined by immunofluorescence staining.
RESULTS
MI significantly increased sympathetic nerve activity (SNA) and ventricular arrhythmias, and prolonged APD dispersion and APD alternans (p < 0.01). Ghrelin treatment significantly increased ventricular fibrillation threshold (VFT), shortened APD dispersion and APD alternans, inhibited SNA and promoted vagus nerve activities (p < 0.01). Ghrelin also markedly reversed abnormal expression of TH in the peri-infarcted area of the heart (p < 0.01).
DISCUSSION/CONCLUSION
Ghrelin provides a sustained electrophysiological protection by the increase of VFT and improvement of APD dispersion and APD alternans. The mechanism may be related to the regulation of autonomic nerve and sympathetic nerve remodeling. Thus, ghrelin represents a novel drug to prevent ventricular arrhythmia in ischemic heart disease.
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10.1159/000519330
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pubmed_381_11439
|
Spherical implosions in inertial confinement fusion are inherently sensitive to perturbations that may arise from experimental constraints and errors. Control and mitigation of low-mode (long wavelength) perturbations is a key milestone to improving implosion performances. We present the first 3D radiation-hydrodynamic simulations of directly driven inertial confinement fusion implosions with an inline package for polarized crossed-beam energy transfer. Simulations match bang times, yields (separately accounting for laser-induced high modes and fuel age), hot spot flow velocities and direction, for which polarized crossed-beam energy transfer contributes to the systematic flow orientation evident in the OMEGA implosion database. Current levels of beam mispointing, imbalance, target offset, and asymmetry from polarized crossed-beam energy transfer degrade yields by more than 40%. The effectiveness of two mitigation strategies for low modes is explored.
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10.1103/PhysRevLett.129.095001
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pubmed_1055_20542
|
Cryptochromes are flavin- and pterin-containing photoreceptors of the cryptochrome/photolyase family. They play critical roles in organisms, among are which light-dependent and light-independent roles in biological rhythms. The present work aimed at describing a cryptochrome gene in the oyster Crassostrea gigas by (i) a characterization and phylogenetic analysis and (ii) by studying its expression in the relationship to rhythmic valve behavior in different entrainment regimes. Cryptochrome expression was focused on the adductor muscle of the oyster, the effector of the valve behavior. The results suggest involvement of Cgcry1 in oyster rhythmicity as a sensor of environmental zeitgebers, associated with circadian rhythms and potentially to tidal activity. The characterized gene belongs to type 1 cryptochrome/insect-type cry. Additionally, Cgcry1 presented a daily oscillation under L:D entrainment, which disappeared in constant darkness. Transcript expression of Cgcry1 also oscillated at tidal frequency under tidal entrainment and in constant darkness. Finally, exposure of tidally entrained oysters to saxitoxin (STX)-producing alga Alexandrium minutum induced a dose effect response in oysters by first altering Cgcry1 expression and then the behavior of oysters with increasing concentrations of toxins. This study initiates the characterization of the molecular clock in the oyster C. gigas and its interactions with environmental zeitgebers.
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10.1080/07420528.2016.1181645
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pubmed_224_11198
|
The relationship between release of membrane lipid peroxidation products and phospholipase action was examined. Rat liver microsomes and phosphatidylcholine liposome-phospholipase A2 preparations were subjected to iron ascorbate-induced lipid peroxidation. Peroxidation products were characterized by measurement of malondialdehyde and lipid peroxides. Experiments were designed to demonstrate phospholipase dependent removal of peroxidation products origination in the membrane. Increased lysophosphatidylcholine formation was evident following lipid peroxidation in phospholipase A2-containing liposomes which was inhibited by p-bromophenacyl bromide and mepacrine. Lipoxygenase-dependent oxygen consumption, as well as peroxide transfer from microsomes to the incubation medium, was largely dependent on phospholipase and could be diminished by phospholipase inhibitors. Furthermore, lipid hydroperoxides formed by subjecting phosphatidylcholine liposomes to iron ascorbate-induced peroxidation, or those present in aged liposomes, were effectively reduced by glutathione peroxidase when phospholipase A2 was present in the assay. Low level glutathione peroxidase activity was observed in the absence of phospholipase A2.
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10.1016/0003-9861(83)90608-2
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pubmed_940_1361
|
Patients with successfully repaired coarctation of the aorta have impaired distensibility. Age at surgery as well as left ventricular mass index are factors that are related to the distensibility index.
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10.1016/s0002-9149(98)00575-x
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pubmed_1090_9196
|
Surgical therapy of the main bile duct is an important aspect of liver disease. The authors examine the advisability of using a Kehr drain in benign and malignant disease of the main bile duct, and draw the conclusion that, with precise indications, this technique still has an important role to play in the resolution of biliary tract disease.
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pubmed_1090_9196
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pubmed_169_4562
|
Human group O rhesus negative erythrocytes were spherocyted and fixed in glutaraldehyde, then coated initially with HBsAg and subsequently with anti-HBs. The resulting reagent was found to agglutinate in the presence of HBsAg positive serum, but not in HBsAg negative serum. The assay was evaluated for blood donor screening (39,962 donations) over a 6-month period, and was compared with Hepatest (RPHA) and AUSRIA-2 (RIA) for the study of two established HBsAg panels.
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10.1016/0022-1759(78)90242-9
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pubmed_159_19469
|
Magnon-phonon hybrid excitations are studied theoretically in a two-dimensional antiferromagnet with an easy axis normal to the plane. We show that two magnon bands and one phonon band are intertwined by the magnetoelastic coupling through a nontrivial SU(3) topology, which can be intuitively perceived by identifying a skyrmion structure in the momentum space. Our results are insensitive to lattice details and generally applicable to two-dimensional antiferromagnets. We show this by developing a continuum theory as the long-wavelength approximation to the tight-binding model. The theoretical results can be probed by measuring the thermal Hall conductance as a function of the temperature and the magnetic field. We envision that the magnetoelastic coupling in antiferromagnets can be a promising venue in search of various topological excitations, which cannot be found in magnetic or elastic models alone.
|
10.1103/PhysRevLett.124.147204
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pubmed_798_12763
|
PURPOSE
The aim of this study was to evaluate the usefulness of imaging for correct clinical and therapeutic management of patients with scrotal disease.
MATERIALS AND METHODS
Between 2000 and 2007, 801 patients with suspected scrotal disease underwent colour Doppler ultrasonography (CDUS) at our centre. In 46 patients, the CDUS study was followed by magnetic resonance imaging (MRI).
