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pubmed_1000_16259 | Cold denaturation of yeast phosphoglycerate kinase (yPGK) was investigated by a combination of far UV circular dichroism (CD), steady-state and time-resolved fluorescence, and small angle X-ray scattering. It was shown that cold denaturation of yPGK cannot be accounted for by a simple two-state process and that an intermediate state can be stabilized under mild denaturing conditions. Comparison between far UV CD and fluorescence shows that in this state the protein displays a fluorescence signal corresponding mainly to exposed tryptophans, whereas its CD signal is only partially modified. Comparison with spectroscopic data obtained from a mutant missing the last 12 amino-acids (yPGK delta404) suggests that lowering the temperature mainly results in a destabilization of hydrophobic interactions between the two domains. Small angle X-ray scattering measurements give further information about this stabilized intermediate. At 4 degrees C and in the presence of 0.45 M Gdn-HCl, the main species corresponds to a protein as compact as native yPGK, whereas a significant proportion of ellipticity has been lost. Although various techniques have shown the existence of residual structures in denatured proteins, this is one example of a compact denatured state devoid of its main content in alpha helices. | 10.1002/(sici)1097-0134(20000201)38:2<226::aid-prot10>3.0.co;2-h |
pubmed_464_24829 | The mammalian Y chromosome is critical for male sex determination and spermatogenesis. However, linking each Y gene to specific aspects of male reproduction has been challenging. As the Y chromosome is notoriously hard to sequence and target, functional studies have mostly relied on transgene-rescue approaches using mouse models with large multi-gene deletions. These experimental limitations have oriented the field toward the search for a minimum set of Y genes necessary for male reproduction. Here, considering Y-chromosome evolutionary history and decades of discoveries, we review the current state of research on its function in spermatogenesis and reassess the view that many Y genes are disposable for male reproduction. | pubmed_464_24829 |
pubmed_262_10324 | Magnetosome biomineralization and magnetotaxis in magnetotactic bacteria are controlled by numerous, mostly unknown gene functions that are predominantly encoded by several operons located within the genomic magnetosome island (MAI). Genetic analysis of magnetotactic bacteria has remained difficult and requires the development of novel tools. We established a Cre-lox-based deletion method which allows the excision of large genomic fragments in Magnetospirillum gryphiswaldense. Two conjugative suicide plasmids harboring lox sites that flanked the target region were subsequently inserted into the chromosome by homologous recombination, requiring only one single-crossover event, respectively, and resulting in a double cointegrate. Excision of the targeted chromosomal segment that included the inserted plasmids and their resistance markers was induced by trans expression of Cre recombinase, which leaves behind a scar of only a single loxP site. The Cre helper plasmid was then cured from the deletant strain by relief of antibiotic selection. We have used this method for the deletion of 16.3-kb, 61-kb, and 67.3-kb fragments from the genomic MAI, either in a single round or in subsequent rounds of deletion, covering a region of approximately 87 kb that comprises the mamAB, mms6, and mamGFDC operons. As expected, all mutants were Mag(-) and some were Mot(-); otherwise, they showed normal growth patterns, which indicates that the deleted region is not essential for viability in the laboratory. The method will facilitate future functional analysis of magnetosome genes and also can be utilized for large-scale genome engineering in magnetotactic bacteria. | 10.1128/AEM.02805-09 |
pubmed_278_4568 | Head-out water immersion alters respiratory compliance which underpins defining pressure at a "Lung centroid" and the breathing "Static Lung Load". In diving medicine as in designing dive-breathing devices a single value of lung centroid pressure is presumed as everyone's standard. On the contrary, we considered that immersed respiratory compliance is disparate among a homogenous adult group (young, healthy, sporty). We wanted to substantiate this ample scattering for two reasons: (i) it may question the European standard used in designing dive-breathing devices; (ii) it may contribute to understand the diverse individual figures of immersed work of breathing. Resting spirometric measurements of lung volumes and the pressure-volume curve of the respiratory system were assessed for 18 subjects in two body positions (upright Up, and supine Sup). Measurements were taken in air (Air) and with subjects immersed up to the sternal notch (Imm). Compliance of the respiratory system (Crs) was calculated from pressure-volume curves for each condition. A median 60.45% reduction in Crs was recorded between Up-Air and Up-Imm (1.68 vs 0.66 L/kPa), with individual reductions ranging from 16.8 to 82.7%. We hypothesize that the previously disregarded scattering of immersion-reduced respiratory compliance might participate to substantial differences in immersed work of breathing. | 10.1038/s41598-021-88925-x |
pubmed_1038_20221 | Expression of several cytokines has been demonstrated in Hodgkin and Reed-Sternberg (H&RS) cells in vitro and in vivo. In order to determine whether interleukin-1 beta (IL-1 beta), IL-3, IL-6, GM-CSF, G-CSF, and TNF-alpha are elevated in Hodgkin's disease (HD), we tested the sera of untreated patients with HD by means of sensitive sandwich ELISAs. GM-CSF was detected in 22/56 patients (39%; range 40-140 pg/ml), IL-3 in 5/40 (13%; range 13-26 pg/ml), and IL-6 in 32/56 patients (57%; range 12-332 pg/ml). TNF-alpha and IL-1 beta were detected in only 3/43 patients (7%; range: TNF-alpha: 36-66 pg/ml; IL-1 beta: 389-1505 pg/ml) and G-CSF not at all. All patients with measurable IL-3 levels had both elevated IL-6 and GM-CSF levels, and the majority of patients with elevated IL-6 also had elevated GM-CSF levels and vice versa. In contrast, the 3/40 patients with both measurable IL-beta and TNF-alpha did not have elevated IL-3, IL-6, or GM-CSF levels. Cytokine levels were independent of stage or the presence of B-symptoms, and there was no correlation with any other clinical or laboratory parameter. Elevations of the respective cytokines might be a means to maintain normal blood cell counts in the respective patients with HD. | pubmed_1038_20221 |
pubmed_957_669 | To make full use of tea seed cake protein (TSCP), this study investigated the physicochemical and functional properties of TSCP, including the TSCP extract and three ultrafiltration fractions TSCP-1 (Mw > 10 kDa), TSCP-2 (3.5 kDa < Mw < 10 kDa), and TSCP-3 (Mw < 3.5 kDa). After ultrafiltration, the content, thermal stability, and surface hydrophobicity of TSCP were increased, and the molecular weight distribution and structure of TSCP showed significant differences. In terms of functionality, each fraction showed its advantages. Specifically, compared with the others, TSCP had better solubility and foaming properties, and TSCP-1 had significantly higher oil absorption capacity, and TSCP-2 had better water absorption capacity and emulsifying properties, and TSCP-3 can flow more easily (p < 0.05). In terms of nutritional value, the content of essential amino acids in all samples was sufficient. The degree of hydrolysis of TSCP was highest (80.98 ± 1.50%), and ultrafiltration decreased digestibility. These results indicated that ultrafiltration effectively improved the structure and functional properties of TSCP, and the obtained fractions can be applied to different scenarios. Practical Application: Tea seed cakes are rich in protein and usually regarded as byproducts during oil processing. Because of its good functional properties, tea seed cake proteins obtained by ultrafiltration have the potential to be used as ingredients for food. | 10.1111/1750-3841.16324 |
pubmed_1052_22725 | BACKGROUND
Nutrients such as ω-3 fatty acids including fish oil components eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) suppress the growth and promote apoptosis of tumor cells, improve immune function and reduce the effects of systemic inflammatory response syndrome. We sought to investigate the effect of ω-3 fish oil fat emulsion-based parenteral nutrition (PN) on nutritional state, immune function, inflammatory reaction, expression of tumor factors and complication incidence in patients after surgical resection of gastric cancer.
METHODS
Forty-eight patients after surgical operation of gastric tumor in hospital were randomly divided into the control group and intervention group. Patients in both groups were treated with iso-nitrogen and iso-caloric parenteral nutrition support. In addition, the intervention group received ω-3 fish oil fat emulsion and the control group received soybean oil. The indicators of nutrition, immune function and inflammation in the two groups were detected on the day before the operation and postoperative day 6. The rate of complication was compared between the two groups.
RESULTS
There was no significant difference in nutritional state, liver function and renal function between the two groups (P > 0.05). However, the levels of inflammatory markers were significantly decreased (P < 0.01), and the rate of complication was also decreased in the intervention group as compared with the control group.
CONCLUSIONS
ω-3 fish oil fat emulsion-based parenteral nutrition alleviates the inflammatory reaction and reduces the rate of inflammatory complications. | 10.1186/1475-2891-13-25 |
pubmed_872_12749 | The Milwaukee County General Assistance Medical Program implemented strategies to improve the delivery of care to its patients that include patient education and a Nurse Telephone Line. The partnership between a county-funded program and an academic health center has been very productive and resulted in improvements to the program that benefit underserved patients. The outcomes of these educational strategies are described. | pubmed_872_12749 |
pubmed_1091_11153 | OBJECTIVE
To evaluate the costs of using dextrose gel as a primary treatment for neonatal hypoglycemia in the first 48 hours after birth compared with standard care.
STUDY DESIGN
We used a decision tree to model overall costs, including those specific to hypoglycemia monitoring and treatment and those related to the infant's length of stay in the postnatal ward or neonatal intensive care unit, comparing the use of dextrose gel for treatment of neonatal hypoglycemia with placebo, using data from the Sugar Babies randomized trial. Sensitivity analyses assessed the impact of dextrose gel cost, neonatal intensive care cost, cesarean delivery rate, and costs of glucose monitoring.
RESULTS
In the primary analysis, treating neonatal hypoglycemia using dextrose gel had an overall cost of NZ$6863.81 and standard care (placebo) cost NZ$8178.25; a saving of NZ$1314.44 per infant treated. Sensitivity analyses showed that dextrose gel remained cost saving with wide variations in dextrose gel costs, neonatal intensive care unit costs, cesarean delivery rates, and costs of monitoring.
CONCLUSIONS
Use of buccal dextrose gel reduces hospital costs for management of neonatal hypoglycemia. Because it is also noninvasive, well tolerated, safe, and associated with improved breastfeeding, buccal dextrose gel should be routinely used for initial treatment of neonatal hypoglycemia.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry: ACTRN12608000623392. | 10.1016/j.jpeds.2018.02.036 |
pubmed_916_18191 | It is commonly assumed that attentional inhibitory functioning decreases with age, even though empirical evidence is mixed. These inconsistencies possibly stem from methodological artifacts: distractor inhibition is typically assessed with the negative priming paradigm, which confounds inhibition and episodic retrieval. In the present study, we investigated age differences in a sequential distractor repetition paradigm (Giesen, Frings, & Rothermund, 2012) that provides independent estimates of distractor inhibition and episodic retrieval processes. Older (60+ yrs) and younger (below 30 years) adults identified target letters that were flanked by distractors (JKJ). Inhibitory processes were preserved in older adults, who showed reliable distractor repetition benefits resulting from persistent distractor inhibition; however, a significant loss of inhibition was apparent for the older subgroup of participants (65+ yrs) compared with a subgroup of young-old participants (60 to 64 years). No age differences were found for episodic retrieval processes of stimulus-response bindings that were indexed by an interaction of distractor repetition and response relation. Findings highlight the importance of dissociating between distractor inhibition and retrieval processes that are differently implicated in age-related cognitive change. | 10.1037/pag0000022 |
pubmed_788_13884 | PURPOSE
To relate pronuclear patterns (PN) and zygote cytoplasmic appearance and embryo morphology.
METHODS
The usefulness of PN classification described by Tesarik et al. 1999 (patterns p0-5) and Scott et al. 2000 (Z1-4), for embryo selection is assessed.
RESULTS
Sinchrony on polarization and number of nucleolar precursor bodies (NPB) were associated with good quality embryos (p0 60.9% and p3 67.3%, and Z1 62.5% and Z2 64.7%; p<0.01). Pattern 4 zygotes were associated with small number of NPB developed into multinucleated embryos (14.3%) and poor quality embryos (61.9%). No significant differences were found in the pregnancy rate between transfer of at least one good prognosis PN pattern and transfer of poor prognosis PN patterns, although 75% of the transfers included at least one embryo derived from a pattern 0 zygote, and 55% included embryos from categories Z1 or Z2.
CONCLUSIONS
Sequential assessment involving the evaluation of oocyte quality, the classification of PN patterns and embryo morphology allows a more accurate evaluation of embryos to be selected for transfer. | 10.1007/s10815-006-9099-0 |
pubmed_256_17632 | OBJECTIVE
To evaluate whether low educational attainment is a risk factor for the incidence of dementia and Alzheimer's disease (AD) in the Framingham Study and to determine whether age at onset of dementia is earlier in persons with low educational levels.
DESIGN
A community-based cohort was studied longitudinally for the development of dementia. Diagnosis was made according to strict criteria by two neurologists and a neuropsychologist. Subtype of dementia and year at onset were determined. Incidence rates were compared in three education groups: < grade school, < high school, and > or = high school.
PARTICIPANTS
A total of 3,330 men and women aged 55 to 88 years.
RESULTS
During 17 years of follow-up, 258 incident cases of dementia, including 149 AD cases, were identified. Unadjusted incidence rates were significantly elevated (p < 0.05) for dementia and non-AD dementia among the least educated. The age-adjusted relative risk for subjects with a grade school education or less compared with those who earned a high school diploma was 1.31 (95% confidence interval [CI], 0.90 to 1.90) for dementia generally, 1.04 (95% CI, 0.62 to 1.74) for AD, and 1.75 (95% CI, 1.03 to 2.98) for non-AD dementia. Age at onset of dementia did not vary by educational attainment.
