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pubmed_711_3342 | The present study demonstrates unequivocally the existence of short-chain trans-2-enoyl coenzyme A (CoA) hydratase and beta-ketoacyl CoA reductase activities in the endoplasmic reticulum of rat liver. Subcellular fractionation indicated that all four fractions, namely, mitochondrial, peroxisomal, microsomal, and cytosolic contained significant hydratase activity when crotonyl CoA was employed as the substrate. In the untreated rat, based on marker enzymes and heat treatment, the hydratase activity, expressed as mumol/min/g liver, wet weight, in each fraction was: mitochondria, 684; peroxisomes, 108; microsomes, 36; and cytosol, 60. Following di-(2-ethylhexyl)phthalate (DEHP) treatment (2% (v/w) for 8 days), there was only a 20% increase in mitochondrial activity; in contrast, peroxisomal hydratase activity was stimulated 33-fold, while microsomal and cytosolic activities were enhanced 58- and 14-fold respectively. A portion of the cytosolic hydratase activity can be attributed to the component of the fatty acid synthase complex. Although more than 70% of the total hydratase activity was associated with the mitochondrial fraction in the untreated rat, DEHP treatment markedly altered this pattern; only 11% of the total hydratase activity was present in the mitochondrial fraction, while 49 and 29% resided in the peroxisomal and microsomal fractions, respectively. In addition, all four subcellular fractions contained the short-chain NADH-specific beta-ketoacyl CoA (acetoacetyl CoA) reductase activity. Again, in the untreated animal, reductase activity was predominant in the mitochondrial fraction; following DEHP treatment, there was marked stimulation in the peroxisomal, microsomal, and cytosolic fractions, while the activity in the mitochondrial fraction increased by only 39%. Hence, it can be concluded that both reductase and hydratase activities exist in the endoplasmic reticulum in addition to mitochondria, peroxisomes, and soluble cytoplasm. | 10.1016/0003-9861(86)90186-4 |
pubmed_168_321 | The first images of Jupiter, Io, Europa, and Ganymede from the Galileo spacecraft reveal new information about Jupiter's Great Red Spot (GRS) and the surfaces of the Galilean satellites. Features similar to clusters of thunderstorms were found in the GRS. Nearby wave structures suggest that the GRS may be a shallow atmospheric feature. Changes in surface color and plume distribution indicate differences in resurfacing processes near hot spots on Io. Patchy emissions were seen while Io was in eclipse by Jupiter. The outer margins of prominent linear markings (triple bands) on Europa are diffuse, suggesting that material has been vented from fractures. Numerous small circular craters indicate localized areas of relatively old surface. Pervasive brittle deformation of an ice layer appears to have formed grooves on Ganymede. Dark terrain unexpectedly shows distinctive albedo variations to the limit of resolution. | 10.1126/science.274.5286.377 |
pubmed_954_14705 | Neurodegenerative diseases with distinct genetic etiologies and pathological phenotypes appear to share common mechanisms of neuronal cellular dysfunction, including excitotoxicity, calcium dysregulation, oxidative damage, ER stress and mitochondrial dysfunction. Glial cells, including microglia and astrocytes, play an increasingly recognized role in both the promotion and prevention of neurodegeneration. Sigma receptors, particularly the sigma-1 receptor subtype, which are expressed in both neurons and glia of multiple regions within the central nervous system, are a unique class of intracellular proteins that can modulate many biological mechanisms associated with neurodegeneration. These receptors therefore represent compelling putative targets for pharmacologically treating neurodegenerative disorders. In this review, we provide an overview of the biological mechanisms frequently associated with neurodegeneration, and discuss how sigma-1 receptors may alter these mechanisms to preserve or restore neuronal function. In addition, we speculate on their therapeutic potential in the treatment of various neurodegenerative disorders. | pubmed_954_14705 |
pubmed_1084_20407 | BACKGROUND
Campylobacter jejuni is one of the most important agents of zoonotic disease. Production as well as companion animals can be the infectious source for Campylobacteriosis in humans. Hence, epidemiological research on animal colonization, survival in food of animal origin, and human Campylobacteriosis is of high priority. As such studies involve worldwide co-operations and should include further typing of isolates in reference centers, using a reliable method for transportation is essential. In the case of C. jejuni, a pathogenic and microaerophilic bacterium, special safety precautions as well as particular transport conditions that guarantee survival of isolates are required.
OBJECTIVE
The purpose of this study was to test various media and temperatures for the transportation of C. jejuni under aerobic conditions and to identify a cheap, effective and easy method that is appropriate for long distance transportation and can be applied by most veterinary/medical laboratories with a basic infrastructure.
MATERIALS AND METHODS
We examined Mueller-Hinton (MH) agar with and w/o 2% horse blood and m-CCDA at room temperature and 2 ± 2 (SD)°C under atmospheric conditions for survival of Campylobacter strains.
RESULTS
MH agar with 2% horse blood, suitable transport vials, and an optimum temperature of 2 ± 2°C provided survival of three Campylobacter type strains for at least one month under atmospheric conditions. This was validated by a transport test in which 101 isolates were shipped from Turkey to Austria. All isolates could be recultured and 97% survived more than one month in the transport medium.
CONCLUSION
These findings indicate that the described approach is suitable for inter-laboratory transport of C. jejuni isolates. | 10.1080/01652176.2011.585797 |
pubmed_1080_5060 | Lithium is a widely prescribed drug used for the treatment of bipolar affective illness. Previous reports on its effects on sperm motility and male fertility are conflicting. The effect of lithium on human sperm motility was examined in vitro using the modified transmembrane migration method. This technique takes account of the dilution of lithium that occurs during the incubation. Lithium inhibits human sperm motility in vitro in concentrations comparable with those reported to be achieved in semen after oral administration. | 10.1111/j.1365-2125.1989.tb03565.x |
pubmed_864_4909 | OBJECTIVE
Scarce evidence is available on the cariogenic potential of the widely used commercial sweeteners. The aim of this study was to evaluate the effect of several sweeteners on enamel demineralisation and on the cariogenic properties of Streptococcus mutans biofilms in an artificial caries model.
METHODS
S. mutans-UA159 biofilms were cultured on bovine enamel slabs and exposed to one of the following commercial sweeteners in tablet or powder form: stevia, sucralose, saccharin, aspartame or fructose. Ten percent sucrose and 0.9% NaCl were used as caries-positive and caries-negative controls, respectively. Slabs/biofilms were exposed to the sweeteners three times per day for 5min each time. After 5 days, biofilms were recovered to determine: biomass, bacterial counts and intra- and extracellular polysaccharides. Surface microhardness was measured before and after the experiment to assess enamel demineralisation, expressed as percentage of surface hardness loss (%SHL). Data were analysed using analysis of variance (ANOVA) and Bonferroni (p<0.05).
RESULTS
All tested commercial sweeteners, except fructose, showed less enamel demineralisation than sucrose (p<0.05). Only saccharine showed less biomass and intracellular polysaccharides than the rest of the groups (p<0.05). Stevia, sucralose and saccharine reduced the number of viable cells when compared with sucrose (p<0.05). All sugar alternatives reduced extracellular polysaccharide formation when compared with sucrose (p<0.05).
CONCLUSIONS
Most commercial sweeteners appear to be less cariogenic than sucrose, but still retaining some enamel demineralisation potential. Products containing stevia, sucralose and saccharine showed antibacterial properties and seem to interfere with bacterial metabolism. Further studies are necessary to deepen these findings. | pubmed_864_4909 |
pubmed_394_9191 | The problem of clinically significant interaction of antibiotics and nonsteroid antiinflammatory agents which are ones of the most useful drugs in clinical practice is considered. The data on the mechanisms of intermedicinal interaction of such products are analysed. It is indicated that the number of the clinical trials on the problem is insufficient. | pubmed_394_9191 |
pubmed_323_19165 | INTRODUCTION
In January 2011, Sydney South West Public Health Unit was notified of a large number of people presenting with gastroenteritis over two days at a local hospital emergency department (ED).
METHODS
Case-finding was conducted through hospital EDs and general practitioners, which resulted in the notification of 154 possible cases, from which 83 outbreak cases were identified. Fifty-eight cases were interviewed about demographics, symptom profile and food histories. Stool samples were collected and submitted for analysis. An inspection was conducted at a Vietnamese bakery and food samples were collected and submitted for analysis. Further case ascertainment occurred to ensure control measures were successful.
RESULTS
Of the 58 interviewed cases, the symptom profile included diarrhoea (100%), fever (79.3%) and vomiting (89.7%). Salmonella Typhimurium multiple-locus-variable number tandem repeats analysis (MLVA) type 3-10-8-9-523 was identified in 95.9% (47/49) of stool samples. Cases reported consuming chicken, pork or salad rolls from a single Vietnamese bakery. Environmental swabs detected widespread contamination with Salmonella at the premises.
DISCUSSION
This was a large point-source outbreak associated with the consumption of Vietnamese-style pork, chicken and salad rolls. These foods have been responsible for significant outbreaks in the past. The typical ingredients of raw egg butter or mayonnaise and pate are often implicated, as are the food-handling practices in food outlets. This indicates the need for education in better food-handling practices, including the benefits of using safer products. Ongoing surveillance will monitor the success of new food regulations introduced in New South Wales during 2011 for improving food-handling practices and reducing foodborne illness. | 10.5365/WPSAR.2012.3.1.001 |
pubmed_164_13943 | The purpose of this paper is to show the interactions of Cd and Zn in the freshwater crab Sinopotamon henanense through metallothionein (MT) and malondialdehyde (MDA) level measurements. Laboratory acclimated S.henanense were exposed to Cd (50 µg/L, 100 µg/L, 500 µg/L ), and Zn (100 µg/L, 1000 µg/L) alone and in combined treatments (100 µg/L Zn+50 µg/L Cd, 100 µg/L Zn+100 µg/L Cd, 100 µg/L Zn+500 µg/L Cd, 1000 µg/L Zn+50 µg/L Cd, 1000 µg/L Zn+100 µg/L Cd, 1000 µg/L Zn+500 µg/L Cd) for 7, 14, 21, 28, 35 days. The results demonstrated that the MDA contents increased with exposure time and dose and showed time- and dose-dependence in both gills and hepatopancreas of S.henanense after single Cd exposure, while the changes of MDA levels were not significant with single Zn exposure. The MDA levels decreased when the crabs were exposed to metal mixtures compared to Cd exposure alone, indicating that Zn mediated the cellular toxicity of Cd. MT contents increased after single Cd exposure and also showed a time- and dose-dependence, in a tissue-specific way. Zn showed a limited ability of MT induction both in gills and hepatopancreas of S.henanense. The MT contents represented not a simple addition of single metal exposures but were enhanced at a higher concentration of Zn combined with different Cd concentrations compared to single metal exposure. Whether MT can be used as a biomarker for complex field conditions need to be considered cautiously since different induction patterns of MT were found among single Zn, Cd and combined groups. It is suggested that several biomarkers together as a suite should be used in the monitoring of heavy metal pollution in the aquatic environment. | 10.1371/journal.pone.0080475 |
pubmed_235_16463 | The standard treatment for breast cancer is surgical removal mainly through breast-conserving surgery (BCS). We developed a new technique based on auto-fluorescence (AF) spectral imaging and Raman spectroscopy for fast intraoperative assessment of excision margins in BCS. A new wide-field AF imaging unit based on total internal reflection (TIR) was combined with a Raman spectroscopy microscope equipped with a 785 nm laser. The wavelength of the AF excitation was optimized to 365 nm in order to maximize the discrimination of adipose tissue. This approach allows for the non-adipose regions of tissue, which are at a higher risk of containing a tumor, to be targeted more efficiently by the Raman spectroscopy measurements. The integrated TIR-AF-Raman was tested on small tissue samples as well as fresh wide local excisions, delivering the analysis of the entire cruciate surface of BCS specimens (5.1 × 7.6 cm2) in less than 45 minutes and also providing information regarding the location of the tumor in the specimen. Full automation of the instrument and selection of a faster translation stage would allow for the measurement of BCS specimens within an intraoperative time scale (20 minutes). This study demonstrates that the TIR-AF Raman microscope represents a feasible step towards the development of a technique for intraoperative assessment of large WLE within intraoperative timescales. | 10.1364/BOE.411648 |
pubmed_312_16644 | We have evaluated 147 patients who received primary curative irradiation for breast cancer to determine if there were any common factors that predisposed to failure. There were 10 local recurrences, for an overall local control rate of 93.2%, with a 2 to 16 year follow-up. Disease-free survivals were 85% in Stage I, 69% in Stage II, and 50% in Stage III. Age seemed to be a determinant, with a 31.6% local recurrence rate in women under 50 vs. a 3.1% rate of local recurrence in women age 50 or older when treated. We have also noted a correlation between the radiation dose and local recurrence, with a recurrence rate of 9.1% following a dose of 6000 rad or less, vs. a rate of 4.7% with a dose of 6400 rad or more. The size of the primary carcinoma and the status of the axillary lymph nodes, each considered individually, were not significant prognostic factors. There was no relationship between recurrence and the performance of an axillary dissection. There was evidence suggesting that the recurrence rate was lower when a wide local excision was performed, compared to a lesser procedure. Multiple foci of carcinoma and a high nuclear grade appear to have a poor prognosis. Five of the recurrences occurred early (under 2 years) and three of these were accompanied by fatal distant metastases. None of the five patients with late recurrences (37 to 116 months) developed metastatic disease, suggesting that late recurrences may have a better prognosis. | 10.1016/0360-3016(85)90248-2 |
pubmed_46_20867 | Platelet-agonist interaction results in activation of glycoprotein (GP) IIb-IIIa complex and fibrinogen binding, a prerequisite for platelet aggregation. Fibrinogen binding exposes new antibody binding sites on GPIIb-IIIa (ligand-induced binding sites: LIBS). Signal transduction events, including pleckstrin phosphorylation by protein kinase C (PKC), are considered to regulate GPIIb-IIIa activation. We studied a 16-year-old white male with lifelong mucocutaneous bleeding manifestations and abnormal platelet aggregation and secretion in response to multiple agonists. Pleckstrin phosphorylation was diminished in response to platelet-activating factor (PAF; 4 and 400 nmol/L) and thrombin (0.05 U/mL). Binding of monoclonal antibodies (MoAbs) 10E5 and A2A9, which bind to both resting and activated GPIIb-IIIa, was normal. Binding of MoAb PAC1, which binds to only activated GPIIb-IIIa, was diminished upon activation with PAF, adenosine diphosphate (ADP), thrombin receptor agonist peptide (SFLLRN), A23187, and 1,2-dioctonylglycerol (DiC8). Signal transduction-dependent LIBS expression (studied using MoAb 62) induced by ADP, SFLLRN, and DiC8 and signal transduction-independent LIBS expression induced by RGDS peptide or disintegrin albolabrin were normal or minimally decreased, indicating the presence of intact ligand binding sites. We conclude that the patient's platelets have a defect in inside-out signal transduction-dependent GPIIb-IIIa activation due to an upstream defect in the signal transduction mechanisms rather than in the GPIIb-IIIa complex itself. Our findings extend the spectrum of congenital mechanisms leading to impaired aggregation from defects in GPIIb-IIIa per se to aberrations in signaling mechanisms. | pubmed_46_20867 |
pubmed_1038_9302 | We studied the tolerance phenomenon that develops in long-term recipients of cultured thyroid allografts. Allogeneic mouse thyroids were cultured under hyperbaric oxygen or acidic conditions and then transplanted beneath the kidney capsule of C57BL/6 recipients. Donors differed from the recipients in minor antigens alone, major histocompatibility complex antigens alone, or both. At 35-77 weeks after the first cultured graft, recipients received two more cultured grafts under the capsule of the opposite kidney and were immunized with donor spleen cells (SC). At 5 weeks after the second transplantation, we observed that whereas second grafts carrying new antigens alone were rejected, second grafts carrying new antigens in association with antigens in the first graft were significantly protected. In another set of experiments, normal mice became tolerant to cultured allografts after 2 weeks in parabiosis with tolerant individuals. Tolerant mice showed reduced specific in vivo and in vitro cytotoxic T lymphocyte responses. However, the frequency of CTL precursors of tolerant mice was the same as in normal mice. The reduced in vitro CTL responses were restored to normal levels by the addition of a lymphokine rich medium. Also, we observed that the injection of specifically activated immune SC caused the rejection of cultured allografts in normal but not in tolerant recipients. We conclude that the tolerance that develops in recipients of cultured allografts is an active immunological process that affects the activation and effector function of CTL. | 10.1097/00007890-199204000-00036 |
pubmed_1010_583 | Mg-based alloys might be ideal biomaterials in clinical applications owing to favorable mechanical properties, biodegradability, biocompatibility, and especially their anti-inflammatory properties. However, the precise signaling mechanism underlying the inhibition of inflammation by Mg-based alloys has not been elucidated. Here, we investigated the effects of a Mg-2.1Nd-0.2Zn-0.5Zr alloy (denoted as JDBM) on lipopolysaccharide (LPS)-induced macrophages. THP-1 cell-derived macrophages were cultured on JDBM, Ti-6Al-4V alloy (Ti), 15% extract of JDBM, and 7.5 mM of MgCl2 for 1 h before the addition of LPS for an indicated time; the experiments included negative and positive controls. Our results showed JDBM, extract, and MgCl2 could decrease LPS-induced tumor necrosis factor (TNF) and interleukin (IL)-6 expression. However, there were no morphologic changes in macrophages on Ti or JDBM. Mechanically, extract and MgCl2 downregulated the expression of toll-like receptor (TLR)-4 and MYD88 compared with the positive control and inhibited LPS-induced nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by inactivation of the phosphorylation of IKK-α/β, IKβ-α, P65, P38, and JNK. Additionally, the LPS-induced reactive oxygen species (ROS) expression was also decreased by extract and MgCl2. Interestingly, the expression of LPS-induced TNF and IL-6 could be recovered by knocking down TRPM7 of macrophages, in the presence of extract or MgCl2. Mechanically, the activities of AKT and AKT1 were increased by extract or MgCl2 with LPS and were blocked by a PI3K inhibitor, whereas siRNA TRPM7 inhibited only AKT1. Together, our results demonstrated the degradation products of Mg-based alloy, especially magnesium, and resolved inflammation by activation of the TRPM7-PI3K-AKT1 signaling pathway, which may be a potential advantage or target to promote biodegradable Mg-based alloy applications. | 10.3389/fimmu.2019.02798 |
pubmed_4_21697 | We describe a case of a 29-year-old man from Pakistan who presented with progressive neurologic symptoms over 1 week and was found to have a right parietal cerebral abscess. Neurosurgical drainage cultures showed growth of Actinomyces meyeri, Streptococcus intermedius, and Parvimonas micra. An abscessed molar was identified as the likely port of entry and was extracted. The patient was treated with metronidazole, vancomycin, and doxycycline because of prior anaphylaxis to penicillin. At 6-month follow-up, repeat magnetic resonance imaging showed no signs of residual abscess. Culture-independent identification techniques (e.g., ribosomal sequencing) increasingly identify Actinomyces meyeri as a causative agent and significant pathogen in spontaneous brain abscesses. As understanding about Actinomyces meyeri's prevalence and pathogenesis improves, questions arise about optimal treatment strategy, which we discuss based on a literature review. | 10.1016/j.idcr.2017.07.007 |
pubmed_1074_8829 | BACKGROUND AND OBJECTIVE
caring for people with dementia presents a growing challenge in an ageing society. We urgently need innovative future-oriented concepts of evidence-based health care which would improve the care for people with dementia, even under adverse circumstances. The German Center for Neurodegenerative Diseases (DZNE) in Witten is willing to meet this challenge.