RESULTS
CDUS revealed an inflammatory process in 277 patients (34.58%), testicular trauma in 112 (13.9%), funicular torsion or torsion of the vestigial remnant in 44 (5.4%), findings suggestive of testicular neoplasm in 35 (4.3%) and no abnormality in 41.5%. MRI, used to further investigate the CDUS findings in 46 cases, showed three cases of intraparenchymal haematoma, one of intrascrotal cavernous body rupture, one of testicular abscess with intrascrotal fistula, two of testicular infarction and 15 of neoplasm. MRI allowed the exclusion of focal abnormalities in ten patients with testicular microlithiasis, in three with chronic orchitis and in four with atrophic involution. MRI confirmed the finding of inguinal hernia in three cases.
CONCLUSIONS
On the basis of our experience, CDUS is irreplaceable as an initial approach to patients affected by scrotal disease, whereas MRI is an ideal second-line investigation. MRI offers useful, and in some cases decisive, information, as it is capable of revealing unexpected findings and elucidating complex aspects. MRI helps improve patient management, with an overall reduction in costs.
|
10.1007/s11547-009-0377-7
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pubmed_192_16289
|
Enterotoxigenic Bacteroides fragilis (ETBF) is a Gram-negative, obligate anaerobe member of the gut microbial community in up to 40% of healthy individuals. This bacterium is found more frequently in people with colorectal cancer (CRC) and causes tumor formation in the distal colon of multiple intestinal neoplasia (Apc ) mice; tumor formation is dependent on ETBF-secreted Bacteroides fragilis toxin (BFT). Because of the extensive data connecting alterations in the epigenome with tumor formation, initial experiments attempting to connect BFT-induced tumor formation with methylation in colon epithelial cells (CECs) have been performed, but the effect of BFT on other epigenetic processes, such as chromatin structure, remains unexplored. Here, the changes in gene expression (transcriptome sequencing [RNA-seq]) and chromatin accessibility (assay for transposase-accessible chromatin using sequencing) induced by treatment of HT29/C1 cells with BFT for 24 and 48 h were examined. Our data show that several genes are differentially expressed after BFT treatment and that these changes relate to the interaction between bacteria and CECs. Further, sites of increased chromatin accessibility are associated with the location of enhancers in CECs and the binding sites of transcription factors in the AP-1/ATF family; they are also enriched for common differentially methylated regions (DMRs) in CRC. These data provide insight into the mechanisms by which BFT induces tumor formation and lay the groundwork for future in vivo studies to explore the impact of BFT on nuclear structure and function.
|
10.1128/IAI.00447-18
|
pubmed_637_5654
|
BACKGROUND
Three-dimensional (3D) transthoracic echocardiography (TTE) is superior to two-dimensional Simpson's method for assessment of left ventricular (LV) volumes and LV ejection fraction (LVEF). Nevertheless, 3D TTE is not incorporated into everyday practice, as current LV chamber quantification software products are time-consuming.
AIMS
To evaluate the feasibility, accuracy and reproducibility of new fully automated fast 3D TTE software (HeartModelA.I.; Philips Healthcare, Andover, MA, USA) for quantification of LV volumes and LVEF in routine practice; to compare the 3D LV volumes and LVEF obtained with a cardiac magnetic resonance (CMR) reference; and to optimize automated default border settings with CMR as reference.
METHODS
Sixty-three consecutive patients, who had comprehensive 3D TTE and CMR examinations within 24hours, were eligible for inclusion. Nine patients (14%) were excluded because of insufficient echogenicity in the 3D TTE. Thus, 54 patients (40 men; mean age 63±13 years) were prospectively included into the study.
RESULTS
The inter- and intraobserver reproducibilities of 3D TTE were excellent (coefficient of variation<10%) for end-diastolic volume (EDV), end-systolic volume (ESV) and LVEF. Despite a slight underestimation of EDV using 3D TTE compared with CMR (bias=-22±34mL; P<0.0001), a significant correlation was found between the two measurements (r=0.93; P=0.0001). Enlarging default border detection settings leads to frequent volume overestimation in the general population, but improved agreement with CMR in patients with LVEF≤50%. Correlations between 3D TTE and CMR for ESV and LVEF were excellent (r=0.93 and r=0.91, respectively; P<0.0001).
CONCLUSION
3D TTE using new-generation fully automated software is a feasible, fast, reproducible and accurate imaging modality for LV volumetric quantification in routine practice. Optimization of border detection settings may increase agreement with CMR for EDV assessment in dilated ventricles.
|
10.1016/j.acvd.2016.12.015
|
pubmed_994_7913
|
Newborn screening describes various tests that can occur during the first few hours or days of a newborn's life and have the potential for preventing severe health problems, including death. Newborn screening has evolved from a simple blood or urine screening test to a more comprehensive and complex screening system capable of detecting over 50 different conditions. While a number of papers have described various newborn screening activities around the world, including a series of papers in 2007, a comprehensive review of ongoing activities since that time has not been published. In this report, we divide the world into 5 regions (North America, Europe, Middle East and North Africa, Latin America, and Asia Pacific), assessing the current NBS situation in each region and reviewing activities that have taken place in recent years. We have also provided an extensive reference listing and summary of NBS and health data in tabular form.
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pubmed_994_7913
|
pubmed_722_18349
|
BACKGROUND
Ro ribonucleoprotein particles (Ro RNPs) consist of a non-coding Y RNA bound by Ro60, La and possibly other proteins. The physiological function of Ro RNPs is controversial as divergent functions have been reported for its different constituents. We have recently shown that Y RNAs are essential for the initiation of mammalian chromosomal DNA replication, whereas Ro RNPs are implicated in RNA stability and RNA quality control. Therefore, we investigate here the functional consequences of RNP formation between Ro60, La and nucleolin proteins with hY RNAs for human chromosomal DNA replication.
METHODOLOGY/PRINCIPAL FINDINGS
We first immunoprecipitated Ro60, La and nucleolin together with associated hY RNAs from HeLa cytosolic cell extract, and analysed the protein and RNA compositions of these precipitated RNPs by Western blotting and quantitative RT-PCR. We found that Y RNAs exist in several RNP complexes. One RNP comprises Ro60, La and hY RNA, and a different RNP comprises nucleolin and hY RNA. In addition about 50% of the Y RNAs in the extract are present outside of these two RNPs. Next, we immunodepleted these RNP complexes from the cytosolic extract and tested the ability of the depleted extracts to reconstitute DNA replication in a human cell-free system. We found that depletion of these RNP complexes from the cytosolic extract does not inhibit DNA replication in vitro. Finally, we tested if an excess of recombinant pure Ro or La protein inhibits Y RNA-dependent DNA replication in this cell-free system. We found that Ro60 and La proteins do not inhibit DNA replication in vitro.
