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pubmed_16_19091
OBJECTIVE The purpose of this study was to determine the severity of anal incontinence and its impact on quality of life and sexual function in women after anal sphincteroplasty. STUDY DESIGN Eighty-six women who underwent anal sphincteroplasty during the years 1993 to 2004 were mailed validated survey instruments to evaluate continence status, health-related quality of life, and sexual functioning. Demographic and perioperative data were obtained from patient charts. RESULTS At a mean follow-up time of 5.6 +/- 3.0 years, 6 women (11%) were totally continent; 8 women (15%) were incontinent of flatus only, and 41 women (75%) were incontinent of liquid and/or solid stool. Sexual function scores were not correlated with continence scores; 24% vs 4% of subjects who had undergone an overlapping sphincteroplasty versus an end-to-end sphincteroplasty reported pain during intercourse (P = .04). CONCLUSION Anal continence rates 5 years after anal sphincteroplasty are disappointing, adversely impact quality of life, yet do not appear to relate to sexual function.
10.1016/j.ajog.2006.07.030
pubmed_173_14682
PURPOSE To evaluate the effects of horizontal strabismus surgery on the refractive and astigmatic status of eyes following horizontal muscle surgery using double-angle vector analysis. MATERIALS AND METHODS This was a retrospective analysis of 137 patients (250 eyes) conducted between February 1997 and October 2010 in patients who had unilateral or bilateral recession or monocular recession and/or underwent resection of horizontal muscles by a single surgeon. Refraction data were obtained at 1-2 weeks preoperative and at 4-6 weeks and 4-6 months postoperative. Surgically induced refractive changes were calculated using double-angle vector analysis. RESULTS The mean change in the spherical equivalent (SE) of the refraction was 0.23 ± 0.78 D for surgically induced refractive changes at 4-6 weeks postoperative (SIRC1; p < 0.0001) and 0.14 ± 0.85 D (p = 0.018) for surgically induced refractive changes at 4-6 months postoperative (SIRC2), indicating a small shift in the myopic direction with regression at 4-6 months. The mean amplitudes of the induced cylinders were 0.072 ± 1.22 D (p = 0.262) in SIRC1 and 0.20 ± 1.14 D (p = 0.012) in SIRC2, and the mean axis of the induced plus cylinder was 21.74° in SIRC1, indicating a small shift in the with-the-rule direction, but no statistically significant difference from zero (p = 0.331). The changes in the surgically induced refraction over time (SIRC d), ie, 0.05 ± 0.64 in SE (p = 0.255) and 0.09 ± 0.65 in the cylinder (p = 0.049), were stable. There was no significant correlation between the amounts of horizontal rectus muscle recession and/or resection and the cylinder power of individual induced astigmatism at 4-6 weeks after surgery (p = 0.266) and the myopic shift (p = 0.345). Moreover, there were no significant correlations between the ages of the patients and the spherical equivalent for SIRC1 (p = 0.858) and the induced cylinder for SIRC1 (p = 0.750). CONCLUSION Horizontal rectus muscle surgery tended to induce a transient, statistically significant change in the spherical equivalent of refraction, with a myopic shift that was clinically not important. Our findings did not strongly support that the astigmatism induced changes. There was no correlation between the amount of recession and/or resection and the amount of induced refractive error.
10.3109/09273972.2015.1058401
pubmed_976_2626
OBJECTIVE to verify the efficacy of adjuvant therapy in the prevention of neoplastic recurrence in patients at high risk for lymph-node involvement on surgical examination. METHODS 72 patients, suffering from squamous cell cervical carcinoma Stage IB-IIB (FIGO) who underwent radical hysterectomy with lymph-node involvement confirmed at the final histological examination, were enrolled. All the patients were treated with adjuvant chemotherapy (AC), which included cisplatin, bleomycin and vinblastine, and were followed for a minimum period of six years. The results were compared with those obtained with a historical group of 78 patients, with comparable age, stage and lymph-node involvement, on whom only radical surgery (RS) was performed. RESULTS the average total survival rate of the two groups (RS + AC vs RS) at five years was 63.9% and 55.1%, respectively (chi2 = 1.191; p = NS). The disease-free interval was 55.6% vs 46.2% (chi2 = 1.324; p = NS). The best results were obtained in cases where the common iliac lymph-nodes were affected, with the highest survival rate of 16.9% in the RS+AC group, out of a total of 25 cases. CONCLUSIONS adoption of adjuvant chemotherapy in patients at high risk for lymph-node positivity did not produce statistically significant results in terms of overall and disease-free survival; however, a small number of these patients, approximately 9%, could receive benefit from the treatment.
pubmed_976_2626
pubmed_361_16848
The projections of the magnocellular nuclei of the basal forebrain to the lower brain stem were studied using the WGA-HRP method. Of these nuclei, the nucleus of the vertical and the nucleus of the horizontal limb of the diagonal band of Broca, the magnocellular preoptic nucleus, and the substantia innominata were found to project bilaterally to the caudal midbrain, pons, and medulla. Labeled cells in the medial septal nucleus and in the nucleus basalis were found ipsilaterally only when injections stained the caudal part of the interpeduncular nucleus. The present findings together with other recent reports reveal a more extensive distribution of basal forebrain efferents than was previously thought.
10.1016/0014-4886(89)90136-2
pubmed_680_11642
BACKGROUND Recently, cloudy pomegranate juice (PJ) has become popular due to its rich phenolic and health-promoting effects. The aim of the present work was to evaluate the application of high hydrostatic pressure processing (HPP), pasteurization (PT) and high-temperature short-time sterilization (HTST) on physicochemical properties (color, flow behavior, turbidity, sugars, organic acids, aroma and sensory evaluation) and in vitro bioaccessibility of total phenolics content (TPC), total flavonoids content (TFC) and phenolics of cloudy PJ. RESULTS Compared to HPP, thermal sterilization significantly increased the brightness (L*), redness (a*), total color difference (ΔE) and turbidity, and decreased the TPC and TFC. HPP maintained the volatile profile of cloudy PJ better, while thermal sterilization significantly changed the profile by decreasing alcohols 23.8-32.7% and increasing acids by 33.6%-182.8%. The bioaccessibility of flavonoids, phenolic acids and tannins in the control cloudy PJ after in vitro oral-gastric-intestinal digestion were 1.5%, 4.9%, and 9.0%, respectively, which were not significantly changed by different treatments. CONCLUSION These results contributed to promoting the color quality and health benefits of cloudy PJ rich in phenolics by optimizing the processing conditions in the food industry. © 2022 Society of Chemical Industry.
10.1002/jsfa.12178
pubmed_921_19772
We examined the agreement between reports about physical and psychological status obtained from 286 community-dwelling elderly persons aged 65 years and over (subjects) and their family members (proxies). A total of 205 subject-proxy pairs were studied. Information from subjects was obtained by a self-administered questionnaire, and proxy respondents by an interview-administered questionnaire between Nov. 1997, and Feb 1998. Agreement was assessed by percent agreement and statistical kappa values. Percent agreement ranged from a low of 50.8 for anxiety to a high of 90.4 for difficult in swallowing. Kappa values ranged from a low of 0.21 for anxiety to a high of 0.67 for high frequency of falling. Median kappa values were higher in summary measure of physical status (0.52) than in that of psychological status (0.39). Compared to subjects, their partners tended to report higher level both in physical status and in psychological status, except for sleep compliance and introversion. The median kappa was 0.54 for spouses, whereas it was 0.39 for family members other than spouses. Overall, our finding indicated that partners could be aware of the concrete and directly-observable variables of physical status such as constipation, difficult in swallowing, but not so for subjective variables as psychological status such as depressed condition and introversion. Our results also suggested that the degree of agreement of proxy's perception and understanding of lifestyle of the elderly is closely related to health status of the elderly.
10.3143/geriatrics.37.371
pubmed_122_12643
Over the last two decades, lipids have come to be understood as far more than merely components of cellular membranes and forms of energy storage, and are now also being implicated to play important roles in a variety of diseases, with lipid biomarker research one of the most widespread applications of lipidomic techniques both in research and in clinical settings. Stable isotope labelling has become a staple technique in the analysis of small molecule metabolism and dynamics, as it is the only experimental setup by which biosynthesis, remodelling and degradation of biomolecules can be directly measured. Using state-of-the-art analytical technologies such as chromatography-coupled high resolution tandem mass spectrometry, the stable isotope label can be precisely localized and quantified within the biomolecules. The application of stable isotope labelling to lipidomics is however complicated by the diversity of lipids and the complexity of the necessary data analysis. This article discusses key experimental aspects of stable isotope labelling in the field of mass spectrometry-based lipidomics, summarizes current applications and provides an outlook on future developments and potential.
10.3390/biom8040151
pubmed_63_23854
INTRODUCTION Calcific myonecrosis is a rare condition characterized by a calcified lesion. Because this lesion sometimes presents as a huge mass with unique radiographic characteristics, it can be confused with soft tissue sarcoma. The appropriate treatment is still controversial. We report here three cases diagnosed as calcific myonecrosis of the lower leg and discuss its clinical presentation, diagnosis and options for treatment. PATIENTS AND METHODS Three patients presented as expanding masses in the anterior or lateral compartment muscle and occurred more than 10 years after an initial injury. Plain radiographs showed a large soft tissue mass with extensive amorphous calcifications. Computed tomograms revealed a low-density tumor with scattered calcifications. Magnetic resonance imaging showed a bright, high-signal area on T2-weighted imaging consistent with fluid. Two patients underwent excisions for histopathological evaluation and one was treated conservatively because of the absence of disability. RESULTS Two operative patients had no complication and the returned to work without evidence of deterioration of the disease. In a patient treated conservatively, the mass was not enlarged and was still painless at 2-year follow-up. CONCLUSION The key points for diagnosis were (1) amorphous liner calcification, (2) anterior or lateral compartment, (3) previous injury (several decades) of the tibia or femur, and (4) compartment syndrome. Although calcific myonecrosis is not commonly encountered, it must be considered in the differential diagnosis of an expanding intramuscular mass. In asymptomatic masses where the diagnosis is recognized, observation may be possible and unnecessary aggressive surgical intervention should be avoided.
10.1007/s00402-009-0890-0
pubmed_915_24121
BACKGROUND To test the hypothesis that in profile smiling view, for ideal aesthetics, a tangent to the labial face of the maxillary central incisor crowns should be approximately parallel to the true vertical line and thereby perpendicular to the true horizontal line. METHODS An idealized female image was created with computer software and manipulated using the same software to construct an "ideal" female profile image with proportions, and linear and angular soft tissue measurements, based on currently accepted criteria for idealized Caucasian profiles. The maxillary incisor labial face tangent was altered in 5° increments from 70 to 120°, creating a range of images, shown in random order to 70 observers (56 lay people and 14 clinicians), who ranked the images from the most to the least attractive. The main outcome was the preference ranks of image attractiveness given by the observers. RESULTS The most attractive inclination of a tangent to the labial face of the maxillary incisor crowns in profile view in relation to the true horizontal line was 85°, i.e. 5° retroclined from a perpendicular 90° inclination. The most attractive range appears to be between 80 and 90°. Excessive proclination appeared to be less desirable than retroclination. Beyond 105° most observers recommend treatment. CONCLUSION In natural head position, the ideal inclination of the maxillary incisor crown labial face tangent in profile view will be approximately parallel to the true vertical line and thereby approximately perpendicular to the true horizontal line.
10.1186/s40902-019-0214-4
pubmed_731_8170
Background: We have reported that bioactive sutures coated with bone marrow-derived mesenchymal stem cells (BMSCs) enhance tendon repair strength in an in vivo rat model. We have additionally shown that growth differentiation factor 8 (GDF-8, also known as myostatin) simulates tenogenesis in BMSCs in vitro. The purpose of this study was to determine the possibility of BMSC-coated bioactive sutures treated with GDF-8 to increase tendon repair strength in an in vivo rabbit tendon repair model. Methods: Rabbit BMSCs were grown and seeded on to 4-0 Ethibond sutures and treated with GDF-8. New Zealand white rabbits' bilateral Achilles tendons were transected and randomized to experimental (BMSC-coated bioactive sutures treated with GDF-8) or plain suture repaired control groups. Tendons were harvested at 4 and 7 days after the surgery and subjected to tensile mechanical testing and quantitative polymerase chain reaction. Results: There were distinguishing differences of collagen and matrix metalloproteinase RNA level between the control and experimental groups in the early repair periods (day 4 and day 7). However, there were no significant differences between the experimental and control groups in force to 1-mm or 2-mm gap formation or stiffness at 4 or 7 days following surgery. Conclusions: BMSC-coated bioactive sutures with GDF-8 do not appear to affect in vivo rabbit tendon healing within the first week following repair despite an increased presence of quantifiable RNA level of collagen. GDF-8's treatment efficacy of the early tendon repair remains to be defined.
10.1177/1558944718792708
pubmed_590_16823
OBJECTIVE Elevated polyclonal serum immunoglobulin free light chains (FLCs; combined FLCκ+FLCλ [cFLC]) are associated with adverse clinical outcomes and increased mortality; we investigated cFLC and cardiovascular disease (CVD) events in type 2 diabetes. RESEARCH DESIGN AND METHODS In a cohort study of 352 south Asian patients with type 2 diabetes, serum cFLC, high-sensitivity C-reactive protein (hsCRP), and standard biochemistry were measured. CVD events over 2 years were recorded and assessed using multiple logistic regression. RESULTS cFLC levels were elevated significantly in 29 of 352 (8%) patients with CVD events during 2 years of follow-up (50.7 vs. 42.8 mg/L; P = 0.004). In multivariate analysis, elevated cFLC (>57.2 mg/L) was associated with CVD outcomes (odds ratio 3.3 [95% CI 1.3-8.2]; P = 0.012) and remained significant after adjusting for age, albumin-to-creatinine ratio, diabetes duration, or treatment. CONCLUSIONS cFLC elevation is a novel marker for CVD outcomes in type 2 diabetes that warrants further investigation.
