title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
|---|---|---|---|
Modulation of autoimmune rheumatic diseases by oestrogen and progesterone. | Sexual dimorphism is evident in the risk and expression of several human autoimmune diseases. Differences in disease manifestations observed between sexes are likely to involve immunomodulation by sex steroids, nonhormonal factors encoded by genes on the X and Y chromosomes, and immunological phenomena unique to pregnancy. In systemic lupus erythematosus (SLE), and perhaps other autoantibody-mediated diseases, oestrogen seems to increase the risk of disease in genetically predisposed women by targeting key immune pathways, including the type 1 interferon (IFN) response, differentiation of CD4(+) T helper cells and survival of autoreactive B cells. By contrast, progesterone seems to reduce the risk of SLE by counteracting the effects of oestrogen on some of these same pathways, which suggests that the balance between oestrogen and progesterone can determine disease expression. In this Review we focus on the roles of the sex steroid hormones oestrogen and progesterone in modulating the risk and expression of SLE and rheumatoid arthritis. Intensive research in this area promises to identify novel therapeutic strategies and improve understanding of the immunological requirements and complications of pregnancy, and is expected to define the mechanisms behind sexual dimorphism in autoimmunity, immunity and other aspects of human health--a newly announced directive of the NIH. | 25,155,581 | [
-0.1072791,
-0.07261648,
0.087745,
-0.04764436,
-0.1328185,
-0.3350903,
0.1364131,
0.07989294,
-0.1348689,
0.1800323,
-0.172973,
0.008186254,
0.1429233,
-0.03709056,
-0.5515341,
-0.2993549,
0.1882343,
-0.1349425,
0.02097811,
0.02032506,
0.08285651,
0.4560424,
-0.2415386,
... |
Plasmodium falciparum and Plasmodium vivax genotypes and efficacy of intermittent preventive treatment in Papua New Guinea. | Intermittent preventive treatment of infants (IPTi) reduces early childhood malaria-related morbidity. While genotypic drug resistance markers have proven useful in predicting the efficacy of antimalarial drugs in case management, there are few equivalent data relating to their protective efficacy when used as IPTi. The present data from an IPTi trial in Papua New Guinea demonstrate how these markers can predict protective efficacy of IPTi for both Plasmodium falciparum and Plasmodium vivax. | 25,155,586 | [
0.001109866,
0.01000315,
0.02541484,
-0.2182145,
-0.1173873,
-0.4074271,
-0.2723759,
-0.07369372,
0.3289307,
-0.1363146,
0.247553,
0.3829854,
-0.1050075,
0.0192483,
-0.2179291,
-0.4170591,
-0.2437871,
-0.01722948,
-0.1094938,
0.2147562,
0.09709265,
0.1159068,
-0.1488519,
... |
Differential subcutaneous adipose tissue gene expression patterns in a randomized clinical trial of efavirenz or lopinavir-ritonavir in antiretroviral-naive patients. | Gene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms behind body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here, we evaluated early changes in adipose tissue gene expression and their relationship to fat changes in ART-naive HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline and weeks 16 and 48. mRNA changes of 11 genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy, and inflammation were assessed through reverse transcription-quantitative PCR (RT-qPCR). Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (P < 0.05). After 16 weeks of exposure to the drug regimen, transcripts of CEBP/A, ADIPOQ, GLUT4, LPL, and COXIV were significantly down-regulated in the EFV arm compared to the LPV/r arm (P < 0.05). Significant correlations were observed between LPL expression change and trunk fat change at week 16 in both arms and between CEBP/A or COXIV change and trunk fat change at the same time point only in the EFV arm and not in the LPV/r arm. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV and LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm. (This was a substudy of a randomized clinical trial [LIPOTAR study] registered at ClinicalTrials.gov under identifier NCT00759070.). | 25,155,608 | [
0.1446021,
0.1937574,
0.08333526,
0.04730612,
0.008850818,
-0.5035535,
-0.1441191,
0.2116769,
0.235657,
-0.2713901,
0.1314303,
0.03931224,
0.1532028,
0.3665596,
-0.5577703,
-0.2395181,
-0.5123194,
-0.2281335,
-0.4875488,
0.4827474,
-0.1673999,
0.26428,
-0.2321559,
-0.00... |
Risk factors for acute kidney injury (AKI) in infants with melamine-associated urolithiasis and follow-up: a multi-center retrospective analysis. | Abstract An epidemic of urinary tract stones was noted among infants in China, 2008. This event was believed to be associated with consumption melamine-contaminated powdered formula. The patients with symptoms and clinical manifests had already been analyzed in our previous studies. In this study, our aim is to investigate the risk factors of melamine-associated acute kidney injury (AKI) and the potential relationship toward children growth in our five years follow-up. A total of 619 infants with melamine-associated urolithiasis were admitted into 20 different hospitals in the Gansu province, China. All clinical data were divided into AKI and control groups according to the occurrence of AKI. Univariate and multivariate analyses were performed with a logistic regression model to assess the independent risk factors of AKI. Logistic regression analysis revealed that the odds ratio (OR) of AKI was 19.62 in the group of infants who consumed Sanlu® milk powdered infant milk formula. A higher prevalence of AKI was observed in infants age of 6-11 months (OR: 9.59, p < 0.01) and 12-17 months (OR: 5.06, p < 0.01). Multivariate analysis also indicated that any one symptoms of upper respiratory tract infection (URTI), diarrhea, dehydration and fever (OR: 4.29, p < 0.01) were independent risk factors of AKI. Therefore, this study demonstrated that high melamine infant formula (Sanlu® milk powdered infant formula), age (6-17 months) and symptoms of URTI, diarrhea, dehydration or fever were risk factors of AKI in infants with melamine-associated urolithiasis. | 25,155,621 | [
-0.05043017,
-0.1175561,
-0.08388973,
0.153354,
-0.01928783,
-0.2455471,
-0.2263163,
0.1211794,
0.03397561,
-0.06055569,
-0.118314,
0.393395,
0.1616365,
0.3043667,
-0.01435751,
0.08937889,
-0.006037821,
-0.06091908,
-0.02870826,
0.03562823,
0.4550781,
-0.2260084,
-0.59971... |
Highly sensitive fluorescent probe for clenbuterol hydrochloride detection based on its catalytic oxidation of eosine Y by NaIO4. | A highly sensitive fluorescent probe for clenbuterol hydrochloride (CLB) detection has been first designed based on its catalytic effect on NaIO4 oxidating eosine Y (R). And this environment-friendly, simple, rapid, selective and sensitive fluorescent probe has been utilized to detect CLB in the practical samples with the results consisting with those obtained by GC/MS. The structures of R and CLB were characterized by infrared spectra. The mechanism of the proposed assay for the detection of CLB was also discussed. | 25,155,629 | [
0.1940622,
-0.05890564,
-0.0423319,
0.1405501,
-0.1549161,
0.1616073,
-0.2067166,
0.07446101,
0.09199325,
-0.1705433,
-0.03376234,
0.489106,
0.1714638,
0.2375959,
-0.3148301,
-0.3435487,
-0.515589,
0.4317392,
0.3501123,
0.3647618,
0.2456834,
0.1933167,
-0.2213868,
0.214... |
Captive marsupial nutrition. | Marsupials comprise an interesting group of mammals, which are increasingly being kept as pets. Few actual feeding trials have been published, although many anecdotal diets have years of usage with good success. Marsupials have dental and digestive tract adaptations that allow them to use specific niches in their environments. Knowing the diet in the wild is instrumental in designing diets used in captivity. | 25,155,664 | [
-0.1185969,