CONCLUSIONS/SIGNIFICANCE
We conclude that RNPs containing hY RNAs and Ro60, La or nucleolin are not required for the function of hY RNAs in chromosomal DNA replication in a human cell-free system, which can be mediated by Y RNAs outside of these RNPs. These data suggest that Y RNAs can support different cellular functions depending on associated proteins.
|
10.1371/journal.pone.0013673
|
pubmed_894_6972
|
A type I DNA topoisomerase has been isolated from the nuclei of the flagellate Trypanosoma cruzi, using poly(ethylene glycol) fractionation and chromatography on hydroxyapatite and on phosphocellulose. The relaxation activity was ATP-independent, enhanced by Mg2+ and spermidine. The enzyme removed supercoils from negative and positive superhelical DNAs. Topoisomerase activity was associated with a polypeptide of Mr about 65000 as shown by glycerol gradient centrifugation and by electrophoresis on sodium dodecyl sulfate/polyacrylamide gels.
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10.1111/j.1432-1033.1983.tb07592.x
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pubmed_484_20448
|
In this brief diagnostic description of medical education in Mexico, we present the origin and first 10 years of the Program that arose from the agreement for collaboration of the National Academy of Medicine of Mexico and the National Autonomous University of Mexico for development of the general physician. By comparing elements used in the national survey of continuous medical education with that of the Program, we are able to obtain the level achieved through positioning, academic administrative organization, and national coverage. With regard to the characteristics of the Program, evaluation of learning is detailed. We conclude with the observation that the second decide of the Program should be total institutionalization.
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pubmed_484_20448
|
pubmed_855_9013
|
We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site randomized control study. In this program, a nurse under physician supervision monitors the patient's airway status at home and provides instructions to individuals via the telephone, helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan. Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and randomly assigned to either the telemedicine or control group. After a six-month study period, an 83% reduction in hospitalization was demonstrated in the telemedicine group versus the control group, with a P value of 0.01. Improvement of peak expiratory flow and symptoms were also shown in the study group. We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring, compliance with prescribed daily prophylactic anti-inflammatory steroid medications, and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration.
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pubmed_855_9013
|
pubmed_506_8815
|
Connexin (Cx) 37 suppresses vascular and cancer cell proliferation. The C terminus and a channel able to function are necessary, and neither by itself is sufficient, for Cx37 to mediate growth suppression. Cx37 supports transmembrane and intercellular signaling by forming functional hemichannels (HCs) and gap junction channels (GJCs), respectively. Here we determined whether Cx37 with HC, but not GJC, functionality would suppress proliferation of rat insulinoma (Rin) cells comparably to wild-type Cx37 (Cx37-WT). We mutated extracellular loop residues hypothesized to compromise HC docking but not HC function (six cysteines mutated to alanine, C54A,C61A,C65A, C187A,C192A,C198A (designated as C6A); N55I; and Q58L). All three mutants trafficked to the plasma membrane and formed protein plaques comparably to Cx37-WT. None of the mutants formed functional GJCs, and Cx37-C6A did not form functional HCs. Cx37-N55I and -Q58L formed HCs with behavior and permeation properties similar to Cx37-WT (especially Q58L), but none of the mutants suppressed Rin cell proliferation. The data indicate that determinants of Cx37 HC function differ from other Cxs and that HC functions with associated HC-supported protein-protein interactions are not sufficient for Cx37 to suppress Rin cell proliferation. Together with previously published data, these results suggest that Cx37 suppresses Rin cell proliferation only when in a specific conformation achieved by interaction of the C terminus with a Cx37 pore-forming domain able to open as a GJC.
|
10.1074/jbc.M114.583054
|
pubmed_86_3732
|
Cardiac self-perception was measured in obese and normal weight subjects. Subjects had to judge whether a tone was coincident with their own heartbeat or slightly mismatched. A signal-detection analysis was used to measure sensory sensitivity to the heartbeat separate from nonsensory, response-bias factors. Subjects were able to perform the heartbeat-detection task, with an average sensory sensitivity d' of .58. No significant differences in sensory sensitivity were found between obese and normal-weight subjects, nor were any sex differences noted. Measurement of response bias (Ln beta) indicated that obese subjects had a significantly more lax response criterion than normal-weight subjects. Results are discussed in terms of Schachter's (1971) internality-externality theory of obesity and ramifications for weight control are discussed.
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pubmed_86_3732
|
pubmed_403_24276
|
This Editorial analyzes the manuscripts accepted, after a careful peer-reviewed process, for the Special Issue "Applications in Electronics Pervading Industry, Environment and Society-Sensing Systems and Pervasive Intelligence" of the Sensors MDPI journal [...].
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10.3390/s20247295
|
pubmed_759_5709
|
According to a succession of samples taken at Ihotry, Madagascar, Lygodactylus tuberifer, a very rare gecko in the biotope sampled for Lygodactylus verticillatus in 1965, invaded the latter's habitat until its population reached, in the sampled biotope and using the L. verticillatus population as a gauge, an almost 700-fold increase by the end of 1972. Population growth then stopped abruptly, and a steep crash brought L. tuberifer down to 31 times less individuals within six months, whereupon sampling was discontinued.
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pubmed_759_5709
|
pubmed_689_12291
|
Peripheral artery disease (PAD) is a progressive atherosclerotic disease that negatively affects individuals' functional status and health-related quality of life (HRQOL). This study aimed to investigate the HRQOL and associated factors in patients with PAD in Korea. We conducted a cross-sectional study using self-administered questionnaires in a tertiary hospital in Seoul. We measured HRQOL using the EuroQol-5 dimensions-5 levels (EQ-5D-5L) questionnaire and the functional status using a PAD-specific walking impairment questionnaire. We also measured health behavior, social support, walking impairment, general health perceptions, and clinical characteristics; lastly, we performed a descriptive analysis and multiple linear regression analysis. Participants of this study comprised 138 patients (mean age 69.04 ± 10.94 years; men 91.3%). The mean EQ-5D-5L utility score was 0.81 ± 0.17. The patients' HRQOL was significantly associated with claudication pain (β = -0.188, p = 0.012), walking distance (β = 0.371, p < 0.001), and stair climbing (β = 0.315, p = 0.001). The regression model predicted 60.4% of patients' HRQOL (F = 15.92, p < 0.001). Our study showed that less severe claudication pain and a low degree of difficulty in walking distance and stair climbing were significantly related to better HRQOL. To enhance patients' HRQOL, health professionals should focus on managing symptoms and improving functional status.