CONCLUSIONS
After age adjustment, low educational attainment was not a significant risk factor for the incidence of dementia generally or of AD. Low educational attainment was associated with increased risk of non-AD dementia, perhaps because of deleterious smoking habits and other risk factors for stroke in the least-educated individuals. Adequately adjusting for age and examining subtypes of dementia are important in assessing the influence of education on dementia incidence. | 10.1212/wnl.45.9.1707 |
pubmed_526_18610 | Fecal microbiota transplant has become more acceptable as a therapeutic for recurrent Clostridium difficile infection. The FDA has an enforcement discretion policy for practitioner's performing this therapy, which includes informed consent for this experimental treatment. This manuscript describes a typical procedure that can be followed that includes the important aspects of this preparation and treatment. | 10.1309/LMCI95M0TWPDZKOD |
pubmed_117_15296 | Megachile sculpturalis (Smith, 1853) (Hymenoptera: Megachilidae) is an invasive solitary bee that is rapidly spreading all over Europe. The present study aims to update the distribution of this species in Italy. The research led to the collection of 177 records, obtained through bibliographic research and data-mining from websites, blogs and social networks. We here present the first record of M. sculpturalis on a Mediterranean island and discuss its possible effect on the native ecosystem. Given the particular discovery of M. sculpturalis on Elba Island (Tuscany), we suggest possible monitoring, containment and possible eradication measures of the species. | 10.3897/BDJ.8.e57783 |
pubmed_659_8490 | Acupuncture and moxibustion have been accepted as add-on options for primary dysmenorrhea (PD); however, the clinical evidence is still inadequate. We searched AMED, CENTRAL, EMBASE, PubMed, Web of Science, CBM, CNKI, VIP, Wangfang database, ANZCTR, ClinicalTrials.gov, and the WHO ICTRP, from their inception to February 2021. The pooled analysis of 13 RCTs with 675 participants for VAS showed that acupuncture and moxibustion were more effective in managing PD than the control group with the MD of -1.93 (95% CI [-2.80, -1.06] and -2.67 (95% CI [-4.96, -0.38]). With the CMSS, seven studies with 487 participants showed that these modalities were more effective than the control group with the MD of -7.58 (95% CI [-10.97, -4.19]) and -3.78 (95% CI [-6.90, -0.66]). The findings indicated that acupuncture and moxibustion could relieve pain effectively and has fewer adverse events (AEs) in managing PD. | 10.1177/10547738221086984 |
pubmed_297_3284 | The cytoskeletal protein doublecortin (DCX) is a marker for neuronal cells retaining high potential for structural plasticity, originating from both embryonic and adult neurogenic processes. Some of these cells have been described in the subcortical white matter of neonatal and postnatal mammals. In mice and humans it has been shown they are young neurons migrating through the white matter after birth, reaching the cortex in a sort of protracted neurogenesis. Here we show that DCX+ cells in the white matter of neonatal and young Cetartiodactyla (dolphin and sheep) form large clusters which are not newly generated (in sheep, and likely neither in dolphins) and do not reach the cortical layers, rather appearing "trapped" in the white matter tissue. No direct contact or continuity can be observed between the subventricular zone region and the DCX+ clusters, thus indicating their independence from any neurogenic source (in dolphins further confirmed by the recent demonstration that periventricular neurogenesis is inactive since birth). Cetartiodactyla include two orders of large-brained, relatively long-living mammals (cetaceans and artiodactyls) which were recognized as two separate monophyletic clades until recently, yet, despite the evident morphological distinctions, they are monophyletic in origin. The brain of Cetartiodactyla is characterized by an advanced stage of development at birth, a feature that might explain the occurrence of "static" cell clusters confined within their white matter. These results further confirm the existence of high heterogeneity in the occurrence, distribution and types of structural plasticity among mammals, supporting the emerging view that multiple populations of DCX+, non-newly generated cells can be abundant in large-brained, long-living species. | 10.1007/s00429-018-1708-z |
pubmed_348_2348 | MRI-based study of (3)He gas diffusion in lungs may provide important information on lung microstructure. Lung acinar airways can be described in terms of cylinders covered with alveolar sleeve [Haefeli-Bleuer, Weibel, Anat. Rec. 220 (1988) 401]. For relatively short diffusion times (on the order of a few ms) this geometry allows description of the (3)He diffusion attenuated MR signal in lungs in terms of two diffusion coefficients-longitudinal (D(L)) and transverse (D(T)) with respect to the individual acinar airway axis [Yablonskiy et al., PNAS 99 (2002) 3111]. In this paper, empirical relationships between D(L) and D(T) and the geometrical parameters of airways and alveoli are found by means of computer Monte Carlo simulations. The effects of non-Gaussian signal behavior (dependence of D(L) and D(T) on b-value) are also taken into account. The results obtained are quantitatively valid in the physiologically important range of airway parameters characteristic of healthy lungs and lungs with mild emphysema. In lungs with advanced emphysema, the results provide only "apparent" characteristics but still could potentially be used to evaluate emphysema progression. This creates a basis for in vivo lung morphometry-evaluation of the geometrical parameters of acinar airways from hyperpolarized (3)He diffusion MRI, despite the airways being too small to be resolved by direct imaging. These results also predict a rather substantial dependence of (3)He ADC on the experimentally-controllable diffusion time, Delta. If Delta is decreased from 3 ms to 1 ms, the ADC in normal human lungs may increase by almost 50%. This effect should be taken into account when comparing experimental data obtained with different pulse sequences. | 10.1016/j.jmr.2007.10.015 |
pubmed_369_23121 | PURPOSE
Despite favorable metabolic and vascular effects, thiazolidinedione (TZD) drugs have not convincingly reduced cardiovascular mortality in clinical trials, raising the possibility of countervailing, off-target effects. We previously showed that TZDs block cardiac ATP-sensitive potassium (K(ATP)) channels in pigs. In this study, we investigated whether TZDs affect onset, spectral characteristics, and mortality of ischemic ventricular fibrillation (VF) and whether such effects are recapitulated by a non-selective K(ATP) blocker (glyburide) or a mitochondrial K(ATP) blocker (5-hydroxydecanoate).
METHODS
A total of 121 anesthetized pigs were pre-treated with TZD (pioglitazone or rosiglitazone, 1 mg/kg IV, resulting in clinically relevant plasma concentrations), glyburide (1 mg/kg IV), 5-hydroxydecanoate (5 mg/kg IV) or inert vehicle. Ischemia was produced by occlusion of the left anterior descending coronary artery. In a subset of pigs treated with rosiglitazone or vehicle, ischemic preconditioning was performed.
RESULTS
VF developed in all but 6 pigs. In non-preconditioned pigs, onset of VF occurred sooner with pioglitazone (11±3 min, p<0.05) or rosiglitazone (14±3 min, p=0.06) than with vehicle (20±2 min). Defibrillation of VF was successful in 44% of pigs treated with vehicle, compared with 0% with pioglitazone (p=0.057) and 33% with rosiglitazone (NS). After ischemic preconditioning, defibrillation was successful in 62% of pigs treated with vehicle, compared with 26% treated with rosiglitazone (p=0.03). TZDs attenuated slowing of conduction due to ischemia and shifted ECG power spectra during VF toward higher frequencies. All effects of TZDs were recapitulated by glyburide, but not by 5-hydroxydecanoate, supporting an interaction of TZDs with the sarcolemmal K(ATP) channel.
CONCLUSION
In a porcine model, TZDs promote onset and increase mortality of ischemic VF, associated with alterations of conduction and VF spectral characteristics. Similar effects in a clinical setting might adversely impact cardiovascular mortality. | 10.1007/s10557-012-6384-2 |
pubmed_199_960 | In vitro tetraploidy (IVT+) in dermal fibroblast monolayer cultures has been studied in a series of patients with non-syndrome colon cancer and a control group to determine its value in identification of genetic predisposition for all colon cancers and its relevance to colon cancer occurrence on the basis of clinical history and pedigree data. Among 41 patients with colon cancer 18 (44%) had IVT+. In the control group 3 of 34 individuals (9%) showed IVT+. The difference is statistically significant (p less than 0.001). There was no correlation between a positive family cancer history, sex, age, or the presence of IVT+. Further studies using this possible in vitro biomarker may clarify the role of genetics in non-syndrome colorectal cancer. | 10.3109/00365528509088880 |
pubmed_510_20489 | A visual analogue scale to evaluate fatigue severity (VAS-F) was developed and tested in a sample of 75 healthy individuals and a sample of 57 patients undergoing medical evaluation for sleep disorders. The scale consists of 18 items related to fatigue and energy, has simple instructions, and is completed with minimal time and effort. The VAS-F compares favorably with the Stanford Sleepiness Scale and the Profile of Mood States, and its internal consistency reliabilities are high. Healthy subjects demonstrated significant differences between their evening and morning scores on the VAS-F, while sleep-disordered patients did not. | 10.1016/0165-1781(91)90027-m |
pubmed_183_1096 | OBJECTIVE
Stimulation of invariant natural killer T (iNKT) cells with SGL-S23, a novel synthetic glycolipid analog of alpha-galactosylceramide with an elongated sphingosine chain, has been shown to strongly suppress K/BxN serum transfer arthritis. This study was designed to evaluate the protective effects of SGL-S23 in an effector phase of arthritis.
METHODS
To induce arthritis, C57BL/6 mice were injected with 150 mul of serum from K/BxN mice (KRN TCR-transgenic mice crossed with nonobese diabetic mice). Subsequently, synthetic glycolipid ligands were administered intraperitoneally twice, either 3 times starting on day 0 (the day of K/BxN serum injection) or twice starting on day 3. Neutralizing antibody against interferon-gamma (IFNgamma) interleukin-4 (IL-4), IL-10, or transforming growth factor beta was administered 4 hours before injection of SGL-S23. Recombinant IFNgamma was administered subcutaneously every day. The severity of arthritis was monitored using a macroscopic scoring system. Cytokine production and plasma histamine levels were measured by enzyme-linked immunosorbent assay.
RESULTS
SGL-S23 strongly suppressed K/BxN serum transfer arthritis by inhibiting inflammatory cell infiltration and subsequent destruction of cartilage and bone. The inhibitory effect mediated by SGL-S23 was abolished by neutralization of IFNgamma. Systemic administration of IFNgamma prevented the development of inflammatory arthritis. Histamine release was suppressed by administration of SGL-S23 or IFNgamma. Degranulated mast cells in the synovium were significantly reduced in SGL-S23-treated mice, suggesting that suppression of mast cell activation contributed to the inhibition of arthritis.
CONCLUSION
These findings suggest that activation of iNKT cells with glycolipid ligands holds promise with regard to the treatment of autoimmune diseases such as rheumatoid arthritis. SGL-S23 has clinical benefit over alpha-galactosylceramide since it induces a weaker cytokine production response in iNKT cells, therefore reducing potential side effects caused by excessive cytokine release. | 10.1002/art.22714 |
pubmed_218_3609 | Two experiments were conducted to examine whether children of different ages differ in their ability to reject associative false memories with the Deese-Roediger-McDermott (DRM) paradigm. Two different types of manipulations that are thought to facilitate false memory rejection in adults-slowing the presentation rate and issuing explicit warnings-were analyzed in younger and older children. The results showed that older children were more able than younger children to reject associative false memories through warnings and by slowing the presentation rate. We conclude that although older children are, in general, more prone to produce false memories with the DRM paradigm, they are also more able to reject them when certain conditions facilitate the editing process. | 10.1016/j.jecp.2009.09.004 |
pubmed_101_23913 | INTRODUCTION
Implant material is a more important factor for periprosthetic tibial bone resorption than implant design after total knee arthroplasty (TKA). The virtual perturbation study was planned to perform using single case of proximal tibia model. We determined whether the implant materials' stiffness affects the degree of periprosthetic tibial bone resorption, and whether the effect of material change with the same implant design differed according to the proximal tibial plateau areas.
MATERIALS AND METHODS
This three-dimensional finite element analysis included two cobalt-chromium (CoCr) and two titanium (Ti) tibial implants with different designs. They were implanted into the proximal tibial model reconstructed using extracted images from computed tomography. The degree of bone resorption or formation was measured using the strain energy density after applying axial load. The same analysis was performed after exchanging the materials while maintaining the design of each implant.
RESULTS
The degree of periprosthetic tibial bone resorption was not determined by the type of implant materials alone. When the implant materials were changed from Ti to CoCr, the bone resorption in the medial compartment increased and vice versa. The effect of material composition's change on anterior and posterior areas varied accordingly.
CONCLUSIONS
Although the degree of bone resorption was associated with implant materials, it differed depending on the design of each implant. The effect on the degree of bone resorption according to the materials after TKA should be evaluated while concomitantly considering design. | 10.1371/journal.pone.0246866 |
pubmed_1077_4037 | Wild riverine fishes are known to rely on burst swimming to traverse hydraulically challenging reaches, and yet there has been little investigation as to whether swimming anaerobically in areas of high flow can lead to delayed mortality. Using acoustic accelerometer transmitters, we estimated the anaerobic activity of anadromous adult sockeye salmon (Oncorhynchus nerka) in the tailrace of a diversion dam in British Columbia, Canada, and its effects on the remaining 50 km of their freshwater spawning migration. Consistent with our hypothesis, migrants that elicited burst swimming behaviors in high flows were more likely to succumb to mortality following dam passage. Females swam with more anaerobic effort compared to males, providing a mechanism for the female-biased migration mortality observed in this watershed. Alterations to dam operations prevented the release of hypolimnetic water from an upstream lake, exposing some migrants to supraoptimal, near-lethal water temperatures (i.e., 24°C) that inhibited their ability to locate, enter, and ascend a vertical-slot fishway. Findings from this study have shown delayed post-dam passage survival consequences of high-flow-induced burst swimming in sockeye salmon. We highlight the need for studies to investigate whether dams can impose other carryover effects on wild aquatic animals. | 10.1086/677219 |
pubmed_307_5572 | Proteases have several applications in the food industry. We report the immobilization of procerain B, a novel cysteine protease, on glutaraldehyde-activated chitosan beads through covalent attachment. Glutaraldehyde not only serves as a cross-linking agent but also links the procerain B on the surface of bead through primary amine group (either lysine side chain or N-terminal) by Schiff base linkage. Immobilized procerain B was characterized for optimum functional range and stability with respect to pH and temperature. The chitosan-immobilized procerain B has broad pH and thermal optima. The effects of substrate concentration and reusability of immobilized beads were also studied. It showed nearly 50% activity until the 10th use. | 10.1021/jf200472x |
pubmed_550_23219 | OBJECTIVE
To study incidence rates (Is) of oral cavity and pharynx-throat cancer in adults age 20+ years from 1973 to 2003, and to estimate how many of these cancers occurred in the United States in 2003.
STUDY DESIGN
We used data and software from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program to generate age-adjusted Is, reported as cases per 100,000 person-years.
RESULTS
For oral cancer, the Is for young men were stable, and Is at ages 40+ years declined by one third after the mid 1980s. Is declined by one third in women ages 40 to 74, but increased in the youngest and oldest groups. In 2003 there were 10,432 cases of oral cavity cancer among persons age 20+ years in the United States, and there were 12,157 cases of pharynx-throat cancer.
CONCLUSION
The Is of cancers of the oral cavity and pharynx-throat are stable or declining for men and women in most age groups. Of the nearly 30,000 malignant neoplasms occurring in the SEER "oral cavity-pharynx" category in 2003, almost three quarters (21,455) were detectable during a routine oral examination. | 10.1016/j.tripleo.2007.03.011 |
pubmed_361_11281 | A glycoprotein from the liver, which shares epitopes with chorion (egg envelope or zona pellucida) glycoproteins, is present only in the spawning female fish, Oryzias latipes, under natural conditions. This spawning female-specific (SF) substance is distinct from vitellogenin but closely resembles a major glycoprotein component, ZI-3, of the inner layer (zona radiata interna) of the ovarian egg envelope with respect to some biochemical and immunochemical characteristics. Here we report that the [125I]SF substance, injected into the abdominal cavity of the spawning female fish, was rapidly transported by the blood circulation into the ovary and incorporated into the inner layer of egg envelope of the growing oocytes. The result strongly suggests that the SF substance from the liver is a precursor substance of the major component, ZI-3, of the inner layer of egg envelope in the fish. | 10.1016/0012-1606(89)90301-1 |
pubmed_92_2941 | Global production of chickens has trebled in the past two decades and they are now the most important source of dietary animal protein worldwide. Chickens are subject to many infectious diseases that reduce their performance and productivity. Coccidiosis, caused by apicomplexan protozoa of the genus Eimeria, is one of the most important poultry diseases. Understanding the biology of Eimeria parasites underpins development of new drugs and vaccines needed to improve global food security. We have produced annotated genome sequences of all seven species of Eimeria that infect domestic chickens, which reveal the full extent of previously described repeat-rich and repeat-poor regions and show that these parasites possess the most repeat-rich proteomes ever described. Furthermore, while no other apicomplexan has been found to possess retrotransposons, Eimeria is home to a family of chromoviruses. Analysis of Eimeria genes involved in basic biology and host-parasite interaction highlights adaptations to a relatively simple developmental life cycle and a complex array of co-expressed surface proteins involved in host cell binding. | 10.1101/gr.168955.113 |
pubmed_92_14093 | PURPOSE
This study aimed to describe the range of participation of nursing faculty members and their collaborators in multidisciplinary primary health care in Korea and to analyze facilitators, benefits, barriers, and learned lessons.