-0.08435033,
0.1322188,
0.1242126,
-0.1776544,
-0.1705058,
-0.2877873,
-0.0868086,
0.1792813,
-0.2731505,
0.06808732,
0.04803271,
0.09665101,
-0.2298924,
-0.6956718,
-0.2799574,
-0.4302937,
0.1399774,
-0.0781756,
-0.210049,
-0.2712216,
-0.03564835,
-0.05228956... |
Prescription diets for rabbits. | Dietary management can be used with drug therapy for the successful treatment of many diseases. Therapeutic nutrition is well-recognized in dogs and cats and is beginning to increase among other pet species, including rabbits. The nutritional component of some rabbit diseases (eg, urolithiasis) is not completely understood, and the clinician should evaluate the use of prescription diets based on the scientific literature and individual needs. Long-term feeding trials are needed to further evaluate the efficacy of prescription diets in rabbits. Prescription diets are available for selected diseases in rabbits, including diets for immediate-term, short-term, and long-term management. | 25,155,667 | [
-0.246764,
0.04939717,
0.1243336,
0.1503942,
0.0277103,
-0.1973161,
-0.03691108,
0.004098515,
0.1856611,
0.0260775,
0.08411696,
0.0660529,
0.03215675,
-0.03108721,
-0.4505653,
0.06219507,
-0.3088922,
0.3484539,
-0.1926679,
-0.2728322,
-0.3080614,
0.152828,
-0.2568198,
-... |
The relationship between pelvis-trunk coordination and low back pain in individuals with transfemoral amputations. | Low back pain (LBP) is common in individuals with transfemoral amputation and may result from altered gait mechanics associated with prosthetic use. Inter-segmental coordination, assessed through continuous relative phase (CRP), has been used to identify specific patterns as risk factors. The purpose of this study was to explore pelvis and trunk inter-segmental coordination across three walking speeds in individuals with transfemoral amputations with and without LBP. Nine individuals with transfemoral amputations with LBP and seven without pain were compared to twelve able-bodied subjects. Subjects underwent a gait analysis while walking at slow, moderate, and fast speeds. CRP and CRP variability were calculated from three-dimensional pelvis and trunk segment angles. A two-way ANOVA and post hoc tests assessed statistical significance. Individuals with transfemoral amputation demonstrated some coordination patterns that were different from able-bodied individuals, but consistent with previous reports on persons with LBP. The patient groups maintained transverse plane CRP consistent with able-bodied participants (p = 0.966), but not sagittal (p < 0.001) and frontal plane CRP (p = 0.001). Sagittal and frontal CRP may have been re-optimized based on new sets of constraints, such as protective rigidity of the segments, muscular strength limitations, or prosthesis limitations. Patients with amputations and without LBP exhibited few differences. Only frontal and transverse CRP shifted toward out-of-phase as speed increased in the patient group with LBP. Although a cause and effect relationship between CRP and future development of back pain has yet to be determined, these results add to the literature characterizing biomechanical parameters of back pain in high-risk populations. | 25,155,692 | [
0.155729,
0.0863977,
-0.2116902,
0.08268469,
-0.09671019,
-0.3686713,
0.05502051,
0.216531,
0.08530574,
-0.1470732,
-0.005644384,
-0.3216296,
-0.2627393,
-0.01655677,
0.1343741,
-0.2789235,
-0.403958,
-0.3418973,
-0.5050531,
0.222327,
-0.4220034,
0.02452719,
-0.09761263,
... |
Trunk sway during walking among older adults: norms and correlation with gait velocity. | The aim of this study was to establish quantitative norms for trunk sway during walking for older male and female ambulatory adults at different age groups (65-70, 71-75, 76-80, ≥81). We also assessed the relationship between dynamic trunk sway and gait velocity in older individuals with clinically normal or abnormal gaits. Trunk sway in medio-lateral (roll) and antero-posterior (pitch) planes was measured using a body-mounted gyroscope (SwayStar) during walking on a 4.5 m long instrumented walkway. Of the 284 older adults (mean age 76.8, 54.6% women) in this sample, the mean ± SD value of roll and pitch angles were 6.0 ± 2.0° and 6.7 ± 2.2° respectively. Older women showed significantly greater trunk sway in both roll and pitch angles than older men (p<0.01). In both men and women, there was no significant association of roll angle with age although gait velocity decreased with increasing age. The relationship between roll angle and gait velocity was U-shaped for the overall sample. Among the subgroup with clinically normal gait, increased roll angle was associated with increased gait velocity (p<0.001). However, there was no significant relationship between roll angle and gait velocity among the subgroup with abnormal gait. Therefore, the relationship between medio-lateral trunk sway and gait velocity differs depending on whether gait is clinically normal. We conclude that trunk sway during walking should be interpreted with consideration of both gait velocity and presence of gait abnormality in older adults. | 25,155,693 | [
-0.1945513,
0.03211335,
-0.1999284,
-0.006174571,
0.08416319,
-0.4350178,
-0.3375787,
-0.2062466,
-0.1647477,
-0.4381209,
0.02906761,
-0.3411024,
-0.1804874,
0.05833801,
-0.04897485,
0.03829597,
-0.1395635,
0.4075987,
-0.4295297,
-0.2964088,
0.030118,
0.04762444,
0.045611... |
Semi-automatic segmentation for 3D motion analysis of the tongue with dynamic MRI. | Dynamic MRI has been widely used to track the motion of the tongue and measure its internal deformation during speech and swallowing. Accurate segmentation of the tongue is a prerequisite step to define the target boundary and constrain the tracking to tissue points within the tongue. Segmentation of 2D slices or 3D volumes is challenging because of the large number of slices and time frames involved in the segmentation, as well as the incorporation of numerous local deformations that occur throughout the tongue during motion. In this paper, we propose a semi-automatic approach to segment 3D dynamic MRI of the tongue. The algorithm steps include seeding a few slices at one time frame, propagating seeds to the same slices at different time frames using deformable registration, and random walker segmentation based on these seed positions. This method was validated on the tongue of five normal subjects carrying out the same speech task with multi-slice 2D dynamic cine-MR images obtained at three orthogonal orientations and 26 time frames. The resulting semi-automatic segmentations of a total of 130 volumes showed an average dice similarity coefficient (DSC) score of 0.92 with less segmented volume variability between time frames than in manual segmentations. | 25,155,697 | [
-0.2747247,
0.2733871,
0.05721947,
0.1751001,
0.2702762,
-0.4345042,
0.1148238,
0.02109295,
0.1888862,
-0.1041946,
0.08988117,
-0.05255407,
-0.132006,
-0.3268959,
-0.6383841,
0.1478925,
-0.337959,
0.1274222,
-0.3946887,
-0.2037967,
0.3440353,
0.2582362,
-0.2359123,
0.06... |
Crescent flap for fingertip reconstruction. | A volar advancement flap based on V-Y concept for fingertip reconstruction is described. The crescent flap utilises curved incision to preserve fingertip contour and distal digital crease. Satisfactory outcome was achieved in two patients who underwent fingertip reconstruction using this technique. Its advantages are technical simplicity, minimal donor morbidity, and may be used in situation where conventional V-Y incision is unsuitable. | 25,155,705 | [
-0.09290884,
-0.01690739,
-0.289808,
-0.3251442,
0.1819674,
-0.09383729,
-0.1965467,
0.1258932,
0.1579468,
0.3182448,
0.07446941,
-0.01899132,
-0.2159688,
0.269037,
-0.3354407,
-0.4126835,
-0.00164906,
-0.009505229,
-0.1420249,
-0.2603697,
0.109433,
0.2270629,
-0.09682313... |