10.2337/dc13-2227
pubmed_947_4728
Waterlogging, causing hypoxia stress and nitrogen depletion in the rhizosphere, has been an increasing threat to wheat production. We developed a wheat-sea wheatgrass (SWG) amphiploid showing superior tolerance to waterlogging and low nitrogen. Validated in deoxygenated agar medium for three weeks, hypoxia stress reduced the dry matter of the wheat parent by 40% but had little effect on the growth of the amphiploid. To understand the underlying mechanisms, we comparatively analyzed the wheat-SWG amphiploid and its wheat parent grown in aerated and hypoxic solutions for physiological traits and root transcriptomes. Compared with its wheat parent, the amphiploid showed less magnitude in forming root porosity and barrier to radial oxygen loss, two important mechanisms for internal O2 movement to the apex, and downregulation of genes for ethylene, lignin, and reactive oxygen species. In another aspect, however, hypoxia stress upregulated the nitrate assimilation/reduction pathway in amphiploid and induced accumulation of nitric oxide, a byproduct of nitrate reduction, in its root tips, and the amphiploid maintained much higher metabolic activity in its root system compared with its wheat parent. Taken together, our research suggested that enhanced nitrate assimilation and reduction and accumulation of nitric oxide play important roles in the SWG-derived waterlogging tolerance.
10.3390/plants11010108
pubmed_261_15629
We are exploring the mechanisms underlying how maternal infection increases the risk for schizophrenia and autism in the offspring. Several mouse models of maternal immune activation (MIA) were used to examine the immediate effects of MIA induced by influenza virus, poly(I:C) and interleukin IL-6 on the fetal brain transcriptome. Our results indicate that all three MIA treatments lead to strong and common gene expression changes in the embryonic brain. Most notably, there is an acute and transient upregulation of the α, β and γ crystallin gene family. Furthermore, levels of crystallin gene expression are correlated with the severity of MIA as assessed by placental weight. The overall gene expression changes suggest that the response to MIA is a neuroprotective attempt by the developing brain to counteract environmental stress, but at a cost of disrupting typical neuronal differentiation and axonal growth. We propose that this cascade of events might parallel the mechanisms by which environmental insults contribute to the risk of neurodevelopmental disorders such as schizophrenia and autism.
10.1038/tp.2012.24
pubmed_330_21892
The molecular signaling that underpins synapse loss in neuropathological conditions remains unknown. Concomitant upregulation of the neuronal nitric oxide (NO) synthase (nNOS) in neurodegenerative processes places NO at the center of attention. We found that de novo nNOS expression was sufficient to induce synapse loss from motoneurons at adult and neonatal stages. In brainstem slices obtained from neonatal animals, this effect required prolonged activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and RhoA/Rho kinase (ROCK) signaling. Synapse elimination involved paracrine/retrograde action of NO. Furthermore, before bouton detachment, NO increased synapse myosin light chain phosphorylation (p-MLC), which is known to trigger actomyosin contraction and neurite retraction. NO-induced MLC phosphorylation was dependent on cGMP/PKG-ROCK signaling. In adulthood, motor nerve injury induced NO/cGMP-dependent synaptic stripping, strongly affecting ROCK-expressing synapses, and increased the percentage of p-MLC-expressing inputs before synapse destabilization. We propose that this molecular cascade could trigger synapse loss underlying early cognitive/motor deficits in several neuropathological states.
10.1523/JNEUROSCI.3911-09.2010
pubmed_180_7078
An injury of cyclists during a collision with a car is currently a neglected topic. Most research projects evaluate in detail the injury of pedestrians, but with an increasing number of cyclists it will be necessary to devote more attention to their safety. This study is focused on the most common type of collision and offers insights into the biomechanics of cyclist's head injury without the use of bicycle helmet. Initial mechanical and kinematic conditions that affect Head Injury Criterion (HIC) after a car hits a cyclist were determined using simulation software MADYMO. In relation to HIC, three different shapes of the front part of the car and three basic cyclist's positions were compared.
pubmed_180_7078
pubmed_313_493
BACKGROUND Silicon single-photon avalanche diodes (Si-SPADs) are the most used devices for measuring ultra-weak optical radiant fluxes in many quantum technology fields, such as quantum optics, quantum communication, quantum computing, etc. In all these fields, the detection efficiency is the main parameter, which has to be accurately known for achieving reliable measurements. In this paper we present the improvements performed on the setup described in López et al. (J Mod Opt 62:S21-S27, 2015) for determining the detection efficiency of Si-SPAD detectors with a low measurement uncertainty. The improvement arises from the precise alignment of the Si-SPAD detector and the low deviation reached between the total calculated filter transmission and the individual filter transmission measurements (≤0.05%) performed with an integrating sphere with attached Si-photodiode as standard detector. RESULTS The relative standard uncertainty of the Si-SPAD detection efficiency measurement achieved is now as low as ~0.16%. Furthermore, the investigation of the detection efficiency homogeneity of two commercial Si-SPAD detectors from different manufacturers and with different sensor diameters is also presented. The obtained homogeneity is ≤2.2% within a region of diameter of 40 μm. CONCLUSIONS The detailed analysis presented in this paper shows the potential for achieving low measurement uncertainties for Si-SPAD detector calibration even in the low photon flux range. The low uncertainties are only to be realized for reproducible measurement conditions, i.e. in specific for equal beam sizes and beam shapes and well as for an irradiation of equal active areas of the detector. This, however, will be difficult to obtain when measurements are performed at different national metrology institutes.
10.1186/s40064-016-3735-7
pubmed_999_24492
OBJECTIVES The purpose of this study was to discover regulatory universal mechanisms of normal automaticity in sinoatrial nodal (SAN) pacemaker cells that are self-similar across species. BACKGROUND Translation of knowledge of SAN automaticity gleaned from animal studies to human dysrhythmias (e.g., "sick sinus" syndrome [SSS]) requiring electronic pacemaker insertion has been suboptimal, largely because heart rate varies widely across species. METHODS Subcellular Ca2+ releases, whole cell action potential (AP)-induced Ca2+ transients, and APs were recorded in isolated mouse, guinea pig, rabbit, and human SAN cells. Ca2+-Vm kinetic parameters during phases of AP cycles from their ignition to recovery were quantified. RESULTS Although both AP cycle lengths (APCLs) and Ca2+-Vm kinetic parameters during AP cycles differed across species by 10-fold, trans-species scaling of these during AP cycles and scaling of these to APCL in cells in vitro, electrocardiogram RR intervals in vivo, and body mass (BM) were self-similar (obeyed power laws) across species. Thus, APCL in vitro, heart rate in vivo, and BM of any species can be predicted by Ca2+-Vm kinetics during AP cycles in SAN cells measured in any single species in vitro. CONCLUSIONS In designing optimal heart rate to match widely different BM and energy requirements from mice to humans, nature did not "reinvent pacemaker cell wheels," but differentially scaled kinetics of gears that regulate the rates at which the "wheels spin." This discovery will facilitate the development of novel pharmacological and biological pacemakers featuring a normal, wide-range rate regulation in animal models and the translation of these to humans to target recalcitrant human SSS.
10.1016/j.jacep.2021.02.016
pubmed_456_25351
A novel approach for drug design based on the oral carbapenem analog tebipenem pivoxil (TP) has been proposed. The formation of the tebipenem pivoxil-β-cyclodextrin (TP-β-CD) complex resulted in changes concerning physicochemical properties of TP, which is significant for planning the development of an innovative pharmaceutical formulation as well as in the modifications of biological activity profile of the studied delivery system. The inclusion of TP into β-cyclodextrin (β-CD) was confirmed by spectral (infrared and Raman spectroscopies) and thermal method (differential scanning calorimetry). Precise indications of TP domains responsible for interaction with β-CD were possible through a theoretical approach. The most important physicochemical modifications obtained as an effect of TP inclusion were changes in solubility and its rate depending on acceptor fluids, and an increase in chemical stability in the solid state. Biologically essential effects of TP and β-CD interactions were decreased TP permeability through Caco-2 cell monolayers with the use of efflux effect inhibition and increased antibacterial activity. The proposed approach is an opportunity for development of the treatment in resistant bacterial infections, in which along with physicochemical modifications induced by a drug carrier impact, a carrier synergy with a pharmacological potential of an active pharmaceutical substance could be used.
10.1371/journal.pone.0210694
pubmed_505_10308
The purpose of this study was to determine whether osteoporosis influenced the clinical results of distal radius fractures in women above the age of 40 years. Forty patients underwent bone mineral densitometry of the distal forearm, hip and lumbar spine. Radiographs of both wrists were taken at the time of fracture healing and the difference in ulnar variance, palmar tilt and radial inclination with the contralateral wrist was measured. Wrist mobility, grip strength and pain relief were determined in 35 patients with a follow-up of more than one year. We found that the clinical results correlated better with bone mineral density than with the radiological parameters. Osteoporosis may be one of the factors affecting the outcome of distal radius fractures.
pubmed_505_10308
pubmed_521_4818
Detailed mathematical analysis of the metabolism of cesium-137, which first appeared in the environment as a result of nuclear weapon testing in the atmosphere, made it possible to estimate the irradiation for the population of the U.S.A. with reference to sex and age during the entire life until death. In parallel, demographic analysis of mortality due to leucosis from 1950 until 1986 has shown cohorts of elevated mortality risk in two age groups: 0-1 and 45-54 years, starting from 1953. The radiation component of mortality was plotted for a set of cohorts as a function of the irradiation dose until the moment of death. Additional mortality risk was calculated for 1963 and 1967: 5.9 and 2.3 additional deaths per 1000 subjects per 1 Gy, respectively. The potential of demographic methods for assessment of the ecological situation has been shown.
pubmed_521_4818
pubmed_449_3916
Four female koalas were found to have pyometra and pyovagina at autopsy. All had soiling of fur around the cloaca and were in poor condition. One koala had cystic ovaries in addition to the pyometra while another had extensive peritonitis due to rupture of one of the uterine horns. Chronic cystitis was present in all koalas while one also had pyelonephritis. Microbiological examination revealed a mixed flora of both aerobes and anaerobes.
10.1111/j.1751-0813.1983.tb02836.x
pubmed_1066_9684
AIMS To ascertain the formalities and procedures required for the prescription of PCSK9 inhibitors in the cardiology departments of Spanish hospitals, making proposals for improvement to optimize the prescription process. METHODS A first phase of collecting information about the variables and administrative procedures required for the prescription of PCK9 inhibitors and the elaboration of a specific questionnaire and a second phase of collecting data with an online self-administered questionnaire. RESULTS A total of 88 hospitals participated in the study (mean number of beds 625; mean number of cardiologists 18 ± 10; 78% university hospitals). There was underuse of PCSK9 inhibitors (real prescription of 30 treatments/year; potential prescription of 80), mainly because of not fulfilling the therapeutic positioning report (52%) and application refusal (31%). Beyond the requirements of the therapeutic positioning report, 1.2 ± 0.4 applications are required with 8.5 ± 4.2 variables. Only 21% of hospitals did not require a previous authorization process and in the remaining hospitals, approval from a committee was necessary. The accumulated time of the prescription process was 6 weeks. Discontinuation rates during follow-up were 9% ± 12%. CONCLUSIONS Treatment with PCSK9 inhibitors is clearly underused in Spain. This is mainly due to both inappropriate identification of patients, and complex administrative procedures that could inhibit/discourage prescription by cardiologists and consequently, limit their use. In addition, there is a substantial delay from drug approval tadministration.
10.1016/j.arteri.2021.05.003
pubmed_1108_8493
OBJECTIVE The aim of this study was to assess the feasibility and safety of vaginal removal of ovaries at the time of vaginal hysterectomy. MATERIALS AND METHODS All patients candidate to hystero-salpingo-oophorectomy by transvaginal approach, between 1 March 2004 and 28 February 2007, were admitted in the study. RESULTS Of the 472 women included in the study, 432 (91.5%) underwent hysterectomy and bilateral oophorectomy by vaginal approach. There was only one case of major vessel injury, but no patients required blood transfusion. All the operations were performed only by vaginal route and no conversion to the abdominal route was required. CONCLUSION The need to perform oophorectomy should not be considered a contraindication to vaginal hysterectomy.
10.1007/s00404-008-0879-x
pubmed_1050_19569
The aim of this study was to evaluate two-component mixtures of essential oils (EOs) in sub-inhibitory concentrations for antilisterial protection of minimally processed vegetables. Spanish origanum oil (SOO), Spanish marjoram oil (SMO) and coriander oil (CO) and a mixture of fresh leafy vegetables with red beet were used. The chemical compositions of selected EOs were analyzed by gas chromatography. Carvacrol was the major component of SOO. The dominant active component of SMO was 1,8-cineole, while the major constituent in CO was linalool. The study shows that essential oils in combination, namely SOO + SMO and SOO + CO in a ¼ MIC + ¼ MIC (Minimal Inhibitory Concentration), have a synergistic effect against L. monocytogenes. The reduction of L. monocytogenes in vegetable mixtures treated by EOs in these selected combinations after 24 h of storage was approximately equal to the limit of detection. Furthermore, it was found that the vegetable mixture treated with SOO + SMO had the highest-rated sensorial quality and could therefore meet consumer expectations.