METHODS
An exploratory descriptive research design was utilized. A total of 13 nursing faculty members and 13 multidisciplinary collaborators were interviewed face to face using a brief questionnaire and semi-structured interview guide. Descriptive statistics, comparative analysis, and content analysis were used for data analysis.
RESULTS
About 43% of the nursing faculty had multidisciplinary primary health care experience. Facilitators included a government-funded research/demonstration project, personal belief and expertise in primary health care, and well-delineated role boundaries. Benefits included improved quality of life, more convenient community life, meeting multifaceted needs of community residents, and enhanced research activities. Barriers were lack of teamwork; territoriality and self-protective behaviors; lack of insight into primary health care among stakeholders; nurses undervaluing their work; and the rigid bureaucratic system of public health centers. Learned lessons were the importance of teamwork and its synergistic benefits, the importance of conducting clinically relevant research, having the government's support in the improvement of public health, developing health policies through multidisciplinary primary health care (M-D PHC) work, and respecting each other's territory and expertise.
CONCLUSION
Teamwork should be included in all health professions' curricula, and nursing clinical practicums should include primary health care in all specialty areas. More faculties should engage in multidisciplinary primary health care. The benefits of a multidisciplinary approach to primary health care outweigh the difficulties experienced by multidisciplinary team members. The findings of this study may be useful for future multidisciplinary primary health care work worldwide. | 10.1016/S1976-1317(08)60026-2 |
pubmed_180_15903 | BACKGROUND
The Dutch multidisciplinary sciatica guideline recommends that the team of professionals involved in sciatica care and the patient together decide on surgical or prolonged conservative treatment (shared decision making [SDM]). Despite this recommendation, SDM is not yet integrated in sciatica care. Existing literature concerning barriers and facilitators to SDM implementation mainly focuses on one discipline only, whereas multidisciplinary care may involve other barriers and facilitators, or make these more complex for both professionals and patients. Therefore, this qualitative study aims to identify barriers and facilitators perceived by patients and professionals for SDM implementation in multidisciplinary sciatica care.
METHODS
We conducted 40 semi-structured interviews with professionals involved in sciatica care (general practitioners, physical therapists, neurologists, neurosurgeons, and orthopedic surgeons) and three focus groups among patients (six to eight per group). The interviews and focus groups were audiotaped and transcribed in full. Reported barriers and facilitators were classified according to the framework of Grol and Wensing. The software package Atlas.ti 7.0 was used for analysis.
RESULTS
Professionals reported 53 barriers and 5 facilitators, and patients 35 barriers and 18 facilitators for SDM in sciatica care. Professionals perceived most barriers at the level of the organizational context, and facilitators at the level of the individual professional. Patients reported most barriers and facilitators at the level of the individual professional. Several barriers and facilitators correspond with barriers and facilitators found in the literature (e.g., lack of time, motivation) but also new barriers and facilitators were identified. Many of these new barriers mentioned by both professionals and patients were related to the multidisciplinary setting, such as lack of visibility, lack of trust in expertise of other disciplines, and lack of communication between disciplines.
CONCLUSIONS
This study identified barriers and facilitators for SDM in the multidisciplinary sciatica setting, by both professionals and patients. It is clear that more barriers than facilitators are perceived for implementation of SDM in sciatica care. Newly identified barriers and facilitators are related to the multidisciplinary care setting. Therefore, an effective implementation strategy of SDM in a multidisciplinary setting such as in sciatica care should focus on these barriers and facilitators. | 10.1186/1748-5908-8-95 |
pubmed_978_3813 | A three-month cohort of admissions (N = 300) to an acute psychiatric inpatient unit of a county general hospital was studied to identify factors that differentiate patients with multiple admissions over a 12-month period from those with only a single admission. Patients with more than one admission made up 32 percent of the cohort. Compared with single-admission patients, they were significantly more likely to be chronically unemployed and to have a diagnosis of schizophrenic or affective disorder. Regression analyses indicated that the number of prior psychiatric hospitalizations was the strongest predictor of both the number of hospitalizations and the number of days hospitalized; other significant predictors were a secondary diagnosis of personality disorder, chronic unemployment, self-referral, and being black. The findings indicate that many of the problems of multiple-admission patients are rooted in social disadvantage, and efforts to devise effective interventions should not focus on psychopathology alone. | 10.1176/ps.40.8.820 |
pubmed_880_11703 | INTRODUCTION
Mental retardation is an intellectual disability affecting adaptable, conceptual, social and practical skills, with onset prior to 18 years of age. Prevalence of obesity among women with mental retardation is 18-30% greater than that among women without mental retardation. In the Nachman Village, a governmental institution for adults with mental retardation, the main nutritional difficulties result from residents eating snacks in addition to their balanced meals. Psychological complexity and the ambivalent attitude of families, caregivers and residents prevented the achievement of balanced diets and healthy body weights. The women's house mother took upon herself to detect residents with nutritional problems and started an intervention program aiming at promoting a healthy lifestyle and maintenance of normal body weight.
METHODS
The program 'House Queen' was Launched on a voluntary basis. The staff encouraged the residents to engage in physical activity, restrict snack consumption and amounts of food at meals, eat vegetables and not waste pocket money on non-nutritional foods. Each month one or two residents who lost weight while maintaining a healthy lifestyle received a prize and the title "House Queen". The statistical analysis included 22 residents and was conducted retrospectively from data coLlected during a routine medical follow-up.
RESULTS
A total of 59.1% of the residents were morbidly obese and 27.3% were obese at the beginning of the program. Seventeen months later, they weighed an average of 8 kg Less, and only 36.4% and 18.2% of them were morbidly obese and obese, respectively.
CONCLUSION
These results suggest a correlation between the 'House Queen' program and Lowering body weight, which encourage the authors to broaden the program to other residents in the Village and combine supportive and restrictive attitudes towards a healthy lifestyle for mentally disabled people. | pubmed_880_11703 |
pubmed_320_7834 | Cavernomas of the CNS may involve brain parenchyma as well as the spinal cord and belong to those cerebrovascular malformations that have no arteriovenous shunt and thus are generally angiographically occult. Contrary to computed tomography (CT), which is generally suited to reveal calcifications or acute bleeding, magnetic resonance imaging (MRI) enables detection of even small cavernomas. A frequently associated venous anomaly is helpful for correct diagnosis. | 10.1007/s00117-007-1546-0 |
pubmed_899_9034 | INTRODUCTION
Lymph node evaluation for node-negative non-small cell lung cancer (NSCLC) is associated with long-term survival but it is not clear if smaller tumors require as extensive a pathologic nodal assessment as larger tumors. This study evaluated the relationship of tumor size and optimal extent of lymph node resection using the National Cancer Data Base (NCDB).
MATERIALS AND METHODS
The incremental survival benefit of each additional lymph node that was evaluated for patients in the NCDB who underwent lobectomy for clinical Stage I NSCLC from 2003 to 2006 was evaluated using Cox multivariable proportional hazards regression modeling. The impact of tumor size was assessed by repeating the Cox analysis with patients stratified by tumor size ≥2 cm vs <2 cm.
RESULTS
A median of 7 [interquartile range: 4,11] lymph nodes were examined in 13,827 patients who met study criteria. Following adjustment, the evaluation of each additional lymph node demonstrated a significant survival benefit through 11 lymph nodes. After grouping patients by tumor size, patients with tumors <2 cm demonstrated a significant survival benefit for the incremental resection of each additional lymph node through 4 lymph nodes while patients with tumors ≥2 cm had a significant survival benefit through 14 lymph nodes.
CONCLUSION
Pathologic lymph node evaluation is associated with improved survival for clinically node-negative NSCLC, but the extent of the necessary evaluation varies by tumor size. These results have implications for guidelines for lymph node assessment as well as the choice of surgery vs other ablative techniques for clinical stage I NSCLC. | pubmed_899_9034 |
pubmed_579_9838 | Global sensitivity analysis (SA) was used during the development phase of a binary chemical physiologically based pharmacokinetic (PBPK) model used for the analysis of m-xylene and ethanol co-exposure in humans. SA was used to identify those parameters which had the most significant impact on variability of venous blood and exhaled m-xylene and urinary excretion of the major metabolite of m-xylene metabolism, 3-methyl hippuric acid. This analysis informed the selection of parameters for estimation/calibration by fitting to measured biological monitoring (BM) data in a Bayesian framework using Markov chain Monte Carlo (MCMC) simulation. Data generated in controlled human studies were shown to be useful for investigating the structure and quantitative outputs of PBPK models as well as the biological plausibility and variability of parameters for which measured values were not available. This approach ensured that a priori knowledge in the form of prior distributions was ascribed only to those parameters that were identified as having the greatest impact on variability. This is an efficient approach which helps reduce computational cost. | 10.3389/fphar.2015.00135 |
pubmed_601_5345 | Thyrotropin-releasing hormone (TRH) stimulates maximally both the release of previously synthesized prolactin and the de novo synthesis of prolactin by GH4C1 rat pituitary cells at concentrations less than those necessary to fully occupy the TRH receptor at equilibrium. We have examined the dependency of maximal TRH-enhanced prolactin release and synthesis on receptor number using GH4C1 cell variants with different numbers of TRH receptors. GH4C1 cell variants with increased and decreased numbers of TRH receptors were selected by using a morphological response known as stretching which renders the cells more adherent to the tissue culture substrate. We found that maximal TRH-enhancement of prolactin release or synthesis increased proportionally to the number of TRH receptors per cell, indicating that spare receptors do not exist for TRH on these GH4C1 cells. We also found that occupancy of the TRH receptor by the analogue, N3im-methyl-TRH (MeTRH), in contrast to TRH, closely paralleled stimulated prolactin release in a manner consistent with Clark's receptor-occupancy model. We conclude that differences between apparent Kd and ED50 for TRH do not necessarily result from spare receptors in GH4C1 cells. | 10.1016/0303-7207(85)90081-4 |
pubmed_947_14946 | The engineered protein eCD4Ig has emerged as a promising approach to achieve HIV remission in the absence of antiviral therapy. eCD4Ig neutralizes nearly all HIV-1 isolates and induces antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. To characterize the in vivo antiviral neutralization and possible ADCC effects of eCD4Ig, we fit mathematical models to eCD4Ig, anti–eCD4Ig-drug antibody (ADA), and viral load kinetics from healthy and simian-human immunodeficiency virus AD8 (SHIV-AD8) infected nonhuman primates that were treated with single or sequentially dosed eCD4Ig passive administrations. Our model predicts that eCD4Ig transiently decreases SHIV viral loads due to neutralization only with an in vivo IC50 of ~25 μg/ml but with limited effect due to ADA. Simulations suggest that endogenous, continuous expression of eCD4Ig at levels greater than 105 μg/day, as is possible with Adeno-associated virus (AAV) vector-based production, could overcome the diminishing effects of ADA and allow for long-term remission of SHIV viremia in nonhuman primates. | 10.1126/sciadv.abj5666 |
pubmed_454_11441 | OBJECTIVE
To investigate whether levosimendan diminishes the incidence of heart failure after cardiac surgery.
DESIGN
Prospective, randomized, placebo-controlled clinical study.
SETTING
Cardiac surgery operating room and postanesthesia care unit in a university hospital.
PATIENTS
Two hundred patients assigned to undergo heart valve or combined heart valve and coronary artery bypass grafting surgery.
INTERVENTIONS
Patients were randomized to receive a 24-hr infusion of placebo or levosimendan administered as a 24 μg/kg bolus over 30-mins and thereafter at a dose of 0.2 μg/kg/min.
MEASUREMENTS AND MAIN RESULTS
Heart failure was defined as cardiac index<2.0 L/min/m or failure to wean from cardiopulmonary bypass necessitating inotrope administration for at least 2 hrs postoperatively. Heart failure was less frequent in the levosimendan compared to the placebo group: 15 patients (15%) in the levosimendan and 59 patients (58%) in the placebo group experienced heart failure postoperatively (risk ratio 0.26; 95% confidence interval 0.16-0.43; p<.001). Accordingly, a rescue inotrope (adrenaline) was needed less frequently in the levosimendan compared to the placebo group (risk ratio 0.11; 95% confidence interval 0.01-0.89), p=.005. Intra-aortic balloon pump was utilized in one patient (1%) in the levosimendan and in nine patients (9%) in the placebo group (risk ratio 0.11; 95% confidence interval 0.01-0.87), p=.018. The hospital and the 6-month mortality were comparable between groups. There were no significant differences in major organ failures postoperatively. Eighty-three patients were hypotensive and needed noradrenaline in the levosimendan compared to 52 patients in the placebo group, p<.001. The cardiac enzymes (creatine kinase MB isoenzyme mass) indicating myocardial damage were lower in the levosimendan group on the first postoperative day, p=.011.