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10.3390/ijerph182010941
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pubmed_483_7407
|
Background and aims: Mice orally infected with T. gondii develop Crohn's disease (CD)-like enteritis associated with severe mucosal damage and a systemic inflammatory response, resulting in high morbidity and mortality. Previously, helminthic infections have shown therapeutic potential in experimental colitis. However, the role of S. mansoni in T. gondii-induced CD-like enteritis has not been elucidated. Our study investigated the mechanisms underlying T. gondii-induced ileitis and the potential therapeutic effect of S. mansoni coinfection. Methods: C57BL/6 mice were infected by subcutaneous injection of cercariae of the BH strain of S. mansoni, and 7-9 weeks later, they were orally infected with cysts of the ME49 strain of T. gondii. After euthanasia, the ileum was removed for histopathological analysis; staining for goblet cells; immunohistochemistry characterizing mononuclear cells, lysozyme expression, apoptotic cells, and intracellular pathway activation; and measuring gene expression levels by real-time PCR. Cytokine concentrations were measured in the serial serum samples and culture supernatants of the ileal explants, in addition to myeloperoxidase (MPO) activity. Results:T. gondii-monoinfected mice presented dense inflammatory cell infiltrates and ulcerations in the terminal ileum, with abundant cell extrusion, apoptotic bodies, and necrosis; these effects were absent in S. mansoni-infected or coinfected animals. Coinfection preserved goblet cells and Paneth cells, remarkably depleted in T. gondii-infected mice. Densities of CD4- and CD11b-positive cells were increased in T. gondii- compared to S. mansoni-infected mice and controls. MPO was significantly increased among T. gondii-mice, while attenuated in coinfected animals. In T. gondii-infected mice, the culture supernatants of the explants showed increased concentrations of TNF-alpha, IFN-gamma, and IL-17, and the ileal tissue revealed increased expression of the mRNA transcripts for IL-1 beta, NOS2, HMOX1, MMP3, and MMP9 and activation of NF-kappa B and p38 MAPK signaling, all of which were counterregulated by S. mansoni coinfection. Conclusion:S. mansoni coinfection attenuates T. gondii-induced ileitis by preserving mucosal integrity and downregulating the local inflammatory response based on the activation of NF-kappa B and MAPK. The protective function of prior S. mansoni infection suggests the involvement of innate immune mechanisms and supports a conceptually new approach to the treatment of chronic inflammatory diseases, including CD.
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10.3389/fimmu.2019.00442
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pubmed_637_19755
|
BACKGROUND
Reducing health care costs while improving quality of care has become imperative in neurosurgical care. The Value-Driven Outcome database at the University of Utah identifies cost drivers and tracks changes over time.
METHODS
Retrospective review was performed for transsphenoidal resections of pituitary adenomas from July 2012 to September 2016. Total cost, subcategory costs, and potential cost drivers were evaluated.
RESULTS
There were 272 patients (mean age 51.5 years ± 17.7, 45.6% male) with mean length of stay of 4 days ± 4 evaluated. Total costs included facility utilization (60%), physician professional fees (16%), pharmacy (11%), supplies and implants (7%), laboratory studies (5%), and imaging (1%). Facility costs were driven by neurocritical care unit (30.7%), neurosurgical operating room (16.6%), and neurosurgical floor (11.2%) costs. Multivariable linear regression, after adjusting for length of stay and American Society of Anesthesiologists grade, showed that overall cost was heavily influenced by facility utilization (ρ = 0.98, P = 0.001), pharmacy (ρ = 0.71, P = 0.001), supplies and implants (ρ = 0.51, P = 0.0001), imaging (ρ = 0.51, P = 0.0001), and laboratory (ρ = 0.79, P = 0.001) costs. The top 10 outlier patients accounted for 18.7% of total costs (mean cost for all patients 0.24% ± 0.29).
CONCLUSIONS
Our results highlight the importance of facility utilization and pharmaceutical, supply/implant, imaging, and laboratory costs as overall cost drivers during transsphenoidal pituitary tumor resection. Facility utilization was a stronger cost driver than any other aspect of care. Strategies to mitigate cost include stratifying low-risk patients to an intermediate care unit and reducing length of stay.
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10.1016/j.wneu.2017.05.148
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pubmed_663_11997
|
Anti-VEGF drugs may be employed in the surgical treatment of diabetic retinopathy: 1. Prior to surgery. The intravitreal injection of anti-VEGF drugs leads to a significant reduction of neovascularization, with a reduction in the adherence of the fibrovascular complex to the retina. This simplifies viscodelamination and reduces intraoperative bleeding during delamination and segmentation. To minimize the risk of tractional retinal detachment due to the contraction of fibrovascular tissue, vitrectomy must be performed within one week after the injection. 2. To decrease the risk of postoperative bleeding. Recurrent vitreous hemorrhages after vitrectomy are often due to small bleeding from persistent neovascularization. The injection of anti-VEGF drugs at the end of vitrectomy could prevent bleeding from these vessels by blocking the pro-inflammatory stimulus of the surgical procedure. 3. To treat postoperative vitreous hemorrhage. The intravitreal injection of anti-VEGF drugs in patients with postoperative bleeding leads to resolution of the hemorrhage. 4. To treat rubeosis iridis. In eyes with complete panretinal photocoagulation, the combination of cryotherapy and intravitreal anti-VEGF injection in the same surgical procedure produces a disappearance of iris neovascularization together with a long term effect with no recurrences. In neovascular glaucoma, anti-VEGF drugs can also facilitate filtrating surgery.
|
10.2174/157339909787314202
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pubmed_781_11027
|
AIM
Our aim is to investigate the impact of high fat diet-induced obesity on plasma concentrations of the toxic irinotecan metabolite, SN-38, in mice.
MAIN METHODS
Diet-induced obese (DIO, 60% kcal fed) and lean mice (10% kcal fed) were treated orally with a single dose of 10mg/kg irinotecan to determine pharmacokinetic (PK) parameters. Feces and livers were collected for quantification of irinotecan and its metabolites (SN-38 & SN-38G). SN-38G formation by Ugt1a1 enzyme was analyzed in liver S9 fractions. Expression of the pro-inflammatory cytokine, TNF-α was determined in liver and plasma. Hepatic β-glucuronidase and carboxylesterase enzymes (CES) were also determined.
KEY FINDINGS
AUC0-8 and Cmax of SN-38 increased by 2-fold in DIO mice compared to their lean controls. This was accompanied by a~2-fold reduction in AUC0-8 and Cmax of SN-38G in DIO mice. There were no differences in the PK parameters of irinotecan in DIO or lean mice. Conversion of SN-38 to SN-38G by Ugt1a1 enzyme was reduced by ~2-fold in liver S9 fractions in DIO mice. Furthermore, in DIO mice, β-glucuronidase activity increased by 2-fold, whereas there was no change in CES activity. TNF-α mRNA expression was 3 fold higher in DIO mice.
SIGNIFICANCE
Our study demonstrates that reduced hepatic Ugt1a activity during obesity likely contributes to reduced glucuronidation, and results in higher levels of the toxic metabolite, SN-38. Thus, irinotecan dosage should be closely monitored for effective and safe chemotherapy in obese cancer patients who are at a higher risk of developing liver toxicity.