10.3390/foods9121740
pubmed_64_552
Mangrove provides significant ecosystem services, however, 40% of tropical mangrove was lost in last century due to climate change induced sea-level rise and anthropogenic activities. Sundarban-India, the largest contiguous mangrove of the world lost 10.5% of its green during 1930-2013 which primarily converted to rice-based systems. Presently degraded mangrove and adjacent rice ecology in Sundarban-India placed side by side and create typical ecology which is distinct in nature in respect to soil physicochemical properties, carbon dynamics, and microbial diversities. We investigated the structural and functional diversities of bacteria and archaea through Illumina MiSeq metagenomic analysis using V3-V4 region of 16S rRNA gene approach that drives greenhouse gases emission and carbon-pools. Remote sensing-data base were used to select the sites for collecting the soil and gas samples. The methane and nitrous oxide emissions were lower in mangrove (-0.04 mg m-2 h-1 and -52.8 μg m-2 h-1) than rice (0.26 mg m-2 h-1 and 44.7 μg m-2 h-1) due to less availability of carbon-substrates and higher sulphate availability (85.8% more than rice). The soil labile carbon-pools were more in mangrove, but lower microbial activities were noticed due to stress conditions. A unique microbial feature indicated by higher methanotrophs: methanogens (11.2), sulphur reducing bacteria (SRB): methanogens (93.2) ratios and lower functional diversity (7.5%) in mangrove than rice. These could be the key drivers of lower global warming potential (GWP) in mangrove that make it a green production system. Therefore, labile carbon build-up potential (38%) with less GWP (63%) even in degraded-mangrove makes it a clean production system than wetland-rice that has high potential to climate change mitigation. The whole genome metagenomic analysis would be the future research priority to identify the predominant enzymatic pathways which govern the methanogenesis and methanotrophy in this system.
10.1016/j.scitotenv.2021.146713
pubmed_634_4816
The diagnosis of femoroacetabular impingement (FAI) syndrome requires that 3 prerequisites are met. Patient symptoms and physical examination must be combined with imaging to appropriately make the diagnosis. Imaging, including plain radiographs, magnetic resonance imaging (MRI), and computed tomography, should be interpreted in the context of a high prevalence of cam and pincer morphology, in addition to labral injury, in the general population. All images routinely obtained in current clinical practice are 2-dimensional representations of complex 3-dimensional processes. Although computerized modeling can dynamically manipulate femur and pelvis independently in fluoroscopy-, computed tomography-, and/or MRI-based collision detection models, the exact definition of "impingement" eludes the current literature. High-resolution, high magnet strength (minimum 3 Tesla), physiologic and/or biochemical dynamic MRI has the potential to image both soft and osseous tissues, interacting to best define hip impingement.
10.1016/j.arthro.2019.05.009
pubmed_1092_24480
Hepatitis B virus (HBV) is a driver of hepatocellular carcinoma, and two viral products, X and large surface antigen (LHBS), are viral oncoproteins. During chronic viral infection, immune-escape mutants on the preS2 region of LHBS (preS2-LHBS) are gain-of-function mutations that are linked to preneoplastic ground glass hepatocytes (GGHs) and early disease onset of hepatocellular carcinoma. Here, we show that preS2-LHBS provoked calcium release from the endoplasmic reticulum (ER) and triggered stored-operated calcium entry (SOCE). The activation of SOCE increased ER and plasma membrane (PM) connections, which was linked by ER- resident stromal interaction molecule-1 (STIM1) protein and PM-resident calcium release- activated calcium modulator 1 (Orai1). Persistent activation of SOCE induced centrosome overduplication, aberrant multipolar division, chromosome aneuploidy, anchorage-independent growth, and xenograft tumorigenesis in hepatocytes expressing preS2- LHBS. Chemical inhibitions of SOCE machinery and silencing of STIM1 significantly reduced centrosome numbers, multipolar division, and xenograft tumorigenesis induced by preS2-LHBS. These results provide the first mechanistic link between calcium homeostasis and chromosome instability in hepatocytes carrying preS2-LHBS. Therefore, persistent activation of SOCE represents a novel pathological mechanism in HBV-mediated hepatocarcinogenesis.
10.18632/oncotarget.8109
pubmed_97_15965
Androgen-independent prostate cancer cells may rely on an autocrine loop for growth stimulation, and have been shown to express both the epidermal growth factor receptor (EGFR) and its stimulatory ligands. We have shown here that DU 145 prostate cancer cells have a decreased amount of EGFR in confluent cultures when compared to levels seen in subconfluent cultures. This down-regulation of EGFR numbers is not due to cell proliferation or nutrient depletion, but can be correlated only with whether cell-cell contact exists throughout the culture. This is reminiscent of the situation existing in some tumors whereby EGFR expression is higher in cells at the invading margins of the tumor.
10.1002/pros.2990190106
pubmed_824_9912
BACKGROUND MER proto-oncogene tyrosine kinase (MERTK) is a receptor tyrosine kinase that affects cancer cell proliferation. This study evaluated the effects of the synthetic MERTK inhibitors UNC569 and UNC1062 on in vitro growth of acute myeloid leukaemia (AML) cells. MATERIALS AND METHODS Four AML cell lines expressing MERTK were treated with UNC569 and UNC1062 and analyzed for cell proliferation, immunoblotting, and gene expression. The effects of MERTK knockdown were also evaluated. RESULTS Treatment with the inhibitors suppressed cell growth and induced apoptosis in all cell lines. OCI/AML5 and TMD7 cells, in which MERTK was constitutively phosphorylated by autocrine mechanisms, were highly susceptible to these inhibitors. The treatment reduced the phosphorylation of MERTK and its down-stream signalling molecules, v-akt murine thymoma viral oncogene homolog 1 (AKT) and extracellular signal-regulated kinase (ERK). Similar effects were observed after MERTK knockdown. The inhibitors and the knockdown caused similar changes in mRNA expression. CONCLUSION These MERTK inhibitors are potential molecular-targeted drugs for treating AML expressing constitutively phosphorylated MERTK.
10.21873/anticanres.12208
pubmed_214_24697
Barrett's esophagus progresses to high-grade dysplasia or cancer along the well-established metaplasia-dysplasia-adenocarcinoma sequence. The aim of this study was to evaluate the value of p53, Ki67, and toll-like receptor 5 (TLR5) in prediction of malignant progression of Barrett's metaplasia and low-grade dysplasia. This was a retrospective matched case-control study based on Northern and Central Finland population. Patients diagnosed with esophageal high-grade dysplasia or adenocarcinoma were included. From these patients, all previous endoscopy samples were obtained along with original diagnostic HE-slides and clinical data. Age- and sex-matched patients with non-progressing Barrett's metaplasia and low-grade dysplasia confirmed with follow-up endoscopies were used as controls. Two gastrointestinal pathologist re-reviewed all original HE-slides, and newly made sections to confirm representative tissue material blinded from clinical data. p53, Ki67, and TLR5 were immunohistochemically stained. Final cohort included 45 patients with progressive Barrett's metaplasia (n = 21) or low-grade dysplasia (n = 24), and 92 patients with non-progressive Barrett's metaplasia (n = 52) or low-grade dysplasia (n = 40). In Barrett's metaplasia, aberrant p53 expression was observed in 6% of samples in progressors and 0% in non-progressors. In low-grade dysplasia, aberrant p53 was seen in 56% of samples in progressors and 17% in non-progressors (Odd's ratio 6.7, 95% CI 1.8-24.6). Ki67 or TLR5 showed no association with disease progression. In this matched case-control study, p53 expression associated with a high risk of malignant progression in Barrett's low-grade dysplasia. Routine staining of p53 is indicated in expert confirmed low-grade dysplasia.
10.1007/s00428-022-03340-5
pubmed_1124_18449
We derive the time-dependent univariate and bivariate probability distribution function for an overdamped system with a quadratic potential driven by colored Gaussian noise, whose amplitude depends on the system state x as [x](alpha). Particular attention is paid to the effect of the correlation function of the noise on the statistical properties of the system. We obtain exact expressions for the fractional moments as well as the correlation function of the system and calculate the fractal dimension. We also consider the special case of a constant potential and determine the criteria for anomalous diffusion and stochastic localization of free particles.
10.1103/PhysRevE.65.031105
pubmed_312_11831
X-ray analysis of the complex of netropsin with the B-DNA dodecamer of sequence C-G-C-G-A-A-T-T-BrC-G-C-G reveals that the antitumor antibiotic binds within the minor groove by displacing the water molecules of the spine of hydration. Netropsin amide NH furnish hydrogen bonds to bridge DNA adenine N-3 and thymine O-2 atoms occurring on adjacent base pairs and opposite helix strands, exactly as with the spine of hydration. The narrowness of the groove forces the netropsin molecule to sit symmetrically in the center, with its two pyrrole rings slightly non-coplanar so that each ring is parallel to the walls of its respective region of the groove. Drug binding neither unwinds nor elongates the double helix, but it does force open the minor groove by 0.5-2.0 A, and it bends back the helix axis by 8 degrees across the region of attachment. The netropsin molecule has an intrinsic twist that favors insertion into the minor groove of B-DNA, and it is given a small additional twist upon binding. The base specificity that makes netropsin bind preferentially to runs of four or more A X T base pairs is provided not by hydrogen bonding but by close van der Waals contacts between adenine C-2 hydrogens and CH groups on the pyrrole rings of the drug molecule. Substitution of one or more pyrroles by imidazole could permit recognition of G X C base pairs as well, and it could lead to a class of synthetic "lexitropsins," capable of reading any desired short sequence of DNA base pairs.
10.1073/pnas.82.5.1376
pubmed_546_18593
Midazolam is known to cause a dose-dependent increase and decrease in the contractile force of the myocardium. Whether flumazenil can reverse these effects of midazolam remains unclear. In this study, we determined the cardiac effects of midazolam and the counter effect of flumazenil on midazolam-induced myocardial depression in isolated rabbit hearts. Rabbit hearts were isolated and perfused using the Langendorff technique, and left ventricle pressure and heart rate were measured by a pressure transducer in the left ventricle. One set of hearts were perfused with increasing concentrations of midazolam for 10 min, another set were perfused with concomitant midazolam and flumazenil. Concentrations of 5, 10, 20 and 50 microM midazolam decreased left ventricle pressure significantly (P < 0.01, P < 0.05, P < 0.01, P < 0.01, respectively). Heart rates decreased with concentrations of 10, 20 and 50 microM midazolam (P < 0.01, P < 0.01, P < 0.05, respectively). Flumazenil had no effect on the midazolam-induced decrease in left ventricle pressure and heart rate. Midazolam decreased the cardiac contractile force and heart rate of isolated rabbit hearts in a concentration-dependent manner. The failure of flumazenil to reverse these effects suggest that this cardiac depressant effect of midazolam is not mediated through peripheral benzodiazepine receptors.
10.1006/phrs.1998.0444
pubmed_681_22294
Short-term synaptic plasticity is a defining feature of neuronal activity, but the underlying molecular mechanisms are poorly understood. Depression of synaptic activity might be due to limited vesicle availability, whereas facilitation is thought to result from elevated calcium levels. However, it is unclear whether the strength and direction (facilitation versus depression) of plasticity at a given synapse result from preexisting synaptic strength or whether they are regulated by separate mechanisms. Here we show, in rat hippocampal cell cultures, that increases in the calcium binding protein neuronal calcium sensor-1 (NCS-1) can switch paired-pulse depression to facilitation without altering basal synaptic transmission or initial neurotransmitter release probability. Facilitation persisted during high-frequency trains of stimulation, indicating that NCS-1 can recruit 'dormant' vesicles. Our results suggest that NCS-1 acts as a calcium sensor for short-term plasticity by facilitating neurotransmitter output independent of initial release. We conclude that separate mechanisms are responsible for determining basal synaptic strength and short-term plasticity.
10.1038/nn1117
pubmed_804_7365
We report a case of an 81-year-old woman with multifocal hepatocellular carcinoma who underwent transarterial chemoembolization. The patient had significant superior mesenteric artery (SMA) ostial stenosis, which led to retrograde flow in the retroportal artery to the SMA. The authors adopted several approaches to avoid potential nontarget embolization that might result from the change in the hemodynamics in the hepatoenteric arteries by initially stenting the SMA ostial stenosis as well as the use of the Surefire infusion system and balloon occlusion for delivery of chemoembolization material to tumors in the hepatic lobes. To our knowledge, the collective use of these approaches to avoid potential risks related to SMA ostial stenosis and retrograde flow in a retroportal artery has not been previously described in the literature.
10.1016/j.radcr.2017.10.019
pubmed_165_13351
DNA topoisomerase I is an enzyme involved in several processes related to DNA metabolism. Despite the physiological importance, the regulation of top1 gene expression has not yet been investigated in plants. In order to monitor the possible correlation between levels of top1 transcripts and the proliferative state of the cell, two partially overlapping cDNAs encoding DNA topoisomerase I from Daucus carota have been isolated from a poly(A)(+)-primed library, using an Arabidopsis thaliana probe, and from a cDNA library spanning the 5' region of the top1 transcript, which was constructed using an antisense specific oligonucleotide. The top1 nucleotide sequence encoded an open reading frame of 2370 bp, predicting a protein of 90 kDa. The deduced amino acid sequence showed a similarity of 51% with A. thaliana, 41% with S. cerevisiae, 40% with S. pombe and 31% with H. sapiens, respectively. Southern blot analysis, performed under moderate stringency conditions, showed the presence of a single-copy gene. Evaluation of the top1 mRNA steady-state level revealed, besides a constitutive expression in vegetative carrot tissues, an induced expression related to cell proliferation.
10.1016/s0378-1119(96)00557-4
pubmed_64_6949
Obesity in aged population have surges the occurrence of various metabolic disorders including Nonalcoholic fatty liver disease (NAFLD). Apoptosis in the liver is one of the causative factors for NAFLD-induced liver damage. Plants derived bioactive peptides have been shown as an alternative treatment approach for the treating NAFLD due to its less toxicity. Moderate exercise has been reported to improve cellular physiological function prevent age associated metabolic disorders. In the present study, we evaluate the effects of bioactive dipeptide (IF) derived from alcalase potato-protein hydrolysates and swimming exercise in preventing High Fat Diet (HFD)-induced liver damage in senescence accelerated mouse-prone 8 (SAMP8) mice model. Mouse were fed with HFD for 6 weeks followed by oral IF administration or swimming exercise and both for 8 weeks. HFD induces significant structural changes in liver of HFD fed SAMP8 mouse. Both IF administration and exercise prevent the structural abnormalities induced by HFD, however, combined IF treatment and exercise offer better protection. Combined IF treatment and exercise activate PI3K/Akt cell survival protein and effectively inhibit Fas-FADD-induced apoptosis in HFD fed aged mouse. Oral supplementation of bioactive peptide IF combined with moderate swimming exercise effectively alleviate HFD-induced hepatic injury in aged mice.