CONCLUSIONS
In the present study, levosimendan infusion reduced the incidence of heart failure in cardiac surgery patients but was associated with arterial hypotension and increased requirement of vasopressor agents postoperatively. Improved mortality or morbidity was not demonstrated. | 10.1097/CCM.0b013e3182227b97 |
pubmed_48_17108 | Androgens are considered important in normal prostate physiology and prostate cancer (PCa) pathogenesis. However, androgen-targeted treatment preventing PCa recurrence is still lacking. This indicates additional mediators contributing to cancer development. We sought to determine the prognostic significance of estrogen receptors, ERα and -β, and the aromatase enzyme in PCa. Tissue microarrays were created from 535 PCa patients treated with radical prostatectomy. Expression of ERα, ERβ and aromatase were evaluated using immunohistochemistry. Representative tumor epithelial (TE) and tumor stromal (TS) areas were investigated separately. Survival analyses were used to evaluate the markers correlation to PCa outcome. In univariate analyses, ERα in TS was associated with delayed time to clinical failure (CF) (p = 0.042) and PCa death (p = 0.019), while ERβ was associated with reduced time to biochemical failure (BF) (p = 0.002). Aromatase in TS and TE was associated with increased time to BF and CF respectively (p = 0.016, p = 0.046). Multivariate analyses supported these observations, indicating an independent prognostic impact of all markers. When stratifying the analysis according to different surgical centers the results were unchanged. In conclusion, significant prognostic roles of ERα, ERβ and aromatase were discovered in the in PCa specimens of our large multicenter cohort. | 10.1038/srep33114 |
pubmed_680_7588 | Membrane cleaning is critical for economic and scientific reasons in wastewater treatment systems. Sodium docusate is a laxative agent and removes cerumen (ear wax). Docusate penetrates the hard ear wax, making it softer and easier to remove. The same concept could be applied to soften and remove fouling layers on the membrane surface. Once softened, the foulants can be easily flushed with water. This innovative approach can address the challenge of developing superior methods to mitigate membrane fouling and material degradation. In this study, we evaluated the efficiency of sodium docusate for cleaning fouled forward osmosis membranes with real landfill leachate wastewater. Experiments were conducted to examine the impact of dose rate, contact time, flow or static conditions, and process configuration (forward osmosis (FO) or pressure retarded osmosis (PRO) upon fouling created by landfill leachate dewatering. A remarkable (99%) flux recovery was achieved using docusate at a small concentration of only 0.1% for 30 min. Furthermore, docusate can also effectively restore flux with static cleaning without using pumps to circulate the cleaning solution. Furthermore, cleaning efficiency can be achieved at neutral pH compatible with most membrane materials. From an economic and energy-saving perspective, static cleaning can almost achieve the same cleaning efficiency as kinetic cleaning for fouled forward osmosis membranes without the expense of additional pumping energy compared to kinetic cleaning. Since pumping energy is a major contributor to the overall energy of the forward osmosis system, it can be minimized to a certain degree by using a static cleaning approach and can bring good energy savings when using larger membrane areas. Studies of the contact angle on the membrane surface indicated that the contact angle was decreased compared to the fouled membrane after cleaning (e.g. 70.3° to 63.2° or FO mode and static cleaning). Scanning Electron Microscopy revealed that the cleaning strategy was successful. Infrared Spectroscopy showed that a small amount of sodium docusate remained on the membrane surface. Docusate is more environmentally friendly than acid or alkaline solutions from an environmental perspective. Furthermore, the cleaning solution can be reused for several cycles without discarding it due to the surfactant properties of docusate. | 10.1016/j.chemosphere.2022.136237 |
pubmed_565_7666 | This study examined consequences of binge drinking on relationship conversation qualities (positive tone, general disagreements, drinking disagreements, and talks about drinking) among romantically involved college students. Conversation qualities were predicted with three binging variables: (a) same day binging, (b) prior day binging, and (c) total amount of binging reported. The participants (N=156) completed 10 daily diaries of relationship conversations as well as drinking behaviors. Same day binging increased the occurrence of both drinking disagreements and talks about drinking. However, prior day binging was not associated with any of the four conversation qualities examined. Greater numbers of binges over the duration of the study were associated with less overall positive tone, and more general disagreements, drinking disagreements, and talks about drinking. The implications of the findings for student drinking patterns and relational quality are discussed. | 10.1016/j.addbeh.2005.03.004 |
pubmed_437_5684 | OBJECTIVE
The objective of our study was to determine the satisfaction levels of family members of patients with advanced-stage cancer.
METHOD
This descriptive study was conducted in the palliative care and medical oncology clinics of a university hospital in the province of Izmir between April of 2011 and January of 2012. The study sample consisted of a total of 145 family members, who were selected from among the family members of patients with advanced-stage cancer receiving palliative treatment. The study data were obtained using the Patient Description Form and Family Satisfaction Scale during face-to-face interviews with patients.
RESULTS
Some 67% of patients were female and 33% male, 70% were married, 35% were high school graduates, and 34.5% were housewives. The average total family satisfaction score was 76.87 ± 1.14, and the average scores for the component variables were as follows: information giving 74.37 ± 1.28, availability of care 78.40 ± 1.17, physical care 78.99 ± 1.09, and psychosocial care 74.52 ± 1.30. We found a relationship between the level of satisfaction of family members and (1) gender, (2) occupation, (3) presence of someone supporting the care, and (4) possession of sufficient information about the patient (p < 0.05).
SIGNIFICANCE OF RESULTS
Satisfaction levels of participants were determined to be high. We found that family member satisfaction levels were affected by gender and occupation, the existence of someone supporting the care, and possession of sufficient information about the patient. | 10.1017/S1478951514000534 |
pubmed_504_18482 | Patients with systemic lupus erythematosus (SLE) have a significant increase in cardiovascular (CV) risk although they display a preserved number of circulating angiogenic CD3+CD31+CXCR4+ T cells (Tang), a subpopulation of T cells which promotes repair of damaged endothelium. This happens due to the concomitant expansion of a Tang subset with immunosenescent features, such as the loss of CD28. Therefore, the aim of this study was to elucidate the interplay between Tang subpopulations and endothelial cells in a group of young SLE patients without previous cardiovascular events. Twenty SLE female patients and 10 healthy controls (HCs) were recruited. Flow cytometric analysis of endothelial progenitor cells (EPCs) and Tang subsets were performed and serum levels of interleukin (IL)-6, -8, matrix metalloproteinase (MMP)-9 and interferon (IFN)-γ were measured. Human umbilical vein endothelial cells (HUVECs) proliferation and pro-inflammatory phenotype in response to subjects' serum stimulation were also evaluated. Results showed that the percentage of Tang and EPC subsets was reduced in SLE patients compared with HCs, with a marked increase of senescent CD28null cells among Tang subset. SLE disease activity index-2000 (SLEDAI-2K) was inversed related to Tang cells percentage. Furthermore, IL-8 serum levels were directly correlated with the percentage of Tang and inversely related to the CD28null Tang subsets. We indirectly evaluated the role of the Tang subset on the endothelium upon stimulation with serum from subjects with a low percentage of Tang CD3+ cells in HUVECs. HUVECs displayed pro-inflammatory phenotype with up-regulation of mRNA for IL-6, intercellular adhesion molecule (ICAM)-1 and endothelial leukocyte adhesion molecule (ELAM)-1. Cell proliferation rate was directly related to IL-8 serum levels and EPC percentage. In highly selected young SLE patients without previous CV events, we found that the deterioration of Tang compartment is an early event in disease course, preceding the development of an overt cardiovascular disease and potentially mediated by SLE-specific mechanisms. The overcome of the CD28null subset exerts detrimental role over the Tang phenotype, where Tang could exert an anti-inflammatory effect on endothelial cells and might orchestrate via IL-8 the function of EPCs, ultimately modulating endothelial proliferation rate. | 10.3389/fimmu.2020.572876 |
pubmed_1088_21639 | OBJECTIVE
The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic stem (ES) into Parkinson's disease (PD) model mice as well as the necessity of immunosuppression in allogeneic donor-host combinations.
MATERIALS AND METHODS
ES cells, derived from SvJ129 strain mice, were differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro by an embryoid body (EB)-based multistep differentiation method and used as graft cells for PD mice, which were prepared by injection of 6-hydroxydopamine (OHDA) into C57BL/6, BALB/c and C3H/HeN strains. Mice from each strain were divided into Groups 1-3. Four weeks after the 6-OHDA injection, Group 1 received phosphate-buffered saline in the striatum wounds, while Group 2 received 2 x 10(4) graft cells, and Group 3 mice received 2 x 10(4) graft cells and were also treated with cyclosporine A.
RESULTS
Apomorphine-induced rotational behavior was improved in Groups 2 and 3, but not in Group 1. However, the behavioral improvement ceased later in Group 2, whereas sustained improvement was observed in Group 3 throughout the 8 week observation period after transplantation. ES-derived TH(+) cells were found at the grafted sites at the end of the experiment in Groups 2 and 3, and tended to be more abundant in Group 3.
CONCLUSION
Intra-striatum transplantation of ES-derived dopaminergic neurons was effective in treating PD mice, even in allogeneic donor-host combinations. Immunosuppressive treatment did not have an effect on initial behavioral restoration after transplantation; however, it was necessary for sustained improvement over a prolonged period. | 10.1179/016164108X339378 |
pubmed_613_13971 | Current interest in amyloid fibrils stems from their involvement in neurodegenerative and other diseases and from their role as an alternative structural state for many peptides and proteins. Solid-state nuclear magnetic resonance (NMR) methods have the unique capability of providing detailed structural constraints for amyloid fibrils, sufficient for the development of full molecular models. In this article, recent progress in the application of solid-state NMR to fibrils associated with Alzheimer's disease, prion fibrils, and related systems is reviewed, along with relevant developments in solid-state NMR techniques and technology. | 10.1146/annurev-physchem-032210-103539 |
pubmed_257_6308 | We have previously demonstrated that gonadal steroids stimulate [3H]thymidine incorporation and creatine kinase specific activity in skeletal tissues. In the present study we report that in 20-day-old vitamin D-deficient Wistar-derived rats, 17 beta-estradiol (E2; 5 micrograms/rat) or testosterone (50 micrograms/rat) failed to stimulate [3H]thymidine incorporation into diaphyses of long bones and that the response to these hormones in terms of increased creatine kinase specific activity was less than half the value in normally fed rats. Two daily ip injections of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3; 0.5 ng/g BW], but not 24,25-(OH)2D3 (5 ng/g BW), partially restored the biological responses to E2 in bone of 21-day-old vitamin D-deficient female rats. Vitamin D deficiency did not impair the responsiveness to gonadal steroids in the epiphysis of long bones, uterus, or prostate, in contrast to its effect on diaphysis. In 21-day-old normally fed female rats, neither vitamin D metabolite enhanced the response to E2. When cultures of rat epiphyseal cells were treated daily for 5 days with either 1,25-(OH)2D3 (1 nM) or 24,25-(OH)2D3 (10 nM), followed by E2 (30 nM) for 24 h, creatine kinase activity was significantly higher than in cultures treated daily for 5 days with vehicle alone, and then with E2. The same treatment of rat embryo calvaria bone cells showed that 1,25-(OH)2D3, but not 24,25-(OH)2D3, significantly increased the creatine kinase activity response to E2. These findings suggest that vitamin D metabolites selectively affect the biological responses of skeletal tissues to gonadal steroids. | 10.1210/endo-125-4-1870 |
pubmed_722_3209 | Strawberry (Fragaria × ananassa Duch), a fruit of economic and nutritional importance, is also a model species for fleshy fruits and genomics in Rosaceae. Strawberry fruit quality at different harvest stages is a function of the fruit's metabolite content, which results from physiological changes during fruit growth and ripening. In order to investigate strawberry fruit development, untargeted (GC-MS) and targeted (HPLC) metabolic profiling analyses were conducted. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to explore the non-polar and polar metabolite profiles from fruit samples at seven developmental stages. Different cluster patterns and a broad range of metabolites that exerted influence on cluster formation of metabolite profiles were observed. Significant changes in metabolite levels were found in both fruits turning red and fruits over-ripening in comparison with red-ripening fruits. The levels of free amino acids decreased gradually before the red-ripening stage, but increased significantly in the over-ripening stage. Metabolite correlation and network analysis revealed the interdependencies of individual metabolites and metabolic pathways. Activities of several metabolic pathways, including ester biosynthesis, the tricarboxylic acid cycle, the shikimate pathway, and amino acid metabolism, shifted during fruit growth and ripening. These results not only confirmed published metabolic data but also revealed new insights into strawberry fruit composition and metabolite changes, thus demonstrating the value of metabolomics as a functional genomics tool in characterizing the mechanism of fruit quality formation, a key developmental stage in most economically important fruit crops. | 10.1093/jxb/erq343 |
pubmed_715_2716 | AIMS
To evaluate the effect of weight reduction on parameters of the metabolic syndrome in obese patients according to their pattern of abdominal fat distribution.
METHODS
A longitudinal intervention study, consisting of a 12-week weight reduction programme, including lifestyle modification and adjuvant appetite suppressant, in 38 subjects with visceral obesity and 47 subjects with subcutaneous obesity. Visceral, subcutaneous and total adipose tissue areas were determined by CT scan at the level of L4-L5. Parameters for components of the metabolic syndrome were measured before and after weight reduction.
RESULTS
Reductions in body weight, BMI and subcutaneous adipose tissue area were greater in the subcutaneous than in the visceral obesity group. In contrast, changes in fasting plasma glucose, insulin, and HOMA score were higher in the visceral than in the subcutaneous obesity group. Changes in visceral adipose tissue area were significantly related to changes in fasting plasma glucose, triglycerides and HOMA score.
CONCLUSIONS
Visceral fat reduction induced greater beneficial effects on parameters of the metabolic syndrome than subcutaneous fat reduction. Evaluation of changes in abdominal fat distribution is necessary when obese subjects enter a weight reduction programme. | 10.1111/j.1464-5491.2004.01395.x |
pubmed_186_21743 | BACKGROUND
It is important that postoperative analgesic management after thoracotomy is very effective in order to optimize postoperative recovery. A regional technique such as an epidural or a paravertebral catheter with an infusion of local anesthetic may be supplemented with systemically administered analgesic drugs in order to achieve satisfactory analgesia.
OBJECTIVE
The objective of this observational study was to evaluate whether a paravertebral infusion of local anesthetic delivered via a surgically placed catheter together with systemic analgesics is associated with low pain scores and satisfactory analgesia after thoracotomy for decortication in children.
METHODS
We performed a retrospective analysis of the notes and charts of 83 children admitted with empyema thoracis and managed with thoracotomy and decortication. We collected data on the doses of analgesic drugs (morphine, paracetamol, and ibuprofen) and details of paravertebral infusions, together with postoperative pain scores for the first 48 h after surgery, or earlier if the paravertebral infusion was stopped within 48 h of surgery. Poor quality analgesia was defined as a score of 7 or more on the Visual Analog/Smiley Faces Scale ('VAS/SF').
RESULTS
A total of 81 children were ASA 1 status and two were ASA 3 status. Analgesia comprised intravenous morphine at a mean dose of 20 μg·kg(-1) ·h(-1) , together with oral paracetamol (62.5 mg·kg(-1) /24 h) and ibuprofen (14.2 mg·kg(-1) /24 h). The mean paravertebral bupivacaine dose was 0.29 mg·kg(-1) ·h(-1) . Sixty-four patients (77.1%) had good quality analgesia, 17 (20.5%) patients had moderate quality analgesia, and only two patients (2.4%) had poor quality analgesia.
CONCLUSION
Analgesic outcomes with this regimen appear to be very satisfactory. It compares favorably with an epidural-based regimen. | 10.1111/pan.12921 |
pubmed_781_20965 | The power prior has been widely used in many applications covering a large number of disciplines. The power prior is intended to be an informative prior constructed from historical data. It has been used in clinical trials, genetics, health care, psychology, environmental health, engineering, economics, and business. It has also been applied for a wide variety of models and settings, both in the experimental design and analysis contexts. In this review article, we give an A-to-Z exposition of the power prior and its applications to date. We review its theoretical properties, variations in its formulation, statistical contexts for which it has been used, applications, and its advantages over other informative priors. We review models for which it has been used, including generalized linear models, survival models, and random effects models. Statistical areas where the power prior has been used include model selection, experimental design, hierarchical modeling, and conjugate priors. Frequentist properties of power priors in posterior inference are established, and a simulation study is conducted to further examine the empirical performance of the posterior estimates with power priors. Real data analyses are given illustrating the power prior as well as the use of the power prior in the Bayesian design of clinical trials. | 10.1002/sim.6728 |
pubmed_570_3824 | OBJECTIVES
To evaluate the safety and efficacy of retroperitoneal laparoscopic resection for pheochromocytoma.