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pubmed_781_11027
|
pubmed_800_18051
|
The article is a review of the published foreign literature concerning mechanisms of self-defence of the renal glomerulus and ways for drug correction thereof. The glomerulus self-defence intra- and extracell factors are described in detail. Novel drugs having been approbated in the experiment and in clinical settings intended to slow down the rate of progression of affections of the kidneys are mentioned together with ways for prevention thereof.
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pubmed_800_18051
|
pubmed_892_16224
|
BACKGROUND
Aprotinin has recently been approved for clinical use in cardiopulmonary bypass. Although unfractionated heparin has been the only anticoagulant widely used for cardiopulmonary bypass, disadvantages involving heparin have led to ongoing investigations of alternative anticoagulant agents.
METHODS
The objective of this study was to evaluate the efficacy of aprotinin in combination with other anticoagulant agents, specifically low molecular weight heparin and recombinant hirudin, using a dog model of cardiopulmonary bypass.
RESULTS
The blood conservation resulting from the use of aprotinin was observed only with unfractionated heparin. Efficacy of anticoagulation as measured by protein deposits in the bypass circuit filter revealed an unexpected reduction in the quantity of deposits when aprotinin was used in combination with low molecular weight heparin.
CONCLUSIONS
As alternative anticoagulant agents are sought, the potential benefits of aprotinin in the reduction of operative blood loss must be evaluated independently for each anticoagulant agent.
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pubmed_892_16224
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pubmed_36_20656
|
Three years have passed since the earthquake, in the coastal areas in the disaster area, by population transfer or the like from the temporary housing, the importance of the regeneration and revitalization of the local community has been pointed out. This study performed a preliminary study to aim at the psychological inspection about an effect of the horticultural therapy as the means of the local community reproduction support of the disaster area. Forty five women who are living in the coastal area of Miyagi Prefecture participated in this study. They experienced the Great East Japan earthquake in 2011 and suffered some kind of damage caused by the earthquake. The participants were assigned to two groups, the intervention group and the control group, via a random draw using a computer. The HI group attended the horticultural therapy intervention (HT intervention) sessions for 16 weeks. The HT intervention was designed in collaboration with a horticultural therapist and clinical psychologists. This intervention comprised a total of 16 weekly sessions (120 min each) at the community center and 15 minutes per day at participants' homes. We used five psychological measures for an intervention evaluation. The HI group showed a significant increase in post- intervention SCI-2 total scores, post- intervention SCI-2 membership scores, post-intervention SCI-2 influence scores, post- intervention SCI-2 meeting needs scores, post- intervention SCI-2 shared emotional connection scores, and post- intervention RSES score. We believe that these results suggest the effectiveness of the horticultural therapy as the means of the local community reproduction.
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pubmed_36_20656
|
pubmed_495_20854
|
Eighty patients, referred for further evaluation of prominent iris lesions, were examined with conventional B-mode ultrasound equipment combined with a simplified immersion technique. The axial resolution of this system is about 350 microns. In 20.3% of the cases, the lesion was too small for ultrasound detection. A cystic lesion was diagnosed in 26% and a solid lesion in 53.7% of the patients studied. In 33.4% of the cases, the lesions were not confined to the iris but also appeared in the ciliary body. This last result shows the diagnostic value of the conventional ultrasound examination in the evaluation apparent iris lesions.
|
10.1007/BF01203293
|
pubmed_890_25110
|
Urinary sediment is used to evaluate patients with possible urinary tract diseases. Currently, numerous protocols are applied to detect dysmorphic red blood cells (RBCs) and renal tubular epithelial cells (RTECs) in urinary sediment. However, distinct protocols are used by nephrologists and medical technologists for specimen concentration and observation, which leads to major discrepancies in the differential counts of formed elements such as dysmorphic RBCs and RTECs and might interfere with an accurate clinical diagnosis. To resolve these problems, we first tested a modified urinalysis protocol with an increased relative centrifuge force and concentration factor in 20 biopsy-confirmed glomerulonephritis patients with haematuria. We successfully improved the recovery ratio of dysmorphic RBCs in clinical specimens from 34.7% to 42.0% (P < 0.001). Furthermore, we confirmed the correlation between counts by the modified urinary protocol and Sysmex UF-1000i urinary flow cytometer (r ≥ 0.898, P < 0.001). A total of 28 types of isomorphic and dysmorphic RBCs were detected using a bright field microscope, with results comparable to those using a standard phase contrast microscope. Finally, we applied Sternheimer stain to enhance the contrast of RTECs in the urinary sediments. We concluded that this modified urinalysis protocol significantly enhanced the quality of urinalysis.
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10.1038/srep40521
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pubmed_1077_3456
|
An experimental study in a semi-controlled environment was conducted to examine whether school density in wild-caught Atlantic herring Clupea harengus affects the strength of their collective escape behaviours. Using acoustics, the anti-predator diving responses of C. harengus in two schools that differed in density were quantified by exposing them to a simulated threat. Due to logistical restrictions, the first fish was tested in a low-density school condition (four trials; packing density = 1.5 fish m(-3); c. 6000 fish) followed by fish in a high-density school condition (five trials; packing density = 16 fish m(-3); c. 60 000 fish). The C. harengus in a high-density school exhibited stronger collective diving avoidance responses to the simulated predators than fish in the lower-density school. The findings suggest that the density (and thus the internal organization) of a fish school affects the strength of collective anti-predatory responses, and the extent to which information about predation risk is transferred through the C. harengus school. Therefore, the results challenge the common notion that information transfer within animal groups may not depend on group size and density.
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10.1111/jfb.12520
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pubmed_787_5164
|
DM (myotonic dystrophy) is a dominantly inherited genetic disorder that is the most common cause of muscular dystrophy in adults affecting 1 in 8500 individuals worldwide. Different microsatellite expansions in two loci cause different forms of the disease that share similar features: DM1 (DM type 1) is caused by a tri- (CTG) nucleotide expansion within the DMPK (dystrophia myotonica protein kinase) 3'-untranslated region and DM2 (DM type 2) is caused by a tetra- (CCTG) nucleotide expansion within intron 1 of the ZNF9 (zinc finger 9) gene. The pathogenic mechanism of this disease involves the RNA transcribed from the expanded allele containing long tracts of (CUG)(n) or (CCUG)(n). The RNA results in a toxic effect through two RNA-binding proteins: MBNL1 (muscleblind-like 1) and CUGBP1 (CUG-binding protein 1). In DM1, MBNL1 is sequestered on CUG repeat-containing RNA resulting in its loss-of-function, while CUGBP1 is up-regulated through a signalling pathway. The downstream effects include disrupted regulation of alternative splicing, mRNA translation and mRNA stability, which contribute to the multiple features of DM1. This review will focus on the RNA gain-of-function disease mechanism, the important roles of MBNL1 and CUGBP1 in DM1, and the relevance to other RNA dominant disorders.