10.1007/s11033-021-06317-w
pubmed_1084_21442
The objective of this study was to test the inter-rater reproducibility of the Portuguese version of the PEDro Scale. Seven physiotherapists rated the methodological quality of 50 reports of randomized controlled trials written in Portuguese indexed on the PEDro database. Each report was also rated using the English version of the PEDro Scale. Reproducibility was evaluated by comparing two separate ratings of reports written in Portuguese and comparing the Portuguese PEDro score with the English version of the scale. Kappa coefficients ranged from 0.53 to 1.00 for individual item and an intraclass correlation coefficient (ICC) of 0.82 for the total PEDro score was observed. The standard error of the measurement of the scale was 0.58. The Portuguese version of the scale was comparable with the English version, with an ICC of 0.78. The inter-rater reproducibility of the Brazilian Portuguese PEDro Scale is adequate and similar to the original English version.
pubmed_1084_21442
pubmed_984_20324
INTRODUCTION The purpose of this study was to investigate the method of canal negotiation in the presence of differently C-shaped orifices using the micro-computed tomography technique. METHODS Forty-four extracted mandibular second molars with C-shaped roots were collected from a Chinese population. Size 10 or 15 K files were used to explore the canal orifices when viewed under the surgical operating microscope. Choices in the number and position of the files inserted into the canal system were based on the different orifice shape. After the teeth with files were scanned and reconstructed, the number and position of the files were analyzed. RESULTS Among 44 teeth, a total of 132 initial files were inserted into 83 orifices, in which 42 orifices had only one initial file, 33 with two, and 8 orifices had three files inserted. Eight main canals were not located because of canal bifurcations in the root, calcification, and dentin fusion. CONCLUSION This new method for negotiation combined with careful exploration may provide an effective way for indentifying the nature of the canal system and enhancing debridement in these complex canal anatomies.
10.1016/j.joen.2009.04.011
pubmed_424_15528
The authors collected the absorption spectrum of RPMI 1640 and DMEM substrates that cultivated Hela and CNE by UV-3101 spectrophotometer and analysed the absorbability of proteins in the substrate. The absorption peaks of the RPMI 1 640 culture medium that cultivated cells for different times shifted from 227 to 222 or 218 nm and from 278 to 280 nm respectively; while during growing course of cultivated cells, one of the absorption peaks of DMEM culture medium shifted from 224 nm to one near 221 nm, and the absorption peak 278 nm almost had no shift. All of these shifts show that the content of each amino acid such as tryptophan and casein has already changed. That is, during the growing course of cultivating cancer cells, the tryptophan and casein were not depleted equivalently. In the growth period of Hela and CNE, they consumed different amino acid. So they need different component proportion for amino acid.
pubmed_424_15528
pubmed_655_12240
AIM To determine if either DNA index or p62c-myc is an independent prognostic variable in ovarian cancer. METHODS Multivariate and univariate analyses of the relation between DNA index, p62c-myc, FIGO stage, histological type, tumour grade, completeness of surgery, and patient survival in ovarian cancer were examined. RESULTS Multivariate analysis showed significant association of survival only with stage and grade. There was no relation between survival and DNA index. CONCLUSIONS DNA index is not an independent prognostic variable in ovarian cancer.
10.1136/jcp.51.6.455
pubmed_988_6590
Previous research has shown that arachidonic acid (20:4(n-6)) is preferentially retained in liver triacylglycerol in fasted compared to fed rats consuming a diet containing n-6 fatty acids. It was hypothesized that eicosapentaenoic (20:5(n-3)) and docosahexaneoic acids (22:6(n-3)) would be similarly retained in liver and plasma triacylglycerol of fasted rats consuming a diet containing n-3 fatty acids. In comparison with fed rats, it was observed that in partially fasted rats consuming diets which contained 5% sunflower oil (78% 18:2(n-6)) or 5% marine fish oil (30% 20:5(n-3) and 22:6(n-3)), both liver and plasma had significantly depleted triacylglycerol levels containing higher proportions of both arachidonic and docosahexaneoic acids but a lower proportion of eicosapentaenoic acid (marine fish oil group only). Separation of liver and plasma triacylglycerol by silicic acid column chromatography and silver nitrate TLC showed that the majority of long chain fatty acids utilized during fasting were derived from the triacylglycerol subclasses containing palmitic acid (16:0), palmitoleic acid (16:1(n-7)) and oleic acid (18:1(n-9)) with retention o both highly saturated and polyunsaturated subclasses. Greater utilization of eicosapentaenoic acid than either arachidonic acid or docosahexaenoic acid during fasting may be due to triacylglycerol speciation of the former with readily oxidized monounsaturated fatty acids.
10.1016/0304-4165(90)90214-h
pubmed_215_8477
BACKGROUND The Saccharomyces cerevisiae strain, 22574d, lacks gamma amino butyric acid (GABA) transport activity and cannot grow on this amino acid as sole nitrogen source. Both transport of and growth on this amino acid are restored when the yeast is transformed with a form of mouse gamma actin containing an extended C-terminal sequence (M-g-A). The nature of the mutation in the transporter as well as the complementation mode are addressed. MATERIAL/METHODS The cDNA sequence of the mutated transporter was achieved using reverse transcription, 3'-Race and cloning. For detection, Northern blotting and labeling with 32-P were used. The putative ability of the transporter to interact with gamma actin in vivo was examined by following the interaction in vitro of synthetic peptides corresponding to the C-termini of the gamma actin and the transporter. RESULTS Up to codon 394 the mutated and native transporters are identical. At the 3' end, the mutant is by extended by 32 codons from the delta region of a Ty1 transposon, giving an open reading frame of 426 codons, and a predicted structure of 9 of the 11 transmembrane domains. Peptides corresponding to the carboxy terminal regions of the truncated transporter and the elongated species of gamma actin show the potential to interact in vitro. CONCLUSIONS The mutated GABA transporter mRNA contains an insert from the delta region of a Ty1 transposon. This insertion allows expression of a transporter capable of interacting with elongated gamma actin to rehabilitate the transporter.
pubmed_215_8477
pubmed_958_21659
OBJECTIVE To assess the effects of stereotactic radiosurgery of a cerebral arteriovenous malformation (AVM). DESIGN Prospective. METHOD In November 1991-December 1995 linear acceleration radiosurgery was performed on 29 patients for their 30 cerebral AVMs in the University Hospital Vrije Universiteit, Amsterdam, the Netherlands. There were 15 females and 14 males with a mean age of 37.1 years (range: 13-58). Generally one isocentre was used and 15 Gy was given to the margins of the AVM at the 80% isodose. The mean target volume was 2.4 ml (range; 0.5-8.2). After 6 months, one year and thereafter every year, neurological and MRI-controls took place, in the outpatient ward. Angiography was performed after an average of 35 months (range: 24-70) to check if the AVM had obliterated. RESULTS Angiographic post-treatment results were available in 27 patients and MRI information in one. Angiographic obliteration occurred in 20 patients (71%). No permanent radiation-induced neurological deficit was seen, nor did any hemorrhage occur during the interval between irradiation and obliteration.
pubmed_958_21659
pubmed_1081_18381
BACKGROUND This study was designed to investigate the clinical effects of different treatment methods on stress urinary incontinence (SUI) in perimenopausal women, and to evaluate urodynamic characteristics. METHODS Seventy-two menopausal female patients with stress urinary incontinence were included in the Second Affiliated Hospital of Soochow University from January 2016 to July 2017. The cases were divided into 3 groups of 24 each, depending on the treatment received. Group A patients received treatment with electrical stimulation combined with biofeedback; those in group B received conventional pelvic floor muscle exercise therapy; and those in group C did not have any treatment. Relevant clinical parameters of urination were determined including pelvic floor muscle strengths, urine dynamics indexes and ICS quality of life survey scores; results were averaged in each group for comparisons among the three groups before and after the 60-day study period. RESULTS After treatment for 60 days, both group A and B patients displayed a clear improvement in their urinary incontinence, pelvic floor muscle strength, leakage times, frequency of urination, urine dynamics index and ICS scores (P<0.05), with group A showing the most improvement. Women in group C showed no significant difference before and after the 60-day study period (P>0.05). CONCLUSION Both the method of electrical stimulation combined with biofeedback, and conventional pelvic floor muscle exercises could help perimenopausal women with stress urinary incontinence; however, electrical stimulation combined with biological feedback seems to bring about better clinical effects.
pubmed_1081_18381
pubmed_735_8267
Several studies have reported reprogramming of fibroblasts into induced cardiomyocytes; however, reprogramming into proliferative induced cardiac progenitor cells (iCPCs) remains to be accomplished. Here we report that a combination of 11 or 5 cardiac factors along with canonical Wnt and JAK/STAT signaling reprogrammed adult mouse cardiac, lung, and tail tip fibroblasts into iCPCs. The iCPCs were cardiac mesoderm-restricted progenitors that could be expanded extensively while maintaining multipotency to differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells in vitro. Moreover, iCPCs injected into the cardiac crescent of mouse embryos differentiated into cardiomyocytes. iCPCs transplanted into the post-myocardial infarction mouse heart improved survival and differentiated into cardiomyocytes, smooth muscle cells, and endothelial cells. Lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for drug discovery, disease modeling, and cardiac regenerative therapy.
pubmed_735_8267
pubmed_135_1983
Graphene oxide has aroused significant interest for a range of applications owing to their outstanding physico-chemical properties. Specifically, the presence of a large number of reactive chemical moieties such as hydroxyl, carboxyl, epoxide, and sp2 carbon allows these novel materials to be tailored with additional functionalities with the purpose of tuning intrinsic properties. There has been a vivid discussion on the non-covalent modification of GO; however, a comprehensive summary of the chemical functionalization which enables forming a stable particle is still elusive. Hence, in this study, we summarize recently advanced methodologies used for designing the functional GO for their use in specific applications. Together with a brief discussion on the essential characterization techniques, this study will provide fundamental insight into the latest developments in the preparation of covalently modified GO derivatives, thereby leading to their broader utilization in future.
10.1039/d2cp04082d
pubmed_751_16979
Younger observers (M = 21 years) proved to be better than older observers (M = 68 years) at discriminating one direction of motion from another, highly similar one. Several days' practice steadily improved performance for both groups equally. Improvement was well restricted to the direction with which that observer practiced, and the full gains were retained for at least 1 month. Control measurements with various degrees of optical blur demonstrate that direction discrimination does not require a well-focussed retinal image. This rules out optical factors as the potential cause of the prepractice differences between groups.
10.1093/geronj/41.2.176
pubmed_432_9571
Mechanisms of ventricular tachycardia induced by local application of a properly timed premature stimulus were studied with routine microelectrode technique and extracellular recordings on a ventricular sheet. Thinly sliced preparations obtained from subepicardial muscle of the canine ventricle were used as an approximation of a two-dimensional model. On these preparations, spontaneously sustained tachycardia easily induced by a single premature stimulus. Since delayed after-depolarizations were never evoked by frequent stimulations even in the K+-free and high-Ca++ media, these tachycardias seemed to be induced by re-entrant and circus movement mechanisms. To analyse the re-entrant mechanisms, action potentials generated by normal driving stimuli were recorded from multiple points (40 approximately 50 points) and the spreads of the depolarization and repolarization phases of the action potentials were mapped. The depolarizing wave front on the map always showed a circular or elliptical pattern. Whenever the pattern of spread of the repolarizing wave was similar to that of the depolarizing wave, sustained tachycardia was never brought about by any premature stimulus. On the other hand, when the map of the spread of the repolarizing wave was very complicated and mixed with that of the depolarizing wave, sustained tachycardia was frequently induced. From the above results, it is suggested that the nonuniform recovery of excitability plays a role in the generation of sustained tachycardia. Moreover, a portion of the unidirectional block of the premature impulse was determined by calculated using the conduction velocity of the premature impulse and the effective refractory period in each cell; then a route of re-entry for the premature impulse was simulated.(ABSTRACT TRUNCATED AT 250 WORDS)
10.1253/jcj.50.65
pubmed_648_20684
Three to 5 cycling tests to exhaustion allow prediction of time to exhaustion (TTE) at power output based on calculation of critical power (CP). We aimed to determine the accuracy of CP predictions of TTE at power outputs habitually endured by cyclists. Fourteen endurance-trained male cyclists underwent 4 randomized cycle-ergometer TTE tests at power outputs eliciting (i) mean Wingate anaerobic test (WAnTmean), (ii) maximal oxygen consumption, (iii) respiratory compensation threshold (VT2), and (iv) maximal lactate steady state (MLSS). Tests were conducted in duplicate with coefficient of variation of 5%-9%. Power outputs were 710 ± 63 W for WAnTmean, 366 ± 26 W for maximal oxygen consumption, 302 ± 31 W for VT2 and 247 ± 20 W for MLSS. Corresponding TTE were 00:29 ± 00:06, 03:23 ± 00:45, 11:29 ± 05:07, and 76:05 ± 13:53 min:s, respectively. Power output associated with CP was only 2% lower than MLSS (242 ± 19 vs. 247 ± 20 W; P < 0.001). The CP predictions overestimated TTE at WAnTmean (00:24 ± 00:10 mm:ss) and MLSS (04:41 ± 11:47 min:s), underestimated TTE at VT2 (-04:18 ± 03:20 mm:ss; P < 0.05), and correctly predicted TTE at maximal oxygen consumption. In summary, CP accurately predicts MLSS power output and TTE at maximal oxygen consumption. However, it should not be used to estimate time to exhaustion in trained cyclists at higher or lower power outputs (e.g., sprints and 40-km time trials). Novelty CP calculation enables to predict TTE at any cycling power output. We tested those predictions against measured TTE in a wide range of cycling power outputs. CP appropriately predicted TTE at maximal oxygen consumption intensity but err at higher and lower cycling power outputs.