METHODS
The clinical data of 131 cases of pheochromocytoma were analyzed retrospectively. There were 69 males and 62 females with an age range of 8 to 77 years, including 120 cases of adrenal pheochromocytoma and 11 extraadrenal pheochromocytomas. Retroperitoneal laparoscopic resection was performed in all cases. We divided our practical experience into three stages: (1) the tentative and exploratory stage, (2) the accumulative stage, and (3) the mature stage.
RESULTS
During the tentative and exploratory stage, 10 patients underwent retroperitoneal laparoscopic surgery. The mean diameter of the tumor was 4.2 cm. The mean operation time was 105 minutes, and the median volume of blood loss during surgery was 450 mL. During the accumulative stage, the mean tumor diameter of the 72 cases was 5.6 cm. The mean operation time was 85 minutes and median volume of blood loss was 140 mL. During the mature stage, the mean tumor diameter of the 49 cases (including 11 extra-adrenal pheochromocytoma patients) was 6.7 cm. The mean operation time was 75 minutes and median volume of blood loss was 70 mL. Follow-ups ranging from 1 to 70 months were conducted, with three cases recurring. There were no cases of distant metastases or death.
CONCLUSIONS
Retroperitoneal laparoscopic surgery for pheochromocytoma is feasible and safe. This procedure will be increasingly performed as medical personnel continue to develop their skills and accumulate experience. | 10.1016/j.urology.2010.03.094 |
pubmed_142_8575 | A role for bone-marrow-derived cells (BMDCs) in tissue repair and malignancy onset has been proposed, but their contribution is still debated. We tested the ability of BMDCs containing the inducible kras(V12) oncogene to initiate lung adenocarcinoma. For our experimental strategy, we reconstituted lethally irradiated wild type mice with BMDCs carrying inducible kras(V12) and subsequently induced oncogene expression by 4-OHT administration. Epithelial lung lesions, from adenoma to adenocarcinomas, appeared at successive time points. These results show that lung tumors were derived from donor BMDCs and indicate a direct involvement of bone marrow cells in the development of epithelial cancers. | 10.1038/srep13047 |
pubmed_1026_11943 | Individuals can coordinate small kinematic changes at several degrees of freedom simultaneously in the presence of fatigue, leaving it unclear how overall biomechanical demands at each joint are altered. The purpose of this study was to evaluate trade-offs in joint moments between the trunk, shoulder, and elbow during repetitive upper extremity work. Participants performed four simulated workplace tasks cyclically until meeting fatigue termination criteria. Emergent fatigue-induced adaptations to repetitive work resulted in task-dependent trade-offs in joint moments. In general, reduced shoulder moments were compensated for by increased elbow and trunk joint moment contributions. Although mean joint moment changes were modest (range: 1-3 Nm) across participants, a wide distribution of responses was observed, with standard deviations exceeding 10 Nm. Re-distributing biomechanical demands across joints may alleviate constant tissue loads and facilitate continued task performance with fatigue but may be at the expense of increasing demands at adjacent joints. | 10.1016/j.apergo.2020.103142 |
pubmed_854_20714 | Outstanding historical trees embedded in cities constitute pertinent environmental assets, yet they are widely threatened in third-world cities. Inadequate understanding of this valuable natural-cum-cultural heritage hinders proper conservation. A case study of Guangzhou in south China evaluated floristic composition, age profile and biomass structure of historical trees, assessed their performance in major habitats (institutional, park and roadside), and established a prognosis for future growth and management. The 348 historical trees examined belonged to only 25 species, vis-à-vis 254 trees in the entire urban forest, dominated by five species and native members. Roadside had more trees, followed by institutional and park, with merely the most common four species shared by all habitats. The limited commonality reflected tree-performance differentiation by habitats exerting selection pressure on species. The institutional growth-regime was more conducive to nurturing high-caliber specimens, whereas park is less capable. Individual species achievement by habitats, derived from tree-count ranking and relative-abundance indices, could inform species choice and tree conservation. Few trees exceeded 300 years of age in the millennium-old city, echoing a history of intense tree-city conflicts. Potential life-span, trunk and crown diameters indicated ample opportunities for further expansion of biomass and landscape impacts, which would be straitjacketed by the tightening urban fabric. | 10.1007/s10661-005-6028-0 |
pubmed_751_1819 | It is well known that the costs of care at health maintenance organizations (HMOs) at any point in time have been lower than in the fee-for-service sector, but how costs have changed in each of these sectors has been less well-documented. The only previous study, which examined the HMO experience during the 1960s and early 1970s, found that HMO and fee-for-service costs rose at approximately the same rate. The present study, which extends this analysis to the period 1976-1981, also demonstrates that HMO costs increased at a rate not detectably different from that in the fee-for-service sector. These results are consistent with the earlier conclusions that HMOs cause a once-and-for-all reduction in cost. They also indicate that the public has been willing to pay for much of the increased costs of modern medical technology. Key words: fee-for-service; health maintenance organizations; Rand Health Insurance Study; Group Health Cooperative data. | 10.1097/00005650-198508000-00003 |
pubmed_1047_24457 | Butyrate and other short-chain fatty acids stimulate fetal globin gene expression and have potential for ameliorating the beta globin disorders. Butyrate, however, is rapidly metabolized in vivo and reaches only micromolar concentrations in plasma. We report here that a branched-chain derivative of butyrate, isobutyramide, increases gamma globin gene expression in cultured human erythroid progenitors in vitro and stimulates activity from a minimal gamma globin gene promoter linked to a reporter gene in stable and transient expression assays, with slightly less activity in these in vitro assays than butyrate. In vivo, administration of isobutyramide to anaemic adult baboons rapidly stimulates fetal globin synthesis and F-reticulocyte production. Plasma concentrations at millimolar levels are achieved after a single intravenous or oral dose (500-600 mg/kg), and these concentrations are maintained for 9.5-10.5 h. These results indicate that although isobutyramide has slightly less activity than butyrate in vitro in enhancing fetal globin expression at the cellular and molecular level, its prolonged in vivo half-life may provide superior activity as a therapeutic agent for reactivating fetal globin gene expression in vivo. | 10.1111/j.1365-2141.1994.tb05073.x |
pubmed_19_17935 | BACKGROUND
Reconstruction of circumferential hypopharyngeal defects is often challenging. The aim of the study is to examine the result of our experience and to formulate improved management guidelines.
METHOD
Between 1980 and 2009, all patients who have circumferential pharyngectomy were recruited. Data were recorded prospectively for analysis.
RESULTS
A total of 202 patients were recruited. Majority had primary tumour in the hypopharynx (n=165), and the remaining patients had recurrent laryngeal carcinoma. Radiotherapy was given preoperatively in 72 patients and postoperatively in 108 patients. A pectoralis major (PM) flap was used in 92 (45.5%) patients, a free anterolateral thigh (ALT) flap in 24 (11.9%) patients and a free jejunal flap in 86 (42.6%) patients. Early fistula rate was 23.9% in the PM flap group, 12.5% in the ALT group and 4.6% in the jejunum group. Late anastomotic stricture rate was 27.2% in the PM flap group, 12.5% in the free ALT group and 2.3% in the jejunum group. Early fistula formation significantly increased the risk of subsequent anastomotic stricture (p=0.023). In patients with no stricture, 61.9% of them in the jejunal group were able to resume solid diet, compared with 35.8% and 38.1% in the PM and ALT groups. After PM flap harvesting, 34.8% of the chest wall defects could not be closed primarily, which were best repaired using the lateral thoracic flap. The donor-site morbidity of ALT and jejunal flap was low.
CONCLUSION
In suitable patients, free jejunal flap reconstruction of circumferential pharyngectomy defects achieves the best functional outcome with minimal donor-site morbidity. | 10.1016/j.bjps.2011.03.021 |
pubmed_510_904 | We described Dubin-Johnson syndrome (DJS) with severe cholestasis in a 20-day-old Japanese boy. Although neonatal DJS has been sporadically reported. DJS with severe cholestasis has not to our knowledge been described in the English literature. The ratio of urinary coproporphyrin isomer I to urinary total coproporphyrin in our patient was high (93%). Liver histology showed cytoplasmic pigment granules in the liver cells. Administration of phenobarbital (PB) significantly decreased the levels of bilirubin and bile acids in the serum. There was a significant elevation of 1 beta-hydroxylated bile acids in the urine. It is predicted that severe cholestasis in neonatal DJS may cause metabolic abnormalities in both bilirubin and bile acids transport. | 10.1111/j.1651-2227.1991.tb11867.x |
pubmed_1141_10095 | We report on our clinical experience with a knitted Dacron prosthesis: thin-walled, spirally reinforced InterGard prosthesis. Between 1993 and 1996, 81 prostheses were implanted in 72 patients with an infrainguinal connection. We describe the special features of the prosthesis. The entire group of patients was analyzed. Indications for operation were disabling claudication in 42 cases (51.8%) and critical limb ischemia in 39 (48.0%) cases. The angiographic run-off was poor in 71 (87.9%) implantations. The perioperative mortality rate was 1.2% (1 patient). The primary cumulative patency rate calculated by the life-table method was 70% at 69 months. Our results suggest that PTFE offers no clear advantage over Dacron and the preferential use of PTFE needs to be reassessed. | pubmed_1141_10095 |
pubmed_970_6588 | Pancreatic cancer is one of the five most lethal malignancies and has a poor prognosis due to its abundant stromal barriers and lack of effective available therapies. Although gemcitabine has been used as a standard therapy for several decades, there has been little progress in the improvement of the 5 year survive rate due to the low targeting efficiency for pancreatic cancer cells. To achieve a targeted delivery of gemcitabine to pancreatic cancer cells, we have developed a c(RGDfE) [cyclic (Arg-Gly-Asp-d-Phe-Glu)] conjugated multi-functional nanomedicine delivery system composed of a magnetic core and mesoporous silica shell. These magnetic mesoporous nanoparticles demonstrated sufficient relaxivity properties for detection with magnetic resonance imaging (MRI). These c(RGDfE) peptide conjugated magnetic mesoporous silica nanoparticles [c(RGDfE)-pMMSNs] can target pancreatic cancer cells and increase cellular uptake in human pancreatic cancer cell lines that overexpress integrin ανβ3. Gemcitabine loaded c(RGDfE)-pMMSNs were most efficiently targeted to pancreatic cancer cells (BxPC-3). Growth inhibition of the BxPC-3 cell line was achieved in a time dependent manner consistent with observed drug release behavior. Intracellular targeted gemcitabine delivery using c(RGDfE)-pMMSNs offers a promising approach for the treatment of pancreatic cancer. | 10.1039/c4tb01402b |
pubmed_829_7187 | This study is a continuation of our efforts to understand the interplay in the self-assembly chemistry for formation of molecular sieves from guest organocations and inorganic silicon oxide. In this particular study we focus on the competitive interplay of the organocations and the synthesis cofactor fluoride anion. The anions play a key role in structure determination, as a function of net solution concentration. They compete with the role for the space-filling organocation in determining which molecular sieve host structure will be specified. In this study we look at this competition in the synthesis for a series of 33 different organocations derived from the piperidine ring system. Derivatives were prepared which both fixed substituents on the carbon and nitrogen centers on the ring. Results were discussed in terms of product selectivity from synthesis as a function of solution concentration for the reactants. A total of 17 different host topologies were found in this series, and a correlation was seen for (a) open-framework lattices (low framework densities) under the most concentrated reaction conditions and then (b) high framework density products once the conditions were more dilute. Some surprising synthesis differences are seen in comparing the performance of these structure directing agents (SDAs) in fluoride media vs hydroxide media (the more conventional environment for zeolite/molecular sieve syntheses involving silicate chemistry). Finally molecular modeling was used to understand some of the trends in product selectivity for closely related guest (SDA) candidates. | 10.1021/ja0709122 |
pubmed_678_1995 | Historical documents dating back almost 4500years have alluded to the condition of epilepsy, describing signs and symptoms that are well-known today. Epilepsy was thought to be a mystical disorder by almost all Ancient cultures, including the Babylonians, Egyptians, Greeks, Indians, Iranians and Chinese. Hippocrates was the first to de-mystify the condition of epilepsy, providing a more scientific approach to the condition. As the signs and symptoms of epilepsy occurred without an obvious cause, the idea stood that it was a mystical phenomenon of divine punishment. This portrayal persisted through the early centuries of the common era, including the Middle Ages. It was not until the 16th and 17th century that Paracelsus, le Pois and Sylvius started to investigate internal causes for epilepsy. By the beginning of the 18th century, the general opinion on epilepsy was that it was an idiopathic disease residing in the brain and other inner organs. This resulted in Tissot writing the first modern book on epilepsy. Research continued in the 19th century with Jackson describing different types of seizures and many researchers showing interest in electroencephalography (EEG). The 20th century saw more detailed research being done on epilepsy and EEG, in addition to the establishment of many epilepsy-associated medical societies. The goal of this historical documentation is to provide an overview of the most important milestones in the history of epilepsy. | 10.1016/j.braindev.2017.02.002 |
pubmed_1108_2977 | In Arabidopsis (Arabidopsis thaliana), jasmonate is a key signal required for stamen and pollen maturation and thus for male fertility. Using transcriptional profiling, we have previously identified a set of 13 transcription factors that are proposed to be involved in controlling jasmonate responses in stamens. This finding suggests that a transcriptional cascade regulates the many developmental and biochemical pathways required to ensure fertility; however, the organization of this cascade is currently not understood. Here, we provide a genetic characterization of the role of MYB108 and map its relationship to MYB21 and MYB24, two other transcription factors involved in the jasmonate response in Arabidopsis stamens. Transcriptional profiling and analysis of plants expressing a MYB108:GUS fusion protein demonstrated that MYB108 expression is largely confined to sporophytic tissues of the stamen. Three allelic myb108 mutants exhibited reduced male fertility that was associated with delayed anther dehiscence, reduced pollen viability, and decreased fecundity relative to wild type. These phenotypes were all found to be exacerbated in myb108 myb24 double mutants, which also had shorter stamen filaments. Measurements of MYB108 transcript levels in wild-type and mutant flowers showed that expression of this gene is strongly dependent on MYB21. Taken together, our results indicate that MYB108 and MYB24 have overlapping functions and act downstream of MYB21 in a transcriptional cascade that mediates stamen and pollen maturation in response to jasmonate. | 10.1104/pp.108.132597 |
pubmed_851_23956 | In recent years it has become increasingly clear that astrocytes play a much more active role in neural processes than the traditional view of them as supporting cells suggests. Although not electrically excitable, astrocytes exhibit diverse Ca2+ dynamics across spatial and temporal scales, more or less dependent on the animal's behavioral state. Ca2+ dynamics range from global elevations lasting multiple seconds encompassing the soma up to the finest processes, to short elevations restricted to so-called microdomains within fine processes. Investigations of astrocyte Ca2+ dynamics have particularly benefitted from the development of Genetically-Encoded Calcium Indicators (GECIs). GECI expression can be achieved non-invasively in a cell type-specific manner and it can be genetically targeted to subcellular domains. The GCaMP family, a group of GECIs derived from the green fluorescent protein, has experienced some of the fastest advancements during the past decade. As a consequence we are now facing the challenge of needing to compare published data obtained with different versions of GECIs. With the intention to provide some guidance, here we compared Ca2+ dynamics across scales in awake transgenic mice expressing either the well-established GCaMP3, or the increasingly popular GCaMP6f, specifically in astrocytes. We found that locomotion-induced global Ca2+ elevations in cortical astrocytes displayed only minor kinetic differences and their apparent dynamic ranges for Ca2+ sensing were not different. In contrast, Ca2+ waves in processes and microdomain Ca2+ transients were much more readily detectable with GCaMP6f. Our findings suggest that behavioral state-dependent global astrocyte Ca2+ responses can be studied with either GCaMP3 or GCaMP6f whereas the latter is more appropriate for studies of spatially restricted weak and fast Ca2+ dynamics. | 10.1371/journal.pone.0181113 |
pubmed_720_16060 | BACKGROUND
Virulent Newcastle disease virus (vNDV) causes great economic losses to the poultry industry throughout the world. Despite the endemicity of Newcastle disease (ND) and occurrence of recurrent outbreaks, the nature and genetic features of circulating NDV strains in Iran are largely unknown. Aims: This study was conducted to characterize 13 NDV isolates obtained from different outbreaks in various regions of Iran during 1999-2000 by sequencing and phylogenetic analysis of complete coding sequences of haemagglutinin-neuraminidase (HN) gene.