Lumbar spinal stenosis is a highly genetic condition partly mediated by disc degeneration. | Objective. Lumbar spinal stenosis is one of the most commonly diagnosed spinal disorders in older adults. Although the pathophysiology of the clinical syndrome is not well understood, a narrow central canal or intervertebral foramen is an essential or defining feature. The aim of the present study was to estimate the magnitude of genetic versus environmental influences on central lumbar spinal stenosis and to investigate disc degeneration and stature or bone development as possible genetic pathways.Methods. A classic twin study with multivariate analyses considering lumbar level and other covariates was conducted. The study sample comprised 598 male twins (147 monozygotic and 152 dizygotic pairs), 35-70 years of age, from the population-based Finnish Twin Cohort. The primary phenotypes were central lumbar stenosis as assessed qualitatively on magnetic resonance imaging (MRI) and quantitatively measured dural sac cross-sectional area. Additional phenotypes (to examine possible genetic pathways) included disc bulging and standing height, as an indicator of overall skeletal size or development.Results. The heritability estimate (h²) for qualitatively assessed central lumbar spinal stenosis on MRI was 66.9% (95% confidence interval [95% CI] 56.8,74.5). The broad-sense heritability estimate for dural sac cross-sectional area was 81.2% (95% CI 74.5, 86.1),with a similar magnitude of genetic influences across lumbar levels (h²=72.4–75.6). The additive genetic correlation of quantitatively assessed stenosis and disc bulging was extremely high. There was no indication of shared genetic influences between stenosis and stature.Conclusion. Central lumbar spinal stenosis and associated dural sac dimensions are highly genetic, and disc degeneration (bulging) appears to be one pathway through which genes influence spinal stenosis. | 25,155,712 | [
0.3374998,
-0.03960533,
0.2374183,
0.1415865,
-0.102701,
-0.5759877,
0.0969506,
-0.2383662,
-0.01844108,
-0.1299252,
-0.09274193,
-0.2174288,
-0.1470531,
-0.29851,
-0.161367,
-0.4085532,
-0.4448304,
0.1866161,
-0.1455122,
-0.01392695,
0.1470087,
0.3066427,
-0.007351109,
... |
Renal replacement therapy in neonates. | The incidence of acute kidney injury (AKI) has steadily increased in the last decade in neonates and infants. Despite the extensive proposed pharmacologic approaches to treat or prevent AKI, renal replacement therapy is the only available therapeutic approach to manage the consequences of significant AKI and maintain electrolyte homeostasis and fluid balance in infants with AKI. The objective of this article is to summarize the different approaches and modalities of renal replacement therapy in neonatal intensive care units. | 25,155,724 | [
-0.2262695,
-0.1982216,
-0.1595834,
-0.1727864,
0.1591816,
-0.0921647,
-0.05030078,
-0.1931016,
-0.2249012,
0.05089945,
0.101204,
0.2216296,
-0.2043049,
0.1652541,
-0.07932524,
-0.511652,
-0.3921162,
0.1354625,
-0.2635219,
-0.1716378,
0.02309635,
-0.05920757,
-0.1011168,
... |
Hematuria in the newborn. | Microscopic and gross hematuria, while rare in healthy newborns, is more common in premature infants, particularly those cared for in the neonatal intensive care unit. Hematuria may be transient, but may require evaluation, investigation, and intervention in a timely manner. This article discusses the causes, workup, and treatment of the more common forms of newborn hematuria. | 25,155,729 | [
-0.08395105,
0.2034424,
-0.3148744,
-0.04763779,
0.1031311,
-0.1210076,
-0.2103252,
-0.1633894,
-0.03709522,
-0.1436865,
0.20709,
0.6314569,
-0.2324318,
-0.2109857,
0.03964813,
-0.1040509,
-0.3535032,
0.02197607,
0.2101613,
-0.4970022,
0.1214595,
0.02827407,
-0.02175394,
... |
Nephrotic and nephritic syndrome in the newborn. | Glomerular disorders in infancy can include nephrotic and nephritic syndromes. Congenital nephrotic syndrome (CNS) is most commonly caused by single gene mutations in kidney proteins, but may also be due to congenital infections or passive transfer of maternal antibodies that target kidney proteins. Prenatal findings of increased maternal serum α-fetoprotein and enlarged placenta suggest CNS. Neonatal nephritis is rare; its causes may overlap with those of CNS and include primary glomerulonephritis, systemic disease, infections, and transplacental transfer of maternal antibodies. These syndromes in the neonate can cause significant morbidity and mortality, making urgent diagnosis and treatment necessary. | 25,155,730 | [
-0.07861456,
-0.3320124,
-0.05742386,
-0.1222952,
0.2242103,
-0.1571236,
-0.1875582,
-0.232994,
-0.07453377,
0.2029707,
0.181553,
0.3499051,
0.007272654,
0.1962424,
-0.07481725,
-0.3564596,
-0.5602636,
-0.1846587,
-0.08421544,
-0.1643041,
-0.4090212,
0.1719638,
-0.1485745... |
Diagnosis and management of urinary tract infection and vesicoureteral reflux in the neonate. | Urinary tract infection (UTI) is the most common bacterial infection in febrile newborns, particularly those born prematurely and with a low birth weight. Vesicoureteral reflux (VUR) predisposes to UTI and renal scarring. Half of neonates with UTI may have only low-grade fever or no fever. Jaundice in the absence of any other symptoms or signs may be the only clinical manifestation of UTI in neonates. The urinalysis may be negative in a significant number of neonates with UTI. Newborns with UTI have a high incidence of congenital anomalies of kidney and urinary tract anomalies, and hence should undergo renal imaging. | 25,155,732 | [
0.2053337,
-0.09335903,
-0.2714753,
-0.02324076,
0.09427806,
-0.1927842,
-0.3599045,
-0.3110533,
-0.1828088,
0.03010247,
0.4286101,
0.2475479,
-0.274821,
-0.01832535,
-0.2828115,
-0.2951869,
0.1107619,
0.2871357,
0.1463694,
-0.2696007,
0.2277497,
0.02911377,
-0.3883306,
... |
Disorders of the bladder and cloacal anomaly. | The incidence of congenital urachal, bladder, and cloacal anomalies is low. Urachal remnants are the result of failure or delay in obliteration of the allantois. Exstrophy of the bladder or cloaca can be diagnosed on prenatal ultrasonography and represent a deviation from the normal embryologic sequence. Persistent cloaca is an anomaly occurring in girls, in which a common cavity exists into which the intestinal, urinary, and reproductive tracts all open. It is also often diagnosed on prenatal imaging. | 25,155,736 | [
-0.1405503,
0.1678145,
-0.09381086,
-0.1196854,
0.4950887,
-0.06956071,
-0.4796562,
-0.241949,
-0.02901193,
-0.06975571,
0.4657587,
0.166118,
-0.2072372,
0.2797096,
-0.3310906,
-0.2576402,
-0.4617351,
0.1441069,
-0.0994066,
-0.516687,
0.002828299,
0.3085532,
-0.1662809,
... |
Neuropathic bladder in the neonate. | The management of infants born with myelomeningocele depends on understanding how their bladder stores and empties urine. Storage at low pressure with effective emptying periodically throughout the day is the goal. Intervention is designed to impact on one or both of these processes so that infants can remain infection-free and at the same time allow for appropriate renal growth over time. Urodynamic evaluation plays an important role, so that neonates can be stratified according to their risk. Most patients require intermittent catheterization and pharmacotherapy to achieve these goals at some point in their lives. | 25,155,738 | [
-0.1873848,
-0.004048789,
-0.2649145,
-0.2091858,
-0.04199026,
-0.4610888,
-0.2563217,
-0.3971649,
-0.07834351,
-0.08491669,
0.1605531,
0.07724143,
-0.2440956,
-0.09729648,
-0.3820944,
-0.1454176,
-0.1231109,
0.08994272,
-0.1778505,
-0.2600049,
0.1257769,
0.04446435,
0.02... |