FOCUS OF RESEARCH
the DZNE in Witten supports interdisciplinary research and houses three scientific work groups acting in close co-operation and focusing on 1) care structures, 2) care interventions, and 3) knowledge circulation and implementation research. A comprehensive project plan focuses on people with dementia's perspective in the early stages of the disease. It intends to investigate their needs, requirements und activities as a basis for the development of appropriate concepts. Apart from specific research questions methodological issues arising from the complexity of the subject are of interest.
DISCUSSION
the institutional funding of the location offers an unparalleled opportunity to plan long-term and more complex projects. This might lead to a close co-operation with the Witten/Herdecke University, where health care research is of particular relevance. | 10.1016/j.zefq.2010.07.042 |
pubmed_806_3324 | PURPOSE
To test the hypothesis that the geometry of probe placement with respect to the pleural puncture site affects the risk of pneumothorax after microwave (MW) ablation in the lung.
MATERIALS AND METHODS
Computed tomography-guided MW ablation of the lung was performed in 8 swine under general anesthesia and mechanical ventilation. The orientation of the 17-gauge probe was either perpendicular (90°) or parallel (< 30°) with respect to the pleural puncture site, and the ablation power was 30 W or 65 W for 5 minutes. After MW ablation, swine were euthanized, and histopathologic changes were assessed. Frequency and factors affecting pneumothorax were evaluated by multivariate analysis.
RESULTS
Among 62 lung MW ablations, 13 (21%) pneumothoraces occurred. No statistically significant difference was noted in the rate of pneumothorax between the perpendicular and the parallel orientations of the probe (31% vs 14%; odds ratio [OR], 2.8; P = .11). The pneumothorax rate was equal for 65-W and 30-W ablation powers (21% and 21%; OR, 1.0; P = .94). Under multivariate analysis, 2 factors were independent positive predictors of pneumothorax: ablation zone inclusive of pleural insertion point (OR, 7.7; P = .02) and time since intubation (hours) (OR, 2.7; P = .02).
CONCLUSIONS
Geometries where the pleural puncture site excluded the ablation zone decreased pneumothorax in swine undergoing MW ablation in the lung. Treatment planning to ensure that the pleural puncture site excludes the subsequent ablation zone may reduce the rate of pneumothorax in patients undergoing MW ablation in the lung. | pubmed_806_3324 |
pubmed_254_19191 | BACKGROUND
Although the results of previous studies suggested the effectiveness of physician-led prehospital trauma management, it has been uncertain because of the limited number of high-quality studies. Furthermore, the advantage of physician-led prehospital management might have been overestimated due to the shortened prehospital time by helicopter transportation in some studies. The present study aimed to evaluate the effect of physician-led prehospital management independent of prehospital time. Also, subgroup analysis was performed to explore the subpopulation that especially benefit from physician-led prehospital management.
METHODS
This retrospective cohort study analyzed the data of Japan's nationwide trauma registry. Severe blunt trauma patients, defined by Injury Severity Score (ISS) ≥16, who were transported directly to a hospital between April 2009 and March 2019 were evaluated. In-hospital mortality was compared between groups dichotomized by the occupation of primary prehospital healthcare provider (i.e., physician or paramedic), using 1:4 propensity score-matched analysis. The propensity score was calculated using potential confounders including patient demographics, mechanism of injury, vital signs at the scene of injury, ISS, and total time from injury to hospital arrival. Subpopulations that especially benefit from physician-led prehospital management were explored by assessing interaction effects between physician-led prehospital management and patient characteristics.
RESULTS
A total of 30,551 patients (physician-led: 2976, paramedic-led: 27,575) were eligible for analysis, of whom 2690 propensity score-matched pairs (physician-led: 2690, paramedic-led: 10,760) were generated and compared. Physician-led group showed significantly decreased in-hospital mortality than paramedic-led group (in-hospital mortality: 387 [14.4%] and 1718 [16.0%]; odds ratio [95% confidence interval] = 0.88 [0.78-1.00], p = 0.044). Patients with age < 65 years, ISS ≥25, Abbreviated Injury Scale in pelvis and lower extremities ≥3, and total prehospital time < 60 min were likely to benefit from physician-led prehospital management.
CONCLUSIONS
Physician-led prehospital trauma management was significantly associated with reduced in-hospital mortality independent of prehospital time. The findings of exploratory subgroup analysis would be useful for the future research to establish efficient dispatch system of physician team. | 10.1186/s13049-020-00828-4 |
pubmed_1032_24498 | PURPOSE
We examined the correlates and health implications of household food insecurity among Hispanic/Latino youth (aged 8-16 years), a high food insecurity-risk population.
METHODS
Using the Hispanic Community Children's Health/Study of Latino Youth (n = 1,362) and bivariate and multivariate analyses, we examined the correlates of household and child food insecurity and very low food security. We assessed the influence of four sets of risk/protective factors-child demographic, acculturation, socioeconomic, and family/social support. We then examined associations between food insecurity and four health indicators-body mass index, diet quality, depression, and anxiety-and used modification effects to assess whether these associations differed by sex, age, household income, parent nativity, and acculturative stress levels.
RESULTS
We found high rates of food insecurity: 42% of Hispanic/Latino youth experienced household food insecurity and 33% child food insecurity. Moreover, 10% lived in a very low food secure household. Compared with their food secure peers, Hispanic/Latino youth in food insecure households experienced greater parent/child acculturative and economic stress and weakened family support systems. Associations of food insecurity with health outcomes varied by sex, age, household income, parent nativity, and child acculturative stress levels.
CONCLUSIONS
Food insecurity is highly prevalent among Hispanic/Latino youth and has detrimental health implications, especially for girls, older youth, and youth experiencing acculturative stress. Reducing food insecurity and improving health among Hispanic/Latino youth will likely require comprehensive policies that address their multiple migration, familial, and economic stressors. | 10.1016/j.jadohealth.2018.10.302 |
pubmed_65_3739 | 1. In some anaesthetized preparations, eupnoea is eliminated following a blockade or destruction of neurons in a rostral medullary pre-Botzinger complex. 2. Neurons in this region might underlie the neurogenesis of eupnoea, or be the source of an input which is necessary for eupnoea to be expressed. If the latter, any apnoea following ablation of the pre-Botzinger complex might be reversed by an augmentation in 'tonic input.' Contrariwise, this apnoea should be permanent if the neuronal activities of the pre- Botzinger complex are an exclusive generator of the eupnoeic rhythm. 3. Decerebrate, vagotomized, paralysed and ventilated adult rats were studied. Efferent activity of the phrenic nerve was recorded as an index of ventilatory activity. 4. Blockade or destruction of neuronal activities of the pre-Botzinger complex by unilateral and/or bilateral injections of muscimol or kainic acid eliminated eupnoea only transiently. Eupnoea returned following activation of the peripheral chemoreceptors and spontaneously over time. 5. Results do not support the concept that neuronal activities of the pre-Botzinger complex play an exclusive role in the neurogenesis of eupnoea in vivo. Rather, these neuronal activities appear to provide a tonic input to the ponto-medullary circuit which generates eupnoea and/or appear to be one component of this circuit. | 10.1111/j.1469-7793.1999.00303.x |
pubmed_450_20437 | This study investigated green tea catechins in plasma and urine and chronic disease biomarkers. We hypothesized that plasma and urinary concentration of green tea catechins are associated with cardiovascular disease and diabetes biomarkers. First void urine and fasting plasma samples were collected from 57 generally healthy females aged 38 to 73 years (mean, 52 ± 8 years) recruited in Himeji, Japan. The concentrations of plasma and urinary green tea catechins were determined by liquid chromatography coupled with mass tandem spectrometer. Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, glucose, insulin, glycated hemoglobin, and C-reactive protein in plasma/serum samples were analyzed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman correlation coefficients. The results showed weak associations between plasma total catechin and triglyceride (r = -0.30) and LDL cholesterol (r = -0.28), whereas plasma (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, (-)-epicatechin-3-gallate, and (-)-epicatechin exhibited weak to moderate associations with triglyceride or LDL cholesterol, but little associations with HDL cholesterol, body fat, and body mass index were evident. Urinary total catechin was weakly associated with triglyceride (r = -0.19) and LDL cholesterol (r = -0.15), whereas urinary (-)-epigallocatechin-3-gallate (r = -0.33), (-)-epigallocatechin (r = -0.23), and (-)-epicatechin-3-gallate (r = -0.33) had weak to moderate correlations with triglyceride and similarly with body fat and body mass index. Both plasma (r = -0.24) and urinary (r = -0.24) total catechin, as well as individual catechins, were weakly associated with glycated hemoglobin. Plasma total and individual catechins were weakly to moderately associated with C-reactive protein, but not the case for urinary catechins. In conclusion, we found weak to moderate associations between plasma and urinary green tea catechin concentrations and plasma biomarkers of cardiovascular disease and diabetes. | pubmed_450_20437 |
pubmed_397_22184 | Degenerative brain disorders (neurodegeneration) can be frustrating for both conventional and alternative practitioners. A more comprehensive, integrative approach is urgently needed. One emerging focus for intervention is brain energetics. Specifically, mitochondrial insufficiency contributes to the etiopathology of many such disorders. Electron leakages inherent to mitochondrial energetics generate reactive oxygen free radical species that may place the ultimate limit on lifespan. Exogenous toxins, such as mercury and other environmental contaminants, exacerbate mitochondrial electron leakage, hastening their demise and that of their host cells. Studies of the brain in Alzheimer's and other dementias, Down syndrome, stroke, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Friedreich's ataxia, aging, and constitutive disorders demonstrate impairments of the mitochondrial citric acid cycle and oxidative phosphorylation (OXPHOS) enzymes. Imaging or metabolic assays frequently reveal energetic insufficiency and depleted energy reserve in brain tissue in situ. Orthomolecular nutrients involved in mitochondrial metabolism provide clinical benefit. Among these are the essential minerals and the B vitamin group; vitamins E and K; and the antioxidant and energetic cofactors alpha-lipoic acid (ALA), ubiquinone (coenzyme Q10; CoQ10), and nicotinamide adenine dinucleotide, reduced (NADH). Recent advances in the area of stem cells and growth factors encourage optimism regarding brain regeneration. The trophic nutrients acetyl L-carnitine (ALCAR), glycerophosphocholine (GPC), and phosphatidylserine (PS) provide mitochondrial support and conserve growth factor receptors; all three improved cognition in double-blind trials. The omega-3 fatty acid docosahexaenoic acid (DHA) is enzymatically combined with GPC and PS to form membrane phospholipids for nerve cell expansion. Practical recommendations are presented for integrating these safe and well-tolerated orthomolecular nutrients into a comprehensive dietary supplementation program for brain vitality and productive lifespan. | pubmed_397_22184 |
pubmed_399_19519 | A direct comparison of the intracellular pharmacokinetics of 4'-epi-doxorubicin and doxorubicin was carried out in five patients with leukemia who were given weekly low doses of a combination of these drugs at 20 mg each in an i.v. injection. Blood samples were collected for 48 h after administration and the drug concentrations in leukemic cells were determined by high-performance liquid chromatography (HPLC). The intracellular peak concentrations of 4'-epi-doxorubicin were higher than those of doxorubicin in all patients. The AUC for the intracellular drug concentration vs time curve was significantly higher for 4'-epi-doxorubicin. The intracellular uptake and retention were also studied in vitro after incubation of isolated leukemic blast cells with the two drugs; they showed the same pattern observed in vivo. We conclude that 4'-epi-doxorubicin and doxorubicin exhibit different pharmacokinetics in malignant cells. The therapeutic significance of this finding requires further evaluation. | 10.1007/BF00257622 |
pubmed_469_5187 | Amyloid-β peptide (Aβ) aggregates are known to be correlated with pathological neurodegenerative diseases. The fibril formation process of such peptides in solution is influenced by several factors, such as the ionic strength of the buffer, concentration, pH, and presence of other molecules, just to mention a few. In this paper, we report a detailed analysis of in vitro Aβ42 fibril formation in the presence of cortisol at different relative concentrations. The thioflavin T fluorescence assay allowed us to monitor the fibril formation kinetics, while a morphological characterization of the aggregates was obtained by atomic force microscopy. Moreover, infrared absorption spectroscopy was exploited to investigate the secondary structure changes along the fibril formation path. Molecular dynamics calculations allowed us to understand the intermolecular interactions with cortisol. The combined results demonstrated the influence of cortisol on the fibril formation process: indeed, at cortisol-Aβ42 concentration ratio (ρ) close to 0.1 a faster organization of Aβ42 fragments into fibrils is promoted, while for ρ = 1 the formation of fibrils is completely inhibited. | 10.3390/ijms23116007 |
pubmed_615_17703 | Daphnia magna is a bioindicator organism accepted by several international water quality regulatory agencies. Current approaches for assessment of water quality rely on acute and chronic toxicity that provide no insight into the cause of toxicity. Recently, molecular approaches, such as genome wide gene expression responses, are enabling an alternative mechanism based approach to toxicity assessment. While these genomic methods are providing important mechanistic insight into toxicity, statistically robust prediction systems that allow the identification of chemical contaminants from the molecular response to exposure are needed. Here we apply advanced machine learning approaches to develop predictive models of contaminant exposure using a D. magna gene expression data set for 36 chemical exposures. We demonstrate here that we can discriminate between chemicals belonging to different chemical classes including endocrine disruptors and inorganic and organic chemicals based on gene expression. We also show that predictive models based on indices of whole pathway transcriptional activity can achieve comparable results while facilitating biological interpretability. | 10.1021/es402819c |
pubmed_457_1691 | Three experiments were conducted to test the role that semantic knowledge plays in expert programmer ability. In Experiments 1 and 2, changing the normal semantic structure affected experts more than novices, although experts still outperformed novices. Experiment 3 showed that the experts' advantage was not due merely to their better knowledge of the keywords used in the programming languages. They were also better at searching for types of keywords. Recall and comprehension measures showed the same effects only in Experiment 1. Overall, the results suggest that the role of semantic knowledge in computer programming is more complex than has been previously thought. Merely substituting for keywords or swapping the order of lines still allows the experts to search and attend better to the functions of the program. When semantically complex functions are used, experts are at an equal disadvantage but still outperform novices. | 10.1080/00221309.1990.9921144 |