METHODS
All isolates were analyzed based on the previously determined in vivo pathogenicity indices and amino acid (aa) sequences of fusion (F) protein cleavage site (FPCS).
RESULTS
Phylogenetic analysis based on the HN gene coding region revealed a very close relationship of these viruses with the recently defined genotype XIII, and more specifically, subgenotype XIIIa viruses. Analysis of HN gene nucleotide (nt) sequences revealed that all studied isolates encode for a protein length of 571 aa and there is no C-terminal extension on HN aa sequences. Sequence analysis revealed multiple aa residue substitutions at antigenic sites or neutralizing epitopes on the HN glycoprotein of studied viruses compared with commonly used vaccinal strains.
CONCLUSION
In this study, molecular characterization of vNDV isolates, obtained from commercial poultry farms in Iran, were conducted through complete sequencing and analysis of HN gene. Isolation and molecular characterization of further NDV isolates from other parts of Iran and from neighboring countries in the region will be helpful to identify the nature and origin of indigenous viruses. | pubmed_720_16060 |
pubmed_827_22006 | The paper proposed novel designs to pinch the transverse diffusion of the sample in the injection mode using microelectrodes to generate the potential difference at the channel intersection in the capillary electrophoresis (CE) microchip. A pair of microelectrodes was used to conduct the injection channel and the separation channel, which directly provided the potential to pinch the sample without using a power supply. These new designs of the CE microchip simplify the electric circuitry and improve performance. Simulations were performed using the CFD-ACE[trade mark sign] software. The mechanisms of diffusion and electrophoresis were employed in the numerical simulation. The injection and separation processes of the sample were simulated and the parameters of the present design were investigated numerically. | 10.1039/b313239k |
pubmed_72_11607 | The article presents an analysis of in-depth interviews with 18 leaders of Christian churches in Nairobi, Kenya, regarding the content and context of messages they disseminate to their congregations about sexual behaviour and HIV. The content of messages was nearly consistent across the different denominations. However, three sorts of tensions were identified within pastoral communication about these topics: the need to discuss sex and HIV versus societal taboos against speaking about those issues from the pulpit; traditional cultural norms versus current lifestyles; and the ideals of abstinence and fidelity versus the reality of congregants' sexual behaviour. Although some of the religious leaders accepted the idea of condom use, no denominational patterns were noted on that subject, except with respect to Catholic priests. Pentecostal leaders were notable for describing proactive strategies to address both the ideal/real dilemma and the tension between church norms and current media content about sexuality and HIV. | 10.2989/16085906.2011.626300 |
pubmed_6_10055 | BACKGROUND
Different classification criteria for systemic lupus erythematosus (SLE) have been launched over the years. Our aim was to evaluate the performance of the EULAR/ACR-2019, SLICC-2012 and ACR-1997 classification criteria in a cohort of SLE patients with longstanding disease.
METHODS
Descriptive observational study in 79 patients with established and longstanding SLE. The three classification criteria sets were applied to those patients.
RESULTS
Of the 79 patients, 70 were women (88.6%), with a mean age of 51.8 ± 14 years and a mean disease duration of 15.2 ± 11.5 years. The sensitivity of the different criteria were: 51.9%, 87.3% and 86.1% for ACR-1997, SLICC-2012 and EULAR/ACR-2019, respectively. In total, 68 out of 79 patients (53.7%) met all three classification criteria; 11.4% did not meet any classification criteria and were characterized by low SLEDAI (0.6 ± 0.9), low SLICC/ACR Damage Index (0.88 ± 0.56) and fulfilling only skin domains, antiphospholipid antibodies or hypocomplementemia. To fulfill EULAR/ACR-2019 criteria was associated with low complement levels (p < 0.04), high anti-dsDNA levels (p < 0.001), presence of lupus nephritis III-IV (p < 0.05) and arthritis (p < 0.001).
CONCLUSION
The EULAR/ACR-2019 classification criteria showed high sensitivity, similar to SLICC-2012, in SLE patients with longstanding disease. Patients with serological, articular or renal involvement are more likely to fulfill SLICC-2012 or EULAR/ACR-2019 criteria. | 10.3390/jcm10112377 |
pubmed_64_21178 | BACKGROUND
Pasteurized donor milk (PDM) is typically prescribed to preterm or low birthweight newborns when their mother's own milk is unavailable. In surplus, PDM is prescribed to meet the nutritional needs of healthy newborns in the first few days of life. However, its overuse can undermine efforts to promote and support breastfeeding, waste resources, and reduce the availability of PDM for at-risk newborns. We conducted this study to examine factors associated with the prescription and prolonged use (>48 h) of privately purchased PDM to healthy newborns.
METHODS
Prospective observational study of 2440 mothers of healthy, term, and normal birthweight newborns born at Da Nang Hospital for Women and Children between April and August 2019. In addition to the descriptive analysis, we performed multiple logistic regressions to examine factors associated with the prescription of PDM (n = 2440) and prolonged PDM use among those who used PDM (n = 566).
RESULTS
Twenty-three percent (566/2440) of healthy, term, and birthweight ≥2500 g newborns received PDM and were included in the study. The prevalence of PDM use was higher for cesarean births (OR: 2.05; 95% CI: 1.66, 2.55) and among male newborns (OR: 1.33; 95% CI: 1.09, 1.62), but lower for farmers or workers (vs. other jobs; OR: 0.71; 95% CI: 0.54, 0.93), family income <10 million VND (vs. ≥10 million VND; OR: 0.67; 95% CI: 0.55, 0.82), and duration of skin-to-skin ≥90 min (vs. <90 min; OR: 0.54; 95% CI: 0.39, 0.76). Prolonged PDM use (12.4% of 566 newborns who used PDM) was associated with the mother having a higher socioeconomic status job (professional, small trader or homemaker; OR: 4.00; 95% CI: 1.39, 12.5), being a first-time mother (OR: 3.39; 95% CI: 1.92, 6.01) or having a cesarean birth (OR: 2.09; 95% CI: 1.02, 4.28).
CONCLUSIONS
The prescription and prolonged use of privately purchased PDM was associated with non-medical factors unrelated to the ability to breastfeed effectively. The findings suggest the need for improved breastfeeding communication, counseling and support skills for health staff, development, and application of strict criteria on PDM use for healthy newborns and better routine monitoring of PDM use over time. | 10.3390/nu13041151 |
pubmed_809_19177 | PURPOSE
To estimate the 10-year incidence of cataract and cataract surgery in an older Australian population.
DESIGN
Prospective population-based study.
PARTICIPANTS
Persons at least 49 years old living in 2 postcode areas west of Sydney, Australia.
METHODS
Eye examinations were performed at baseline and at 5- and 10-year follow-up visits. Lens photographs were taken and graded by masked graders using the Wisconsin Cataract Grading System.
MAIN OUTCOME MEASURES
Incidences of nuclear cataract, cortical cataract, posterior subcapsular cataract (PSC), and cataract surgery.
RESULTS
Ten-year person-specific incidences were 36.0% for nuclear cataract, 28.0% for cortical cataract, 9.1% for PSC, and 17.8% for cataract surgery. Corresponding rates were 31.7%, 24.4%, 8.2%, and 14.4%, respectively, in men and 39.3%, 30.8%, 9.8%, and 20.1%, respectively, in women. The incidence for each type of cataract and cataract surgery was positively associated with age (P<0.0001). Women had a significantly higher incidence than men for nuclear cataract (P = 0.04), cortical cataract (P = 0.007), any cataract (P = 0.0006), and cataract surgery (P = 0.03) after adjusting for age. There was no significant gender difference for PSC. The mean age at cataract surgery was 75.8 years, and there was no significant gender difference (P = 0.9). Among persons who developed any cataract, 22% had more than one type and 1.3% had all 3 types present. Nuclear cataract and PSC were significantly associated with visual impairment (visual acuity worse than 20/40).
CONCLUSION
Age- and gender-specific cataract incidences in this study were similar to those reported from the U.S. Beaver Dam Eye Study. In this study, 72% of the participants were affected by cataract or had had cataract surgery over the 10-year follow-up period. | 10.1016/j.ophtha.2007.07.008 |
pubmed_848_2258 | 1. Human soleus muscles were fatigued under ischaemic conditions by intermittent stimulation at 15 Hz. When maximal voluntary plantarflexion was then attempted, the loss of torque was found to be associated with a reduction in voluntary EMG activity. 2. The decrease in EMG activity could not have been due to 'exhaustion' of descending motor drive in the central nervous system since fatigue had been induced by electrical stimulation of peripheral nerve fibres. Similarly, the decrease could not be explained by changes at the neuromuscular junction or muscle fibre membrane, since changes in the M wave (evoked muscle compound action potential) were relatively modest. 3. When the excitability of the soleus motoneurones was tested during fatigue, using the H (Hoffmann) reflex, it was found to be significantly reduced. Control experiments with ischaemia or electrical stimulation, but without fatigue, failed to demonstrate any significant effects on reflex excitability. 4. The findings in this study favour the concept of reflex inhibition of alpha-motoneurones during fatigue. | 10.1113/jphysiol.1990.sp018241 |
pubmed_1133_4871 | Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma, and it is characterized by diffuse cerebral infiltration of malignant lymphoma cells without evidence of a mass lesion. Herein, we report a patient with systemic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) who had central nervous system involvement mimicking LC. A 72-year-old immunocompetent male presented with rapidly progressive dementia. Fluor-deoxy-glucose (FDG) -positron emission tomography revealed increased FDG uptake in the bone and skin. Histopathological examination of the skin lesion revealed PTCL-NOS infiltration. A FLAIR MRI scan of the brain revealed diffuse hyperintense lesions in the cerebral white matter of both hemispheres. These lesions were not enhanced with gadolinium, and there was no perceptible mass effect. We performed a brain biopsy, and the histology results were consistent with PTCL-NOS. The patient was treated with corticosteroid and chemotherapy; however the disease progressed, and he died 4 months after the diagnosis. This was a rare case of systemic lymphoma accompanied with central nervous system involvement mimicking LC. | 10.11406/rinketsu.58.760 |
pubmed_304_11611 | A free energy perturbation (FEP) method was developed that uses ab initio quantum mechanics (QM) for treating the solute molecules and molecular mechanics (MM) for treating the surroundings. Like our earlier results using AM1 semi empirical QMs, the ab initio QM/MM-based FEP method was shown to accurately calculate relative solvation free energies for a diverse set of small molecules that differ significantly in structure, aromaticity, hydrogen bonding potential, and electron density. Accuracy was similar to or better than conventional FEP methods. The QM/MM-based methods eliminate the need for time-consuming development of MM force field parameters, which are frequently required for drug-like molecules containing structural motifs not adequately described by MM. Future automation of the method and parallelization of the code for Linux 128/256/512 clusters is expected to enhance the speed and increase its use for drug design and lead optimization. | 10.1002/jcc.20510 |
pubmed_971_467 | Mice infected with various strains of Salmonella enteritidis and S. typhimurium were found to be more sensitive to the cell wall lipopolysaccharide (LPS) extracted from certain strains of Salmonella than noninfected mice. This hypersensitivity was induced by those smooth or rough strains which possessed a polysaccharide chain longer than that of a glucoseless mutant. The major antigenic group participating in this hypersensitivity was presumed to be in rough core polysaccharide sequence because fractions containing either O side chain or LPS of a heptoseless mutant were ineffective in provoking a hypersensitivity reaction. Conditions for the induction and the phases of development of this hypersensitivity to LPS and for anti-infectious resistance were shown to be different. Present and previously obtained results suggest that the antigens participating in each of these two conditions were different. | 10.1128/iai.4.5.519-524.1971 |
pubmed_115_16958 | Polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP), are widespread in the environment and cause untoward effects, including carcinogenesis, in mammalian cells. However, the molecular mechanism of apoptosis by BaP is remained to be elusive. Pharmacological inhibition of p38 kinase markedly inhibited the BaP-induced cytotoxicity, which was proven as apoptosis characterized by an increase in sub-G(0)/G(1) fraction of DNA content, ladder-pattern fragmentation of genomic DNA, and catalytic activation of caspase-3 with PARP cleavage. Our data also demonstrated that activation of caspase-3 was accompanied with activation of caspase-9 and mitochondrial dysfunction, which was also apparently suppressed by pretreatment with p38 kinase inhibitors. Also, pharmacological inhibition of p38 markedly inhibited the phosphorylation, accumulated expression, and transactivation activity of p53 in BaP-treated cells. Adenoviral overexpression of human p53 (wild-type) further augmented in increase of PARP cleavage and the sub-G(0)/G(1) fraction of DNA content. Furthermore, p53 mediated apoptotic activity in BaP-treated cells was inhibited by p38 kinase inhibitor. The current data collectively indicate that BaP induces apoptosis of Hepa1c1c7 cells via activation of p53-related signaling, which was, in part, regulated by p38 kinase. | 10.1016/j.abb.2005.10.009 |
pubmed_631_2947 | A 3-year-old patient was referred to the oral and maxillofacial department with a fracture of the orbital floor. Due to the lack of clinical symptoms, a conservative approach was chosen. After 3 weeks, an enophthalmos developed. The orbital floor reconstruction was successfully performed through a transconjunctival approach. This case highlights the rarity of pure blowout fractures in young children. The specific presentation and diagnostics of orbital floor fractures in children and the related surgical planning and intervention are discussed. | 10.1055/s-0033-1333880 |
pubmed_72_11577 | This paper reviews biokinetic data for technetium and proposes a biokinetic model for systemic technetium in adult humans. The development of parameter values focuses on data for pertechnetate TcO(-)(4) the most commonly encountered form of technetium and the form expected to be present in body fluids. The model is intended as a default model for occupational or environmental intake of technetium, i.e. applicable in the absence of form- or site-specific information. Tissues depicted explicitly in the model include thyroid, salivary glands, stomach wall, right colon wall, liver, kidneys, and bone. Compared with the ICRP's current biokinetic model for occupational or environmental intake of technetium (ICRP 1993, 1994), the proposed model provides a more detailed and biologically realistic description of the systemic behaviour of technetium and is based on a broader set of experimental and medical data. For acute input of (99m)Tc (T(1/2) = 6.02 h) to blood, the ratios of cumulative (time-integrated) activity predicted by the current ICRP model to that predicted by the proposed model range from 0.4-7 for systemic regions addressed explicitly in both models. For acute input of (99)Tc (T(1/2) = 2.1 × 10(5) year) to blood, the corresponding ratios range from 0.2-30. | 10.1088/0952-4746/35/2/297 |
pubmed_849_22277 | The cardinal features of age-related macular degeneration (AMD) are the accumulation of subretinal debris, subretinal inflammation, neovascularization, and degeneration of the photoreceptors and retinal pigment epithelium (RPE). Thrombospondin-1 (TSP-1) is a major matricellular protein that is physiologically expressed in the RPE and choroid, but severely diminished in eyes with AMD. TSP-1 plays an important role in phagocytosis, potently inhibits neovascularization, and mediates immune suppression and immune privilege. The lack of TSP-1 could have a central role in the pathogenesis of AMD as it is implicated in the major pathways that seem to be deficient in the disease. We here give an overview of the major functions of TSP-1 and how it could intervene in AMD pathogenesis. | 10.1089/jop.2015.0023 |
pubmed_622_10727 | Malignant cells are often resistant to complement activation through the enhanced expression of complement inhibitors. In this work, we examined the protective role of factor H, CD46, CD55, and CD59 in two non-small cell lung cancer cell lines, H1264 and A549, upon activation of the classical pathway of complement. Complement was activated with polyclonal Abs raised against each cell line. After blocking factor H activity with a neutralizing Ab, C3 deposition and C5a release were more efficient. Besides, a combined inhibition of factor H and CD59 significantly increased complement-mediated lysis. CD46 and CD55 did not show any effect in the control of complement activation. Factor H expression was knockdown on A549 cells using small interfering RNA. In vivo growth of factor H-deficient cells in athymic mice was significantly reduced. C3 immunocytochemistry on explanted xenografts showed an enhanced activation of complement in these cells. Besides, when mice were depleted of complement with cobra venom factor, growth was recovered, providing further evidence that complement was important in the reduction of in vivo growth. In conclusion, we show that expression of the complement inhibitor factor H by lung cancer cells can prevent complement activation and improve tumor development in vivo. This may have important consequences in the efficiency of complement-mediated immunotherapies. | 10.4049/jimmunol.178.9.5991 |
pubmed_882_10941 | AIMS AND OBJECTIVES
The aim of this study was to evaluate an intervention with individualised information and emotional support before coronary artery bypass grafting in a controlled randomised trial.