Spatial and temporal organization of signaling pathways. | The development and maintenance of the many different cell types in metazoan organisms requires robust and diverse intercellular communication mechanisms. Relatively few such signaling pathways have been identified, leading to the question of how such a broad diversity of output is generated from relatively simple signals. Recent studies have revealed complex mechanisms integrating temporal and spatial information to generate diversity in signaling pathway output. We review some general principles of signaling pathways, focusing on transcriptional outputs in Drosophila. We consider the role of spatial and temporal aspects of different transduction pathways and then discuss how recently developed tools and approaches are helping to dissect the complex mechanisms linking pathway stimulation to output. | 25,155,749 | [
0.1109594,
-0.251852,
0.004424535,
-0.2441312,
-0.03919666,
-0.349791,
0.0105912,
0.08500347,
-0.1099127,
0.05380085,
0.00599441,
-0.097909,
-0.084521,
-0.1257547,
-0.64079,
-0.1981871,
-0.44279,
0.007459632,
-0.0587741,
-0.1199172,
0.295627,
0.232549,
-0.1066316,
-0.06... |
The somatic genomic landscape of chromophobe renal cell carcinoma. | We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations. | 25,155,756 | [
0.2767026,
0.1413217,
-0.1354493,
-0.2675571,
0.003735686,
-0.2130745,
-0.3202915,
0.3045815,
0.3667037,
0.2554898,
0.08001669,
0.01035553,
-0.3992081,
0.1031047,
-0.2818753,
-0.1933699,
-0.2811373,
0.01927359,
0.6084823,
-0.2776212,
0.2682838,
0.3417344,
-0.1830888,
0.... |
Colonic mucosal fatty acid synthase as an early biomarker for colorectal neoplasia: modulation by obesity and gender. | We have previously reported that colonic pericryptal microvascular blood flow is augmented in the premalignant colonic epithelium, highlighting the increased metabolic demand of the proliferative epithelium as a marker of field carcinogenesis. However, its molecular basis is unexplored. In this study, we assessed the expression of a regulator of the "lipogenic switch," fatty acid synthase (FASN), in early colon carcinogenesis for its potential biomarker utility for concurrent neoplasia. FASN expression (IHC) in the colonic epithelium from azoxymethane and polyposis in rat colon (Pirc) models of colorectal cancer was studied. FASN mRNA expression from endoscopically normal rectal mucosa was evaluated and correlated with colonoscopic findings (pathologic confirmation of neoplasia). FASN expression progressively increased from premalignant to malignant stage in the azoxymethane model (1.9- to 2.5-fold; P < 0.0001) and was also higher in the adenomas compared with adjacent uninvolved mucosa (1.8- to 3.4-fold; P < 0.001) in the Pirc model. Furthermore, FASN was significantly overexpressed in rectal biopsies from patients harboring adenomas compared with those with no adenomas. These effects were accentuated in male (∼2-fold) and obese patients (1.4-fold compared with those with body mass index < 30). Overall, the performance of rectal FASN was excellent (AUROC of 0.81). FASN is altered in the premalignant colonic mucosa and may serve as a marker for colonic neoplasia present elsewhere. The enhanced effects in men and obesity may have implications for identifying patient subgroups at risk for early-onset neoplasia. These findings support the role of rectal FASN expression as a reliable biomarker of colonic neoplasia. | 25,155,760 | [
0.1231656,
-0.3806404,
-0.3679309,
-0.3098259,
0.2144919,
-0.06534306,
-0.02840324,
-0.03383419,
0.1388779,
-0.009137796,
-0.09805003,
0.1089037,
0.1597483,
-0.08982109,
-0.4006631,
-0.254327,
-0.5403857,
-0.2711327,
0.04765546,
0.2063365,
-0.1276938,
0.352438,
-0.3781803... |
Association between the ABO blood group and risk of common cancers. | To investigate the association between five common cancers in western China population and ABO blood group. Using the data from West China Hospital, we retrospectively reviewed 5012 patients with five common cancers. Blood groups were obtained from medical records. The control group was represented by 1979 health check-up examinees. The distributions of ABO blood types of certain cancer patients were investigated to assess the possible correlation between certain cancers and the ABO blood groups. A further meta-analysis was performed based on the studied results to find potential correlation between the ABO blood types and the risk of diseases. A 24.5% increased risk was found in gastric cancer cases with blood type A when compared with those with blood type O (OR = 1.245, 95% CI 1.014 to 1.529, P = 0.036) from our data analysis. This association was further confirmed by the meta-analysis of nine studies (OR = 1.25, 95% CI = 1.12 to 1.39). Our data suggested that blood type A was associated with gastric cancer. | 25,155,765 | [
-0.2016409,
0.06601105,
-0.2350104,
-0.09147755,
0.2044801,
-0.1423178,
-0.1116764,
0.2811975,
-0.1336445,
0.3769737,
0.1940128,
0.4986959,
0.05171484,
-0.2119246,
-0.18911,
-0.07199052,
-0.101849,
0.2071226,
0.4317634,
0.01927094,
-0.0329941,
0.06158352,
-0.3217834,
0.... |
The complexity of newborn screening follow-up in phenylketonuria. | In the United States, and most developed nations, the newborn screening (NBS) panel covers many primary disorders of metabolism, including phenylketonuria (PKU). When an elevated phenylalanine level is identified, the infant is evaluated for PKU and should also be tested for tetrahydrobiopterin (BH4) deficiency. A neonate presented with a phenylalanine level of 254 μmol/L (reference range <138 μmol/L) on newborn screening. The infant's confirmatory phenylalanine was 118 μmol/L (reference range <77 μmol/L). Her urine pterin profile was normal, and initially she had no measurable activity of red blood cell (RBC) dihydropteridine reductase (DHPR). Subsequent study revealed normal levels of CSF tetrahydrobiopterin and neurotransmitter metabolites, and by 18 months of age, her RBC DHPR activity was detectable at 0.5 nmol/min/mgHgb (reference range 0.8-3.9). Sequencing of the QDPR gene for DHPR revealed c.1A>T nucleotide substitution in exon 3 expressed as "p.MET1?" Phenylalanine hydroxylase (PAH) gene sequencing revealed compound heterozygosity for L249F and A300S. Although initial testing suggested the child was affected with DHPR deficiency, further analysis, finding increasing levels of DHPR activity and PAH compound mutant heterozygosity, indicated that the primary disorder is mild hyperphenylalaninemia with carrier status for DHPR deficiency. This is an example of newborn screening results leading to confusing findings requiring extensive biochemical studies and genotyping in order to arrive at the appropriate diagnosis. | 25,155,776 | [
-0.1383555,
0.03965059,
-0.2691625,
-0.1265496,
0.3615445,
-0.1758189,
-0.1178472,
-0.08905059,
0.06544565,
0.1128257,
0.3027128,
0.5794166,
-0.425092,
0.2676827,
-0.404656,
-0.01634549,
-0.3737629,
0.3456656,
0.3779412,
-0.1126635,
0.02843896,
0.3158199,
0.1359107,
-0.... |
[Pulsed-dose rate brachytherapy in cervical cancers: why, how?]. | The end of the production of 192 iridium wires terminates low dose rate brachytherapy and requires to move towards pulsed-dose rate or high-dose rate brachytherapy. In the case of gynecological cancers, technical alternatives exist, and many teams have already taken the step of pulsed-dose rate for scientific reasons. Using a projector source is indeed a prerequisite for 3D brachytherapy, which gradually installs as a standard treatment in the treatment of cervical cancers. For other centers, this change implies beyond investments in equipment and training, organizational consequences to ensure quality. | 25,155,782 | [
-0.2854144,
-0.1449805,
-0.1971388,
0.3529213,
0.028557,
-0.3956033,
-0.05365091,
-0.003180102,
0.3671392,
0.3427223,
0.1664609,
-0.07498395,
-0.1019243,
-0.2956691,
-0.4659215,
-0.26928,
0.1045577,
0.08676036,
-0.02828851,
0.01495399,
0.6771244,
0.2434125,
0.0488998,
0... |