10.1139/apnm-2019-0637
pubmed_49_7664
It has been previously shown that Klebsiella pneumoniae K59 carrying the mannose-inhibitable adhesin-T7 receptor (MIAT) efficiently binds to polymorphonuclear leukocytes (PMNs) incubated at 4 degrees C but is not efficiently bound and internalized by phagocytes incubated at 37 degrees C. Pretreatment of K59 with compounds that bind the MIAT ligand (D-mannose, UV-inactivated T7 phages, and pepsin-digested anti-MIAT antibodies) enables PMNs to phagocytize and kill these bacteria. In this article, we show that the incubation temperature has no direct effect on expression of either the MIAT or the PMN receptors. These receptors were always expressed at 37 degrees C when PMNs were treated with substances that impaired their ability to rearrange their surfaces (glutaraldehyde and cytochalasins B and D). Pretreatment of inert PMNs with concanavalin A or succinyl concanavalin A drastically reduced binding of K59 to phagocytes at both 4 and 37 degrees C. The same pretreatment carried out with metabolically active PMNs enabled them to efficiently phagocytize the MIAT-positive strain. When phagocytes were treated with K59 bacteria, they became unable to ingest and kill a K59 mutant not expressing the MIAT which was sensitive to phagocytosis. If this pretreatment was performed in the presence of D-mannose, UV-inactivated T7 phages, and pepsin-digested anti-MIAT antibodies, PMNs maintained their phagocytic activity against the MIAT-negative strain. In the presence of K59 bacteria, a very low chemiluminescence response was generated; in contrast, a significant response was observed when bacteria were previously absorbed with UV-inactivated T7 phages and pepsin-digested anti-MIAT antibodies. These results support our previous suggestion that the MIAT adhesin triggers changes in the cell surface, inhibiting further binding and phagocytosis.
10.1128/iai.57.3.975-982.1989
pubmed_902_8608
A 56-year-old man was admitted to our hospital with a chief complaint of pain in the right scrotum. On examination, the patient showed neither gynecomastia nor superficial lymphadenopathy. The serum levels of alpha-fetoprotein, human chorionic gonadotropin-beta, and lactate dehydrogenase (LDH) were not elevated. Ultrasonography and computed tomography (CT) demonstrated hematoma and testicular tumor with abundant blood flow in the right testis. CT revealed no evidence of retroperitoneal lymph node enlargement or distant metastasis. Radical orchiectomy was performed under a diagnosis of right testicular tumor. Histological analysis of the lesion indicated a Sertoli cell tumor. The patient is currently well, with no signs of either recurrence or metastasis about 8 months after the operation.
pubmed_902_8608
pubmed_691_13867
Although trisomy 16 is well recognised in spontaneous abortuses, it is infrequent in livebirths and there is little information about the clinical effects. We report two sibs with partial trisomy 16q resulting in infant death. Both children were severely growth retarded with small elfin faces, prominent foreheads, low set ears, abnormal external genitalia, and intractable diarrhoea.
10.1136/jmg.21.5.384
pubmed_126_21336
The preparation of platelet concentrates (PC) from pooled buffy coats has raised concern as to whether activation of lymphocytes may take place during the period of storage. Lymphocytes and HLA-DR-positive cells are of particular relevance, as they may induce a mixed lymphocyte reaction (MLR). Therefore we investigated the degree of leukocyte contamination and determined the quantity of proliferating leukocytes using the monoclonal antibody KI-67. The content of total leukocytes was (0.07 +/- 0.05) x 10(9). Immunostaining of KI-67-positive cells proved that, directly after preparation, only single leukocytes were activated. On days 1, 3 and 5 after preparation the results were identical. Isolated cells were found to be KI-67-positive but there was no significant increase in proliferating cells as would have been expected in an MLR. We conclude that there is no allogenic activation of lymphocytes taking place in these PC during storage. Therefore transfusion of activated lymphocytes seems to be extremely unlikely.
pubmed_126_21336
pubmed_871_6370
The myelin-associated glycoprotein (MAG) gene is an appealing candidate in the 19q13 Multiple Sclerosis (MS) candidate region. Using denaturing high performance liquid chromatography (DHPLC), we identified 14 single nucleotide polymorphisms (SNPs) in MAG coding and regulatory regions, and we tested their possible association with MS in Italian patient and control DNA pools. Eight variations had a frequency <0.05, i.e. below the detection limit in the pools. Of these, Arg537Cys was further studied with individually genotyped individuals and was detected in 1/189 patients and 0/85 controls. The frequency of the six remaining SNPs were not significantly different in pools including a total of 1266 patient and 1612 control chromosomes. Considering the statistical power of the experimental design, these results exclude the MAG gene as an MS susceptibility factor with an odds ratio (OR) equal or higher than 1.3.
10.1016/s0165-5728(02)00061-9
pubmed_536_23452
Liver failure is still a significant clinical problem after transplantation surgery, tissue resections (the Pringle manoeuvre) and haemorrhagic shock. The restoration of blood flow to an ischaemic region leads to tissue injury at a greater rate than the original ischaemic insult, an event termed "ischaemia-reperfusion injury" (I/R). Despite advances in surgical techniques, I/R still poses a problem of clinical importance. In this research, we studied the effect of simvastatin pretreatment on liver and lung injury induced by hepatic I/R. Rats were subjected to 30 min of ischaemia followed by 24 h of reperfusion. Simvastatin (10 mg/kg) was administered orally from three days before the operation. After the reperfusion time, serum ALT, AST, LDH and TNF a levels were studied and liver and lung tissues were stained with haematoxylin and eosin and TUNEL to detect apoptotic cells. Serum aminotransferase activity and LDH and TNFalpha levels were increased markedly by hepatic I/R, and these were suppressed significantly by simvastatin. The tissue injury index and the number of apoptotic cells via TUNEL staining in the liver and lungs were higher in the I/R group than in the I/R + simvastatin group. These results suggest that simvastatin ameliorates I/R-induced liver and lung tissue damage by inhibiting the level of inflammation and the apoptotic pathways. Simvastatin administration may therefore provide protection against the adverse effects of I/R injury in liver transplantation.
pubmed_536_23452
pubmed_749_22330
The PTA-NiMo/ZSM-5 catalyst impregnated with phosphotungstic acid (PTA) was designed for the transformation of Jatropha oil into benzene, toluene, and xylenes (BTX) aromatics. The produced catalyst was characterized by N2 adsorption-desorption, powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), and the temperature-programmed desorption of ammonia (NH3-TPD). The catalytic performance was evaluated by gas chromatography (GC). The liquid products were 70 wt% of the feed oil, and the majority of the liquid products were BTX. The aromatization activity of the catalyst was improved by the addition of PTA and the hierarchical process. The favorable PTA amount was 20 wt% and the yield of BTX was 59 wt% at 380 °C, 3 MPa, H2/oil (v/v) = 1000 and LHSV = 1 h-1 over the PTA20-NiMo/HZ0.5 catalyst (PTA 20 wt%) without sulfurization.
10.1038/srep41654
pubmed_94_4399
OBJECTIVES This study aims to develop a new prognostic score based on changes in serial laboratory data from patients with pediatric acute liver failure (PALF). METHODS We retrospectively reviewed data on 146 patients with PALF at the Seoul National University Children Hospital (SNUCH) and the Asan Medical Center (AMC). Daily morning laboratory records were obtained for up to 7 days after diagnosis of PALF: total bilirubin (TB) (mg/dL), international normalized ratio for prothrombin time (INR) at enrolment; peak TB, peak INR, peak ammonia (μmol/L); the difference between the peak TB and TB at enrollment (ie, Δpeak TB), the difference between the peak INR and INR at enrollment (ie, Δpeak INR), the maximum change in serial TB (ie, Δdaily TB), the maximum change in serial INR level (ie, Δdaily INR). We assigned nontransplanted patients in SNUCH and AMC to derivation and validation cohorts, respectively. RESULTS Δpeak TB, Δdaily TB, Δpeak INR, and Δdaily INR were significantly higher in the nonsurvival group. We developed a new score that can predict mortality in nontransplanted patients (derivation cohort n = 42, validation cohort n = 33). PALF-Delta score (PALF-Ds) = [0.232 × Δpeak TB (mg/dL)] + [2.263 × Δdaily INR] + [0.013 × peak ammonia (μmol/L)] - 4.498. The score yielded AUC 0.918 in the derivation cohort (sensitivity 81%, specificity 91%) and AUC 0.947 in the validation cohort (sensitivity 100%, specificity 89%). CONCLUSION A prognostic scoring system using the change of TB/INR may be useful for predicting mortality in patients with PALF.
10.1097/MPG.0000000000002625
pubmed_656_12641
Health literacy is multidimensional, comprising functional, communicative, and critical thinking dimensions. Understanding health literacy is crucial for clinicians to develop effective health education strategies. In this study, we examined the multiple dimensions of health literacy in Vietnamese adults with chronic comorbidities. A cross-sectional sample of 600 patients, aged ≥18 years with a diagnosis of at least two chronic diseases (cardiovascular conditions, chronic kidney disease, or diabetes), completed the Health Literacy Questionnaire, an instrument assessing nine distinct domains. Descriptive and parametric tests were performed to analyze the health literacy levels for various demographic characteristics. Generalized linear models using backward modelling explored factors associated with higher health literacy. The lowest scoring domains were "Healthcare provider support" and "Appraisal of health information." In multivariate models greater health literacy was associated with those <65 years, having a postsecondary degree or higher level of education, greater income, urban residence, being cared for by spouses/children, and having fewer comorbidities. To improve health literacy, clinicians in primary and acute healthcare settings should build supportive relationships with patients and assist them with understanding and appraising health information.
10.1111/nhs.12785
pubmed_116_4098
1. The effect of external ATP on the membrane current was investigated in PC12 cells by whole-cell voltage-clamp techniques. 2. Lower concentrations of ATP (1 or 10 mumol/L) induced only an inward current at 1 mmol/L EGTA in the K+ pipette solution, while higher concentrations of ATP (100 mumol/L and 1 mmol/L) induced an outward current following the inward current. 3. Lowering the EGTA concentration in the pipette solution induced a larger outward current following ATP application. The membrane potential at which the outward current crossed with the control before ATP application was more negative at lower concentrations of EGTA in the pipette. 4. The development of the outward current was blocked by a Ca(2+)-free external solution, 5 mmol/L tetraethylammonium and a Cs+ pipette solution instead of K+, indicating that the outward current was a Ca(2+)-activated K+ current. 5. Charybdotoxin (0.1 mumol/L) and iberiotoxin (0.1 mumol/L), but not apamin (0.2 mumol/L) blocked the development of the outward current, indicating the ATP-induced outward current is a BK-type Ca(2+)-activated K+ channel current and not the SK type. 6. UTP had no effect on the membrane current, indicating that the ATP-induced current change was not mediated by P2u but by P2x purinoceptor. 7. In conclusion, stimulation of P2x purinoceptors by ATP induces a Ca(2+)-permeable inward current that results in increases in intracellular Ca2+ concentrations and activation of a BK-type Ca(2+)-activated K+ current in PC12 cells.
10.1046/j.1440-1681.1999.02980.x
pubmed_572_19056
The analysis of gait dynamics is helpful for predicting and improving the quality of life, morbidity, and mortality in neuro-degenerative patients. Feature extraction of physiological time series and classification between gait patterns of healthy control subjects and patients are usually carried out on the basis of 1-D signal analysis. The proposed approach presented in this paper departs itself from conventional methods for gait analysis by transforming time series into images, of which texture features can be extracted from methods of texture analysis. Here, the fuzzy recurrence plot algorithm is applied to transform gait time series into texture images, which can be visualized to gain insight into disease patterns. Several texture features are then extracted from fuzzy recurrence plots using the gray-level co-occurrence matrix for pattern analysis and machine classification to differentiate healthy control subjects from patients with Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Experimental results using only the right stride-intervals of the four groups show the effectiveness of the application of the proposed approach.
10.1109/TNSRE.2017.2732448
pubmed_0_18320
BACKGROUND Antipsychotics, especially atypical agents, are widely used in the elderly population to treat behavioural and psychiatric symptoms. Very few studies have compared the risk of falls and fractures among older adults using typical and atypical agents and none of the studies have evaluated differential risk across antipsychotic classes. OBJECTIVE To examine the risk of falls and fractures associated with atypical antipsychotic use and typical antipsychotic use in community-dwelling older adults in the US. METHODS The study involved a retrospective population-based cohort design matched on propensity scores involving older adults (aged ≥50 years) using atypical or typical antipsychotic agents in the IMS LifeLink™ Health Plan Claims Database. Patients taking atypical antipsychotics were matched with patients taking typical antipsychotics using the Greedy 5 → 1 matching technique. The study evaluated the relative risk of hospitalization/emergency room (ER) visits due to falls/fractures in a 1-year follow-up period, and patients treated with atypical antipsychotics were compared with those treated with typical antipsychotics using the Cox proportional-hazards regression model stratified on matched pairs. The covariates adjusted for in the regression model included duration of therapy and exposure to other psychotropic medications that increase the risk of falls and fractures. RESULTS From July 2000 to December 2007, 11 160 (5580 atypical and 5580 typical) users of antipsychotics were obtained after matching on propensity scores. A total of 825 cases of falls/fractures with at least one hospitalization/ER visit following the use of antipsychotic agents were identified. The number of cases with falls/fractures was 450 in atypical antipsychotic users and 375 in typical antipsychotic users. Cox regression model analysis revealed no statistically significant difference between atypical users and typical users with respect to risk of falls/fractures (hazard ratio [HR] 1.01; 95% CI 0.83, 1.22). However, duration of therapy with any antipsychotic medication for >90 days was significantly (HR 1.81; CI 1.35, 2.43) associated with increased risk of falls/fractures compared with <30 days of treatment. CONCLUSIONS No statistically significant difference was found between atypical antipsychotic agents and typical antipsychotic agents with regards to the likelihood of falls/fractures in a large cohort of older adults. However, there is a need to be cautious while prescribing atypical and typical antipsychotics in older adults for long periods of time.