pubmed_345_17352 | Diffuse-type neurofibroma, an uncommon variant of neurofibroma, is associated with neurofibromatosis type 1 in ∼60% of cases. Typically presenting in young adults as ill-defined plaque-like dermal/subcutaneous thickening, most cases are located on the trunk or the head and neck region. Malignant transformation is extremely rare. Nine cases of malignant peripheral nerve sheath tumor (MPNST) arising in diffuse-type neurofibroma (identified in consult files) are described, including clinicopathologic features and follow-up. Five patients were male and 4 female, aged 31 to 59 years (median 49 y). All diffuse-type neurofibromas contained Meissner corpuscles, with tumor sizes ranging between 3.6 and 45 cm (median, 7.4 cm). Five patients had a clinical history of neurofibromatosis type 1, and 1 had Klippel-Trénaunay-Weber syndrome. Six tumors arose on the trunk and 1 each on the leg, arm, and scalp. Increased cellularity, nuclear atypia, and mitoses (range, 1 to 63/50 high-power fields) indicated transition to MPNST, classified as low grade in 5, intermediate to high grade in 1, and high grade in 3 cases, 1 of which exhibited heterologous angiosarcomatous differentiation. S-100 expression was quite strong and diffuse in the neurofibroma components and less extensive or weaker in MPNST. Follow-up, available for all patients (median, 80.5 mo, except 1 recent case), revealed that 1 patient developed local recurrence after 9 months; 1 with metastases at the time of initial diagnosis died 1 month after tumor resection. All other patients were alive without evidence of disease at 15 to 145 months (median, 83 mo). Diffuse-type neurofibroma may show transformation to MPNST in very rare instances. It is important to be aware of possible malignant change, requiring thorough sampling of resection specimens and long-term clinical follow-up of patients with unexcised lesions. | 10.1097/PAS.0000000000000447 |
pubmed_160_13418 | Many rice breeding programs have currently reached yield plateaus as a result of limited genetic variability in parental strains. Dongxiang common wild rice (Oryza rufipogon Griff.) is the progenitor of cultivated rice (Oryza sativa L.) and serves as an important gene pool for the genetic improvement of rice cultivars. In this study, heterotic loci (HLs) associated with six yield-related traits were identified in wild and cultivated rice and investigated using a set of 265 introgression lines (ILs) of O. rufipogon Griff. in the background of the Indica high-yielding cultivar Guichao 2 (O. sativa L.). Forty-two HLs were detected by a single point analysis of mid-parent heterosis values from test cross F(1) offspring, and 30 (71.5%) of these HLs showed significantly positive effects, consistent with the superiority shown by the F(1) test cross population in the six yield-related traits under study. Genetic mapping of hsp11, a locus responsible for the number of spikelets per panicle, confirmed the utility of these HLs. The results indicate that favorable HLs capable of improving agronomic traits are available. The identification of HLs between wild rice and cultivated rice could lead to a new strategy for the application of heterosis in rice breeding. | 10.1016/j.plantsci.2010.12.009 |
pubmed_326_11027 | Features in a sound's spectral envelope are important for perceptual identification but they are likely to be accompanied by spurious features due to distortion by the transmission channel between source and listener. Previous experiments have demonstrated that there is perceptual compensation for this distortion, and the present experiments ask whether the compensation involves a separation of spurious and salient features. Listeners identified words containing a vowel test sound in an /aept/ to /ppt/ continuum, with a carrier phrase before each word. Effects of transmission channels were simulated by filtering the carrier and the /pt/ following the test sound. Filters were pairs with frequency responses that were the difference of the spectral envelopes from the end-point vowels. Contrasts were altered by multiplying decibel values of the carrier filter's frequency response or the test sound's spectral envelope by a positive number. This keeps features such as peaks at the same frequencies but changes the difference in level between peaks and valleys. When the contrasts of the carrier filters and test sound were the same, the continuum's phoneme boundary was shifted in a manner consistent with a perceptual compensation for the filters that affects the neighboring test sound. However, this shift decreased when the carrier-filter's contrast was less than that of the test sound, and increased slightly when the test-sound's contrast was less than the carrier-filter's contrast. Therefore, the amount of compensation increases with the amount of distortion, even when spectral features such as peaks are kept at the same frequencies. So compensation seems to occur before any perceptual extraction of these features. | 10.1121/1.414981 |
pubmed_680_20552 | OBJECTIVE
To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment.
METHODS
We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis.
RESULTS
Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0-4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p=0.002).
CONCLUSION
Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario. | 10.1016/j.nrleng.2021.10.005 |
pubmed_567_3254 | During the '80s, evidence was collected that air pollutants concentrations close to, or lower than, air quality standards could negatively influence public health at short term, i.e. within a few days. The European Union financed, between 1993 and 1995, the study "Short term effects of Air Pollution on Health: a European Approach using epidemiological time-series data" (APHEA-1 project), involving more than 25 millions inhabitants in 15 cities, investigated between 1977 and 1991. In this paper, the main results, already published in various scientific journals, are reported. The health effects were studied as mortality for natural causes, cardiovascular and respiratory diseases, and as emergency hospital admissions for all respiratory diseases, bronchial asthma, and chronic obstructive pulmonary disease (COPD). The pollutants whose measures were available for the analysis are sulphur dioxide (SO2), nitrogen dioxide (NO2), particulate matter (PM) measured either as black smoke or total suspended particulate, and ozone (O3). The analysis was carried out by each participating group following a detailed protocol, defined during various workshops, through the construction of Poisson regression models, adjusted for autocorrelation and overdispersion, accounting for variables influencing the daily count of deaths, such as long time trends, season, temperature, day of the week. This paper reports the results of the meta-analysis, performed using the values of each city, as relative risk of dying or being admitted to hospital associated with increases of 50 micrograms/m3 in the 24 hours average concentrations of each pollutant. The daily number of natural deaths was associated with increases in the levels of PM, SO2, O3, and NO2. Cardiovascular and respiratory deaths were associated with increases of the levels of PM, SO2, and O3; cardiovascular deaths were associated also with increases of NO2 concentrations. Emergency hospital admissions for the whole group of respiratory disorders are less consistently associated with PM, SO2, and NO2, whereas there is evidence of association with O3. COPD admissions are related to the air pollutant levels, especially those of O3. Lastly, NO2 levels may play a role in exhacerbating asthma, and SO2 levels can have an effect on asthma in children. A second study is currently going on, involving over 40 millions residents in 34 cities. The aims of this project are: to evaluate the dose-response relationship, to investigate on synergy among pollutants, on the "harvesting" phenomenon, on the geographical differences inside Europe and with the U.S. through the collaboration with a similar American study now in progress. The existence of an association between daily variations in the levels of urban air pollution and adverse health effects was confirmed in Europe. This association is weak, but it involves the whole resident population, so it is a major cause of concern from the public health point of view. | pubmed_567_3254 |
pubmed_1129_9400 | Introduction
Although the current Zika virus (ZIKV) epidemic is a major public health concern, most reports have focused on congenital ZIKV syndrome, its most devastating manifestation. Severe ocular complications associated with ZIKV infections and possible pathogenetic factors are rarely described. Here, we describe three Venezuelan patients who developed severe ocular manifestations following ZIKV infections. We also analyse their serological response to ZIKV and dengue virus (DENV).
Case presentation
One adult with bilateral optic neuritis, a child of 4 years of age with retrobulbar neuritis [corrected]. and a newborn with bilateral congenital glaucoma had a recent history of an acute exanthematous infection consistent with ZIKV infection. The results of ELISA tests indicated that all patients were seropositive for ZIKV and four DENV serotypes.
Conclusion
Patients with ZIKV infection can develop severe ocular complications. Anti-DENV antibodies from previous infections could play a role in the pathogenesis of these complications. Well-designed epidemiological studies are urgently needed to measure the risk of ZIKV ocular complications and confirm whether they are associated with the presence of anti-flaviviral antibodies. | 10.1099/jmmcr.0.005145 |
pubmed_1031_15111 | AIMS
Aim of the study was to investigate the association between various markers of systemic inflammation and a detailed history of smoking in a large representative sample of the general population.
METHODS AND RESULTS
The effects of chronic smoking on white blood cell (WBC) count, fibrinogen, albumin, plasma viscosity (PV), and high-sensitivity C-reactive protein (CRP) were measured in 2305 men and 2211 women, age 25-74 years, participating in the third MONICA Augsburg survey 1994/95. In men, current smokers showed statistically significantly higher values for WBC count, fibrinogen, PV, and CRP, compared to never smokers, with intermediate, but only slightly increased values for ex-smokers and for occasional smokers. No consistent associations were seen with albumin. Duration of smoking was positively associated with markers of inflammation as were pack-years of smoking. Conversely, duration of abstinence from smoking was inversely related to these markers. Except for WBC count, no such associations were found in women.
CONCLUSION
Data from this large representative population show strong associations between smoking and various markers of systemic inflammation in men. They also show that cessation of smoking is associated with a decreased inflammatory response, which may represent one mechanism responsible for the reduced cardiovascular risk in these subjects. | 10.1016/s0195-668x(03)00260-4 |
pubmed_293_16364 | Vocal fold (VF) mucosal fibrosis results in substantial voice impairment and is recalcitrant to current treatments. To reverse this chronic disorder, anti-fibrotic therapies should target the molecular pathology of aberrant collagen accumulation in the extracellular matrix. We investigated the therapeutic potential of siRNA against Serpinh1, a collagen-specific chaperone that enables cotranslational folding and assembly of procollagens in the endoplasmic reticulum. We implemented a previously validated siRNA construct, conducted transfection experiments using in vitro and in vivo rat models, and measured knockdown efficiency, dose responses, delivery strategies, and therapeutic outcomes. Liposome-mediated delivery of Serpinh1-siRNA downregulated collagen production in naive and scar VF fibroblasts as well as naive VF mucosa; moreover, sustained Serpinh1 knockdown in fibrotic VF mucosa reversed scar-associated collagen accumulation within 4 weeks. Analysis of therapeutic effects at the transcriptome level showed evidence of cell cycle upregulation, catabolism, matrix disassembly, and morphogenesis. These findings indicate that Serpinh1-siRNA holds potential as a molecular therapy for chronic VF mucosal fibrosis. | 10.1016/j.omtn.2019.04.014 |
pubmed_1070_18229 | Decreased expression or function of UCP3 could reduce energy expenditure and increase the storage of energy. The aim of our study was to investigate the influence of -55CT polymorphism of the UCP3 gene on insulin concentrations and metabolic parameters secondary to two hypocaloric diets in obese patients. A population of 131 obese (body mass index >30), nondiabetic outpatients was analyzed in a prospective way. Before and after 2 months on two different hypocaloric diets, bipolar electrical bioimpedance, blood pressure measurement, serial assessment of nutritional intake with 3 d of written food records, and biochemical analysis were performed. The statistical analysis was performed based on a dominant model. With diet type I (low fat) and diet type II (low carbohydrate) in probands with both wild-type alleles, we observed decreases in BMI, weight, fat mass, systolic blood pressure, leptin levels, and insulin concentrations. In addition, with diet type II, a decrease in diastolic blood pressure, total cholesterol, and triglyceride levels was detected. Secondary to diet type I, a decrease in waist circumference and TNF-alpha was observed. Carriers of the T variant experienced decreases in BMI, weight, and fat mass on both diets, without statistical changes in biochemical parameters. In probands with both C alleles, both diets decreased insulin concentrations, blood pressure, and leptin concentrations. Weight reduction was similar with C and T alleles, independent of macronutrient distribution. | 10.1055/s-0028-1087172 |
pubmed_642_17421 | Aerobic plate counts of fresh pond-reared shrimp ( Penaeus stylirostris , Penaeus vannamei , and Penaeus setiferus ) ranged from 1.5 × 103 to 1.3 × 104 per gram. Coryneform bacteria and Vibrio spp. dominated the microbial flora of shrimp. Aerobic plate counts of pond waters ranged from 6.1 × 102 to 2.2 × 104 per milliliter. Vibrio spp. usually were dominant in pond waters. Enterococci and coliform levels in shrimp were low. Fecal coliforms were present in only one of 11 shrimp samples. No Escherichia coli was recovered from pond-reared shrimp. Salmonella , Vibrio parahaemolyticus , Bacillus cereus , and Clostridium perfringens were not recovered from either shrimp or pond waters. No relationship could be established between changes in numbers and types of microorganisms in pond-reared shrimp or pond waters and changes in characteristics of the pond waters such as temperature, salinity, dissolved oxygen, and pH. | 10.4315/0362-028X-41.1.20 |
pubmed_727_10186 | The family situation of the young addict and the young person who has attempted suicide features anomalous relatives rather than psychiatric pathology as such. These relatives condition disturbed interpersonal relations within the family and these are responsible for the abnormal behavior of the patients. In both groups under examination, the family nucleus proved to be disturbed. Rather than the external structure of the family, the decisive factor was the communication between the various members, namely family cohesion proved to be only partial or actually inexistent in about 70% of cases. A substantial difference between the two groups was the father's affective behaviour towards his wife; the addict's father showed a prevalence of a parasitic attitude, while the mother was more hyper-protective with a tendency to establish a relationship of ambiguous dependence with the child, the young person finding it hard to release himself from this. | pubmed_727_10186 |
pubmed_922_13416 | BACKGROUND
A defining feature of sexual reproduction is the transmission of genomic information from both parents to the offspring. There is now compelling evidence that the inheritance of such genetic information is accompanied by additional epigenetic marks, or stable heritable information that is not accounted for by variations in DNA sequence. The reversible nature of epigenetic marks coupled with multiple rounds of epigenetic reprogramming that erase the majority of existing patterns have made the investigation of this phenomenon challenging. However, continual advances in molecular methods are allowing closer examination of the dynamic alterations to histone composition and DNA methylation patterns that accompany development and, in particular, how these modifications can occur in an individual's germline and be transmitted to the following generation. While the underlying mechanisms that permit this form of transgenerational inheritance remain unclear, it is increasingly apparent that a combination of genetic and epigenetic modifications plays major roles in determining the phenotypes of individuals and their offspring.
OBJECTIVE AND RATIONALE
Information pertaining to transgenerational inheritance was systematically reviewed focusing primarily on mammalian cells to the exclusion of inheritance in plants, due to inherent differences in the means by which information is transmitted between generations. The effects of environmental factors and biological processes on both epigenetic and genetic information were reviewed to determine their contribution to modulating inheritable phenotypes.