Linking algal growth inhibition to chemical activity: baseline toxicity required 1% of saturation. | Recently, high-quality data were published on the algal growth inhibition caused by 50 non-polar narcotic compounds, of which 39 were liquid compounds with defined water solubility. In the present study, the toxicity data for these liquids were applied to challenge the chemical activity range for baseline toxicity. First, the reported effective concentrations (EC50) were divided by the respective water solubilities (S water), since the obtained EC50/S water ratio essentially equals the effective chemical activity (Ea50). The majority of EC50/S water ratios were within the expected chemical activity range of 0.01-0.1 for baseline toxicity, and none of the ratios were significantly below 0.01. On a practical level, these findings suggest EC50 values for baseline toxicity to be at or above 1% of liquid solubility, which would have been accurate or conservative for all 39 liquids with defined water solubility in the applied dataset. On an environmental risk assessment level, predicted no-effect concentrations (PNECs) for baseline toxicity could even be set as a percentage of saturation, which can easily be extended to mixtures. However, EC50 values well below 1% of liquid saturation can still occur and would be a direct indication of excess toxicity. | 25,155,827 | [
-0.1651774,
-0.009747064,
-0.04039606,
-0.3164781,
0.1919206,
0.01295904,
0.003720918,
-0.03258168,
0.1924569,
-0.3558534,
-0.1480001,
0.01016783,
-0.04907079,
0.2212286,
-0.06080539,
0.09693446,
-0.3648151,
0.5388795,
0.09659433,
0.6523246,
0.03535657,
0.3523881,
-0.1438... |
ART and uterine pathology: how relevant is the maternal side for implantation? | Assisted reproduction technology (ART) has become a standard treatment for infertile couples. Increased success rates obtained over the years have resulted primarily from improved embryo quality, but implantation rates still remain lower than expected. The uterus, an important player in implantation, has been frequently neglected. While a number of uterine pathologies have been associated with decreased natural fertility, less information exists regarding the impact of these pathologies in ART. This report reviews the evidence to help clinicians advise ART patients. An electronic search of PubMed and EMBASE was performed to identify articles in the English, French or Spanish language published until May 2014 which addressed uterine pathology and ART. Data from natural conception were used only in the absence of data from ART. Studies were classified in decreasing categories: RCTs, prospective controlled trials, prospective non-controlled trials, retrospective studies and experimental studies. Studies included in lower categories were only used if insufficient evidence was available. Pooled data were obtained from systematic reviews with meta-analyses when available. The summary of the evidence for the different outcomes and the degree of the recommendation for interventions were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) statement recommendations. There is strong evidence that surrogacy is effective for uterine agenesia. For the remaining pathologies, however, there is very little evidence that the established treatments improve outcomes, or that these pathologies have a negative effect on ART. In the presence of an apparently normal uterus, assessing endometrial receptivity (ER) is the goal; however diagnostic tests are still under development. The real effect of different uterine/endometrial integrity pathologies on ART is not known. Moreover, currently proposed treatments are not based on solid evidence, and little can be done to assess ER in normal or abnormal conditions. No strong recommendations can be given based on the published experience, bringing an urgent need for well-designed studies. In this context, we propose algorithms to study the uterus in ART. | 25,155,826 | [
-0.0418111,
0.1154299,
0.2675487,
0.01662363,
0.2636806,
-0.02750673,
0.08089456,
-0.2575259,
0.3172924,
0.05318619,
0.05837182,
0.05807165,
-0.1808807,
-0.2426839,
-0.3491338,
-0.3409582,
-0.3740542,
0.01231787,
-0.3606075,
-0.2532991,
-0.04653042,
0.1185542,
-0.1750602,... |
Management of a major atlanto-axial instability secondary to a lytic lesion of C2. | Management of C1-C2 instability is very challenging, especially when tumoral lesions are involved. We present the case of a 65-year-old male, with a recently discovered small cell lung carcinoma, presenting progressive tetraparesis due to a secondary lesion involving the body of C2 with complete collapse of its anterior part and major C1-C2 instability in all planes. The patient underwent a reconstructive surgery of the upper cervical spine during two sessions. First, an emergency surgery was done by a high anterior cervical approach, where reconstruction of the body of C2 was done by an original technique using a C3 body to odontoid long screw with bone cement filling around the screw at the level of C2, and an anterior buttress plate put from C2 to C4. A posterior surgery was performed after 48 h to stabilize the spine posteriorly with C1 to C5 instrumentation. The patient recovered from his neurological symptoms, and underwent complementary adjuvant radiotherapy with chemotherapy later on. Literature is sparse on the treatment of major C1-C2 instability, especially when a secondary lesion is involved, the current case shows a successful treatment strategy with an original technique that was never described before in the literature. The patient was pain free at 1 year follow-up with a stable construct. | 25,155,833 | [
-0.1603401,
0.2074567,
0.30132,
-0.1790226,
-0.05474357,
-0.387876,
-0.3415004,
-0.0679028,
0.1416337,
0.1176646,
0.01633903,
-0.2418225,
-0.267561,
-0.5172977,
-0.03599992,
-0.1808654,
-0.1784865,
-0.1224768,
-0.1125597,
0.2003509,
0.1786692,
0.259167,
-0.118002,
0.037... |
AMPD1 functional variants associated with autism in Han Chinese population. | Autism is a childhood neurodevelopmental disorder with high heterogeneity. Following our genome-wide associated loci with autism, we performed sequencing analysis of the coding regions, UTR and flanking splice junctions of AMPD1 in 830 Chinese autism individuals as well as 514 unrelated normal controls. Fourteen novel variants in the coding sequence were identified, including 11 missense variants and 3 synonymous mutations. Among these missense variants, 10 variants were absent in 514 control subjects, and conservative and functional prediction was carried out. Mitochondria activity and lactate dehydrogenase assay were performed in 5 patients' lymphoblast cell lines; p.P572S and p.S626C showed decreased mitochondrial complex I activity, and p.S626C increased lactate dehydrogenase release in medium. Conclusively, our data suggested that mutational variants in AMPD1 contribute to autism risk in Han Chinese population, uncovering the contribution of mutant protein to disease development that operates via mitochondria dysfunction and cell necrosis. | 25,155,876 | [
-0.2465996,
-0.1645144,
0.03062484,
0.1221188,
0.07685373,
0.0717619,
-0.2928719,
0.4682965,
0.1317801,
-0.009826595,
-0.09959975,
0.3401525,
0.0227685,
0.1209379,
0.1127664,
0.2207823,
-0.6016715,
-0.2357291,
0.01275483,
0.1369628,
0.1261672,
0.4582848,
-0.07087041,
0.... |