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10.1042/BST0371281
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pubmed_1_3005
|
Novel wide-bandgap semiconducting polymers are designed and synthesized for multijunction polymer solar cell (PSC) applications. In single-junction PSCs, BDT-FBT-2T exhibits efficiencies exceeding 6.5% for active layer thicknesses between 90 and 250 nm, with the highest efficiency of 7.7% at 100 and 250 nm. This enables tandem PSCs to be created with an efficiency of 8.9%.
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10.1002/adma.201501626
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pubmed_1042_5901
|
The experience of one surgeon (R.H.) with intraoperative frozen sections (FS) performed on thyroid nodules over a 10-year period was studied to assess the utility of FS in follicular thyroid lesions. One hundred and ten patients with dominant or solitary nodules demonstrating a follicular growth pattern were evaluated. The FS slides and subsequently the permanent sections of the nodules were reviewed by the pathologists in the study (M.P.B., VAL.) without knowledge of the original diagnoses. Our results indicate: (1) if the FS was definitively benign (58 patients), the final diagnosis was benign [these lesions consisted of adenomatous nodule, nodular goiter, follicular adenoma, and Hürthle cell adenoma); (2) if an FS diagnosis of malignancy was rendered (4 patients), it was confirmed on permanent sections (follicular variant of papillary carcinoma in all 4); and (3) if the FS diagnosis was deferred (48 patients), the final diagnosis was benign in all but 10 (21 %) (of these 10, 6 had minimally invasive follicular carcinoma [2 of the Hürthle cell type], and 4 had follicular variants of papillary carcinoma). Overall, sensitivity, specificity, and accuracy rates for FS diagnoses were 29, 100, and 91%. Because unilateral lobectomy may be acceptable therapy for well-differentiated thyroid cancers, and because the efficiency of FS evaluation in diagnosing malignancy is low (only 4 malignancies of 110 total patients were diagnosed at FS, or 3.6% overall), we conclude that in this era of cost-containment, FS is not useful in the evaluation of follicular thyroid nodules identified preoperatively as follicular lesions by fine-needle aspiration cytology. Several recommendations concerning the 3 categories of FS diagnosis (i.e., definitively benign, definitively malignant-especially the follicular variant of papillary carcinoma-and deferred) are also put forward.
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10.1007/BF02921471
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pubmed_1138_18402
|
The mode of action of carbachol in stimulation of transepithelial Cl- secretion in intact human intestinal T84 epithelial monolayers has been investigated in order to determine whether a DIDS-insensitive exit pathway (via CFTR) coexists with a DIDS-sensitive exit pathway at the apical membrane. Carbachol stimulates a transient inward Isc due to Cl- secretion whose magnitude is related to the basal level of inward Isc. The inward current responses to both carbachol and hypo-osmotic media are abolished in nominally Ca(2+)-free media. The action of apical DIDS (100 microM) upon carbachol-stimulated Isc depends on the initial value of the basal Isc. At basal Isc levels < 10 microA cm-2, 100 microM DIDS applied to the apical cell border abolishes the inward Isc following exposure to both carbachol and hypo-osmotic media. In contrast a VIP-stimulated inward Isc is observed in the presence of 100 microM DIDS. After VIP stimulation of inward Isc, or if spontaneous basal values of Isc were > 10 microA cm-2, the carbachol stimulation of inward Isc was largely insensitive to 100 microM DIDS. The data are consistent with the participation of both DIDS-sensitive and DIDS insensitive pathways for Cl- at the apical membrane of human intestinal T84 epithelial cells.
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10.1016/0167-4889(94)90144-9
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pubmed_605_10825
|
We study the rheology of a soft particulate system where the interparticle interactions are weakly attractive. Using extensive molecular dynamics simulations, we scan across a wide range of packing fractions (ϕ), attraction strengths (u), and imposed shear rates (γ[over ̇]). In striking contrast to repulsive systems, we find that at small shear rates generically a fragile isostatic solid is formed even if we go to ϕ≪ϕ_{J}. Further, with increasing shear rates, even at these low ϕ, nonmonotonic flow curves occur which lead to the formation of persistent shear bands in large enough systems. By tuning the damping parameter, we also show that inertia plays an important role in this process. Furthermore, we observe enhanced particle dynamics in the attraction-dominated regime as well as a pronounced anisotropy of velocity and diffusion constant, which we take as precursors to the formation of shear bands. At low enough ϕ, we also observe structural changes via the interplay of low shear rates and attraction with the formation of microclusters and voids. Finally, we characterize the properties of the emergent shear bands, and thereby, we find surprisingly small mobility of these bands, leading to prohibitively long time scales and extensive history effects in ramping experiments.
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10.1103/PhysRevE.94.052608
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pubmed_894_7331
|
Michigan dairy herds with continuous Dairy Herd Improvement Association records 1969 to 1978 were identified. Herds that were exposed to polybrominated biphenyl in 1974 at concentrations generally not causing residues in tissue or milk fat greater than .3 microgram/g were compared with control herds of comparable size, breed, and location. Analysis of covariance with herd size as a covariable was used to compare measures of herd performance between groups. Relationships of exposure to response within the exposed group were evaluated by multiple regression of the measures on the mean logarithmic concentration of polybrominated biphenyl in tissue with herd size as a second independent variable. Herd size, milk production, and fat production were greater and age was less in exposed herds. Lack of interactions of year by group indicated that all differences predated exposure. Regressions of these characteristics on exposure within years were not significant. Data on other measures were available only for 1976 to 1978. Percent culls, number of culls, and number of new cows were greater for exposed than control herds, but regressions of these characteristics on exposure were negative in some years. Calving intervals were shorter for exposed herds than for control herds, but regressions on exposure were not consistent.
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10.3168/jds.S0022-0302(83)81939-0
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pubmed_301_13580
|
The results of studies on the effect of pineal indole hormone melatonin on the life span of mice, rats, fruit flies, and worms are critically reviewed. In mice, long-term administration of melatonin was followed by an increase in their life span in 12 experiments and had no effect in 8 of 20 different experiments. In D. melanogaster, the supplementation of melatonin to the nutrient medium during developmental stages gave contradictory results, but when melatonin was added to food throughout the life span, an increase in the longevity of fruit flies has been observed. Melatonin decreased the survival of C. elegans but increased the clonal life span of planaria Paramecium tertaurelia. Available data suggest antioxidant and atherogenic effects of melatonin. Melatonin alone turned out to be neither toxic nor mutagenic in the Ames test and revealed clastogenic activity in high concentration in the COMET assay. Melatonin inhibits mutagenesis induced by irradiation and by indirect chemical mutagens and inhibits the development of spontaneous and chemical-induced tumors in mice and rats. Further studies and clinical trials are needed to verify that melatonin is both safe and has geroprotector efficacy for humans.