SEARCH METHODS
Articles indexed in PubMed were searched using keywords related to transgenerational inheritance, epigenetic modifications, paternal and maternal inheritable traits and environmental and biological factors influencing transgenerational modifications. We sought to clarify the role of epigenetic reprogramming events during the life cycle of mammals and provide a comprehensive review of how the genomic and epigenomic make-up of progenitors may determine the phenotype of its descendants.
OUTCOMES
We found strong evidence supporting the role of DNA methylation patterns, histone modifications and even non-protein-coding RNA in altering the epigenetic composition of individuals and producing stable epigenetic effects that were transmitted from parents to offspring, in both humans and rodent species. Multiple genomic domains and several histone modification sites were found to resist demethylation and endure genome-wide reprogramming events. Epigenetic modifications integrated into the genome of individuals were shown to modulate gene expression and activity at enhancer and promoter domains, while genetic mutations were shown to alter sequence availability for methylation and histone binding. Fundamentally, alterations to the nuclear composition of the germline in response to environmental factors, ageing, diet and toxicant exposure have the potential to become hereditably transmitted.
WIDER IMPLICATIONS
The environment influences the health and well-being of progeny by working through the germline to introduce spontaneous genetic mutations as well as a variety of epigenetic changes, including alterations in DNA methylation status and the post-translational modification of histones. In evolutionary terms, these changes create the phenotypic diversity that fuels the fires of natural selection. However, rather than being adaptive, such variation may also generate a plethora of pathological disease states ranging from dominant genetic disorders to neurological conditions, including spontaneous schizophrenia and autism. | 10.1093/humupd/dmz017 |
pubmed_409_19966 | From a sample of 1,956 adolescent delinquents referred to us by the court for physical, psychological, psychiatric, educational, and social examinations, 71 delinquents convicted of homicide were matched with 71 nonviolent delinquents by age, race, sex, and socioeconomic status (SES). These two groups were compared on the basis of these evaluations by stepwise discriminant analysis, matched pairs, two-tailed t-tests, and nonparametric tests. Adolescents who kill have a tetrad of symptoms: (1) criminally violent family members; (2) gang membership; (3) severe educational difficulties; and (4) alcohol abuse. | 10.1002/1097-4679(199007)46:4<472::aid-jclp2270460416>3.0.co;2-f |
pubmed_596_1873 | OBJECTIVES
The association between aortic stenosis (AS) and acquired von Willebrand disease type 2A has been described. It may be present in up to 90% of patients with AS. Shear stress has been proposed as the underlying mechanism; however, the physiopathology of this condition is not completely understood. No specific treatment has been studied in this specific population besides aortic valve replacement (AVR). As a coadjuvant therapy, some cardiac surgery centers use desmopressin routinely. The authors report the first stage of an ongoing study designed to compare the effects of desmopressin versus placebo in patients with severe AS scheduled for AVR. Because of the different incidences of the acquired von Willebrand type 2A reported in the literature, the first stage was conducted to describe the incidence of this clinical association in the present population, allowing the sample size for the second stage of the study to be obtained.
DESIGN
A prospective cohort study.
SETTING
A single academic medical center.
PARTICIPANTS
Thirteen patients with severe AS scheduled for AVR.
INTERVENTION
None.
MEASUREMENTS AND MAIN RESULTS
Patients with severe AS scheduled for AVR were studied preoperatively with a von Willebrand laboratory panel. Results were negative for acquired von Willebrand disease type 2A in all patients. The second stage of the trial was stopped.
CONCLUSION
Contrary to previous reports, no correlation was found between AS and acquired von Willebrand disease type 2A. Further studies are needed to ascertain whether this lack of association is caused by a specific characteristic of the present population, the small sample size, or other factors. | 10.1053/j.jvca.2011.02.011 |
pubmed_783_1449 | Lipoprotein(a) (Lp(a)) is an independent risk factor for the development of cardiovascular disease. Vascular smooth muscle cell (SMC) motility and plasticity, functions that are influenced by environmental cues, are vital to adaptation and remodelling in vascular physiology and pathophysiology. Lp(a) is reportedly damaging to SMC function via unknown molecular mechanisms. Apolipoprotein(a) (apo(a)), a unique glycoprotein moiety of Lp(a), has been demonstrated as its active component. The aims of this study were to determine functional effects of recombinant apo(a) on human vascular SMC motility and explore the underlying mechanism(s). Exposure of SMC to apo(a) in migration assays induced a potent, concentration-dependent chemorepulsion that was RhoA and integrin αVβ3-dependent, but transforming growth factor β-independent. SMC manipulation through RhoA gene silencing, Rho kinase inhibition, statin pre-treatment, αVβ3 neutralising antibody and tyrosine kinase inhibition all markedly inhibited apo(a)-mediated SMC migration. Our data reveal unique and potent activities of apo(a) that may negatively influence SMC remodelling in cardiovascular disease. Circulating levels of Lp(a) are resistant to lipid-lowering strategies and hence a greater understanding of the mechanisms underlying its functional effects on SMC may provide alternative therapeutic targets. | pubmed_783_1449 |
pubmed_979_3780 | Somatic hypermutation introduces single base changes into the rearranged variable (V) regions of antigen activated B cells at a rate of approximately 1 mutation per kilobase per generation. This is nearly a million-fold higher than the typical mutation rate in a mammalian somatic cell. Rampant mutation at this level could have a devastating effect, but somatic hypermutation is accurately targeted and tightly regulated. Here, we provide an overview of immunoglobulin gene somatic hypermutation; discuss mechanisms of mutation in model organisms that may be relevant to the hypermutation mechanism; and review recent advances toward understanding the possible role(s) of DNA repair, replication, and recombination in this fascinating process. | 10.1016/s1383-5742(99)00003-4 |
pubmed_324_16593 | The protoapigenone analogue WYC02-9, a novel synthetic flavonoid, has been shown to act against a variety of experimental tumors. However, its effects on prostate cancer and its mechanism of action are unknown. Thus, WYC02-9 was investigated for its cytotoxicity against DU145 prostate cancer cells, as was the underlying mechanisms by which WYC02-9 might induce DNA damage and apoptotic cell death through reactive oxygen species (ROS). WYC02-9 inhibited the cell growth of three prostate cancer cell lines, especially DU145 cells. In DU145 cells, WYC02-9 increased the generation of intracellular ROS, followed by induction of DNA damage and activation of the ATM-p53-H2A.X pathway and checkpoint-related signals Chk1/Chk2, which led to increased numbers of cells in the S and G2/M phases of the cell cycle. Furthermore, WYC02-9 induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9, caspase-3, and PARP. The above effects were all prevented by the ROS scavenger N-acetylcysteine. Administration of WYC02-9 in a nude mouse DU145 xenograft model further identified the anti-cancer activity of WYC02-9. These findings therefore suggest that WYC02-9-induced DNA damage and mitochondria-dependent cell apoptosis in DU145 cells are mediated via ROS generation. | 10.1016/j.freeradbiomed.2011.01.015 |
pubmed_363_926 | Based on column experiments, the oxidative degradations of some chlorinated hydrocarbons under three less-reduced redox conditions were investigated. The results showed that in the presence of nitrate and manganese oxide, 1,2-dechloroethane (1,2-DCA) and vinyl chloride (VC) could be oxidized. The transformation rates of 1,2-DCA under denitrification and manganese reduction were 1.18/h and 0.54/h, respectively, while those of VC were 0.29/h and 0.15/h, respectively. In the presence of iron, degradation of VC was not clear. In addition, the degradation of 1,2-DCA was inhibited. For other chlorinated hydrocarbons, such as 1,1,1-trichloroethane, trichloroethene, cis-dichloroethene and trans-dichloroethene, no degradation occurred under the three studied redox conditions. Monochlorobenzene exhibited relative high removal in the columns, however, due to its high soil adsorption potential, it was not known yet whether microbial activities were involved. | pubmed_363_926 |
pubmed_258_8590 | BACKGROUND
High-dose statins are recommended as preventive drugs in guidelines for patients with ischaemic stroke undergoing thrombectomy. Not only in clinical practice but also based on large-scale studies, low-dose statins have been widely used and demonstrated to be efficient in Asian populations. However, it remains unknown whether a low-dose statin is related to the prognosis of patients with thrombectomy. Can low-dose statins reduce the risk of bleeding at the same time?
METHODS
We prospectively collected data from patients with acute ischaemic stroke undergoing intra-arterial thrombectomy. Efficacy outcomes were National Institutes of Health Stroke Scale (NIHSS) score improvement at 7 days after admission and a favourable functional outcome (FFO) at 90 days. Safety outcomes were rates of in-hospital haemorrhage events and death within 2 years.
RESULTS
We included 256 patients in this study. Compared with the control group, the low-dose statin group had a higher NIHSS improvement rate at 7 days, a higher FFO rate at 90 days and a lower death rate within 2 years. The low-dose statin group had a lower percentage of gastrointestinal haemorrhage. Statin use was significantly related to an improved NIHSS score (p = 0.028, OR = 1.773) at 7 days and FFO (P < 0.001, OR = 2.962) at 90 days and to lower death rates (P = 0.025, or = 0.554) within 2 years.
CONCLUSION
In Asian acute ischaemic stroke patients with intra-arterial thrombectomy, low-dose statin use was significantly related to NIHSS improvement at 7 days, FFO at 90 days and decreased death rates within 2 years. | 10.1016/j.jocn.2022.07.001 |
pubmed_1072_20403 | While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs) is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST), which are not only effective but also confer protection in 70-90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo. | 10.3389/fimmu.2017.01272 |
pubmed_552_813 | We report a case of latent cardiac sarcoidosis in reference to differential diagnosis from giant cell myocarditis. A 68-year-old woman succumbed to subarachnoid hemorrhage and acute myocardial infarction within a period of 3 days. Autopsy revealed white fibrotic lesions in the lateral wall of the left ventricle and interventricular septum of the heart in addition to acute myocardial infarction of the anterior wall. Histology showed fibrotic granulomatous lesions with infiltration of lymphocytes and epithelioid cells. Many multinucleated giant cells of Langhans and foreign body types were scattered among these lesions. There was no lesion in the bilateral hilar lymph nodes, but typical epithelioid granuloma was noticed in the lymph node of the carina, liver, and spleen. So we concluded that the heart lesion was a case of cardiac sarcoidosis. Striation could not be seen in the multinucleated giant cells of the cardiac sarcoid lesion, and, using light microscopy, it seemed to us that these cells had no relation to the cardiac muscles. However, by immunohistochemistry (PAP method) some giant cells tested positive for myoglobin, and others tested positive for lysozyme. The fact that giant cells are not always derived from the cardiac muscle can't be used, as a criterion for the diagnosis of cardiac sarcoidosis. Giant cells in the lung and lymph nodes tested positive only for lysozyme. Hence, using only cardiac histology, it is difficult to make a differential diagnosis between cardiac sarcoidosis and giant cell myocarditis, especially in cases where there is multiple organ involvement. | pubmed_552_813 |
pubmed_902_14386 | OBJECTIVE
To explore therapeutic effects of emergency medial malleolus osteotomy for the treatment of fractures of talar neck and dislocation of talar body.
METHODS
From 1995. 6 to 2007. 10, among 24 patients with fractures of talar neck and dislocation of talar body, 18 patients were male and 6 patients were female, ranging in age from 28 to 58 years (mean 35.4 years). The duration from injury to the emergency ward ranged from 0.5 to 12 h. All the patients were treated in 5 hours after hospitalization with emergency medial malleolus osteotomy and internal fixation. Firstly, osteotomy was made above the medial malleolus tip; Secondly, the medial malleolus was turned over downward to uncover the talus; Then, the fracture of talus can be reduced in direct visidn.
RESULTS
All the patients were followed up ranged from 6 to 60 months. According to Kenwright evaluation standards, 18 patients obtained an excellent results, 4 good and 2 fair.