10.2165/11537890-000000000-00000
pubmed_550_19001
The aim of the present study was to evaluate differences in resistance patterns of Escherichia coli in different parts of the digestive tract of veal calves. Therefore, after slaughter, the lower intestinal tract of 19 calves was sampled at five locations (duodenum, jejunum, cecum, colon, and rectum), and up to three E. coli isolates per sample underwent susceptibility testing for seven antimicrobial agents (gentamicin, amoxycillin + clavulanic acid, tetracycline, trimethoprim + sulfamethoxazole, ampicillin, nalidixic acid, and enrofloxacin), using the Kirby-Bauer disk diffusion method. Multiresistance (resistance to more than two compounds) was present in 93.5% of all isolates (n = 179). For gentamicin, nalidixic acid, and enrofloxacin, the percentage of resistant E. coli isolates was significantly lower in the duodenum and jejunum than in the cecum, colon, and rectum. For ampicillin, the percentage of resistance was significantly lower in the jejunum, compared to the other segments of the intestinal tract. For the other antimicrobials tested, no significant differences in the percentage of resistant isolates throughout the intestinal tract were detected. In conclusion, resistance among enteric E. coli from veal calves can reach high levels and prevalence depends on localization of sampling. These considerations should be taken into account when further fine-tuning sampling protocols for indicator bacteria.
10.1089/mdr.2007.744
pubmed_762_15335
This study addresses the relative importance of CD134 (OX40) and CD137 (4-1BB) in the costimulation of CD4+ and CD8+ T cells under comparable conditions of antigenic stimulation. We demonstrate that CD134 is capable of directly costimulating CD8+ T cells. However, costimulation of CD8+ T cells by CD134 is less potent than that triggered by CD137. The higher costimulatory activity of CD137, when compared with CD134, correlates well with its faster expression kinetics and higher levels on CD8+ T cells. Furthermore, induction of CD137 expression on CD8+ T cells is highly sensitive to low levels of TCR stimulation, which is in contrast with CD134. Conversely, CD134 is more effective than CD137 in costimulating CD4+ T cells. This, however, could not be attributed to differential expression. We also demonstrate that the transient nature of CD134 and CD137 expression on activated CD4+ T cells is the resultof proteolytic shedding. Consistent with the greater ability of CD137 to costimulate CD8+ T cells, stimulation of CD137 in vivo is considerably more effective than CD134 in augmenting anti-tumor immune responses. Therefore, agents that stimulate signaling via CD137 are likely to be more useful in clinical conditions where highly effective CD8+ CTL responses are required.
10.1002/1521-4141(200212)32:12<3617::AID-IMMU3617>3.0.CO;2-M
pubmed_686_22339
Laboratory bioassays were carried out with four neonicotinoid insecticides on multiple strains of Bemisia tabaci (Gennadius) to evaluate resistance and cross-resistance patterns. Three imidacloprid-resistant strains and field populations from three different locations in the southwestern USA were compared in systemic uptake bioassays with acetamiprid, dinotefuran, imidacloprid and thiamethoxam. An imidacloprid-resistant strain (IM-R) with 120-fold resistance originally collected from Imperial Valley, California, did not show cross-resistance to acetamiprid, dinotefuran or thiamethoxam. The Guatemala-resistant strain (GU-R) that was also highly resistant to imidacloprid (RR=109-fold) showed low levels of cross-resistance when bioassayed with acetamiprid and thiamethoxam. However, dinotefuran was more toxic than either imidacloprid or thiamethoxam to both IM-R and GU-R strains as indicated by low LC50s. By contrast, a Q-biotype Spanish-resistant strain (SQ-R) of B. tabaci highly resistant to imidacloprid demonstrated high cross-resistance to the two related neonicotinoids. Field populations from Imperial Valley (California), Maricopa and Yuma (Arizona), showed variable susceptibility to imidacloprid (LC50s ranging from 3.39 to 115 microg ml(-1)) but did not exhibit cross-resistance to the three neonicotinoids suggesting that all three compounds would be effective in managing whiteflies. Yuma populations were the most susceptible to imidacloprid. Dinotefuran was the most toxic of the four neonicotinoids against field populations. Although differences in binding at the target site and metabolic pathways may influence the variability in cross-resistance patterns among whitefly populations, comparison of whitefly responses from various geographic regions to the four neonicotinoids indicates the importance of ecological and operational factors on development of cross-resistance to the neonicotinoids.
10.1079/ber2005385
pubmed_601_2329
A short (5 min) incubation of cultured Chinese hamster fibroblasts with the specific beta-agonist isoproterenol (1 microM) leads to an increase in the intracellular content of cAMP and a decrease in radiosensitivity of the cells. Prolonged (up to 1 h) incubation induces a desensitization of the cAMP system to isoproterenol and causes a decrease both in the cAMP-stimulating and radioprotective effect of isoproterenol. There were no detectable changes in the beta-adrenoreceptor number or binding affinity of beta-receptors to the radiolabelled beta-antagonist dihydroalprenolol in desensitized cells; cAMP-phosphodiesterase activity was also the same as in intact cells. It is proposed that a 1 h incubation of the cells with isoproterenol induces the first step of desensitization, i.e. the functional "uncoupling' of beta-receptors from adenylate cyclase. Thus, the presence of beta-receptors in cells is not enough for the realization of the radioprotective potency of isoproterenol; an intact, non-desensitized, state of the cAMP system is obligatory.
10.1080/09553008514551851
pubmed_512_17906
BACKGROUND Giant cell arteritis is an immune-mediated disease of medium and large-sized arteries that affects mostly people older than 50 years of age. Treatment with glucocorticoids is the gold-standard and prevents severe vascular complications but is associated with substantial morbidity and mortality. Tocilizumab, a humanised monoclonal antibody against the interleukin-6 receptor, has been associated with rapid induction and maintenance of remission in patients with giant cell arteritis. We therefore aimed to study the efficacy and safety of tocilizumab in the first randomised clinical trial in patients with newly diagnosed or recurrent giant cell arteritis. METHODS In this single centre, phase 2, randomised, double-blind, placebo-controlled trial, we recruited patients aged 50 years and older from University Hospital Bern, Switzerland, who met the 1990 American College of Rheumatology criteria for giant cell arteritis. Patients with new-onset or relapsing disease were randomly assigned (2:1) to receive either tocilizumab (8 mg/kg) or placebo intravenously. 13 infusions were given in 4 week intervals until week 52. Both groups received oral prednisolone, starting at 1 mg/kg per day and tapered down to 0 mg according to a standard reduction scheme defined in the study protocol. Allocation to treatment groups was done using a central computerised randomisation procedure with a permuted block design and a block size of three, and concealed using central randomisation generated by the clinical trials unit. Patients, investigators, and study personnel were masked to treatment assignment. The primary outcome was the proportion of patients who achieved complete remission of disease at a prednisolone dose of 0·1 mg/kg per day at week 12. All analyses were intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01450137. RESULTS Between March 3, 2012, and Sept 9, 2014, 20 patients were randomly assigned to receive tocilizumab and prednisolone, and ten patients to receive placebo and glucocorticoid; 16 (80%) and seven (70%) patients, respectively, had new-onset giant cell arteritis. 17 (85%) of 20 patients given tocilizumab and four (40%) of ten patients given placebo reached complete remission by week 12 (risk difference 45%, 95% CI 11-79; p=0·0301). Relapse-free survival was achieved in 17 (85%) patients in the tocilizumab group and two (20%) in the placebo group by week 52 (risk difference 65%, 95% CI 36-94; p=0·0010). The mean survival-time difference to stop glucocorticoids was 12 weeks in favour of tocilizumab (95% CI 7-17; p<0·0001), leading to a cumulative prednisolone dose of 43 mg/kg in the tocilizumab group versus 110 mg/kg in the placebo group (p=0·0005) after 52 weeks. Seven (35%) patients in the tocilizumab group and five (50%) in the placebo group had serious adverse events. INTERPRETATION Our findings show, for the first time in a trial setting, the efficacy of tocilizumab in the induction and maintenance of remission in patients with giant cell arteritis. FUNDING Roche and the University of Bern.
pubmed_512_17906
pubmed_662_1583
The long-term effects of an extended-wear contact lens (perfilcon A [Permalens]) for myopia were evaluated in 106 patients who had successfully worn the lens for four to eight years (median, 4.94 years). Visual acuity was 6/12 (20/40) or better in 95% of the 207 eyes fitted. Corneal neovascularization, when encountered (8.7%), was mild and did not reduce visual acuity. There were no cases of infectious corneal ulcer or scarring or of permanent visual loss from use of the lens. In selected patients, use of extended-wear lenses seems to be a reasonable form of optical correction of myopia, and they deserve further study. The use of these lenses is discussed as an alternative to the experimental procedure of radial keratotomy.
10.1001/archopht.1981.03930020839004
pubmed_978_13720
Prealbumin, albumin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, ceruloplasmin, haptoglobin, transferrin, IgG, IgM and IgA were studied in blood serum of healthy donors and of patients with chronic alcoholism by means of cross immuno-electrophoresis and immunodiffusion. Only content of alpha 1-antitrypsin was distinctly altered in blood serum of the patients with alcoholism as compared with normal state, while individual variations in content of the proteins studied were considerably higher in blood serum of the patients. At the same time, distinct dissimilarity of the patterns studied was found between healthy donors and patients with chronic alcoholism when concentration ratios of some positively and negatively charged acute phase proteins were calculated (alpha 1-antitrypsin/albumin, haptoglobin/albumin, haptoglobin/transferrin).
pubmed_978_13720
pubmed_847_8287
During infection, intracellular pathogens inevitably face the pressure of hypoxia. Mycobacterium tuberculosis and Mycobacterium bovis represent two typical intracellular bacteria, but the signalling pathway of their adaptation to hypoxia remains unclear. Here, we report a new mechanism of the hypoxic adaptation in M. bovis driven by the second messenger molecule c-di-GMP. We found that c-di-GMP was significantly accumulated in bacterial cells under hypoxic stress and blocked the inhibitory activity of ArgR, an arginine metabolism gene cluster regulator, which increased arginine synthesis and slowed tricarboxylic acid cycle (TCA cycle) and aerobic respiration. Meanwhile, c-di-GMP relieved the self-inhibition of argR expression, and ArgR could interact with the nitrite metabolic gene regulator Cmr, promoting the positive regulation of Cmr and, thereafter, the nitrite respiration. Consistently, c-di-GMP significantly induced the expression of arginine and nitrite metabolism gene clusters and increased the mycobacterial survival ability under hypoxia. Therefore, we found a new function of the second messenger molecule c-di-GMP and characterized ArgR as a metabolic switching regulator that can coordinate the c-di-GMP signal to trigger hypoxic adaptation in mycobacteria. Our findings provide a potential new target for blocking the life cycle of M. tuberculosis infection.
10.1111/1462-2920.15987
pubmed_1051_16330
OBJECTIVE Cognitive down-regulation of craving involves a neural network within the prefrontal cortex. Tobacco use disorder (TUD) and trait impulsivity have been associated with prefrontal cortex impairments and down-regulation deficits. However, general deficits in down-regulation of craving (regarding non-drug-related cues) compared to never-smokers (NS), differential alterations between drug-related and non-drug-related cues, as well as its links to subject characteristics (smoking severity, trait impulsivity) have so far sparsely been investigated in TUD. METHOD In this study, 78 subjects (37 TUD & 42 NS) underwent functional magnetic resonance imaging while performing a down-regulation of craving task. Two reward cue-types were presented (drug cues and alternative rewards). Subjects applied down-regulation of craving during a LATER condition and up-regulated their craving during a NOW condition. Subjective craving ratings were assessed after each trial. To evaluate down-regulation of craving, we investigated the LATER versus NOW condition. RESULTS TUD subjects showed no differences in down-regulation on a behavioral level, neither compared to NS nor between the two reward cue-types. On a neurofunctional level, we found a stronger BOLD response in the middle temporal gyrus in TUD subjects compared to NS in the alternative reward condition. No differences between the two reward cue-types were found within TUD subjects. During down-regulation across both reward cue-types, we identified significant negative associations between activation of control areas and smoking severity. CONCLUSIONS Results neither indicate evidence for the expected general alterations in down-regulation of craving in TUD, compared to NS, nor specific alterations between drug-related and alternative reward cues on a neurofunctional level. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
10.1037/adb0000820
pubmed_1111_2468
Abstract behavior-guiding rules and strategies allow monkeys to avoid errors in rarely encountered situations. In the present study, we contrasted strategy-related neuronal activity in the dorsolateral prefrontal cortex (PFdl) and the orbital prefrontal cortex (PFo) of rhesus monkeys. On each trial of their behavioral task, the monkeys responded to a foveal visual cue by making a saccade to one of two spatial targets. One response required a leftward saccade, the other required a saccade of equal magnitude to the right. The cues instructed the monkeys to follow one of two response strategies: to stay with their most recent successful response or to shift to the alternative response. Neurons in both areas encoded the stay and shift strategies after the cue appeared, but there were three major differences between the PFo and the PFdl: (1) many strategy-encoding cells in PFdl also encoded the response (left or right), but few, if any, PFo cells did so; (2) strategy selectivity appeared earlier in PFo than in PFdl; and (3) on error trials, PFo neurons encoded the correct strategy-the one that had been cued but not implemented-whereas in PFdl the strategy signals were weak or absent on error trials. These findings indicate that PFo and PFdl both contribute to behaviors guided by abstract response strategies, but do so differently, with PFo encoding a strategy and PFdl encoding a response based on a strategy.