BACKGROUND
Anxiety is a typical phenomenon in patients who are to undergo cardiac surgery. Preoperative anxiety has been shown to correlate to adverse postoperative outcomes. Emotional support could be an effective measure to reduce preoperative anxiety.
DESIGN AND METHODS
Patients with planned first coronary artery bypass grafting were randomised into an intervention group (n = 139) and a control group (n = 114). The patients of the control group were routinely informed as usual. The patients of the intervention group received a dialogue with individualised information and emotional support one day before surgery in addition to standard care. This intervention of ~30 minutes was based on a supportive psychotherapy model and was delivered by trained nurses. The primary outcome was the change in anxiety before operation. The secondary outcomes consisted of changes in postoperative anxiety, time on intensive care unit and in-hospital mortality.
RESULTS
Significantly reduced anxiety was found in the intervention group patients compared to control patients before coronary artery bypass grafting (p < 0·001) and five days after surgery (p < 0·001). Both groups did not differ in in-hospital mortality and duration of stay in the intensive care unit.
CONCLUSIONS
Our short-term psychosocial intervention in patients undergoing coronary artery bypass grafting had a beneficial effect on reducing pre- and postoperative anxiety that was better than routine information alone.
RELEVANCE TO CLINICAL PRACTICE
These results advocate training for nurses and physicians to provide emotional support to patients before coronary artery bypass grafting. | 10.1111/jocn.13055 |
pubmed_809_22281 | The aim of this publication is to present a time saving diagnostic algorithm consisting of two-dimensional (2D), three-dimensional (3D) and four-dimensional (4D) ultrasound (US) technologies. This algorithm of eight steps combines different imaging modalities and render modes which allow a step by step analysis of 2D, 3D and 4D diagnostic criteria. Advanced breast US systems with broadband high frequency linear transducers, full digital data management and high resolution are the actual basis for two-dimensional breast US studies in order to detect early breast cancer (step 1). The continuous developments of 2D US technologies including contrast resolution imaging (CRI) and speckle reduction imaging (SRI) have a direct influence on the high quality of three-dimensional and four-dimensional presentation of anatomical breast structures and pathological details. The diagnostic options provided by static 3D volume datasets according to US BI-RADS analogue assessment, concerning lesion shape, orientation, margin, echogenic rim sign, lesion echogenicity, acoustic transmission, associated calcifications, 3D criteria of the coronal plane, surrounding tissue composition (step 2) and lesion vascularity (step 6) are discussed. Static 3D datasets offer the combination of long axes distance measurements and volume calculations, which are the basis for an accurate follow-up in BI-RADS II and BI-RADS III lesions (step 3). Real time 4D volume contrast imaging (VCI) is able to demonstrate tissue elasticity (step 5). Glass body rendering is a static 3D tool which presents greyscale and colour information to study the vascularity and the vascular architecture of a lesion (step 6). Tomographic ultrasound imaging (TUI) is used for a slice by slice documentation in different investigation planes (A-,B- or C-plane) (steps 4 and 7). The final step 8 uses the panoramic view technique (XTD-View) to document the localisation within the breast and to make the position of a lesion simply reproducible. | 10.1016/j.ejrad.2007.07.025 |
pubmed_325_9330 | PURPOSE OF REVIEW
The review examines current evidence and thinking regarding the relationship between the larynx and obstructive sleep apnoea (OSA) in adults.
RECENT FINDINGS
Drug-induced sleep endoscopy has an emerging role in the identification of laryngeal obstruction associated with sleep apnoea and may be adjunctive to awake dynamic assessment in specific cases. Nocturnal stridor and OSA is a common and treatable finding in patients with multiple system atrophy. Acromegaly can cause OSA by obstruction at the laryngeal level via supraglottic soft tissue hypertrophy or decreased vocal fold mobility. Emerging evidence suggests a relationship between OSA, laryngopharyngeal reflux, and laryngeal sensory dysfunction including chronic cough. The mechanisms remain unclear and warrant further investigation.
SUMMARY
The larynx plays an important role in assessment and treatment of adult sleep apnoea. Laryngeal afferent sensory pathways play a critical role in reflexes controlling airway patency during sleep. Airway obstruction at the laryngeal level should be considered and assessed especially in OSA patients nonresponsive to standard therapies. Isolated laryngeal airway obstruction is rare but identification of specific conditions is important as they are amenable to appropriate treatments. OSA can also affect normal laryngeal function. People with OSA exhibit higher levels of laryngeal inflammation, laryngopharyngeal reflux, and chronic cough. Treatment with continuous positive airway pressure has a potential role in improving laryngeal symptomatology in these cases. | 10.1097/MOO.0000000000000209 |
pubmed_71_15792 | OBJECTIVES
To investigate further whether inorganic lead is a carcinogen among adults, or associated with increased blood pressure and kidney damage, via a large mortality study.
METHODS
We conducted internal analyses via Cox regression of mortality in three cohorts of lead-exposed workers with blood lead (BL) data (USA, Finland, UK), including over 88 000 workers and over 14 000 deaths. Our exposure metric was maximum BL. We also conducted external analyses using country-specific background rates.
RESULTS
The combined cohort had a median BL of 26 µg/dL, a mean first-year BL test of 1990 and was 96% male. Fifty per cent had more than one BL test (mean 7). Significant (p<0.05) positive trends, using the log of each worker's maximum BL, were found for lung cancer, chronic obstructive pulmonary disease (COPD), stroke and heart disease, while borderline significant trends (0.05≤p≤0.10) were found for bladder cancer, brain cancer and larynx cancer. Most results were consistent across all three cohorts. In external comparisons, we found significantly elevated SMRs for those with BLs>40 µg/dL; for bladder, lung and larynx cancer; and for COPD. In a small subsample of the US cohort (n=115) who were interviewed, we found no association between smoking and BL.
CONCLUSIONS
We found strong positive mortality trends, with increasing BL level, for several outcomes in internal analysis. Many of these outcomes are associated with smoking, for which we had no data. A borderline trend was found for brain cancer, not associated with smoking. | 10.1136/oemed-2017-104311 |
pubmed_245_14933 | Chemotherapy is one of the most important treatment modalities for advanced hepatocellular carcinoma (HCC). On the basis of the results of two pivotal Phase III placebo-controlled studies, sorafenib is currently acknowledged worldwide as the standard therapeutic agent for advanced HCC. Following the introduction of sorafenib for the treatment of HCC, Phase III trials of numerous other agents as first-line or second-line chemotherapy have been conducted to determine if any of these agents might offer superior survival benefit to sorafenib. In 2016, a clear survival benefit of regorafenib over placebo was demonstrated in HCC patients showing disease progression after sorafenib treatment. A year later, in 2017, lenvatinib has been shown to be non-inferior to sorafenib, in terms of the overall survival, in chemo-naïve patients with advanced HCC. More recently, promising outcomes have also been reported with new agents, such as nivolumab and cabozantinib. At present, various novel combination regimens including these agents are currently under development. Hepatic arterial infusion chemotherapy (HAIC) is frequently adopted for the treatment of locally advanced HCC in Japan, based on reports of high response rates and favorable long-term outcomes. Although some randomized controlled trials of HAIC plus sorafenib vs. sorafenib alone as first-line therapy have been conducted in patients with advanced HCC, no firm evidence of the superiority of one over the other has been established yet. In the future, demonstration of the survival advantage of HAIC and the recognition of HAIC as one of the standard treatments for patients with advanced HCC are expected. | 10.1093/jjco/hyx180 |
pubmed_1084_19769 | Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients. | 10.4103/2230-8210.85574 |
pubmed_669_13275 | Copper is an essential mineral for pigs, thus it is used as a feed additive in the forms of copper sulfate. Therefore, this study aimed at characterizing the fecal microbiota shifts in pigs as fed by different forms of copper supplementation. 40 growing pigs aged 73 ± 1 days with an average weight of 30.22 ± 1.92kg were randomly divided into 5 groups. The control group (CON) fed with basal diet, while treatment groups were fed a basal diet supplemented with 100 ppm/kg of copper sulfate (CuSO4), Cu-glycine complex (CuGly), Cu-amino acid complex (CuAA), and Cu-hydroxy(4methylthio)butanoate chelate complex (CuHMB) for 28 days of trial, respectively. The data presented the comparison between inorganic and organic copper supplementation through gut microbiota in growing pigs. Alpha and Beta diversity anaylsis resulted in copper supplementation did shifted gut microbioal community structure. At the phylum level, Firmicutes and Bacteroidetes were the most abundant phyla at all times regardless of treatment. At the genus level, the relative abundances of Prevotella, Lactobacillus, Megasphaera, and SMB53 of the CuGly and CuHMB groups were significantly higher than those of copper sulfate and basal diet groups. Overall, this study may provide the potential role of organic copper replacing inorganic copper, resulting in increased beneficial bacteria in the pig gut. | 10.5187/jast.2021.e118 |
pubmed_18_19627 | The central skull base (CSB) constitutes a frontier between the extracranial head and neck and the middle cranial fossa. The anatomy of this region is complex, containing most of the bony foramina and canals of the skull base traversed by several neurovascular structures that can act as routes of spread for pathologic processes. Lesions affecting the CSB can be intrinsic to its bony-cartilaginous components; can arise from above, within the intracranial compartment; or can arise from below, within the extracranial head and neck. Crosssectional imaging is indispensable in the diagnosis, treatment planning, and follow-up of patients with CSB lesions. This review focuses on a systematic approach to this region based on an anatomic division that takes into account the major tissue constituents of the CSB. | 10.1016/j.nic.2009.06.001 |
pubmed_547_19293 | Vascular deficiency, such as deleterious change of endothelial cells, becomes the prominent feature of hippocampal microvessels during the processes of aging in rodents and it seems to be associated with deficiency of intellectual behavior in aged subjects. The hippocampal microvessels and hippocampal pyramidal neurons form and accumulate intermediates of advanced Maillard reaction (glycation) end products, specifically N()-carboxymethyl lysine (CML) and CML in rodents during the processes of aging. CML facilitates proliferation of endothelial cells in culture. However, further conjugation of CML with the substance(s) seems to occur in the microvessels and pyramidal neurons of hippocampus and it brings about deleterious change of endothelial cells and pyramidal neuron death. This would cause deficiency of recognition and reference memory in rodents during the processes of aging. In man in Alzheimer's disease (AD), one might speculate that formation and accumulation of CML in the hippocampal microvessels initiate the accumulation of amyloid to produce cerebral amyloid angiopathy and it brings about hypoglycemia and hypoxia in the hippocampal pyramidal neurons. Furthermore, formation and accumulation of CML in the hippocampal pyramidal neurons initiate the deposition of neurofibrillary tangles and senile plaques which cause neuronal death. In this way, vascular deficiency of hippocampal microvessels seems to be associated with the demented disease, the atrophic process of the brain and accumulation of amyloid in the brain in man. In terms of vascular deficiency concerns, the vascular change of the retinal capillaries becomes also a prominent feature during the processes of aging and it has a positive correlation with the vascular change of hippocampal capillary. In man during senescence, one might also speculate that vascular change of eye capillaries would become the early market for diagnosis of dementia in AD. | 10.1016/S0361-9230(03)00082-0 |
pubmed_313_18069 | A key debate in ecology centres on the relative importance of niche and neutral processes in determining patterns of community assembly with particular focus on whether ecologically similar species with similar functional traits are able to coexist. Meanwhile, molecular studies are increasingly revealing morphologically indistinguishable cryptic species with presumably similar ecological roles. Determining the geographic distribution of such cryptic species provides opportunities to contrast predictions of niche vs. neutral models. Discovery of sympatric cryptic species increases alpha diversity and supports neutral models, while documentation of allopatric/parapatric cryptic species increases beta diversity and supports niche models. We tested these predictions using morphological and molecular data, coupled with environmental niche modelling analyses, of a fig wasp community along its 2700-km latitudinal range. Molecular methods increased previous species diversity estimates from eight to eleven species, revealing morphologically cryptic species in each of the four wasp genera studied. Congeneric species pairs that were differentiated by a key morphological functional trait (ovipositor length) coexisted sympatrically over large areas. In contrast, morphologically similar species, with similar ovipositor lengths, typically showed parapatric ranges with very little overlap. Despite parapatric ranges, environmental niche models of cryptic congeneric pairs indicate large regions of potential sympatry, suggesting that competitive processes are important in determining the distributions of ecologically similar species. Niche processes appear to structure this insect community, and cryptic diversity may typically contribute mostly to beta rather than alpha diversity. | 10.1111/mec.13985 |
pubmed_443_3655 | Of 580 patients randomly assigned to short-term, double-blind treatment with either mirtazapine, amitriptyline or placebo, a total of 217 patients clinically judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study (mirtazapine, n = 74; amitriptyline, n = 86 and placebo, n = 57). The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data. Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo (p < 0.05), and a significantly longer time to relapse was shown on the survival analysis. There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks, with fewer patients relapsing. There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis (p < 0.05). The significant advantage for mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks. At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response. Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms, but there was no difference from placebo in the proportion of patients with sustained response. Mirtazapine was well tolerated with a side-effect profile similar to that of placebo. The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain. Objectively measured weight gain was more frequent with amitriptyline (22% of patients) compared with mirtazapine (13% of patients). Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo, in particular sedative and anticholinergic side effects. The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression, which on some measures showed an advantage compared with amitriptyline, coupled with its improved side-effect profile, commends this antidepressant for the long-term treatment of depression. | 10.1097/00004850-199803000-00002 |