CONCLUSION
It is easy and clearly to perform medial malleolus osteotomy. The blood circulation of talus is preserved. So it is an effective method to treat the fractures of talar neck and dislocation of talar body. | pubmed_902_14386 |
pubmed_278_3880 | Acute poisoning is considered one of the most important medical emergencies, resulting in severe morbidity and mortality, and is an economic burden on governments. This study aimed to determine the extent of acute adult intoxication among the population located in the Najran area, Saudi Arabia, over the last 3 years (from January 2017 to December 2019). The study is a hospital-based retrospective observational study. The data of all acutely intoxicated adult patients were collected from patients' files of King Khalid Hospital, the main hospital in the Najran area. In this study, the total number of intoxicated patients was 852. Patients were divided into three groups according to their age: 15-25 years, 26-35 years and >35 years. Accidental intoxication was predominant (64.6%), especially with therapeutic drugs (60.2%), predominantly acetaminophen and amphetamine, which intoxicated 24.5% and 23.4% of the patients, respectively. Moreover, this study showed that 10.6% of patients were intoxicated with overdoses of alcohol, mostly among patients aged over 35 years. Furthermore, the present study revealed that 23.9% of patients were intoxicated with household chemicals, especially Clorox bleach or Flash. Patients presented with a wide range of symptoms; some were even asymptomatic. Overall, patients' outcomes were good; mortalities were few (1.2%), and most fatalities were found in patients aged over 35 years (60%). The present study showed that pharmaceutical drugs constituted the most common causative agents in acute intoxication. Household chemicals, especially Clorox bleach, Flash and pesticides, are highly implicated in the acute toxicity problem. Drug abuse, especially amphetamine and alcohol, still represents a great threat facing people from the Najran region. It is crucial to deliver effective public health education programmes to increase community awareness about the predisposing risk factors of acute toxicity, whether as overdoses or suicide attempts. | 10.1177/00368504211011339 |
pubmed_1134_9401 | A solvent-exchange process was applied to three fluorescent dyes belonging to the 2-benzimidazolyl-7-diethylaminocoumarin series (namely Coumarin 7 (1), Coumarin 30 (2), and one of their derivatives bearing a butyl chain (3)). The three compounds only differ by the substitution of the nitrogen atom of the benzimidazolyl group. They were first dissolved in acetone and then suddenly placed in an aqueous environment where they generated molecular assemblies. The size and shape of the latter were studied by fluorescence microscopy and transmission and scanning electron microscopy. It appeared that 1 gave aggregates and flat microcrystals that evolved toward elongated structures. 2 formed straight nanofibers that are 10-20 microm long and exhibit a crystal structure. 3 gave short fibers (1 micromx25 nm), which finally arrange into entangled solid nanofibers. The formation of fibers arising from low-molecular-weight molecules was particularly interesting. The optical properties of the free-standing particles in suspension were analyzed and compared to those of highly dilute dyes, with the aim to get additional information about the dye arrangement in the nanostructures. | 10.1021/la702197h |
pubmed_1102_5889 | Melatonin (MT) is an indoleamine hormone that can counteract ischemia‑induced organ injury through its antioxidant effects. The aim of the present study was to investigate the protective effects of exogenous MT against hemorrhagic shock (HS)‑induced hepatic ischemic injury in rats, and the role of the nuclear factor (NF)‑κB signaling pathway in this process. A rat model of HS‑induced hepatic ischemic injury was established. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ, interleukin (IL)‑6 and IL‑1β were measured every 6 h, and the 24‑h survival rate of the rats was analyzed. All surviving rats were sacrificed after 24 h. Pathological changes in the liver and the hepatocyte apoptosis rate were observed by hematoxylin and eosin staining and TUNEL assay, respectively, and the expression levels of NF‑κB p65 and NF‑κB inhibitor α (IκBα) were analyzed by reverse transcription‑quantitative PCR analysis and western blotting. The results demonstrated that the serum levels of ALT, AST, LDH, GDH, TNF‑α, IFN‑γ, IL‑6 and IL‑1β gradually increased after HS compared with those in rats subjected to a sham procedure, but this increase was attenuated by MT. Furthermore, the survival rate of the MT group was significantly higher compared with that of the HS group. The degree of pathological hepatic injury, the hepatocyte apoptosis rate, and the hepatic levels of TNF‑α, IFN‑γ, IL‑6 and IL‑1β were significantly decreased in the MT group compared with the HS group. In addition, the mRNA expression of NF‑κB p65 was significantly decreased and the mRNA expression of IκBα was significantly increased in the MT group compared with the sham group. Furthermore, the NF‑κB p65 protein levels in the MT group were significantly increased in the cytosol but decreased in the nucleus, and the IκBα protein levels were increased while those of phosphorylated IκBα were decreased compared with those in the HS group. Therefore, it may be inferred that exogenous MT alleviates HS‑induced hepatic ischemic injury in rats via the inhibition of NF‑κB activation and IκBα phosphorylation. | pubmed_1102_5889 |
pubmed_955_3667 | Phthalimide analogs N-substituted with n-butyl, tert-butyl, hexyl and adamantyl groups were designed and prepared as simplified analogs of thalidomide and methylthalidomide. All the compounds prepared except N-n-butylphthalimide showed thalidomidal activity on 12-O-tetradecanoylphorbol-13-acetate-induced tumor necrosis factor (TNF)-alpha production by human leukemia HL-60 cells. Among the investigated compounds, including thalidomide and methylthalidomide, N-adamantylphthalimide showed the most potent TNF-alpha production-enhancing activity. | 10.1248/cpb.43.177 |
pubmed_660_10742 | Magnetic resonance imaging of rare cystic prostate cancers using multiparametric MRI (mp-MRI, 3 Tesla) shows, especially in solid tumor masses, the criteria of ESUR-MR classification with a PI-RADS >3 ("probably malignant"). In association with additional morphological evidence of intracystic hemorrhage and evidence of villous tumor nodules and irregular septa on the cyst wall, further malignancy criteria are met. MRI complementary to TRUS may be useful for targeted biopsy in solid tumor areas. | 10.1007/s00120-014-3528-y |
pubmed_778_10782 | In the present study male and female brown trout (Salmo trutta f. fario) were exposed to environmentally relevant concentrations of bisphenol A (1.75, 2.40, 5.00 microg l(-1)) during the late prespawning and spawning period and the effect of this contaminant on maturation, quantity and quality of semen and eggs was investigated. In males exposed to estimated BPA concentrations of 1.75 and 2.40 microg l(-1) semen quality was lower than in the control in the beginning of spawning (reduced sperm density, motility rate, and swimming velocity) and in the middle of spawning (reduced swimming velocity, at 2.40 microg l(-1) BPA also reduced sperm motility rate). Therefore, production of high quality semen was restricted to the end of the spawning season and delayed for approximately 4 weeks in comparison to the control. At BPA exposure levels of 5.00 microg l(-1) only one of eight males gave semen of low quality (reduced semen mass, motility rate, and swimming velocity). The percentage of ovulated females was similar for the control group and the groups exposed to estimated BPA concentrations of 1.75 and 2.40 microg l(-1), whereas at 5.00 microg l(-1) BPA females did not ovulate during the investigation. While brown trout of the control group ovulated between the 28 October and 12 November, brown trout exposed to estimated BPA concentrations of 1.75 microg l(-1) BPA ovulated approximately 2 weeks later and brown trout exposed to 2.40 microg l(-1) BPA approximately 3 weeks later. Therefore, the tested BPA concentrations affected the percentage of ovulated females and the time point of ovulation. No effect was observed on the quality of eggs (egg mass, percentile mass increase during hardening, egg fertility). | 10.1016/j.aquatox.2005.08.004 |
pubmed_1104_12128 | The vacuolar [H(+)]-ATPases (V-ATPases) are composed of a peripheral V(1) domain and a membrane-embedded V(0) domain. Reversible dissociation of the V(1) and V(0) domains has been observed in both yeast and insects and has been suggested to represent a general regulatory mechanism for controlling V-ATPase activity in vivo. In yeast, dissociation of the V-ATPase is triggered by glucose depletion, but the signaling pathways that connect V-ATPase dissociation and glucose metabolism have not been identified. We have found that nocodazole, an agent that disrupts microtubules, partially blocked dissociation of the V-ATPase in response to glucose depletion in yeast. By contrast, latrunculin, an agent that disrupts actin filaments, had no effect on glucose-dependent dissociation of the V-ATPase complex. Neither nocodazole nor latrunculin blocked reassembly of the V-ATPase upon re-addition of glucose to the medium. The effect of nocodazole appears to be specifically through disruption of microtubules since glucose-dependent dissociation of the V-ATPase was not blocked by nocodazole in yeast strains bearing a mutation in tubulin that renders it resistant to nocodazole. Because nocodazole has been shown to arrest cells in the G(2) phase of the cell cycle, it was of interest to determine whether nocodazole exerted its effect on dissociation of the V-ATPase through cell cycle arrest. Glucose-dependent dissociation of the V-ATPase was examined in four yeast strains bearing temperature-sensitive mutations that arrest cells in different stages of the cell cycle. Because dissociation of the V-ATPase occurred normally at both the permissive and restrictive temperatures in these mutants, the results suggest that in vivo dissociation is not dependent upon cell cycle phase. | 10.1074/jbc.M100637200 |
pubmed_999_7204 | RATIONALE/STUDY DESIGN
A major challenge in the development of HIV vaccines is finding immunogens that elicit protection against a broad range of viral strains. Immunity to a narrow range of viral strains may protect infants of HIV-infected women or partners discordant for HIV. We hypothesized that immunization to the relevant viral variants could be achieved by exposure to infectious virus during prophylaxis with antiretroviral drugs. To explore this approach in an animal model, macaques were exposed to live virus (SIVmne or HIV-2287) during prophylaxis with parenteral tenofovir and humoral and cellular immune responses were quantified. Subsequently, experimental animals were challenged with homologous virus to evaluate protection from infection, and if infection occurred, the course of disease was compared to control animals. Experimental animals uninfected with SIVmne were challenged with heterologous HIV-2287 to assess resistance to retroviral infection.
METHODOLOGY/PRINCIPAL FINDINGS
Juvenile female Macaca nemestrina (N = 8) were given ten weekly intravaginal exposures with either moderately (SIVmne) or highly (HIV-2287) pathogenic virus during tenofovir prophylaxis. Tenofovir protected all 8 experimental animals from infection, while all untreated control animals became infected. Specific non-neutralizing antibodies were elicited in blood and vaginal secretions of experimental animals, but no ELISPOT responses were detected. Six weeks following the cessation of tenofovir, intravaginal challenge with homologous virus infected 2/4 (50%) of the SIVmne-immunized animals and 4/4 (100%) of the HIV-2287-immunized animals. The two SIVmne-infected and 3 (75%) HIV-2287-infected had attenuated disease, suggesting partial protection.
CONCLUSIONS/SIGNIFICANCE
Repeated exposure to SIVmne or HIV-2287, during antiretroviral prophylaxis that blocked infection, induced binding antibodies in the blood and mucosa, but not neutralizing antibodies or specific cellular immune responses. Studies to determine whether antibodies are similarly induced in breastfeeding infants and sexual partners discordant for HIV infection and receiving pre-exposure antiretroviral prophylaxis are warranted, including whether these antibodies appear to confer partial or complete protection from infection. | 10.1371/journal.pone.0240495 |
pubmed_895_16875 | BACKGROUND
To characterize changes in global protein expression in kidneys of transgenic rats overexpressing human selenoprotein M (SelM) in response to increased bioabivility of selenium (Sel), total proteins extracted from kidneys of 10-week-old CMV/hSelM Tg and wild-type rats were separated by 2-dimensional gel electrophoresis and measured for changes in expression.
RESULTS
Ten and three proteins showing high antioxidant enzymatic activity were up- and down-regulated, respectively, in SelM-overexpressing CMV/hSelM Tg rats compared to controls based on an arbitrary 2-fold difference. Up-regulated proteins included LAP3, BAIAP2L1, CRP2, CD73 antigen, PDGF D, KIAA143 homolog, PRPPS-AP2, ZFP313, HSP-60, and N-WASP, whereas down-regulated proteins included ALKDH3, rMCP-3, and STC-1. After Sel treatment, five of the up-regulated proteins were significantly increased in expression in wild-type rats, whereas there were no changes in CMV/hSelM Tg rats. Only two of the down-regulated proteins showed reduced expression in wild-type and Tg rats after Sel treatment.
CONCLUSIONS
These results show the primary novel biological evidences that new functional protein groups and individual proteins in kidneys of Tg rats relate to Sel biology including the response to Sel treatment and SelM expression. | 10.1186/1559-0275-10-10 |
pubmed_118_17772 | PURPOSE
Correct staging is imperative for colorectal cancer (CRC) since it influences both prognosis and management. Several imaging methods are used for this purpose, with variable performance. Positron emission tomography-magnetic resonance (PET/MR) is an innovative imaging technique recently employed for clinical application. The present study was undertaken to compare the staging accuracy of whole-body positron emission tomography-computed tomography (PET/CT) with whole-body PET/MR in patients with both newly diagnosed and treated colorectal cancer.
METHODS
Twenty-six patients, who underwent same day whole-body (WB) PET/CT and WB-PET/MR, were evaluated. PET/CT and PET/MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Correct staging was compared between methods using McNemar's Chi square test.
RESULTS
The two methods were in agreement and correct for 18/26 (69%) patients, and in agreement and incorrect for one patient (3.8%). PET/MR and PET/CT stages for the remaining 7/26 patients (27%) were discordant, with PET/MR staging being correct in all seven cases. PET/MR significantly outperformed PET/CT overall for accurate staging (P = 0.02).
CONCLUSION
PET/MR outperformed PET/CT in CRC staging. PET/MR might allow accurate local and distant staging of CRC patients during both at the time of diagnosis and during follow-up. | 10.1007/s00261-016-0985-3 |
pubmed_626_16912 | Neural stem cells (NSCs) play a crucial role in the development and maturation of the central nervous system. Recently studies suggest that antipsychotic drugs regulate the activities of NSCs. However, the molecular mechanisms underlying antipsychotic-induced changes of the activity of NSCs, particularly protein expression, are still unknown. We studied the growth and protein expression in haloperidol (HD) and risperidone (RS) treated rat NSCs. The treatment with RS (3microM) or HD (3microM) had no effect on morphology of NSCs after 24h, but significantly promotes or inhibits the differentiation of NSCs after a 96h of treatment. 2-DE based proteomics was performed at 24h, a stage before phenotypic expression of NSCs. Gel image analysis revealed that 30 protein spots in HD- and 60 spots in RS-treated groups were differentially regulated in their expression compared to control group (p<0.05; ANOVA). When these spots were compared between the two drug-treated groups, 23 spots overlapped leaving 7 HD-specific and 37 RS-specific spots. Of these 67 spots, 32 different proteins were identified. The majority of the differentially regulated proteins were classified into several functional groups, such as cytoskeletal, calcium regulating protein, metabolism, signal transduction and proteins related to oxidative stress. Our data shows that atypical RS expressed more proteins than typical HD, and these results might explain the molecular mechanisms underlying the different effects of both drugs on NSCs activities as described above. Identified proteins in this experiment may be useful in future studies of NSCs differentiation and/or understanding in molecular mechanisms of different neural diseases including schizophenia. | 10.1016/j.neuint.2009.05.007 |
pubmed_1025_11109 | UNLABELLED
In this study we aimed to evaluate the three-dimensional (3D) transthoracic echocardiography (TTE) in the assessment of cardiac valve morphology.
METHODS
Bidimensional (2D) and real-time 3D TTE was performed in 104 patients consecutive with cardiac catheterisation, prior to valve surgery. Using surgical findings as the gold standard, 2D and 3D TTE were compared for adequate recognition and accurate detection of morphology. A scoring protocol was used for recognition of the valvular segments (0= inadequate, 1 = adequate).
RESULTS
Adequate echographic visualization of the valve segments was more frequently obtained by 3D than 2D TTE imaging (731/770 by 3D TTE vs. 693/770 by 2D TTE, p < 0.01). The valve leaflets segments were more clearly identified by 3D TTE rather than by 2D TTE (502/531 vs. 471/531, p <0.01). The assessment of commissures was similar by both methods (229/239 vs. 222/239, p=0.09). Total 3D TTE scores for mitral and aortic valves were significantly better than 2D ITE scores (mean score 12.91+/-1.62 by 3D vs 11.58+/-1.02 by 2D, p=0.02). This superiority of 3D TTE was irrespective of rhythm (p <0.05 for both sinus rhythm and atrial fibrillation). Using surgical classification of valvular disease as gold standard, the sensibility and specificity were 91% and 84 % for 3D TTE, and 85% and 77% for 2D TTE, respectively.