10.1523/JNEUROSCI.5816-10.2011
pubmed_1017_15792
The indication of liver transplantation (LT) for the treatment of advanced hepatocellular carcinoma (HCC) is expanding. However, portal vein tumor thrombus (PVTT) has been still accepted as an absolute contraindication. We experienced an unexpectedly good prognosis in selected patients. Therefore, we tried to identify the prognostic factors after LT for HCC with major PVTT. Among 282 patients who underwent living donor liver transplantation (LDLT) for HCC from January 2009 to December 2013, 11 (3.9%) patients with major PVTT that was preoperatively diagnosed were investigated. The 1-, 3-, and 5-year recurrence-free survival rates were 63.6%, 45.5%, and 45.5%, respectively, and all recurrent cases showed intrahepatic and extrahepatic recurrence. The 1-, 3-, and 5-year overall survival rates were 72.7%, 63.6%, and 63.6%, respectively, and 2 patients with delayed recurrence survived approximately 5 years after LT. Main portal vein (PV) invasion (P < 0.01), high alpha-fetoprotein × protein induced by vitamin K absence/antagonist-II (AP) score (≥20,000; P < 0.01), high standardized uptake value (SUV) ratio (tumor/background liver) in positron emission tomography (≥2.1; P < 0.01), and a large original tumor (≥7 cm; P = 0.03) were significant risk factors for recurrence. In conclusion, if the PVTT has not expanded to the main PV and the AP score is not high, we can consider LDLT as a curative treatment option. Liver Transplantation 23:19-27 2017 AASLD.
10.1002/lt.24610
pubmed_179_12770
PURPOSE Brain-computer interfaces (BCIs) aim to provide access to augmentative and alternative communication (AAC) devices via brain activity alone. However, while BCI technology is expanding in the laboratory setting there is minimal incorporation into clinical practice. Building upon established AAC research and clinical best practices may aid the clinical translation of BCI practice, allowing advancements in both fields to be fully leveraged. METHOD A multidisciplinary team developed considerations for how BCI products, practice, and policy may build upon existing AAC research, based upon published reports of existing AAC and BCI procedures. OUTCOMES/BENEFITS Within each consideration, a review of BCI research is provided, along with considerations regarding how BCI procedures may build upon existing AAC methods. The consistent use of clinical/research procedures across disciplines can help facilitate collaborative efforts, engaging a range-individuals within the AAC community in the transition of BCI into clinical practice.
pubmed_179_12770
pubmed_534_6577
Wollastonite application in cadmium-contaminated soils can reduce cadmium concentrations in plant, while the side effect is the synchronous immobilization of micronutrients, which reduces micronutrient uptake in plant, inducing micronutrient deficient symptoms. Accordingly, we investigated whether the supplement of Zn and Mn fertilizers after the wollastonite addition could promote the growth and photosynthesis in amaranth (Amaranthus tricolor L.). In this study, plants were cultivated in cadmium-contaminated soil under micronutrient fertilization alone, wollastonite addition, and combination of wollastonite and micronutrient fertilization treatments. Then, plant biomass; photosynthesis parameters; and total Cd, Zn, and Mn concentrations were investigated. Moreover, chemical extractions were performed on soil samples. The results show that application of wollastonite decreased Cd, Zn, and Mn concentrations in plant and availability in soil and it increased the gas exchange ability of plants. But, it reduced the chlorophyll content in leaves and had no positive influence on plant biomass. In comparison, Zn and Mn fertilization after wollastonite application greatly increased plant biomass and photosynthetic ability. It also reduced Cd phytoavailability more efficiently. Therefore, synergistic improvement of physiological status of farmland crop by sequential treatment with first wollastonite for cadmium immobilization, and then micronutrient fertilization to avoid micronutrient deficiency, was demonstrated.
10.1007/s11356-015-5888-2
pubmed_931_22543
The structure of the title compound, a fentanyl derivative with formula C(36)H(36)N(3)O(3) (+)·Cl(-)·2CH(3)OH, crystallizes as a racemic mixture. The organic cation has an extended conformation and the structure displays O-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonding.
10.1107/S1600536806021817
pubmed_567_19648
This paper is based on a paper presented at a British Dental Association caries prevention symposium. It represents the views of the authors and does not necessarily represent the views of any organisation with which they, or the work reported, are associated.
pubmed_567_19648
pubmed_194_9667
The hypothesis that different receptor sites for algesic agents exist at free nerve endings in skeletal muscle has been tested by administering bradykinin and 5-hydroxytryptamine (5-HT) repeatedly in anaesthetized cats and evaluating the response behaviour of single group IV afferent units from the gastrocnemius-soleus muscle. Repeated intraarterial administration of bradykinin at intervals of 1 and 2 min usually elicited fibre responses without tachyphylaxis. Injections of equieffective doses of 5-HT, however, given in the same manner evoked fibre reactions that were strongly tachyphylactic. In units responding to both bradykinin and 5-HT a refractoriness to 5-HT could be induced by repeated injections of this agent without impairing the stimulating potency of bradykinin on the same nerve ending. Such a lack of cross-tachyphylaxis seems to apply also to the effects of histamine on one side and bradykinin or 5-HT on the other. These findings suggest that bradykinin, 5-HT and probably histamine exert their excitatory action on muscular group IV afferent units via different receptor sites.
10.1007/BF00583640
pubmed_482_12661
While 1,2-addition represents the most common mode of alkyne hydroboration, herein we describe a new 1,1-hydroboration mode. It is the first demonstration of gem-(H,B) addition to an alkyne triple bond. With the superior [CpRu(MeCN)3]PF6 catalyst, a range of silyl alkynes reacted efficiently with HBpin under mild conditions to form various synthetically useful silyl vinyl boronates with complete stereoselectivity and broad functional group compatibility. An extension to germanyl alkynes and the hydrosilylation of alkynyl boronates toward the same type of products were also achieved. Mechanistically, this process features a new pathway featuring gem-(H,B) addition to form the key α-boryl-α-silyl Ru-carbene intermediate followed by silyl migration. It is believed that the orbital interaction between boron and Cβ in the coplanar relationship between the boron atom and the ruthenacyclopropene ring preceding boron migration is responsible for the new reactivity. Control experiments and DFT (including molecular dynamics) calculations provided important insights into the mechanism, which excluded the involvement of a metal vinylidene intermediate. This study represents a new step forward not only for alkyne hydroboration but also for other geminal additions of alkynes.
10.1021/jacs.0c05334
pubmed_660_869
Indian demographic history includes special features such as founder effects, interpopulation segregation, complex social structure with a caste system and elevated frequency of consanguineous marriages. It also presents a higher frequency for some rare mendelian disorders and in the last two decades increased prevalence of some complex disorders. Despite the fact that India represents about one-sixth of the human population, deep genetic studies from this terrain have been scarce. In this study, we analyzed high-density genotyping and whole-exome sequencing data of a North and a South Indian population. Indian populations show higher differentiation levels than those reported between populations of other continents. In this work, we have analyzed its consequences, by specifically assessing the transferability of genetic markers from or to Indian populations. We show that there is limited genetic marker portability from available genetic resources such as HapMap or the 1,000 Genomes Project to Indian populations, which also present an excess of private rare variants. Conversely, tagSNPs show a high level of portability between the two Indian populations, in contrast to the common belief that North and South Indian populations are genetically very different. By estimating kinship from mates and consanguinity in our data from trios, we also describe different patterns of assortative mating and inbreeding in the two populations, in agreement with distinct mating preferences and social structures. In addition, this analysis has allowed us to describe genomic regions under recent adaptive selection, indicating differential adaptive histories for North and South Indian populations. Our findings highlight the importance of considering demography for design and analysis of genetic studies, as well as the need for extending human genetic variation catalogs to new populations and particularly to those with particular demographic histories.
10.1007/s00439-014-1462-0
pubmed_409_21128
1. In order to distinguish between models of anion secretion, the effects of transport inhibitors on saliva flow rate and electrolyte composition were studied during the plateau phase of secretion in rabbit mandibular salivary glands. 2. Bumetanide, an inhibitor of Na+,K+,2Cl- co-transport, inhibited flow rate (by 60%) and reduced Cl- concentration. K+ and HCO3- concentrations were increased. Forskolin, an adenylate cyclase activator which inhibits ductal transport, did not significantly affect this pattern of changes. 3. Amiloride, used at concentrations that would inhibit Na(+)-H+ exchange, inhibited flow rate (by 30%). Cl- concentration was initially increased before subsequently decreasing at the same time as HCO3- concentration increased. These concentration changes can probably be attributed to ductal transport. When amiloride was applied to glands perfused with nominally HCO3- -free solutions, inhibition of flow rate was rapid and almost complete. 4. When amiloride and bumetanide were both present in the perfusate, flow rate was inhibited by 92%. The pattern of electrolyte changes was not significantly different from that observed in the presence of bumetanide alone. 5. Inhibition of K+ channel activity using Ba2+ also inhibited flow rate. Cl- concentration was increased as was K+ concentration. HCO3- concentration was not increased. 6. The anion exchange inhibitor DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) had no effect on either flow rate or electrolyte concentration. It did, however, elicit secretion in the absence of acetylcholine. 7. The data suggest that Na(+)-H+ and Cl- -HCO3- exchangers are unlikely to be involved in fluid and electrolyte secretion in these glands as suggested by some authors. Most of the data can be explained by postulating the existence of non-specific anion channels in the apical membranes of the acinar cells.
10.1113/jphysiol.1990.sp018111
pubmed_56_18594
The complement fixation test (CFT) is a serological test that can be used to detect the presence of specific antibodies or antigens to diagnose infections, particularly diseases caused by microbes that are not easily detected by standard culture methods. We report here, for the first time, a poly(dimethylsiloxane) (PDMS)/glass slide hybrid microfluidic device that was used to manipulate the solution compartment and communication within the microchannel to establish sampler and indicator systems of CFT. Two types of on-chip CFT, solution-based and solid phase agar-based assays, were successfully demonstrated for biomarker carcinoembryonic antigen (CEA) and recombinant avian influenza A (rH7N9) virus protein detection. In addition, the feasibility of the on-chip CFT in assaying real biopsy was successfully demonstrated by specifically detecting rH7N9 and CEA in human serum. The results demonstrated that the miniaturized assay format significantly reduced the assay time and sample consumption. Exemption from protein immobilization, blocking, complicated washing steps and expensive enzyme/fluorescein conjugates highlights the merits of on-chip CFT over ELISA. Most attractively, the on-chip agar-based CFT results can be imaged and analysed by smartphone, strengthening its point-of-care application potential. We anticipate that the on-chip CFT reported herein will be a useful supplemental or back-up tool for on-chip immunoassays such as ELISA for disease diagnosis and food inspection.
pubmed_56_18594
pubmed_579_7948
In this article, I present a framework for understanding the impact of aging-related declines in cognitive resources on functioning. I make the assumption that aging is associated with an increase in the costs of cognitive engagement, as reflected in both the effort required to achieve a specific level of task performance and the associated depletion or fatigue effects. I further argue that these costs result in older adults being increasingly selective in the engagement of cognitive resources in response to these declines. This selectivity is reflected in (a) a reduction in the intrinsic motivation to engage in cognitively demanding activities, which, in part, accounts for general reductions in engagement in such activities, and (b) greater sensitivity to the self-related implications of a given task. Both processes are adaptive if viewed in terms of resource conservation, but the former may also be maladaptive to the extent that it results in older adults restricting participation in cognitively demanding activities that could ultimately benefit cognitive health. I review supportive research and make the general case for the importance of considering motivational factors in understanding aging effects on cognitive functioning.
10.1177/1745691614527465
pubmed_172_9447
To elucidate the role of prolactin on testicular function, we treated mature rats with ovine prolactin (oPRL) and investigated the dose and time-dependent changes in testicular LH, FSH and prolactin receptors as well as in serum gonadotropin and steroid levels. Twelve week-old rats were injected sc with a single dose of various amounts of oPRL (0.2, 1 and 5 IU) and killed on the first, second and third days after the treatment. Testicular LH receptor decreased to 59% of the control level as a function of time while prolactin receptor increased to 244% maximally of the control level on the second day. In contrast, FSH receptor changed in a different fashion. Smaller amounts of oPRL (0.2 and 1 IU) raised the receptor level to 193% of the control level on the first day whereas a larger amount (5 IU) did not change the receptor, which tended to remain in a low level throughout the experimental period. The serum FSH level significantly increased in every group on the second day, then returned to the control range by the third day. On the other hand, the serum testosterone level changed in a characteristic manner, decreased significantly in every group on the first day though not in a dose-dependent fashion, returned to normal on the second day and significantly increased in the 0.2 IU group on the third day (p less than 0.01). Similarly, the serum estradiol level decreased in the oPRL-treated groups on the first day and was restored on the second day.(ABSTRACT TRUNCATED AT 250 WORDS)
10.1507/endocrj1954.33.469
pubmed_515_16594
BACKGROUND Live attenuated vaccine strain of measles virus (MV) has promising antitumor activity and is undergoing clinical testing in three different phase I cancer trials. The virus uses one of two receptors, CD46 which is ubiquitously expressed on all nucleated cells or CD150 which is expressed on immune cells, to infect cells. To minimize potential toxicity due to indiscriminate infection of normal cells, we have generated a fully retargeted MV that infects cells exclusively through the prostate-specific membrane antigen (PSMA) receptor, which is overexpressed on prostate cancer cells and tumor neovasculature. METHODS A single-chain antibody (scFv) specific for the extracellular domain of PSMA (J591) was inserted as a C-terminal extension on the MV attachment protein. Specificity of infection by the PSMA targeted virus was evaluated in parallel with the parental MV and a control virus which binds to CD38, a myeloma antigen. Antitumor activity of the PSMA retargeted virus was tested in both LNCaP and PC3-PSMA tumor xenograft models, with and without low dose external beam radiation. RESULTS Replication of the PSMA targeted virus was comparable to the parental MV. The PSMA scFv efficiently redirected virus infection and cytopathic killing exclusively to PSMA positive prostate cancer cells and not PSMA negative cells. There was an additive effect on cell killing from radiation treatment and virotherapy. The PSMA virus induced tumor regression of LNCaP and PC3-PSMA tumor xenografts. Extensive areas of MV infection and apoptosis were seen in virus treated tumors. CONCLUSIONS The PSMA retargeted virus warrants further investigation as a virotherapy agent.