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10.1080/01926230390257885
|
pubmed_247_4762
|
The hemidesmosome is the major attachment structure of the epidermal basal cell visible ultrastructurally in skin. The importance of its components to cultured cell attachment to substratum is not understood, however. A component of the hemidesmosome, the 230-kDa bullous pemphigoid antigen (p230), has been shown to be present in an insoluble or particulate fraction of cultured cells. In order to more fully characterize its potential importance for cell-matrix adhesion in cultured keratinocytes, specific antibodies were raised to the C-terminal region of p230 expressed as a bacterial fusion protein. Such antibodies recognize the hemidesmosome of epidermis, binding on the cytoplasmic region of its plaque. In addition, keratinocytes cultured in a 0.15 mM Ca(2+)-defined medium contain a detergent-resistant pool of p230 which appears to lie in the same focal plane as the culture substrate and has a patchy or irregular distribution by indirect immunofluorescence. Treatment of cultured cells at 4 degrees C with trypsin or pronase sufficient to release keratinocytes from the culture dish does not affect the electrophoretic migration of p230 on SDS-gels, suggesting that p230 is not exposed to the extracellular space. In cells cultured in 0.15 mM Ca2+, 230-kDa BP antigen is localized to discrete clusters resting near the basal plasma membrane of the cell by immunogold staining following brief detergent treatment and fixation. These clusters are approximately 0.1 micron in diameter, which is similar in size to the in vivo hemidesmosome. Fully formed electron dense hemidesmosomal plaques are not observed under the same culture conditions, however. It appears that these clusters are early precursors of the hemidesmosome.
|
10.1016/0014-4827(91)90360-7
|
pubmed_196_14115
|
The programmed cell death ligand-1 antibody, atezolizumab, is an immune checkpoint inhibitor approved for the treatment of various cancers. Herein, we describe a case of an 87-year-old man with advanced urothelial carcinoma. After surgery, atezolizumab was given. Subsequently, he developed generalized myasthenia gravis (MG) with elevated creatinine kinase and positive anti-striated muscle antibody. Although intravenous immunoglobulin was started, the patient developed cardiac arrhythmia and arrest. Our case not only reported MG as an immune-related adverse event of atezolizumab but also emphasized the significance of the programmed cell death-1 pathway in the pathogenesis of MG.
|
10.7759/cureus.5002
|
pubmed_238_17798
|
BACKGROUND
Invasion of the intestinal mucosa by T. gondii elicits a local immune response of variable intensity. These reactions can be lethal in C57BL/6 mice. The tissue damage caused by inflammation and the functional effects depend on the host immunity, strain, and developmental form of the parasite. We investigated the effects of acute oral infection with T. gondii on histoarchitecture, enteric nervous system (ENS), and inflammatory markers in the jejunum and ileum of mice.
METHODS
Female C57BL/6 mice were divided into a control group and a group orally infected with 1000 sporulated T. gondii oocysts (ME-49 strain). After 5 days, jejunum and ileum were collected and processed for analyzes (e.g., histological and histopathological examinations, ENS, cytokine dosage, myeloperoxidase, nitric oxide activity).
MAIN RESULTS
In infected mice, we observed a significant increase in serotonin-immunoreactive cells (5-HT IR) in the intestinal mucosa, as well as cellular infiltrates in the lamina propria, periganglionitis, and ganglionitis in the myenteric plexus. We also noted decreased neuron density in the jejunum, increased population of enteric glial cells in the ileum, histomorphometric changes in the intestinal wall, villi, and epithelial cells, remodeling of collagen fibers, and increased myeloperoxidase activity, cytokines, and nitric oxide in the intestine.
CONCLUSIONS AND INFERENCES
Acute infection of female mice with T. gondii oocysts resulted in changes in ENS and a marked increase in 5-HT. These changes are consistent with its modulatory role in the development of moderate acute inflammation. The use of this experimental model may lend itself to studies aimed at understanding the pathophysiological mechanisms of intestinal inflammation in humans involving ENS.
|
10.1016/j.lfs.2022.120985
|
pubmed_648_22788
|
BACKGROUND
Investigating effects of whole diets on blood pressure (BP) can contribute to development of diet-based recommendations for health. Our aim was to assess the relationship between dietary patterns and BP in a sample of free-living Australian adults.
METHODS
Usual dietary patterns of participants recruited to dietary intervention studies were assessed using factor analysis (two 24-h recalls). The mean of seven days of daily, seated BP measurements were used.
RESULTS
Complete data from 251 participants (112 males; mean age 55.1(9.1) (SD) years; body mass index (BMI) 29.5(3.9) kg/m2) was included. Three dietary patterns were identified. Only Dietary Pattern 2 was positively associated with home systolic BP (β = 1.88, 95% CI 0.16, 3.60) after adjusting for age, sex, BMI, anti-hypertensive medication, smoking, education, physical activity and energy intake. This dietary pattern was characterised by high consumption of low-fibre bread, pasta, noodles and rice, meat dishes, poultry dishes and egg dishes, mixed cereal dishes, salted nuts and low consumption of milk and yoghurt (low-fat), vegetable juice, vegetables and high-fibre bread. Dietary Pattern 2 was also positively associated with intakes of energy (P = 0.002) and sodium (P = 0.005) and inversely associated with potassium intake (P = 0.002). After adjustment for energy, only the inverse association with potassium remained (P < 0.001).
CONCLUSIONS
In this sample of Australian adults, Dietary Pattern 2 was associated with higher BP and thus chronic disease risk, supporting the evidence that diets high in energy and sodium, and low in potassium from vegetables and dairy, are detrimental to cardiovascular health.
|
10.1186/s12937-019-0519-2
|
pubmed_445_419
|
Although the clinical interpretation of its results varies greatly among perinatologists, the dehydroepiandrosterone sulfate (DHEA-S) loading test has become an integral part of fetal monitoring in many centres dealing with high-risk pregnancies. Currently four main metabolic responses to administration of DHEA-S to the mother are monitored to predict the functional state of the fetoplacental unit: the metabolic clearance of DHEA-S, the metabolic clearance of DHEA-S into estradiol, the conversion of DHEA-S into estradiol or esterol, and the increase in the plasma concentrations of DHEA and androstenedione after administration of DHEA-S. This article critically reviews each of these responses and its possible clinical interpretation, and assesses the clinical future of the DHEA-S loading test.