CONCLUSIONS
Real-time 3D was superior to 2D TTE forthe accurate localization and identification of valvular pathology, irrespective of heart rhythm. | pubmed_1025_11109 |
pubmed_543_296 | Eggs and egg dishes are important vehicles for Salmonella infections. Salmonella enteritidis, Salmonella typhimurium and Salmonella heidelberg, which can be isolated from chicken ovaries and feces, have been implicated in approximately 50% of the foodborne salmonellosis outbreaks in the United States. In this study, the growth of these three organisms, inoculated into yolks and albumen, was compared at 4, 10 and 25 degrees C. Regardless of whether 10(2) cfu/g or 10(4) cfu/g was inoculated into the yolk or albumen, populations of all strains increased 3 logs or more in number in one day when incubated at 25 degrees C. Maximum numbers of Salmonella ranged from 10(8) to 10(10) cfu/g. All strains grew at 10 degrees C, but peak numbers were lower and occurred later than those at 25 degrees C. Populations of the three Salmonella strains inoculated into eggs stored at 4 degrees C grew sporadically; in some test groups populations declined. The potential for Salmonella in contaminated feces to establish in the interior of eggs was examined by monitoring shell penetration. At 25 degrees C, all three Salmonella strains penetrated the shell in 3 days, but at 4 degrees C, only S. typhimurium was found in one membrane sample. When hatchery conditions were simulated by incubating eggs at 35 degrees C for 30 min followed by storage at 4 degrees C, penetration was enhanced. Penetration was observed by day 1-3 when eggs were exposed to 10(4) cfu Salmonella/g feces. Increasing the inoculum to 10(6) cfu/g feces resulted in 50-75% of the contents of eggs to be contaminated by day 1. All Salmonella-positive samples were detected by enrichment. Results of this study indicate that S. enteritidis, S. typhimurium, or S. heidelberg present in feces can penetrate to the interior of eggs and grow during storage. | 10.1016/0168-1605(94)00042-5 |
pubmed_955_8383 | Presentation of antigen by the major histocompatibility complex to T lymphocytes without the requisite costimulatory signals does not induce an immune response but rather results in a state of antigen-specific unresponsiveness, termed anergy. To determine which costimulatory signals are critical for the T cell commitment to activation or anergy, we developed an in vitro model system that isolated the contributions of alloantigen and each candidate costimulatory molecule. Here, we show that transfectants expressing HLA-DR7 and either B7 or intercellular adhesion molecule 1 (ICAM-1) deliver independent costimulatory signals resulting in alloantigen-induced proliferation of CD4-positive T lymphocytes. Although equivalent in their ability to costimulate maximal proliferation of alloreactive T cells, B7 but not ICAM-1 induced detectable interleukin 2 secretion and prevented the induction of alloantigen-specific anergy. These results are consistent with the hypothesis that blockade of the ICAM-1:lymphocyte function-associated 1 pathway results in immunosuppression, whereas blockade of the B7:CD28/CTLA4 pathway results in alloantigen-specific anergy. This approach, using this model system, should facilitate the identification of critical costimulatory pathways which must be inhibited in order to induce alloantigen-specific tolerance before human organ transplantation. | 10.1084/jem.178.5.1753 |
pubmed_250_1961 | Structural properties of polymer brushes tethered on a periodically nanopatterned substrate are investigated by computer simulations. The substrate consists of an alternating succession of two different types of equal-width parallel stripes, and the polymers are end-tethered selectively on every second stripe. Three distinct morphologies of the nanopatterned brush have been identified, and their range of stability has been determined in terms of a single universal parameter that combines the grafting density, the polymer length, and the stripe width. We propose scaling relations for the average brush height and for the architectural properties of the outer surface of the nanopatterned brush under good solvent conditions. Our analysis provides guidelines for fabricating well-defined and tunable nanopatterned polymeric films. | 10.1021/la802536v |
pubmed_1022_23499 | That surface size has an impact on attention has been well-known in advertising research for almost a century; however, theoretical accounts of this effect have been sparse. To address this issue, we review studies on surface size effects on eye movements in this paper. While most studies find that large objects are more likely to be fixated, receive more fixations, and are fixated faster than small objects, a comprehensive explanation of this effect is still lacking. To bridge the theoretical gap, we relate the findings from this review to three theories of surface size effects suggested in the literature: a linear model based on the assumption of random fixations (Lohse, 1997), a theory of surface size as visual saliency (Pieters etal., 2007), and a theory based on competition for attention (CA; Janiszewski, 1998). We furthermore suggest a fourth model - demand for attention - which we derive from the theory of CA by revising the underlying model assumptions. In order to test the models against each other, we reanalyze data from an eye tracking study investigating surface size and saliency effects on attention. The reanalysis revealed little support for the first three theories while the demand for attention model showed a much better alignment with the data. We conclude that surface size effects may best be explained as an increase in object signal strength which depends on object size, number of objects in the visual scene, and object distance to the center of the scene. Our findings suggest that advertisers should take into account how objects in the visual scene interact in order to optimize attention to, for instance, brands and logos. | 10.3389/fpsyg.2013.00902 |
pubmed_301_21026 | Three-dimensional degradable porous polymeric structures with high porosities (93-98%) and well-interconnected pore networks have been prepared by freeze-drying polymer solutions in the presence of a leachable template followed by leaching of the template. Templates of the pore network were prepared by fusing sugar or salt particles to form a well-connected structure. The interstices of the template were then filled with a polymer solution (5-15% w/v) in 1,4-dioxane, followed by freeze-drying of the solvent. Subsequent leaching of the sugar template ensures the connectivity of the pore network. The scaffold architecture consists of relatively large interconnected pores modeled after the template and smaller pores resulting from the freeze-drying process. The total porosity of the resultant porous structures is determined by the interstitial space of the leachable template and by the polymer concentration in the freeze-drying solution. The freezing temperature also has an effect on the final morphology of the porous structures. Compared with freeze-drying and combination of freeze-drying /particulate leaching techniques, this method facilitates higher interconnectivity of the scaffolds. Porous structures have been prepared from several relevant polymers in the biomedical and tissue-engineering field: poly(D,L-lactide) (PDLLA), 1000PEOT70PBT30, a segmented poly(ether ester) based on polyethylene oxide and polybutylene terephthalate, and poly(epsilon-caprolactone) (PCL). The mechanical properties of the porous structures prepared by this technique depend on the nature of the polymer, porosity, and the freezing temperature. With porosities in the range of 95-97%, the compression moduli of scaffolds prepared from the different polymers could be varied between 13.0 and 301.5 kPa. | 10.1002/jbm.b.10066 |
pubmed_297_22477 | The need to obtain informed consent prior to any sterilisation is a very well-established ethical and legal obligation. South African law, however, does not specifically state who is responsible for obtaining informed consent before performing a sterilisation. This has implications for the liability of a surgeon or gynaecologist in circumstances where the informed consent is defective. Due to the vagueness of the applicable law, a surgeon or gynaecologist might be held liable, even in situations where he/she did not obtain the consent and relied on a nurse or assistant to procure the relevant informed consent. This article explores the relevant statutory law and canvasses two legal cases that came before the court regarding defective informed consent and the resultant liability for damages. We also make recommendations for proposed amendments to the current law to provide further clarity. | 10.7196/SAMJ.2018.v108i7.13141 |
pubmed_300_16366 | As a well-recognized clinical phenomenon, persistent detectable viral genome in liver or sera in the absence of other serological markers for active hepatitis B virus (HBV) replication is called occult HBV infection. The main mechanism through which occult infection occurs is not completely understood and several possible explanations, such as integration into human genome and maintenance in peripheral mononuclear cells, exist. Occult HBV infection has been reported in different populations, especially among patients with Hepatitis C (HCV) related liver disease. The probable impact of occult HBV in patients with chronic HCV infection has been previously investigated and the evidence suggests a possible correlation with lower response to anti-viral treatment, higher grades of liver histological changes, and also developing hepatocellular carcinoma. However, in the absence of conclusive results, further studies should be conducted to absolutely assess the impact of occult HBV contamination on the HCV related liver disease. | 10.4103/1319-3767.56089 |
pubmed_422_519 | OBJECTIVES
To define the optimal role for radiotherapy (RT) after radical prostatectomy (RP) and to characterize specific patterns of PSA failure in this setting.
METHODS
The records of 105 patients who underwent RT after RP (69 received therapeutic RT because of an elevated prostate-specific antigen [PSA] level, 36 received immediate adjuvant RT) were reviewed. The median follow-up was 35 months after RT and 57 months after RP. Radiation success was defined as achievement and maintenance of a PSA less than 0.2 ng/mL. Preoperative, pathologic, and postoperative characteristics were examined for their ability to predict success after RT. Patterns of PSA recurrence after RT were also examined by determining the PSA nadir, PSA velocity, and timing of androgen-deprivation therapy.
RESULTS
Of 105 patients, 47 experienced biochemical failure. Actuarial 3 and 5-year progression-free survival estimates for all patients were 55% and 43%, respectively. Significant favorable predictors of response to RT by multivariate analysis were preoperative PSA less than 20 ng/mL and the use of adjuvant RT. However, patients who received therapeutic RT with a pre-RT PSA less than 1.0 ng/mL demonstrated progression-free outcome equivalent to those who received adjuvant RT. Two distinct patterns of PSA failure were observed on the basis of PSA nadir after RT. Patients whose PSA failed to reach a nadir less than 0.2 ng/mL after RT had progression with a high PSA velocity (1.5 ng/mL/yr). Patients whose PSA reached a nadir less than 0.2 ng/mL but who subsequently had treatment failure progressed later with a lower PSA velocity (0.36 ng/ml/yr).
CONCLUSIONS
RT is effective in select patients after RP. Given the low PSA velocity consistent with persistent local disease in nearly 50% of patients in whom RT failed, more effective local therapy is needed after RP in high-risk patients. | 10.1016/s0090-4295(99)00299-x |
pubmed_282_20382 | BACKGROUND
In Canada, one year after bariatric surgery follow-up appointments become less frequent and surgical recipients must cope with weight management more independently. Up to 50% of patients experience weight regain by two years post-surgery. Understanding the lived experiences of those who have gone through the bariatric process may shed light on what is needed to support others moving forward. Therefore, the purpose of the study was to gain an understanding of the physical, psychological, social, and clinic-related experiences of individuals who have undergone bariatric surgery at least two years prior.
PURPOSE
The purpose of the study was to gain an understanding of the physical, psychological, social, and clinic-related experiences of individuals who have undergone bariatric surgery at least two years prior.
METHODS
In-depth, individual semi-structured interviews lasting approximately 60 min were conducted. Interviews were transcribed verbatim and inductive content analysis was used to identify emerging themes. Methods were employed throughout to support data trustworthiness.
RESULTS
Participants (n = 28; 21 female) were primarily middle-aged (mean: 49.7 ± 12.7 years old), Caucasian (71%), and completed bariatric surgery more than three years. The data fell naturally into four primary themes, namely physical changes and challenges, psychological experiences, social functioning and support, and clinic-related experiences and reflections.
CONCLUSIONS
Generally, participants described positive improvements in their physical, psychological, and social state since surgery. However, concerns pertaining to several unanticipated outcomes of the surgery were underscored and informed the recommendations for other patients to be prepared to relearn about ones' body, utilize the support services available, and be aware that social relationships may change and/or require tending. Participants' insights can be used to help others meet with long-term success post-bariatric surgery. | 10.1007/s11136-017-1652-z |
pubmed_597_18559 | A highly stretchable hybrid nanogenerator has been developed using a micro-patterned piezoelectric polymer P(VDF-TrFE), PDMS-CNT composite, and graphene nanosheets. Mechanical and thermal energies are simultaneously harvested from a single cell of the device. The hybrid nanogenerator exhibits high robustness behavior even after 30% stretching and generates very stable piezoelectric and pyroelectric power outputs due to micro-pattern designing. | 10.1002/adma.201303570 |
pubmed_635_8202 | Difficulties arising during tracheostomy tube insertion can be rapidly fatal if the airway is not adequately controlled. We report a case of difficult tracheostomy in a gentleman with severe subcutaneous emphysema following a previously failed tracheostomy attempt. Tracheostomy tube insertion through the pre-existing stoma failed repeatedly due to rapidly increasing distance of trachea from the skin and unexpected false passages; however, the trachea was eventually cannulated using a regular endotracheal tube. | 10.4103/0259-1162.123272 |
pubmed_58_4083 | OBJECTIVE
Our objective was to evaluate the clinical usefulness of positron emission tomography/computed tomography using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG-PET/CT) for staging cancer of the external auditory canal (EAC).
STUDY DESIGN
Retrospective case review.
SETTING
Tertiary referral center.
PATIENTS
Twenty-three patients (seven men, 16 women, mean age of 59.6-year-old) who underwent FDG-PET/CT and high-resolution CT within 1 month for staging cancer of the EAC between July 2006 and December 2014 were enrolled in this study.
INTERVENTION
FDG-PET/CT, high-resolution CT.
MAIN OUTCOME MEASURES
Sensitivity, specificity, and accuracy for diagnosing nodal metastases.
RESULTS
Most primary tumors were FDG-avid and maximum standardized uptake values were 7.72 ± 3.04 and 9.06 ± 3.94 for the early (60 min) and delayed (120 min) phases of FDG-PET/CT, respectively. FDG-PET/CT was capable of detecting small nodal metastases (short axis <10 mm), and patient-based sensitivity, specificity, and accuracy of FDG-PET/CT for the N staging were 71.4, 81.3, and 78.3%, respectively. There were no patients with distant metastases in our cohort. Compared with the combination of clinical examination and conventional imaging methods, additional FDG-PET/CT resulted in a change in the surgical strategy in five patients (21.7%).
CONCLUSIONS
Most primary cancers of the EAC are FDG-avid, and FDG-PET/CT is useful for detecting small nodal metastases, followed by the change in the surgical strategy. | 10.1097/MAO.0000000000001791 |
pubmed_625_8667 | Colorectal cancer (CRC) is one of the most common neoplasias worldwide, and its incidence is increasing. Consumption of prebiotics is a useful strategy in order to prevent this important disease. These nutraceutical compounds might exert protective biological functions as antitumors. In order to test the chemopreventive effect of GOS-Lu (galacto-oligosaccharides derived from lactulose) prebiotic preparation against this cancer, an animal model (Rattus norvegicus F344) was used. In this model, two doses of azoxymethane (10 mg/kg) and two treatments with dextran sodium sulfate (DSS) were administered to the animals. Animals were fed for 20 weeks, and either control drinking water or drinking water containing 10% (w/w) GOS-Lu prebiotic preparation was provided to them. Animals were sacrificed after those 20 weeks, and their digestive tract tissues were analyzed. The results revealed a statistically significant reduction in the number of colon tumors in the GOS-Lu cohort with respect to control animals. Metagenomics sequencing was used for studying colon microbiota populations, revealing significant reductions in populations of pro-inflammatory bacteria families and species, and significant increases in interesting beneficial populations, such as Bifidobacterium. Therefore, oral administration of the prebiotic GOS-Lu preparation may be an effective strategy for preventing CRC. | 10.3389/fmicb.2018.02004 |
pubmed_1045_3296 | KHEYLRF-NH(2) (AF2) is the most abundant FMRFamide-related peptide (FaRP) in Ascaris suum and also in many other parasitic and free-living nematodes. The AF2 abundance in the highly diverse nematodes and its potent and profound effects on the neuromuscular systems make AF2 and its receptor(s) very attractive targets for the discovery of novel broad-spectrum anthelmintics. Although FaRP receptors are believed to belong to the large family of G-protein coupled receptors (GPCRs), to date no AF2 receptor(s) have been cloned so there is no final proof to show that they are indeed G-protein coupled. In this study, using A. suum body wall muscle membranes, we showed that: (1) AF2 effectively (EC(50) 57 nM) induced a dose-dependent stimulation of [35S]GTP gamma S binding to the membranes, which is a hallmark of G-protein activation; (2) the high affinity binding of [125I-Tyr(4)]AF2 was inhibited in a dose-dependent manner by GTP with a K(i) of 10.5 nM (so-called guanine nucleotide effect, characteristic for GPCRs). Collectively, our results provide direct evidence for G-protein involvement in AF2-triggered receptor activation and thus confirm that the receptor for AF2 in A. suum is a GPCR. | 10.1016/s0006-291x(02)03054-1 |
pubmed_565_9665 | Monkeys can learn to directly control the movements of an artificial actuator by using a brain-machine interface (BMI) driven by the activity of a sample of cortical neurons. Eventually, they can do so without moving their limbs. Neuronal adaptations underlying the transition from control of the limb to control of the actuator are poorly understood. Here, we show that rapid modifications in neuronal representation of velocity of the hand and actuator occur in multiple cortical areas during the operation of a BMI. Initially, monkeys controlled the actuator by moving a hand-held pole. During this period, the BMI was trained to predict the actuator velocity. As the monkeys started using their cortical activity to control the actuator, the activity of individual neurons and neuronal populations became less representative of the animal's hand movements while representing the movements of the actuator. As a result of this adaptation, the animals could eventually stop moving their hands yet continue to control the actuator. These results show that, during BMI control, cortical ensembles represent behaviorally significant motor parameters, even if these are not associated with movements of the animal's own limb. | 10.1523/JNEUROSCI.4088-04.2005 |
pubmed_254_18714 | BACKGROUND
We propose a modified lung ultrasound (LUS) score in neonates with respiratory distress syndrome (RDS), which includes posterior instead of lateral lung fields, and a 5-grade rating scale instead of a 4-grade rating scale. The purpose of this study was to evaluate the reproducibility of the rating scale and its correlation with blood oxygenation and to assess the ability of early post-birth scans to predict the mode of respiratory support on day of life 3 (DOL 3). As a secondary objective, the weight of posterior scans in the overall LUS score was assessed.
METHODS
We analyzed 619 serial lung scans performed in 70 preterm infants < 32 weeks gestation and birth weight < 1500 g. Assessments were performed within 24 h of birth (LUS0) and on days 2, 3, 5, 7, 10, 14, 21 and 28. LUS scores were correlated with oxygen saturation over fraction of inspired oxygen (S/F) and mode of respiratory support. Interrater agreement was determined with the intraclass correlation coefficient (ICC) and Cronbach's alpha. Probabilities of the need for various respiratory support modes on DOL 3 were assessed with ordinal logistic regression. Least square (ls) means of the posterior and anterior pulmonary field scores were compared.
RESULTS
The LUS score correlated significantly with S/F (Spearman rho = -0.635; p < 0.0001) and had excellent interrater agreement (ICC = 0.94, 95% CI 0.93-0.95; Cronbach's alpha = 0.99). Significant predictors of ventilation requirements on DOL 3 were LUS0 (p < 0.016) and birth weight (BW) (p < 0.001). In the ROC analysis, LUS0 had high reliability in prognosing invasive ventilation on DOL 3 (AUC = 0.845 (95% DeLong CI: 0.738-0.951; p < 0.001)). Invasive ventilation was the most likely mode of respiratory support for LUS0 scores: ≥7 (in infants with BW 900 g), ≥ 10 (in infants with BW 1050 g) and ≥ 15 (in infants with BW 1280 g). Posterior fields exhibited significantly higher average scores than anterior fields. Respective ls means (confidence levels) were 4.0 (3.8-4.1) vs. 2.2 (2.0-2.4); p < 0.001.