10.1002/pros.20962
pubmed_16_1406
Bullous pemphigoid is an autoimmune skin blistering disorder that can present with several different degrees of severity. The treatment modality employed by the treating physician varies from localised topical therapy and anti-inflammatory treatments with minimal side effects to immunosuppressive agents associated with significant adverse reactions. Deciding which therapy to use with a particular patient can be a challenge, and the treating physician must take into account the severity of disease, the overall medical condition of the patient and potential drug interactions. This article provides a comprehensive review of current medical therapies, as well as an overall approach to the patient with bullous pemphigoid.
10.1517/14656566.7.17.2403
pubmed_785_21
Size tunable aqueous Ag2S quantum dots emitting in the near-infrared region were synthesized through decomposition of meso-2,3-dimercaptosuccinic acid (DMSA) in water. The resulting NIR QDs are highly cyto- and hemocompatible, have quantum yields as high as 6.5% and are effective optical imaging agents based on in vitro evaluation.
10.1039/c4nr02935f
pubmed_381_21449
BACKGROUND Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016. OBJECTIVES To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue. SEARCH METHODS For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials. SELECTION CRITERIA We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings. DATA COLLECTION AND ANALYSIS Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes. MAIN RESULTS The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT. AUTHORS' CONCLUSIONS There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
10.1002/14651858.CD011376.pub3
pubmed_809_13886
BACKGROUND In our varied roles as health care professionals and researchers, many women with rheumatoid arthritis (RA) have commented to us about their feelings of inability to cope with everyday tasks, especially within their role as mothers. AIMS This study explored the health and life experiences of mothers with RA in order to increase knowledge about this group of women and inform health care professionals who provide them with support before and after becoming a mother. METHODS A phenomenological approach was adopted, and individual face-to-face semi-structured interviews were carried out with a sample of seven women, aged 21-41 years, who had lived with RA for 3-11 years and had one or more children under five years of age (total range of ages being 1-7 years). The data were analysed using Colaizzi's procedural steps. RESULTS The five major themes that emerged were inner strength, depression, labelling, failure, and pre- and post-natal education. Sub-themes included issues such as putting on a brave face, spirituality, guilt, burden, feeling 'robbed of motherhood', isolation, coping methods and lack of information. CONCLUSIONS This in-depth study informs health care professionals for their role as support provider for mothers with RA. Further research needs to be carried out to include multicultural experiences, which may or may not differ. As a step forward, we have implemented a local support group for mothers with RA, which will hopefully add benefit to existing rheumatology, midwifery and health visiting services.
10.1002/msc.116
pubmed_285_10749
OBJECTIVES To describe tobacco control policies and activities at a nationally representative sample of Aboriginal community-controlled health services (ACCHSs). DESIGN, SETTING AND PARTICIPANTS The Talking About The Smokes (TATS) project used a quota sampling design to recruit 34 ACCHSs around Australia. Between April 2012 and October 2013, a representative at each ACCHS completed a survey about the service's tobacco control policies and activities. Questions about support for smoke-free policies were also included in the TATS project survey of 2435 Aboriginal and Torres Strait Islander members of the communities served by the ACCHSs. MAIN OUTCOME MEASURES ACCHS tobacco control policies and activities. RESULTS Thirty-two surveys were completed, covering 34 sites. Most ACCHSs (24/32) prioritised tobacco control "a great deal" or "a fair amount", and all services had smoke-free workplace policies. Most had staff working on tobacco control and had provided tobacco control training within the past year. A range of quit-smoking information and activities had been provided for clients and the community, as well as extra smoking cessation support for staff. There was strong support for smoke-free ACCHSs from within the Aboriginal communities, with 87% of non-smokers, 85% of ex-smokers and 77% of daily smokers supporting a complete ban on smoking inside and around ACCHS buildings. CONCLUSIONS The high level of commitment and experience within ACCHSs provides a strong base to sustain further tobacco control measures to reduce the very high smoking prevalence in Aboriginal and Torres Strait Islander populations.
10.5694/mja15.00200
pubmed_52_7668
AIM The Alberta Infant Motor Scale (AIMS) is an infant developmental test, which can be used to evaluate motor performance from birth to independent walking. Between 1990 and 1992 Piper and Darrah determined reference values in a cohort in Canada. To our knowledge no study has been carried out to determine whether the Canadian data are representative for other countries. In the present study we aimed to establish whether the AIMS test needs new reference values for Dutch children. METHODS Motor performance of 100 Dutch children, aged 0-12 months, was measured using the AIMS test. RESULTS The mean percentile score of the Dutch children was 28.8 (+/-22.9, range 1-85). The percentile scores of the group were significantly lower than scores of the Canadian norm population (p < 0.001), whereby 75% of the Dutch children scored below the 50th percentile. These lower scores were not be explained by sex, racial differences or congenital disorders and were seen in all age groups. CONCLUSION We conclude that new reference values on the AIMS test for the age group of 0-12 months need to be established for Dutch children. It is recommended that the need for new normative data is also determined in all other European countries.
10.1111/j.1651-2227.2007.00111.x
pubmed_410_22529
Diagnosis and management of axial spondyloarthritis (axSpA) has vastly improved over the past two decades. With advances in the discernment of immunopathogenesis of this disease, new therapies have become available, which are associated with substantial improvement in symptoms, signs and quality of life. The four broad categories of approved treatment options are physical therapy and exercise (which have been known to be beneficial for millennia), NSAIDs (since the 1950s), TNF inhibitors (first FDA approval in 2003) and IL-17 inhibitors (first FDA approval in 2016). In addition, there have been a host of new developments in the axSpA field, including new treatment guidelines, the FDA approval of three biologic DMARDs to treat non-radiographic axSpA, the FDA and EMA approval of Janus kinase (JAK) inhibitors for ankylosing spondylitis, new data on the effect of biologic DMARDs on structural progression in ankylosing spondylitis, strategy trials on tapering or stopping TNF inhibitors in patients in remission, trials of treat-to-target strategy in axSpA, and several new molecules in phase III studies. This Review explores the developments in the management of axSpA.
10.1038/s41584-022-00761-z
pubmed_512_24165
The blast crisis of chronic myelogenous leukemia (CML) can be hematological or extramedullary. About 25% of these cases fulfill the criteria for mixed phenotype acute leukemia. We here report a case of a second blast crisis of CML which was extramedullary and was immunophenotypically bilineage T/myeloid.
10.4103/0377-4929.174824
pubmed_869_15864
Patients with the specific problem of a collapsed Nakamura volar type, scaphoid synovial pseudarthrosis with avascular necrosis on both magnetic resonance imaging and intraoperative inspection were studied to determine the ability of a trapezoidal wedge-shaped structural bone graft vascularised by the 1,2 intercompartmental supraretinacular artery to simultaneously achieve correction of the scaphoid dimension and a high union rate. Fifteen patients with this specific problem were followed for a mean of 32.1 months and achieved union in all cases at a mean of 11.5 weeks. Improvements were seen postoperatively in wrist flexion and extension, grip strength, degree of dorsal intercalated segment instability and degree of scaphoid collapse. Two complications relating to the fixation technique occurred. Although technically difficult, it is possible to achieve a high rate of union for scaphoid pseudarthrosis while correcting substantial collapse deformity by the use of a structural, wedge-shaped, vascularised bone graft.
10.1016/J.JHSB.2006.11.018
pubmed_239_25080
Doxorubicin (DOX) is one of the most commonly used and effective chemotherapeutic agents. Despite its clinical benefits, the use of DOX is often limited by serious adverse effects, such as severe cardiotoxicity and myelosuppression. Recent progress in chemical synthesis has enabled the design of modified anthracyclines with a sugar moiety being a desirable subject of research. A series of new analogues of DOX has been synthesised, in which the amino group in the daunosamine moiety was replaced by a formamidine system containing the rest of the cyclic secondary amine with gradually increased ring size. An additional product containing the oxazoline ring in daunosamine moiety was obtained during the synthesis of formamidinodoxorubicin from DOX. Formamidine derivatives demonstrate better anticancer properties when compared with parental DOX, such as lower cardiotoxicity and comparable or higher antiproliferative activity. Also the analogue containing the oxazoline ring in the structure shows promising results. Structural modifications in the sugar moiety, involving oxazoline ring formation, increase the anticancer activity in terms of apoptosis induction and genotoxicity. It can be concluded that chemical modification at the C3' position is a good method to increase the activity against cancer cells in vitro.
10.1016/j.lfs.2017.04.009
pubmed_933_16705
BACKGROUND Hematoma volume is a major determinant of outcome in patients with intracerebral hemorrhage (ICH). Accurate volume measurements are critical for predicting outcome and are thought to be more difficult in patients with oral anticoagulation-related ICH (OAT-ICH) due to a higher frequency of irregular shape. We examined hematoma shape and methods of volume assessment in patients with OAT-ICH. METHODS We performed a case-control analysis of a prospectively identified cohort of consecutive patients with ICH. We retrospectively reviewed 50 consecutive patients with OAT-ICH and 50 location-matched non-OAT-ICH controls. Two independent readers analyzed CT scans for hematoma shape and volume using both ABC/2 and ABC/3 methods. Readers were blinded to all clinical variables including warfarin status. Gold-standard ICH volumes were determined using validated computer-assisted planimetry. RESULTS Within this cohort, median INR in patients with OAT-ICH was 3.2. Initial ICH volume was not significantly different between non-OAT-ICH and OAT-ICH (35 +/- 38 cc vs. 53 +/- 56 cc, P = 0.4). ICH shape did not differ by anticoagulation status (round shape in 10% of OAT-ICH vs. 16% of non-OAT-ICH, P = 0.5). The ABC/3 calculation underestimated median volume by 9 (3-28) cc, while the ABC/2 calculation did so by 4 (0.8-12) cc. CONCLUSIONS Hematoma shape was not statistically significantly different in patients with OAT-ICH. Among bedside approaches, the standard ABC/2 method offers reasonable approximation of hematoma volume in OAT-ICH and non-OAT-ICH.
10.1007/s12028-009-9296-7
pubmed_1114_1563
Quantum blobs are the smallest phase space units of phase space compatible with the uncertainty principle of quantum mechanics and having the symplectic group as group of symmetries. Quantum blobs are in a bijective correspondence with the squeezed coherent states from standard quantum mechanics, of which they are a phase space picture. This allows us to propose a substitute for phase space in quantum mechanics. We study the relationship between quantum blobs with a certain class of level sets defined by Fermi for the purpose of representing geometrically quantum states.
10.1007/s10701-012-9636-x
pubmed_936_8096
In this work, sampling was carried out in the urban area of Madrid to analyze the content of total heavy metals (Zn, Pb, Cu, Cr, Ni, and Cd) in the street dust. Contamination was evaluated using various indices, such as the Contamination Factor (CF), Enrichment Factor (EF), Geo-accumulation Index (Igeo), Potential Ecological Risk Index (RI), Pollution Load Index (PLI), the Human Health Index Hazard Index (HI), and Cancer Risk (CR). Pollution indices were related to traffic density and color. Traffic density was the factor that most influenced the values of the pollution indexes, but no significant differences were found with the color of street dust. The concentration of heavy metals in the urban dust of Madrid had the following sequence: Zn (895) &gt; Cu (411) &gt; Pb (290) &gt; Cr (100) &gt; Ni (42) &gt; Cd (1.25 mg kg-1). The pollution levels were high or very high in Pb, Zn, and Cd regarding the environmental pollution indexes. Ingestion was the main route of exposure to heavy metals contained in street dust. The CR for adults and children is less than 1 × 10-6, which means that there is no risk for the population. However, the HI was 10 times higher in children than in adults.
10.3390/ijerph19095263
pubmed_689_6583
Attainable levels of signal-to-background ratio (SBR) in Raman spectroscopy of biological samples is limited by the presence of endogenous fluorophores. It is customary to remove the ubiquitous fluorescence background using postacquisition data processing. However, new approaches are needed to reduce background contributions and maximize the fraction of the sensor dynamical range occupied by Raman photons. Time-resolved detection using pulsed lasers and time-gated measurements can be used to address the signal-to-background problem in biological samples by limiting light detection to nonresonant interaction phenomena with relaxation time scales occurring on sub-nanosecond time scales, thereby excluding contributions from resonant phenomena such as fluorescence. A time-gated Fourier-transform spectrometer was assembled using a commercially available interferometer, a single channel single-photon avalanche diode and time tagging electronics. A time gate of 300 ps increased the signal-to-background-ratio of the 1440 cm-1 Raman band from 36% to 69% in an olive oil sample hereby demonstrating the potential of this approach for autofluorescence suppression.
10.1002/jbio.202100188
pubmed_155_5082
A 68-year-old woman had a marked decrease in visual acuity, increased intraocular pressure, and acute iridocyclitis. She developed a pigmented hypopyon simulating an occult intraocular melanoma. Two anterior chamber paracenteses showed growth of Listeria monocytogenes. The patient received systemic intravenous penicillin, topical fortified gentamicin sulfate drops, and intraocular injections of cephaloridine. On discharge from the hospital after a two-week stay, visual acuity had improved and intraocular pressure had decreased.
10.1016/0002-9394(78)90196-4