Characterization of long-term in vitro culture-related alterations of human tonsil-derived mesenchymal stem cells: role for CCN1 in replicative senescence-associated increase in osteogenic differentiation. | Although mesenchymal stem cells (MSC) isolated from bone marrow and adipose tissues are known to be subjected to in vitro culture-related alterations in their stem cell properties, such data have not been reported in human tonsil-derived MSC (T-MSC). Here, we investigated the culture-related changes of phenotypes, the senescence, and the differentiation potential of T-MSC. T-MSC were serially passaged by a standard protocol, and their characteristics were assessed, including MSC-specific surface antigen profiles, the senescence, and the differentiation potentials into adipocytes, chondrocytes and osteocytes. Up to at least passage 15, we found no alterations in either MSC-specific surface marker, CD14, CD34, CD45, CD73 and CD90, or the mRNA expression of embryonic stem cell gene markers, Nanog, Oct4-A and Sox-2. However, the expression of CD146, recently identified another MSC marker, dramatically decreased with increasing passages from ~ 23% at passage 3 to ~ 1% at passage 15. The average doubling time increased significantly from ~ 38 h at passage 10 to ~ 46 h at passage 15. From passage 10, the cell size increased slightly and SA-β-gal staining was evident. Both Alizarin Red S staining and osteocalcin expression showed that the osteogenic differentiation potential increased up to passage 10 and decreased thereafter. However, the adipogenic and chondrogenic differentiation potential decreased passage-dependently from the start, as evidenced by staining of Oil Red O and Alcian Blue, respectively. Consistent with a passage-dependent osteogenic differentiation, the expression of CCN1, an angiogenic protein known to be related to both senescence and osteogenesis, also increased up to passage 10. Furthermore, ectopic expression of small interfering RNA against CCN1 at passage 10 significantly reversed Alizarin Red S staining and osteocalcin expression. Altogether, our study demonstrates the characterization of long-term in vitro cultured T-MSC and that CCN1 may be involved in mediating a passage-dependent increase in osteogenic potential of T-MSC. | 25,155,898 | [
-0.04480363,
-0.2268606,
-0.2965006,
-0.1224112,
-0.03361549,
-0.329262,
-0.2255269,
0.2095249,
0.1860295,
0.1350898,
-0.1024998,
0.1485322,
-0.06440863,
0.01881994,
-0.5246906,
0.3893871,
-0.007264879,
-0.04034314,
-0.1921639,
0.1548633,
0.2851154,
-0.04047816,
-0.181754... |
[Freehand SPECT for navigation and sentinel node detection in breast cancer]. | The sentinel lymph node (SLN) is a standard for the surgical treatment of axillary localized breast cancer N0. It is based on a double isotopic and color detection. With a gamma detecting probe connected to an infrared camera, Déclipse SPECT system (Surgiceye(®)) is able to detect and locate any radioactive source in 3D. Mobile character for use in the operating room is particularly interesting for the intraoperative detection of SLN. We illustrate its usefulness in a clinical case where the preoperative identification of SLN by lymphoscintigraphy was not informative. | 25,155,906 | [
-0.2609341,
-0.165401,
-0.1675044,
0.100901,
-0.4782936,
-0.4554262,
-0.346276,
-0.3492842,
-0.0219434,
0.1946843,
-0.02351451,
0.0938004,
0.134237,
-0.4486243,
-0.5185348,
-0.4359951,
-0.7686778,
0.1901688,
0.4034736,
0.09445231,
0.4296283,
0.1431617,
-0.1179041,
0.548... |
Ultrasound-based tracking strategy for endoluminal devices in cardiovascular surgery. | Magnetic endovascular navigation of wireless or soft-tethered endoluminal devices was recently proposed in the literature. This approach allows for innovative therapeutic procedures, but developing a real-time tracking strategy, compatible with magnetic dragging, is a challenging problem and is not yet solved. Two-dimensional (2D) imaging ultrasound (US)-based tracking algorithms applied to a platform for cardiovascular treatment, i.e. the MicroVAST platform, were implemented and tested for deriving the optimal strategy for tracking endovascular devices dragged by magnetic locomotion. The algorithm, based on the combination of Shi-Tomasi features detector, Lucas-Kanade features tracking and watershed segmentation technique, was demonstrated to be the most reliable and accurate solution for the implementation of the tracking strategy of soft-tethered endoluminal devices. Our results encourage the development of US-based tracking algorithms for endoluminal devices in cardiovascular surgery, paving the way to a robust three-dimensional (3D) imaging US-based tracking strategy implementation. Copyright © 2014 John Wiley & Sons, Ltd. | 25,155,910 | [
-0.0831985,
0.4159622,
-0.3230858,
-0.1888338,
-0.005893175,
-0.4527944,
-0.1439299,
-0.08940673,
0.0518821,
0.1545094,
0.06693421,
0.1098287,
0.00009154154,
-0.04747915,
-0.5569165,
0.3708364,
-0.8385178,
-0.09764495,
-0.2863341,
-0.09659185,
0.3546086,
0.09767666,
-0.22... |
Multiple squamous cell carcinomas following introduction of nilotinib. | Nilotinib is a second generation tyrosine kinase inhibitor, used in the treatment of chronic myelogenous leukaemia (CML). We assessed a 72-year-old woman who was treated with nilotinib for CML. During the year following commencement of nilotinib, the patient developed eight squamous cell carcinomas (SCCs) on her legs. Development of SCC is a previously unreported adverse reaction to nilotinib. | 25,155,911 | [
-0.08906313,
0.007328005,
0.01193659,
-0.5176201,
0.3033246,
0.02011131,
-0.2422121,
-0.04725959,
0.2210667,
0.1789813,
0.1098145,
0.3830113,
-0.03548051,
0.03002008,
-0.05451982,
-0.2316353,
-0.02876797,
0.1283488,
-0.232327,
-0.1375481,
0.1563807,
0.2666,
0.1066217,
0... |
Optimization of physicochemical properties and safety profile of novel bacterial topoisomerase type II inhibitors (NBTIs) with activity against Pseudomonas aeruginosa. | Type II bacterial topoisomerases are well validated targets for antimicrobial chemotherapy. Novel bacterial type II topoisomerase inhibitors (NBTIs) of these targets are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. We now disclose the optimization of a class of NBTIs towards Gram-negative pathogens, especially against drug-resistant Pseudomonas aeruginosa. Physicochemical properties (pKa and logD) were optimized for activity against P. aeruginosa and for reduced inhibition of the hERG channel. The optimized analogs 9g and 9i displayed potent antibacterial activity against P. aeruginosa, and a significantly improved hERG profile over previously reported analogs. Compound 9g showed an improved QT profile in in vivo models and lower clearance in rat over earlier compounds. The compounds show promise for the development of new antimicrobial agents against drug-resistant Pseudomonas aeruginosa. | 25,155,913 | [
0.03130213,
-0.05185875,
-0.3135653,
-0.4014227,
-0.01620913,
-0.2026988,
-0.1451923,
0.2728685,
0.1717362,
-0.3972959,
0.1773314,
0.06727037,
0.08631362,
0.1422544,
-0.5548329,
-0.3574449,
-0.6209896,
-0.04728762,
-0.2263794,
0.0317841,
0.3496083,
0.2859204,
-0.1385193,
... |
Postmortem urinary catecholamine levels with regard to the cause of death. | Previous studies suggested that serum catecholamines are useful for investigating stress responses in the death process. The present study analyzed postmortem urinary adrenaline (Ad), noradrenaline (Nad) and dopamine (DA) in serial forensic autopsy cases (n=199: 154 males and 45 females; age >9years; survival time <0.5-168h; within 10days postmortem) to investigate the differences among the causes of death with special regard to hyperthermia (heatstroke; n=11) and hypothermia (cold exposure; n=10); other cases included fatalities from injury (n=47), mechanical asphyxiation (n=18), drowning (n=14), intoxication (n=31), fire fatality (n=33) and natural death (n=35). Each catecholamine level in urine was independent of the age or gender of the subjects, postmortem interval over 10days or survival time, and did not correlate with the blood level. Urinary Adr and Nad levels were similar to those of clinical serum reference ranges, while DA was higher in all cases. Adr and Nad were higher in blunt head injury, methamphetamine abuse, hypothermia (cold exposure) and hyperthermia (heat stroke), but were low in mechanical asphyxia, drowning, fire fatality, sedative-hypnotic intoxication and acute cardiac death. DA was higher in injury, drowning, fire fatality, methamphetamine abuse and acute cardiac death, but was lower in mechanical asphyxiation and sedative-hypnotic intoxication. These profiles were quite different from those of serum levels, involving a predominant increase of DA, and may be useful for differentiating hyperthermia (heatstroke) and hypothermia (cold exposure) from drowning, sedative-hypnotic intoxication and sudden cardiac death. | 25,155,919 | [