CONCLUSIONS
Post-birth LUS predicts ventilation requirements on DOL 3. Scores of posterior pulmonary fields have a predominant weight in the overall LUS score. | 10.1186/s12887-020-02485-z |
pubmed_386_8474 | BACKGROUND
Despite the efforts, the level of dental caries remains prevalent in developed countries; It hasincreased in developing countries due to dietary changes. The aim of this study was to assess the effect of an educational intervention on the oral health of students in Chabahar city.
METHODS
This quasi-experimental study carried out on 200 students selected with systematic cluster sampling from schools located in Chabahar city, (100 students in each case and control groups). The data was collected using a questionnaire before the intervention, that was lecturing on oral health, and immediately and 3 months later. Data were analyzed using the SPSS software version 11.
RESULTS
The mean age of participants was 11.3 ± 1.3 years. The findings indicated that rate of oral self-care behaviors were significantly increased in the case group compared to the control group after the intervention (tooth brushing for twice a day 69%, Flossing tooth 34%, mouthwash 69%, and regular visiting a dentist 6% in case group versus 47% (p< 0.002), 14% (p< 0.001), 57% (p< 0.03) and 5% (p< 0.007) in the control group (, , , respectively.
CONCLUSION
Lecturing is an effective and cheap method on the promotion of oral health preventive behaviors particularly in deprived areas like Chabahar city. | pubmed_386_8474 |
pubmed_877_8189 | Because certain hereditary diseases show autistic behavior, and autism often runs in families, researchers seek genes underlying the pathophysiology of autism, thus core behaviors. Other researchers argue environmental factors are decisive, citing compelling evidence of an autism epidemic in the United States beginning about 1980. Recognition that environmental factors influence gene expression led to synthesis of these views - an 'epigenetic epidemic' provoked by pervasive environmental agents altering expression of vulnerable genes, inducing characteristic autistic biochemistries in many mothers and infants. Two toxins most implicated in the U.S. autism epidemic are analgesic/antipyretic acetaminophen (Tylenol) and oral antibiotic amoxicillin/clavulanate (Augmentin). Recently herbicide glyphosate (Roundup) was exponentially implicated. What do these toxins have in common? Acetaminophen depletes sulfate and glutathione required to detoxify it. Oral antibiotics kill and glyphosate inhibits intestinal bacteria that synthesize methionine (precursor of sulfate and glutathione, and required to methylate DNA), bacteria that synthesize tryptophan (sole precursor of neuroinhibitor serotonin), and bacteria that restrain ammonia-generating anaerobes. Sulfate plus glutathione normally sulfate fetal adrenal androgen dehydroepiandrosterone to DHEAS - major precursor of placental/postnatal estrogens. Glyphosate (and heavy metals) also inhibit aromatase that turns androgens to estrogens. Placental/postnatal estrogens dehydrate/mature brain myelin sheaths, mature corpus callosum and left hemisphere preferentially, dilate brain blood vessels, and elevate brain serotonin and oxytocin. Stress-induced weak androgens and estrogen depletion coherently explain white matter asymmetry and dysconnection in autism, extreme male brain, low brain blood flow, hyperexcitability, social anxiety, and insufficient maternal oxytocin at birth to limit fetal brain chloride/water and mature GABA. | 10.1016/j.clnesp.2017.10.005 |
pubmed_972_11212 | Although controversial, seasonal variations in testosterone have been observed in several populations of men throughout the world. This finding might have an impact on screening and treatment of hypogonadism. We examined the circannual patterns of sex hormones in the Southwest United States. A prospectively assembled database of almost 11 000 patients in a men's health practice was used to collect data on testosterone, estradiol, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and dehydroepiandrosterone-sulfate (DHEA-S). Patient age, address, and date of visit were recorded. Of note, testosterone-estrogen ratio (T/E ratio) and free testosterone were calculated values. The data were grouped by month and by season (3-month intervals beginning with June, July, and August as summer). Analysis of variance was used to compare hormone levels between seasonal and monthly data sets, with P < .05 regarded as statistical significance. Statistically significant differences in estradiol (P = .02), T/E ratio (P < .01), FSH (P = .02), and SHBG (P < .01) were observed between seasons. Peak-to-trough variations were as follows: 6% for estradiol, 16.5% for T/E ratio, 11.0% for FSH, and 11.6% for SHBG. The T/E ratio peaked in the spring and was at its nadir in the fall. No differences in testosterone (P = .21), LH (P = .25), free testosterone (P = .08), and DHEA-S (P = .11) were observed. Statistically significant evidence of variation in estradiol and T/E ratio were identified in the men included in this study. Although this is consistent with seasonal body habitus changes, physical activity levels, and hypothesized hormonal patterns, the variability reported in the literature makes further trials covering a broader geographic region important to confirm the findings. | 10.2164/jandrol.112.016386 |
pubmed_93_23679 | A striking feature of Burkholderia contaminans strain MS14 is the production of a glycolipopeptide named occidiofungin. Occidiofungin has a broad range of antifungal activities against plant and animal pathogens. In this study, a complete covalent structure characterization and identification of the whole genomic DNA region for the occidiofungin gene (ocf) cluster are described. Discovery of the presence of 2,4-diaminobutyric acid and 3-chloro-β-hydroxytyrosine and elucidation of the structure of a novel C(18) fatty amino acid residue have been achieved. In addition, seven additional putative open reading frames (the genes from ocfI to ocfN [ocfI-N] and ORF16) were identified. Transcription of all the putative genes ocfI-N identified in the region except ORF16 was regulated by both ambR1 and ambR2. Elucidation of the structure and the ocf gene cluster provides insight into the biosynthesis of occidiofungin and promotes future aims at understanding the biosynthetic machinery. This work provides new avenues for optimizing the production and synthesis of structural analogs of occidiofungin. | 10.1128/AEM.00377-11 |
pubmed_408_10921 | The physiological effects of elastic compression stockings on venous disorders of the leg have been studied in three groups of 10 patients. These patients were divided by examination and ascending venography into those with (a) a normal venous system in the leg, (b) superficial varicose veins and (c) a post-phlebitic limb. In a randomised cross-over trial each group wore Eesiness NHS two-way stretch or Sigvaris medium compression below-knee stockings for three weeks. In the post-phlebitic limb group a further comparison was made with Sigvaris strong compression below-knee stockings after a 6-week rest period. The effects were objectively compared using foot volumetry and sodium (24Na) subcutaneous tissue clearance. The physiological benefits of Sigvaris medium and strong compression stockings were comprehensively demonstrated by both methods of assessment in patients with the post-phlebitic limb. Benefit from Sigvaris medium compression stockings was also demonstrated in the patients with varicose veins. In the group with normal veins there were negligible. | pubmed_408_10921 |
pubmed_703_11001 | The elongation step in transcription has gained attention for its roles in regulation of eukaryotic gene expression and for its influence on RNA processing. Sophisticated genetic analyses have identified factors and/or conditions that may affect transcription elongation rate or processivity; however, differentiation of direct and indirect effects on transcription is difficult using in vivo strategies. Therefore, effective, reproducible in vitro assays have been developed to test whether a given factor or condition can have a direct effect on the kinetics of transcription elongation. We have adapted a fully reconstituted transcription system for RNA polymerase I (Pol I) for kinetic analysis of transcription elongation rate in vitro. The assay described here has proven to be effective in the characterization of defects or enhancement of wild-type transcription elongation by RNA Pol I. Since transcription elongation by RNA Pol I has only recently gained significant attention, this assay will be a valuable resource for years to come. | 10.1007/978-1-61779-376-9_37 |
pubmed_1100_15419 | OBJECTIVES
To estimate the excess mortality of injecting drug users (IDU) stratified by HIV serostatus compared with the general population in Italy. To compare total and cause-specific mortality in HIV-positive versus HIV-negative IDU, in order to identify possible HIV-related non-AIDS causes of death in this population.
METHODS
All IDU attending two drug-treatment centres in Rome who underwent HIV testing between 1985 and 1991 were enrolled into a prospective study. The end-point of the study was death from any cause by 31 December 1991. Mortality rates were compared using age-adjusted standardized mortality ratios and person-time techniques.
RESULTS
Of the 2431 IDU, 1661 (68.3%) were HIV-seronegative and 82 seroconverted. Of 181 deaths, comprising 89 from AIDS and 92 from other causes, the mortality rate was 4.5 and 0.8 per 100 person-years in HIV-seropositives and HIV-seronegatives, respectively. For non-AIDS mortality in HIV-seropositives, the overall rate was 1.7 per 100 person-years. Deaths from overdose and endocarditis/embolus tended to be higher in HIV-seropositive than HIV-seronegative IDU, although there was no difference in the rate of deaths due to pneumonia by HIV serostatus.
CONCLUSIONS
These data are consistent with other studies demonstrating a higher frequency of mortality among HIV-seropositive IDU. The excess in overdose mortality among HIV-seropositives is disturbing and merits further investigation. | 10.1097/00002030-199403000-00008 |
pubmed_1123_5868 | Immunohistochemical loss of keratin (K)13 is one of the most valuable diagnostic criteria for discriminating carcinoma in situ (CIS) from non-malignancies in the oral mucosa while K13 is stably immunolocalized in the prickle cells of normal oral epithelium. To elucidate the molecular mechanism for the loss of K13, we compared the immunohistochemical profiles for K13 and K16 which is not expressed in normal epithelia, but instead enhanced in CIS, with their mRNA levels by in-situ hybridization in formalin-fixed paraffin sections prepared from 23 CIS cases of the tongue, which were surgically removed. Reverse transcriptase-PCR was also performed using RNA samples extracted from laser-microdissected epithelial fragments of the serial paraffin sections in seven of the cases. Although more enhanced expression levels for K16 were confirmed at both the protein and gene levels in CIS in these seven cases, the loss of K13 was associated with repressed mRNA levels in four cases, but not in the other three cases. The results suggest that the loss of K13 is partly due to its gene repression, but may also be due to some unknown post-translational events. | 10.1038/modpathol.2011.218 |
pubmed_327_22880 | AIM
To determine the relative risk of a poor visual outcome following posterior capsule rupture during cataract surgery.
METHODS
Prospective data were collected on consecutive eyes undergoing cataract extraction. The patient's age, preoperative visual acuity, ocular comorbidity, grade of surgeon, and operative complications were documented. The best spectacle corrected visual acuity was recorded at discharge from the hospital service.
RESULTS
From a total of 1533 cases, 1420 (92.6%) eyes had complete follow up data. Posterior capsule rupture occurred in 59 (4.1%) cases. Eyes with posterior capsule rupture were 3.8 times more likely to have a final best spectacle corrected visual acuity less than 6/12.
CONCLUSIONS
Eyes having posterior capsule rupture during cataract surgery have a significant risk of reduced visual acuity. | 10.1136/bjo.85.2.222 |
pubmed_804_6542 | Perceptual learning, improvement in discriminative ability as a consequence of training, is one of the forms of sensory system plasticity that has driven profound changes in our conceptualization of sensory cortical function. Psychophysical and neurophysiological studies of auditory perceptual learning have indicated that the characteristics of the learning, and by implication the nature of the underlying neural changes, are highly task specific. Some studies in animals have indicated that recruitment of neurons to the population responding to the training stimuli, and hence an increase in the so-called cortical "area of representation" of those stimuli, is the substrate of improved performance, but such changes have not been observed in other studies. A possible reconciliation of these conflicting results is provided by evidence that changes in area of representation constitute a transient stage in the processes underlying perceptual learning. This expansion - renormalization hypothesis is supported by evidence from studies of the learning of motor skills, another form of procedural learning, but leaves open the nature of the permanent neural substrate of improved performance. Other studies have suggested that the substrate might be reduced response variability - a decrease in internal noise. Neuroimaging studies in humans have also provided compelling evidence that training results in long-term changes in auditory cortical function and in the auditory brainstem frequency-following response. Musical training provides a valuable model, but the evidence it provides is qualified by the fact that most such training is multimodal and sensorimotor, and that few of the studies are experimental and allow control over confounding variables. More generally, the overwhelming majority of experimental studies of the various forms of auditory perceptual learning have established the co-occurrence of neural and perceptual changes, but have not established that the former are causally related to the latter. Important forms of perceptual learning in humans are those involved in language acquisition and in the improvement in speech perception performance of post-lingually deaf cochlear implantees over the months following implantation. The development of a range of auditory training programs has focused interest on the factors determining the extent to which perceptual learning is specific or generalises to tasks other than those used in training. The context specificity demonstrated in a number of studies of perceptual learning suggests a multiplexing model, in which learning relating to a particular stimulus attribute depends on a subset of the diverse inputs to a given cortical neuron being strengthened, and different subsets being gated by top-down influences. This hypothesis avoids the difficulty of balancing system stability with plasticity, which is a problem for recruitment hypotheses. The characteristics of auditory perceptual learning reflect the fact that auditory cortex forms part of distributed networks that integrate the representation of auditory stimuli with attention, decision, and reward processes. | 10.1016/j.heares.2018.03.011 |
pubmed_1051_12743 | BACKGROUND
To date, health-effects research on environmental stressors has rarely focused on behavioral and mental health outcomes. That lack of research is beginning to change. Science and policy experts in the environmental and behavioral health sciences are coming together to explore converging evidence on the relationship-harmful or beneficial-between environmental factors and mental health.
OBJECTIVES
To organize evidence and catalyze new findings, the National Academy of Sciences, Engineering, and Medicine (NASEM) hosted a workshop 2-3 February 2021 on the interplay of environmental exposures and mental health outcomes.
METHODS
This commentary provides a nonsystematic, expert-guided conceptual review and interdisciplinary perspective on the convergence of environmental and mental health, drawing from hypotheses, findings, and research gaps presented and discussed at the workshop. Featured is an overview of what is known about the intersection of the environment and mental health, focusing on the effects of neurotoxic pollutants, threats related to climate change, and the importance of health promoting environments, such as urban green spaces.
DISCUSSION
We describe what can be gained by bridging environmental and psychological research disciplines and present a synthesis of what is needed to advance interdisciplinary investigations. We also consider the implications of the current evidence for a) foundational knowledge of the etiology of mental health and illness, b) toxicant policy and regulation, c) definitions of climate adaptation and community resilience, d) interventions targeting marginalized communities, and e) the future of research training and funding. We include a call to action for environmental and mental health researchers, focusing on the environmental contributions to mental health to unlock primary prevention strategies at the population level and open equitable paths for preventing mental disorders and achieving optimal mental health for all. https://doi.org/10.1289/EHP9889. | 10.1289/EHP9889 |
pubmed_751_13639 | The effectiveness of a rural regionalized perinatal care (RPC) program was evaluated by a controlled, population-based design. The RPC program, begun in a carefully selected study region in July 1975, evolved into a system of care which included the following major components: identification of high-risk pregnancies and high-risk newborn infants; obstetric and newborn consultation and referral services between Level I, II, and III centers; professional education for physicians, nurses, and other health professionals; and nutrition and social work consultation. Substantial resources were made available from 1975 to 1980 to implement this "total package" of RPC. A matched, control region was identified which, except for the RPC program, was as comparable as possible to the study region. It was hypothesized that the RPC intervention would have the following effects when the study region was compared with the control region: reduction in fetal and neonatal mortality, no increase in postneonatal mortality, and reduction in obstetric and newborn morbidity. These findings were reported previously. This paper presents results of hypothesized reductions in adverse developmental, neurologic, maternal-infant attachment, and selected physical health outcomes. A sample of 447 infants was assessed by an extensive battery of instruments at 1 year, adjusted for gestational age. The most notable findings were mothers' reports of receptive language development and observations of maternal attachment behaviors that significantly favored the study region. No significant differences between study and control regions were observed for Bayley Mental and Motor Scores, abnormal neurologic signs, and the physical health measures.(ABSTRACT TRUNCATED AT 250 WORDS) | pubmed_751_13639 |
pubmed_157_22030 | Flow-mediated dilation (FMD) relies on reactive hyperemia to stimulate the endothelium to release nitric oxide, causing smooth muscle relaxation. Hypercapnia also produces vasodilation, which is thought to be nitric oxide-independent. The purpose of this study was to compare and contrast the effects of hypercapnia and reactive hyperemia as stimuli for brachial artery dilation. On separate days, twenty-five participants underwent vasodilation studies via reactive hyperemia or hypercapnia (i.e. 10 mmHg increase in end-tidal carbon dioxide [PetCO2)]). During both studies changes in brachial artery diameter were recorded using continuous ultrasound imaging. Heart rate (HR) was measured throughout both tests. Resting HR (63 ± 11 versus 68 ± 14 beats min(-1), p = 0.0027) and baseline brachial artery diameter measurements (4.57 ± 1.51 versus 5.28 ± 1.86 mm, p = 0.022) were significantly different between reactive hyperemia and hypercapnia, respectively. HR at peak dilation (65 ± 11 versus 76 ± 14 beats min(-1), p < 0.0001), peak vessel dilation (8.68 ± 4.50 versus 5.28 ± 1.86%, p = 0.002), and time to peak dilation (90.8 ± 120.1 versus 658.3 ± 226.6 s, p < 0.0001) were also significantly different between reactive hyperemia and hypercapnia. The dynamics by which reactive hyperemia and hypercapnia stimulate vasodilation appear to differ. Hypercapnia produces a smaller and slower vasodilatory effect than reactive hyperemia. Further research is necessary to better understand the mechanisms of vasodilation under hypercapnic conditions. | 10.1088/0967-3334/37/3/380 |
pubmed_893_24040 | BACKGROUND
Schizophrenia, a neurodevelopmental disorder, involves abnormalities in functional connectivity (FC) across distributed neural networks, which are thought to antedate the emergence of psychosis. In a cohort of adolescents and young adults at clinical high risk (CHR) for psychosis, we applied data-driven approaches to resting-state fMRI data so as to systematically characterize FC abnormalities during this period and determine whether these abnormalities are associated with psychosis risk and severity of psychotic symptoms.