pubmed_244_20152 | Background: Use of adaptive servo-ventilation (ASV) has been questioned in patients with central sleep apnea (CSA) and chronic heart failure (CHF). This study aims to detail the present use of ASV in clinical practice. Methods: Descriptive, cross-sectional, multicentric study of patients undergoing long term (≥3 months) ASV in the Cantons of Geneva or Vaud (1,288,378 inhabitants) followed by public or private hospitals, private practitioners and/or home care providers. Results: Patients included (458) were mostly male (392; 85.6%), overweight [BMI (median, IQR): 29 kg/m2 (26; 33)], comorbid, with a median age of 71 years (59-77); 84% had been treated by CPAP before starting ASV. Indications for ASV were: emergent sleep apnea (ESA; 337; 73.6%), central sleep apnea (CSA; 108; 23.6%), obstructive sleep apnea (7; 1.5%), and overlap syndrome (6; 1.3%). Origin of CSA was cardiac (n = 30), neurological (n = 26), idiopathic (n = 28), or drug-related (n = 22). Among CSA cases, 60 (56%) patients had an echocardiography within the preceding 12 months; median left ventricular ejection fraction (LVEF) was 62.5% (54-65); 11 (18%) had a LVEF ≤45%. Average daily use of ASV was [mean (SD)] 368 (140) min; 13% used their device <3:30 h. Based on ventilator software, apnea-hypopnea index was normalized in 94% of subjects with data available (94% of 428). Conclusions: Use of ASV has evolved from its original indication (CSA in CHF) to a heterogeneous predominantly male, aged, comorbid, and overweight population with mainly ESA or CSA. CSA in CHF represented only 6.5% of this population. Compliance and correction of respiratory events were satisfactory. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04054570. | 10.3389/fmed.2020.00105 |
pubmed_295_765 | Chimeric antigen receptor T (CAR-T) cells targeting CD19 came into clinical practice for the treatment of B cell lymphoma in 2018. However, patients being treated for B cell lymphoma often suffer from comorbidities such as chronic pain, cardiovascular diseases and arthritis. Thus, these patients frequently receive concomitant medications that include nonsteroidal anti-inflammatory drugs (NSAIDs) like cyclooxygenase (COX) inhibitors. Celecoxib, a selective COX-2 inhibitor, and aspirin, a non-selective COX-1 and COX-2 inhibitor, are being used as anti-inflammatory, analgesic and anti-pyretic drugs. In addition, several studies have also focused on the anti-neoplastic properties of COX-inhibitors. As the influence of COX-inhibitors on CD19.CAR-T cells is still unknown, we investigated the effect of celecoxib and aspirin on the quantity and quality of CD19.CAR-T cells at different concentrations with special regard to cytotoxicity, activation, cytokine release, proliferation and exhaustion. A significant effect on CAR-T cells could be observed for 0.1 mmol/L of celecoxib and for 4 mmol/L of aspirin. At these concentrations, we found that both COX-inhibitors could induce intrinsic apoptosis of CD19.CAR-T cells showing a significant reduction in the ratio of JC-10 red to JC-10 green CAR-T cells from 6.46 ± 7.03 (mean ± SD) to 1.76 ± 0.67 by celecoxib and to 4.41 ± 0.32 by aspirin, respectively. Additionally, the ratios of JC-10 red to JC-10 green Daudi cells were also decreased from 3.41 ± 0.30 to 0.77 ± 0.06 by celecoxib and to 1.26 ± 0.04 by aspirin, respectively. Although the cytokine release by CD19.CAR-T cells upon activation was not hampered by both COX-inhibitors, activation and proliferation of CAR-T cells were significantly inhibited via diminishing the NF-ĸB signaling pathway by a significant down-regulation of expression of CD27 on CD4+ and CD8+ CAR-T cells, followed by a clear decrease of phosphorylated NF-ĸB p65 in both CD4+ and CD8+ CAR-T cells by a factor of 1.8. Of note, COX-inhibitors hampered expansion and induced exhaustion of CAR-T cells in an antigen stress assay. Collectively, our findings indicate that the use of COX-inhibitors is a double-edged sword that not only induces apoptosis in tumor cells but also impairs the quantity and quality of CAR-T cells. Therefore, COX-inhibitors should be used with caution in patients with B cell lymphoma under CAR-T cell therapy. | 10.3389/fimmu.2021.670088 |
pubmed_57_22561 | UNLABELLED
We report the diversity of latent membrane protein 1 (LMP1) gene founder sequences and the level of Epstein-Barr virus (EBV) genome variability over time and across anatomic compartments by using virus genomes amplified directly from oropharyngeal wash specimens and peripheral blood B cells during acute infection and convalescence. The intrahost nucleotide variability of the founder virus was 0.02% across the region sequences, and diversity increased significantly over time in the oropharyngeal compartment (P = 0.004). The LMP1 region showing the greatest level of variability in both compartments, and over time, was concentrated within the functional carboxyl-terminal activating regions 2 and 3 (CTAR2 and CTAR3). Interestingly, a deletion in a proline-rich repeat region (amino acids 274 to 289) of EBV commonly reported in EBV sequenced from cancer specimens was not observed in acute infectious mononucleosis (AIM) patients. Taken together, these data highlight the diversity in circulating EBV genomes and its potential importance in disease pathogenesis and vaccine design.
IMPORTANCE
This study is among the first to leverage an improved high-throughput deep-sequencing methodology to investigate directly from patient samples the degree of diversity in Epstein-Barr virus (EBV) populations and the extent to which viral genome diversity develops over time in the infected host. Significant variability of circulating EBV latent membrane protein 1 (LMP1) gene sequences was observed between cellular and oral wash samples, and this variability increased over time in oral wash samples. The significance of EBV genetic diversity in transmission and disease pathogenesis are discussed. | 10.1128/JVI.03378-13 |
pubmed_317_14916 | This white paper provides a summary of presentations and discussions at a cardiovascular (CV) end point adjudication think tank cosponsored by the Cardiac Safety Research Committee and the US Food and Drug Administration (FDA) that was convened at the FDA's White Oak headquarters on November 6, 2013. Attention was focused on the lack of clarity concerning the need for end point adjudication in both CV and non-CV trials: there is currently an absence of widely accepted academic or industry standards and a definitive regulatory policy on how best to structure and use clinical end point committees (CECs). This meeting therefore provided a forum for leaders in the fields of CV clinical trials and CV safety to develop a foundation of initial best practice recommendations for use in future CEC charters. Attendees included representatives from pharmaceutical companies, regulatory agencies, end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding when CV end point adjudication should be considered in trials conducted by cardiologists and by noncardiologists as well as detailing key issues in the composition of a CEC and its charter. In addition, it presents several recommended best practices for the establishment and operation of CECs. The science underlying CV event adjudication is evolving, and suggestions for additional areas of research will be needed to continue to advance this science. This manuscript does not constitute regulatory guidance. | pubmed_317_14916 |
pubmed_930_5416 | Fundamental and clinical studies have been performed on BRL 25000 (clavulanic acid 1 part-amoxicillin 2 parts) granules in the pediatric field. The antibacterial activities of BRL 25000 and amoxicillin (AMPC) were investigated against clinically isolated and laboratory stocked strains. BRL 25000 was superior to AMPC against strains of E. coli, Salmonella sp. and Klebsiella sp., and similar against Gram-positive cocci. Serum concentrations of AMPC and clavulanic acid (CVA) were measured 0.25, 0.5, 1, 2, 4 and 6 hours after administration of BRL 25000 granules at dose levels of 7.5, 10, 15 and 20 mg/kg. At 7.5 mg/kg peak level of AMPC of 2.69 micrograms/ml was achieved about 2 hours after dosing with a biological half-life of 1.64 hours; corresponding value for CVA was 0.53 micrograms/ml at 1 hour with a T 1/2 of 1.46 hours. At 10 mg/kg, AMPC also peaked after 2 hours (3.82 micrograms/ml) and the T 1/2 was 1.63 hours, whilst for CVA the value was 0.56 micrograms/ml with a T 1/2 of 1.24 hours. Value for AMPC at 15 mg/kg was 5.18 micrograms/ml at 1 hour post dose with a T 1/2 of 1.48 hours, and for CVA 4.01 micrograms/ml at 1 hour with a T 1/2 of 0.89 hour. At the highest dose of 20 mg/kg, AMPC level reached 4.21 micrograms/ml after 2 hours with a T 1/2 of 2.39 hours, and the CVA peak was 1.64 micrograms/ml at 1 hour with a T 1/2 of 1.01 hours. The 6 hours urinary recovery of AMPC and CVA following administration of the BRL 25000 granules ranged from 38-64% and 2-33%, respectively. In the clinical studies, the BRL 25000 granules are administered to 15 cases with pediatric infections and the clinical response was excellent or good in all cases treated (100%). Bacteriological investigation was performed on 13 strains from 12 cases and all strains were eradicated (100%). Regarding side effects, elevation of eosinophil was observed in 1 case and vomiting in 3 cases. | pubmed_930_5416 |
pubmed_430_12670 | Factors to consider while administering antihistaminic agents: The dosage and time of administration should be related to the expected histamine release or the histamine release which has already taken place. The antihistaminic agents selected for treatment must take a) the type of receptor that is to be blocked (H1, H2), and b) additional pharmacologic properties such as sedation into account. H1-antagonists can be used to treat symptoms of various forms of acute and chronic urticaria, including physical urticaria, cholinergic urticaria and allergic rhinitis. Their indication for allergic forms of bronchial asthma has limitations. Antihistamines suppress the starter function of histamines and therefore, the development of further mediators. Furthermore, they influence the role of histamines in physiologic neurotransmitter processes. The combination of H1- and H2-antagonists can be beneficial in certain cases. Topical application of H1-antagonists leads to an anaesthetising , antipruritic effect and limits vessel permeability. The effect is noticeable after approximately 30 minutes. It is of therapeutical use if applied prior to histamine release. | pubmed_430_12670 |
pubmed_582_1725 | Reactive oxygen and nitrogen species are thought to contribute to pathogenesis of many cardiovascular diseases including hypertension, atherosclerosis, restenosis, heart failure, and diabetic vascular complications. Some of these reactive oxygen species also play an important role in vascular signaling. In this chapter, we describe various techniques that we have successfully employed to reliably measure superoxide and hydrogen peroxide. Because reactive oxygen species are capable of rapidly inactivating nitric oxide and because endothelial function characterized by nitric oxide bioavailability is an important indicator of vascular health, we have also included novel techniques capable of directly measuring nitric oxide radical from vascular cells and tissues. | 10.1007/978-1-59745-571-8_20 |
pubmed_539_18561 | Juvenile paddlefish prey upon single zooplankton by detecting a weak electric signature resulting from its feeding and swimming motions. Moreover, it has recently been shown that paddlefish make use of stochastic resonance near the threshold for prey detection: a process termed behavioral stochastic resonance. But this process depends upon an external source of electric noise. A swarm of plankton, for example, Daphnia, can provide this noise. Assuming that juvenile paddlefish attack single Daphnia as outliers in the vicinity of the swarm, making use of noise from the swarm, we calculate the spatial distribution of the average phase locking period for the subthreshold signals acting at the paddlefish rostrum. Numeric evaluation of analytic formulas supports the notion of a noise-induced widening of the capture area quantitatively. | 10.1103/PhysRevE.63.031910 |
pubmed_859_1258 | Plasmonic core-satellite nanostructures assembled from simple building blocks have attracted extensive attention since they were reported by the way of DNA-directed assembly in 1998, because of their unique enhanced and synergistic optical properties and widespread potential applications in biosensing, imaging, drug delivery, and diagnostics. In this review, we introduce the synthetic methods of core-satellite nanostructures, emphazising the bottom-up synthesis method, including DNA, molecular, protein, peptide, amino acids, metal ion-assisted assembly, electrostatic adsorption assembly, clicked-to-assembly, and in situ deposition. Than we review and discuss their morphology classification, and summarize influencing factors of morphology. This is followed by overviews on optical properties, including localized surface plasmon resonance, surface-enhanced Raman scattering, surface-enhanced fluorescence and quenching, and applications in the biomedical field. Finally, the challenges and prospects of these kinds of nanostructures are discussed. | 10.1007/s00604-022-05559-0 |
pubmed_720_6911 | To characterize the consequences of eliminating essential functions needed for peptidoglycan synthesis, we generated deletion mutations of Acinetobacter baylyi by natural transformation and visualized the resulting microcolonies of dead cells. We found that loss of genes required for peptidoglycan precursor synthesis or polymerization led to the formation of polymorphic giant cells with diameters that could exceed ten times normal. Treatment with antibiotics targeting early or late steps of peptidoglycan synthesis also produced giant cells. The giant cells eventually lysed, although they were partially stabilized by osmotic protection. Genome-scale transposon mutant screening (Tn-seq) identified mutations that blocked or accelerated giant cell formation. Among the mutations that blocked the process were those inactivating a function predicted to cleave murein glycan chains (the MltD murein lytic transglycosylase), suggesting that giant cell formation requires MltD hydrolysis of existing peptidoglycan. Among the mutations that accelerated giant cell formation after ß-lactam treatment were those inactivating an enzyme that produces unusual 3->3 peptide cross-links in peptidoglycan (the LdtG L,D-transpeptidase). The mutations may weaken the sacculus and make it more vulnerable to further disruption. Although the study focused on A. baylyi, we found that a pathogenic relative (A. baumannii) also produced giant cells with genetic dependencies overlapping those of A. baylyi. Overall, the analysis defines a genetic pathway for giant cell formation conserved in Acinetobacter species in which independent initiating branches converge to create the unusual cells. | 10.1371/journal.pgen.1008195 |
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