-0.5065359,
0.1353513,
-0.3575108,
-0.08697868,
0.04405963,
-0.5447701,
-0.3169965,
-0.2288008,
-0.05896093,
0.1833334,
0.1691442,
0.3772625,
0.09531554,
0.06433058,
-0.05172825,
-0.1562043,
-0.3704606,
0.09186263,
-0.02115837,
0.2017373,
0.2135318,
-0.06312566,
-0.371081... |
Cyclosporine A regulates pro-inflammatory cytokine production in ulcerative colitis. | Crohn's disease (CD) and ulcerative colitis (UC) are the two major forms of inflammatory bowel diseases (IBD), which are defined as relapsing inflammations of the gastrointestinal tract. Cyclosporine A (CsA) is a potential rescue treatment to avoid colectomy in severe steroid-refractory UC patients. The molecular mechanism of action of CsA in UC is nevertheless still not well understood. The aim of this study was to investigate the effect of CsA on a possible modulation of cytokine production by peripheral blood mononuclear cells (PBMCs) of controls and patients with UC or CD. Upon CsA treatment, analyses of cytokine levels revealed a significant reduction of IL-13 expression in PBMCs from patients with UC, whereas other cytokine expression levels remained unaffected. To address the question whether CsA treatment impinges on the induction of cell death, apoptosis assays were performed using CD4(+) T cells from peripheral blood of patients suffering from either UC or CD. It became clear that CsA treatment resulted in a specific induction of apoptosis in samples from controls and patients with UC but not with CD. Apoptosis induction was not mediated via the mitochondrial apoptosis pathway. The present data support the concept that CsA treatment modulates pro-inflammatory cytokine production and T cell survival in UC via the induction of apoptosis and might therefore help to explain the clinical efficacy of CsA in patients with UC. | 25,155,925 | [
-0.09842237,
-0.03531218,
-0.06931709,
-0.09054575,
0.3206682,
-0.011505,
-0.04394319,
0.2639236,
0.2120055,
0.0186884,
-0.07090699,
-0.1386026,
0.2946037,
0.01385279,
-0.323972,
0.1801483,
-0.2250638,
-0.2429114,
-0.3691092,
0.3336833,
0.06921992,
0.2410868,
-0.08265072,... |
Familial risk for alcohol dependence and developmental changes in BMI: the moderating influence of addiction and obesity genes. | Familial loading for alcohol dependence (AD) and variation in genes reported to be associated with AD or BMI were tested in a longitudinal study. Growth curve analyses of BMI data collected at approximately yearly intervals and obesity status (BMI > 30) were examined. High-risk males were found to have higher BMI than low-risk males, beginning at age 15 years (2.0 kg/m(2) difference; p = 0.046), persisting through age 19 years (3.3 kg/m(2) difference; p = 0.005). CHRM2 genotypic variance predicted longitudinal BMI and obesity status. Interactions with risk status and sex were also observed for DRD2 and FTO gene variation. Variation at loci implicated in addiction may be influential in determining susceptibility to increased BMI in childhood and adolescence. | 25,155,933 | [
-0.005530235,
0.01864239,
-0.4907318,
-0.2140459,
0.04000581,
-0.377364,
-0.04251178,
-0.09021007,
-0.3313213,
0.01903088,
0.2404395,
-0.03197725,
0.1395138,
0.03117253,
-0.3106463,
-0.03851384,
-0.06009077,
0.3254566,
0.2555014,
0.1647177,
-0.06939806,
-0.04151755,
-0.27... |
Genetic epidemiology of pharmacogenetic variations in CYP2C9, CYP4F2 and VKORC1 genes associated with warfarin dosage in the Indian population. | Warfarin, a widely used anticoagulant, exhibits large interindividual variability in dose requirements. CYP2C9 and VKORC1 polymorphisms in various ethnic groups have been extensively studied as genetic markers associated with variable drug response. However, allele frequencies of these variants have not been assessed in major ethnic groups in the Indian population. To study the functional variants known to affect warfarin dosing, we reanalyzed genotype microarray datasets generated as a part of genome-wide association studies as well as data from the Indian Genome Variation database. We examined data from 2680 individuals across 24 ethnically diverse Indian subpopulations. Allelic distribution of VKORC1 (-1639G>A) showed a greater degree of variation across Indian subpopulations, with frequencies as low as 6.5% in an out-group subpopulation to >70% in Tibeto-Burmans. Risk allele frequency of CYP4F2*3 (V433M) was higher in north Indians (0.30-0.44), as compared with other world populations, such as African-American (0.12), Caucasian (0.34) and Hispanic (0.23). TheVKORC1 variant (-1639A) was shown to be prevalent amongst Tibeto-Burmans, whereas CYP2C9 (R144C, I359L) and CYP4F2 (V433M) variants were observed in considerable variability amongst Indo-Europeans. The frequency of CYP2C9*3 (I359L) in north Indians was found to be higher than in most Asian populations. Furthermore, geographical distribution patterns of these variants in north India showed an increased trend of warfarin extensive metabolizers from the Himalayan to Gangetic region. Combined allele frequency (CYP2C9*3 and CYP4F2*3) data suggest that poor metabolizers varied in the range of 0.38-1.85% in Indo-Europeans. Based on genotypic distribution, the majority of the Indian subpopulation might require higher doses for stable anticoagulation, whereas careful assessment is required for Tibeto-Burmans who are expected to have intermediate dose requirement. This is the largest global genetic epidemiological study examining variants associated with warfarin that could potentially be valuable to clinicians in optimizing dosage strategies. | 25,155,935 | [
0.3149819,
0.2385377,
0.2536752,
-0.2132805,
-0.3239488,
-0.243755,
-0.1447686,
0.2573573,
-0.008184333,
-0.04633822,
0.2533959,
0.3612323,
-0.1529994,
-0.08660212,
-0.02246841,
-0.3707603,
-0.3536454,
0.3847618,
0.520558,
-0.2221284,
-0.03426378,
0.5162895,
-0.07995507,
... |
Enteral granulocyte-colony stimulating factor and erythropoietin early in life improves feeding tolerance in preterm infants: a randomized controlled trial. | To evaluate the efficacy and safety of enteral recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEPO) in preventing feeding intolerance. An interventional randomized control trial was conducted in 90 preterm infants born at ≤33 weeks gestational age. The neonates were assigned to 4 groups; 20 received rhG-CSF, 20 received rhEPO, 20 received both, and 30 received distilled water (placebo control). The test solution was given at the beginning of enteral feeding and was discontinued when enteral intake reached 100 mL/kg/day or after a maximum of 7 days, whichever came first. Feeding tolerance and adverse effects of treatment were assessed. Serum granulocyte colony-stimulating factor and erythropoietin levels were measured on days 0 and 7 of treatment. All neonates tolerated the treatment without side effects. Neonates who received rhG-CSF and/or rhEPO had better feeding tolerance, as reflected by earlier achievement of 75 mL/kg/day, 100 mL/kg/day, and full enteral feeding of 150 mL/kg/day with earlier weight gain and a shorter hospital stay (P < .05). The risk of necrotizing enterocolitis was reduced from 10% to 0% in all treatment groups (P < .05). There was a shorter duration of withholding of feeding secondary to feeding intolerance among neonates receiving both rhG-CSF and rhEPO compared with those receiving placebo (P < .05). Serum levels of granulocyte colony-stimulating factor and erythropoietin at 0 and 7 days did not differ across the treatment groups. Enteral administration of rhG-CSF and/or rhEPO improves feeding outcome and decreases the risk of necrotizing enterocolitis in preterm neonates. The mechanism may involve the prevention of villous atrophy. | 25,155,966 | [