METHODS
Fifty-one CHR participants and 47 matched healthy controls (HCs) were included in our analyses. Twelve of these CHR participants developed psychosis within 3.9 years. We estimated one multivariate measure of FC and studied its relationship to CHR status, conversion to psychosis and positive symptom severity.
RESULTS
Multivariate analyses revealed between-group differences in whole-brain connectivity patterns of bilateral temporal areas, mostly affecting their functional connections to the thalamus. Further, more severe positive symptoms were associated with greater connectivity abnormalities in the anterior cingulate and frontal cortex.
CONCLUSIONS
Our study demonstrates that the well-established FC abnormalities of the thalamus and temporal areas observed in schizophrenia are also present in the CHR period, with aberrant connectivity of the temporal cortex most associated with psychosis risk. | 10.1016/j.bpsc.2016.12.008 |
pubmed_594_17311 | The nature of the interaction of the transition-state analogue inhibitor L-leucinephosphonic acid (LPA) with the leucine aminopeptidase from Aeromonas proteolytica (AAP) was investigated. LPA was shown to be a competitive inhibitor at pH 8.0 with a K(i) of 6.6 microM. Electronic absorption spectra, recorded at pH 7.5 of [CoCo(AAP)], [CoZn(AAP)], and [ZnCo(AAP)] upon addition of LPA suggest that LPA interacts with both metal ions in the dinuclear active site. EPR studies on the Co(II)-substituted forms of AAP revealed that the environments of the Co(II) ions in both [CoZn(AAP)] and [ZnCo(AAP)] become highly asymmetric and constrained upon the addition of LPA and clearly indicate that LPA interacts with both metal ions. The X-ray crystal structure of AAP complexed with LPA was determined at 2.1 A resolution. The X-ray crystallographic data indicate that LPA interacts with both metal centers in the dinuclear active site of AAP and a single oxygen atom bridge is absent. Thus, LPA binds to the dinuclear active site of AAP as an eta-1,2-mu-phosphonate with one ligand to the second metal ion provided by the N-terminal amine. A structural comparison of the binding of phosphonate-containing transition-state analogues to the mono- and bimetallic peptidases provides insight into the requirement for the second metal ion in bridged bimetallic peptidases. On the basis of the results obtained from the spectroscopic and X-ray crystallographic data presented herein along with previously reported mechanistic data for AAP, a new catalytic mechanism for the hydrolysis reaction catalyzed by AAP is proposed. | 10.1021/bi0100891 |
pubmed_196_3046 | Multiple sclerosis is an inflammatory disease of the CNS characterized by neurologic impairment resulting from primary demyelination and axonal damage. The pathogenic mechanisms of disease development include Ag-specific T cell activation and Th1 differentiation, followed by T cell and macrophage migration into the CNS. CCL2 is a chemokine that induces migration of monocytes, memory T cells, and dendritic cells. We previously demonstrated that picomolar levels of CCL2 strongly restrict the development of inflammation in models of inflammatory bowel disease. Moreover, CCR2 deficiency in T cells promotes a program inducing the accumulation of Foxp3+ regulatory T cells while decreasing the levels of Th17 cells in vivo. In the current study, the effect of picomolar levels of CCL2 on the autoimmune inflammatory response associated with a multiple sclerosis-like disease in mice was analyzed. We found that low dosages of CCL2 were effective in suppressing MOG-induced experimental autoimmune encephalomyelitis (EAE), and they downregulated chronic EAE. The modulation of EAE by CCL2 was associated with downregulation of Th1/Th17 cells and upregulation of TGF-β and induction of regulatory CD4+Foxp3 T cells. Most strikingly, these low levels of CCL2 induced formation of highly functional regulatory T cells. Thus, this study strongly supports the potential use of CCL2 as a regulatory mediator for treating inflammatory autoimmune diseases. | 10.4049/jimmunol.1900424 |
pubmed_406_11517 | Cytospectrophotometry of agar films soaked with serum albumin and of nervous tissue cells has shown that the histochemical colour reaction of proteins with Amido Black 10 B obeys Beer's law and that the spectral characteristics of this reaction are not significantly changed after fixation and histological procedure of nervous tissue. In cats, after in situ electrostimulation, and in rats, after anticipation stress, quantitative changes in the total protein content per cell were revealed in nerve and glial cells of cat sympathetic ganglion and rat spinal cord with the aid of cytospectrophotometry of Amido Black-stained sections. Staining with Amido Black 10B is recommended for cytospectrophotometric determinations of total protein and of separate protein fractions in nervous system cells. | pubmed_406_11517 |
pubmed_321_8795 | OBJECTIVE
To estimate the association of pregnancy loss with common air pollutant exposure. Ambient air pollution exposure has been linked to adverse pregnancy outcomes, but few studies have investigated its relationship with pregnancy loss.
DESIGN
Prospective cohort study.
SETTING
Not applicable.
PATIENT(S)
A total of 343 singleton pregnancies in a multisite prospective cohort study with detailed protocols for ovulation and pregnancy testing.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Timing of incident pregnancy loss (from ovulation).
RESULT(S)
The incidence of pregnancy loss was 28% (n = 98). Pollutant levels at women's residences were estimated using modified Community Multiscale Air Quality models and averaged during the past 2 weeks (acute) and the whole pregnancy (chronic). Adjusted Cox proportional hazards models showed that an interquartile range increase in average whole pregnancy ozone (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.07-1.17) and particulate matter <2.5 μm (HR 1.13, 95% CI 1.03-1.24) concentrations were associated with faster time to pregnancy loss. Sulfate compounds also appeared to increase risk (HR 1.58, 95% CI 1.07-2.34). Last 2 weeks of exposures were not associated with loss.
CONCLUSION(S)
In a prospective cohort of couples trying to conceive, we found evidence that exposure to air pollution throughout pregnancy was associated with loss, but delineating specific periods of heightened vulnerability await larger preconception cohort studies with daily measured air quality. | 10.1016/j.fertnstert.2017.09.037 |
pubmed_605_11230 | AIMS
The aim of the study was to evaluate the safety and efficacy of left atrial appendage occlusion (LAAO) with the AMPLATZER Cardiac Plug (ACP) or Amulet using aspirin alone (ASA) as post-implantation antithrombotic treatment.
METHODS AND RESULTS
This was a single-centre, prospective, non-randomised study on LAAO with the ACP or Amulet in a consecutive cohort (n=110) treated by ASA alone post implantation. The primary outcome was device-related thrombosis, while secondary outcomes were ischaemic stroke or major bleeding. Clinical follow-up was conducted after six weeks and 12 months with TEE and cardiac CT. One hundred and seven patients were included in the analysis. Three patients were excluded due to a mechanical valve prosthesis. CHA2DS2-VASc score was 4.4±1.6 and HAS-BLED 4.1±1.1. Successful implantation was obtained in all patients with a periprocedural complication rate of 4.6%. Median follow-up was 2.3 years, with a total of 265 patient-years. Device-related thrombosis was detected in 2/107 (1.9%) cases. Stroke occurred in 6/107 patients, with an annualised rate of 2.3%, which is a 61% risk reduction compared to the predicted rate. Annual risk of major bleeding was reduced by 57%.
CONCLUSIONS
LAAO with the ACP or Amulet was safely performed with ASA monotherapy after implantation without an increased risk of device-related thrombosis or stroke. | 10.4244/EIJ-D-16-00726 |
pubmed_648_19945 | Numerous rheumatologic autoimmune diseases, among which rheumatoid arthritis, are chronic inflammatory diseases capable of inducing multiple cumulative articular and extra-articular damage, if not properly treated. Nevertheless, benign conditions may, similarly, exhibit arthritis as their major clinical finding, but with short-term duration instead, and evolve to spontaneous resolution in a few days to weeks, without permanent articular damage. Such distinction-self-limited arthritis with no need of immunosuppressive treatment or chronic arthritis at early stages?-represents one of the greatest challenges in clinical practice, once many metabolic, endocrine, neoplastic, granulomatous, infectious diseases and other autoimmune conditions may mimic rheumatoid arthritis. Indeed, the diagnosis of rheumatoid arthritis at early stages is a crucial step to a more effective mitigation of the disease-related damage. As a prototype of chronic inflammatory autoimmune disease, rheumatoid arthritis has been linked to oxidative stress, a condition in which the pool of reactive oxygen species increases over time, either by their augmented production, the reduction in antioxidant defenses, or the combination of both, ultimately implying compromise in the redox signaling. The exact mechanisms through which oxidative stress may contribute to the initiation and perpetuation of local (in the articular milieu) and systemic inflammation in rheumatoid arthritis, particularly at early stages, still remain to be determined. Furthermore, the role of antioxidants as therapeutic adjuvants in the control of disease activity seems to be overlooked, as a little number of short studies addressing this issue is currently found. Thus, the present review focuses on the binomial rheumatoid arthritis-oxidative stress, bringing insights into their pathophysiological relationships, as well as the implications of potential diagnostic oxidative stress biomarkers and therapeutic interventions directed to the oxidative status in patients with rheumatoid arthritis. | 10.1155/2019/7536805 |
pubmed_675_15366 | Evaluation of in vivo potencies plays an important role in drug discovery. Traditionally, the cellular activity and percent of plasma protein binding of a test agent are evaluated separately, with the plasma protein binding-adjusted cellular potency computation used to estimate in vivo potency. This process is costly, takes weeks to complete, and is increasingly unreliable for compounds that bind extensively to plasma proteins. Described in this article is a simple, high-throughput human plasma in-cell Western (ICW) assay that directly incorporates plasma protein binding into a cellular pharmacodynamic assay to provide a rapid and accurate estimate of in vivo potencies. The assay is versatile and can be readily employed for various targets that require short treatment periods for displaying maximal biological responses. © 2021 Wiley Periodicals LLC. Basic Protocol: Concentration-dependent human plasma ICW assay to determine test compound IC50 against the target of interest. | 10.1002/cpz1.51 |
pubmed_628_17034 | Anticalins comprise a novel class of receptor proteins with predetermined ligand specificities which were engineered using the lipocalin fold. Attractive features of these artificial ligand-binding proteins include their small size and monomeric nature, being composed of a single polypeptide chain. Here we report the construction of a functional fusion protein from two independent anticalins, a so-called duocalin. The gene for the fusion protein was assembled from nucleotide sequences encoding an anticalin with fluorescein specificity on the one hand and an anticalin with digoxigenin specificity on the other. Both engineered lipocalins were previously selected from a random library prepared on the basis of the bilin-binding protein, a natural lipocalin abundant in insects. The corresponding fusion protein was expressed in a secretable form in E. coli cells and isolated from the periplasmic fraction using the Strep-tag method. The major fraction of the purified protein appeared to possess the proper pattern of altogether four disulphide bonds. The ligand-binding behaviour of the fusion protein was investigated both by solid phase ELISA and in fluorescence titration experiments. Our results demonstrate that the novel fusion protein has retained both ligand specificities. Up to now, dimerized ligand-binding proteins were mostly derived from recombinant antibody fragments. Compared with those constructs the duocalins, either with bispecific or with bivalent target recognition properties, should provide useful reagents for various purposes in biotechnology. | 10.1515/BC.2001.166 |
pubmed_477_3529 | This study was undertaken to determine the in vitro enamel fluoride uptake and distribution from fluoride-containing orthodontic cements after 21 days' exposure and the effect on acid demineralization. Three successive acid-etch biopsy specimens were taken from tne facial middle third of thirty maxillary central incisors. Orthodontic bands were cemented to these teeth, ten each with (A) zinc phosphate, (B) zinc phosphate containing 5 percent SnF2, and (C) silicophosphate cement, respectively. The teeth were suspended individually in synthetic saliva at 37 degrees C. in a shaking incubator for 21 days. The bands were removed, the cement was cleaned off, and three successive biopsies were carried out electrometrically and for calcium by atomic absorption spectroscopy. Fluoride concentrations were adjusted to depths of 10.0, 20.0, and 30.0 micron for the three biopsies, respectively. The acquired fluoride was calculated and the data were analyzed statistically. In addition, six teeth each with bands cemented with cements A, B, and C, respectively, were incubated in synthetic saliva for 21 days, after which the bands were loosened and the teeth were suspended for a further 3 months in a caries-producing medium. After careful cleaning, the enamel surfaces were examined by microradiography and scanning electron microscopy for demineralization. Results showed that acquired fluoride at the first depth was highest with cement C, followed by cement B, with cement A producing a net loss of fluoride. Further, the greater the fluoride uptake, the more resistant the enamel was to demineralization. | 10.1016/s0002-9416(81)90463-2 |
pubmed_14_17735 | The classification of human gliomas is currently based solely on neuropathological criteria. Prognostic and therapeutic parameters are dependent upon whether the tumors are deemed to be of astrocytic or oligodendroglial in origin. We sought to identify molecular reagents that might provide a more objective parameter to assist in the classification of these tumors. In order to identify mRNA transcripts for genes normally transcribed exclusively by oligodendrocytes. Northern blot analysis was carried out on RNA samples from 138 human gliomas. Transcripts encoding the myelin basic protein (MBP) were found in an equally high percentage of tumors that by neuropathological criteria were either astrocytic or oligodendroglial. In contrast, proteolipid protein (PLP) and cyclic nucleotide phosphodiesterase (CNP) mRNA molecules were found significantly more often in oligodendrogliomas than in astrocytomas. The strongest association with histological typing was found with the transcript for the myelin galactolipid biosynthetic enzyme UDP-galactose: ceramide galactosytransferase (CGT), which was about twice as frequently detected in tumors of oligodendroglial type. Results of glycolipid analyses were previously reported on a subset of the tumors studied herein. Statistical analyses of both molecular and biochemical data on this subset of astrocytomas, oligoastrocytomas, and oligodendrogliomas were performed to determine if a panel of markers could be used to separate astrocytic and oligodendroglial tumors. The presence of asialo GM1 (GA1) and the absence of paragloboside occurred most frequently in oligodendrogliomas. Ceramide monohexoside (CMH) levels correlated highly with the expression of mRNA for 4 myelin proteins: CGT, MBP, CNP, and PLP. The best combination of 2 markers of oligodendroglial tumors was CGT and GA1; the best combination of 3 markers was the presence of CGT, GA1, and the absence of paragloboside. We conclude that this combination of markers could be useful in distinguishing between astrocytic and oligodendroglial tumors. | 10.1093/jnen/61.4.329 |
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