|
pubmed_445_419
|
pubmed_359_1583
|
The aim was to study whether aerobic fitness measured by a maximal endurance running test at adolescence predicts prevalence of hypertension or blood pressure levels in adulthood. From the 413 (197 slow runners and 216 fast runners) participating in a 2000-meter running test at adolescence in 1976 and responding to a health and fitness questionnaire in 2001, 29 subjects (15 very slow runners and 14 very fast runners) participated in a clinical follow-up study in 2001. Compared to those who were fast runners in adolescence, those who were slow runners tended to have higher age-adjusted risk of hypertension at follow-up (OR 2.7, 95 % CI 0.9 to 7.5; p=0.07). The result persisted after further adjustment for body mass index at follow-up (OR 2.9, 95 % CI 1.0 to 8.3; p=0.05). Diastolic blood pressure was higher for very slow runners at adolescence compared to very fast runners, the age-adjusted mean diastolic blood pressure being 90 mm Hg (95 % CI 86 to 93) vs. 83 mm Hg (95 % CI 80 to 87), age-adjusted p=0.013. High endurance type fitness in adolescence predicts low risk of hypertension and low resting diastolic blood pressure levels in adult men.
|
10.1055/s-2004-821109
|
pubmed_651_11930
|
Changes in the suppressor T-lymphocyte activity were studied in 11 patients with duodenal ulcer during treatment with cimetidine. The drug was administered intravenously in a dose of 200 mg four times a day for a fortnight. Suppressor T-cell activity was determined by the Shou et al. method using two-stage culture before treatment, after 4 days of the treatment, just before drug withdrawal, and 2 days and 2 wk after the treatment. Suppressor T-cell activity significantly decreased soon after starting the treatment, remained low throughout the treatment, and rapidly and significantly increased following drug withdrawal.
|
10.1016/0165-2478(84)90036-1
|
pubmed_1009_13494
|
Rapid mechanical changes have been associated with electrical activity in a variety of non-muscle excitable cells. Recently, mechanical changes have been reported in cochlear hair cells. Here we describe electrically evoked mechanical changes in isolated cochlear outer hair cells (OHCs) with characteristics which suggest that direct electrokinetic phenomena are implicated in the response. OHCs make up one of two mechanosensitive hair cell populations in the mammalian cochlea; their role may be to modulate the micromechanical properties of the hearing organ through mechanical feedback mechanisms. In the experiments described here, we applied sinusoidally modulated electrical potentials across isolated OHCs; this produced oscillatory elongation and shortening of the cells and oscillatory displacements of intracellular organelles. The movements were a function of the direction and strength of the electrical field, were inversely related to the ionic concentration of the medium, and occurred in the presence of metabolic uncouplers. The cylindrical shape of the OHCs and the presence of a system of membranes within the cytoplasm--laminated cisternae--may provide the anatomical substrate for electrokinetic phenomena such as electro-osmosis.
|
10.1038/322365a0
|
pubmed_558_22003
|
The Hox genes and its evolutionary sister, the ParaHox genes, are widely distributed among animals. Although it has been expected that hemichordates and echinoderms have a single set of Hox genes and most likely a single set of ParaHox genes, it is not known whether the ortholog of Hox8 is absent in hemichordates, and in turn, consensus view about Hox/ParaHox gene complements in hemichordates has not been established. In this study, we isolated either complete or nearly complete coding sequences of 12 Hox genes, including the ortholog of the Hox8 that has not been reported in the previous studies, and three ParaHox genes from the recently discovered indirect-developing acorn worm, Balanoglossus simodensis. Our data suggest that the ancestral hemichordate had intact complements of ambulacrarian prototypical Hox and ParaHox genes, consisting of 12 and three members, respectively.
|
10.1007/s00427-009-0298-4
|
pubmed_665_8172
|
We describe a case of renal cell carcinoma metastases to the thyroid gland invading local veins and extending to the neck veins causing superior vena cava (SVC) syndrome.
|
10.1007/s00270-003-0248-x
|
pubmed_906_19722
|
Preovulatory GnRH secretion in ewes, measured in portal blood and cerebrospinal fluid, starts at the time of the LH surge, approximately 4 h after the onset of estrous behavior, and lasts as long as receptivity (36-48 h), which is much longer than the LH surge. This study tested the hypothesis that the extended GnRH secretion is involved in the maintenance of receptive behavior, prolonging the initial triggering effect of E2. Ovariectomized ewes were subjected to artificial estrous cycles and infused intracerebroventricularly either with a water soluble GnRH antagonist (Teverelix, Exp 1 and 2) or GnRH (Exp 3 and 4) after preovulatory E2 challenges of various intensity. The GnRH antagonist infused for 20 h (0.5 mg/ml, flow rate 3 microl/min) following a treatment with 2 x 30-mm E2 implants for 24 h (Exp 1) significantly reduced receptivity 36-48 h post E2 compared with vehicle infusion. By contrast, when the GnRH antagonist was infused with E2 implants still present (Exp 2: E2 for 48 h, GnRH antagonist given 24-44 h after E2 insertion, n = 14) receptivity was not affected. Administration of GnRH (0.5 mg/ml, flow rate 3 microl/min) when receptivity began to decline (Exp 3: 30-48 h after a 6-h 2 x 30-mm E2 implants n = 12) resulted in significantly higher receptivity scores at 48 and 52 h post E2 in GnRH treated animals compared with vehicle treated. GnRH infusion of ewes under subthreshold E2 treatment (Exp 4: GnRH 6-24 h after implantation of 1 x 30-mm E2 for 3 h, n = 12 in a cross-over design) significantly increased their receptivity compared with vehicle administration at 18 and 24 h post E2 insertion, but receptivity remained lower than when induced by high doses of E2. Our results demonstrate for the first time that GnRH is involved in the control of receptivity in a ruminant species and suggest that in the cycling ewe the sustained preovulatory GnRH secretion plays a physiological role in extending the duration of estrous behavior. They also indicate that it is possible to dissociate a direct effect of E2 on estrous behavior from its effect via stimulation of GnRH secretion.
|
10.1210/endo.143.1.8605
|
pubmed_487_2358
|
Fifteen new diterpenoid glycosides (1a-n, 2) were isolated from an Argentine collection of the bitter fern Gleichenia quadripartita along with the known flavonoid glycoside afzelin. Structure elucidation was accomplished by 1D and 2D NMR spectroscopy and by high-resolution MS analyses. In addition, X-ray crystallographic analysis of a monocrystal of 1a as well as chemical derivatization of 1h and 1m were performed to confirm their structures.
|
10.1021/np070119m
|
pubmed_501_7529
|
Tricyclic antidepressants are believed to act by inhibiting reuptake of biogenic amines into the presynaptic neuron. This fundamental information can be exploited to characterize the reuptake mechanism in detail and to suggest modifications in drug structure aimed at improving therapeutic value. Knowledge of the three-dimensional geometry of tricyclic antidepressants is a prerequisite for such a research. Hence generation of possible geometries for such structures by theoretical and computer simulation methods has been attempted. Only a limited number of reasonable structures were obtained for most of the molecules, indicating that the obtained structures are likely to be close to actual structures. This has been somewhat substantiated by a study on the structure of imipramine hydrochloride by X-ray crystallographic methods.
|
pubmed_501_7529
|
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