0.2181586,
-0.1880993,
-0.09344965,
-0.185109,
0.1962778,
-0.2179088,
0.0799097,
-0.4339585,
0.09288406,
-0.07750937,
-0.04220774,
0.08021231,
-0.4102813,
0.1855033,
0.09531604,
-0.3827098,
-0.1014205,
0.1400726,
-0.2244095,
-0.07112099,
-0.1794695,
0.1933136,
0.1413879,
... |
Structure-guided design of thiazolidine derivatives as Mycobacterium tuberculosis pantothenate synthetase inhibitors. | The pantothenate biosynthetic pathway is essential for the persistent growth and virulence of Mycobacterium tuberculosis (Mtb) and one of the enzymes in the pathway, pantothenate synthetase (PS, EC: 6.3.2.1), encoded by the panC gene, has become an appropriate target for new therapeutics to treat tuberculosis. Herein, we report nanomolar thiazolidine inhibitors of Mtb PS developed by a rational inhibitor design approach. The thiazolidine compounds were discovered by using energy-based pharmacophore modelling and subsequent in vitro screening, which resulted in compounds with a half maximal inhibitory concentration (IC50) value of (1.12 ± 0.12) μM. These compounds were subsequently optimised by a combination of modelling and synthetic chemistry. Hit expansion of the lead by chemical synthesis led to an improved inhibitor with an IC50 value of 350 nM and an Mtb minimum inhibitory concentration (MIC) of 1.55 μM. Some of these compounds also showed good activity against dormant Mtb cells. | 25,155,986 | [
0.06569428,
-0.04727387,
-0.09852879,
-0.008341963,
-0.09789561,
0.01635987,
-0.1485709,
0.3835548,
0.01954301,
-0.4527242,
0.1928058,
0.2524449,
-0.1154718,
0.1874224,
-0.4069412,
0.2129945,
-0.44979,
0.172599,
0.2068361,
0.3078285,
0.3454231,
0.4416651,
-0.2199401,
0.... |
Instrumental variable methods to assess quality of care the marginal effects of process-of-care on blood pressure change and treatment costs. | Hypertension is poorly controlled. Team-based care and changes in the process of care have been proposed to address these quality problems. However, assessing care processes is difficult because they are often confounded even in randomized behavioral studies by unmeasured confounders based on discretion of health care providers. To evaluate the effects of process measures including number of counseling sessions about lifestyle modification and number of antihypertensive medications on blood pressure change and payer-perspective treatment costs. Data were obtained from two prospective, cluster randomized controlled clinical trials (Trial A and B) implementing physician-pharmacist collaborative interventions compared with usual care over six months in community-based medical offices in the Midwest. Multivariate linear regression models with both instrumental variable methods and as-treated methods were utilized. Instruments were indicators for trial and study arms. Models of blood pressure change and costs included both process measures, demographic variables, and clinical variables. The analysis included 496 subjects. As-treated methods showed no significant associations between process and outcomes. The instruments used in the study were insufficient to simultaneously identify distinct process effects. However, the post-hoc instrumental variable models including one process measure at a time while controlling for the other process demonstrated significant associations between the processes and outcomes with estimates considerably larger than as-treated estimates. Instrumental variable methods with combined randomized behavioral studies may be useful to evaluate the effects of different care processes. However, substantial distinct process variation across studies is needed to fully capitalize on this approach. Instrumental variable methods focusing on individual processes provided larger and stronger outcome relationships than those found using as-treated methods which are subject to confounding. | 25,155,998 | [
0.1493879,
0.6128092,
-0.194114,
0.003035091,
0.08333265,
-0.5773323,
0.193885,
0.4552802,
0.1019915,
-0.2310327,
0.0381947,
0.1583525,
-0.04321848,
-0.2918604,
-0.2950828,
0.3428097,
-0.2706343,
0.08381994,
0.1203715,
0.2339348,
-0.1284915,
0.1032045,
0.03027094,
-0.04... |
Transport in technicolor: mapping ATP-binding cassette transporters in sea urchin embryos. | One quarter of eukaryotic genes encode membrane proteins. These include nearly 1,000 transporters that translocate nutrients, signaling molecules, and xenobiotics across membranes. While it is well appreciated that membrane transport is critical for development, the specific roles of many transporters have remained cryptic, in part because of their abundance and the diversity of their substrates. Multidrug resistance ATP-binding cassette (ABC) efflux transporters are one example of cryptic membrane proteins. Although most organisms utilize these ABC transporters during embryonic development, many of these transporters have broad substrate specificity, and their developmental functions remain incompletely understood. Here, we review advances in our understanding of ABC transporters in sea urchin embryos, and methods developed to spatially and temporally map these proteins. These studies reveal that multifunctional transporters are required for signaling, homeostasis, and protection of the embryo, and shed light on how they are integrated into ancestral developmental pathways recapitulated in disease. | 25,156,004 | [
-0.0006798932,
-0.3494861,
-0.04242526,
-0.05412962,
0.001032207,
-0.2801788,
-0.0682554,
0.1519251,
0.064243,
0.06423438,
0.2611722,
0.1194766,
-0.08819201,
0.1813009,
-0.2863122,
-0.2402022,
-1.047574,
0.04361372,
-0.02369613,
-0.3858707,
0.1579603,
0.1845332,
-0.350592... |
Usefulness of quantifying leukocytes in first-voided urine to predict positivity for Chlamydia trachomatis in asymptomatic men at high risk for chlamydial infection. | Chlamydia trachomatis causes acute non-gonococcal urethritis, but some infected men are asymptomatic. We examined leukocytes in uncentrifuged first-voided urine (FVU) from asymptomatic men at high risk for chlamydial infection by automated urine particle analyzers to assess whether the quantification of urinary leukocytes could predict chlamydial infection in these men. We enrolled 209 asymptomatic men, whose female sexual partners had been diagnosed as having a genital chlamydial infection. Their FVU specimens were examined for quantification of leukocytes with automated urine particle analyzers and tested for Neisseria gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum by nucleotide acid amplification tests. Eleven men positive for N. gonorrhoeae or M. genitalium were excluded from further analysis. In the remaining 198 men, 84 positive for C. trachomatis (42.4%) had 1.8-1666.9 white blood cells (WBCs)/μl (median, 43.3 WBCs/μl) in their FVU, whereas 114 negative for C. trachomatis had 0.1-1378 WBCs/μl (median, 4.8 WBCs/μl). A receiver operating characteristic (ROC) curve was constructed to examine the sensitivity and specificity of leukocytes counts for predicting chlamydial infection. A cut-off point of leukocyte counts of 12.5 WBCs/μl was determined from the ROC curve, resulting in a sensitivity of 86.9% and specificity of 88.6% for predicting chlamydial infection. Leukocyte quantification in FVU by automated urine particle analyzers showed good performance in predicting the positivity and negativity for chlamydial infection in asymptomatic men. This test could potentially develop into a relevant tool for preselecting asymptomatic men prior to C. trachomatis screening. | 25,156,010 | [
-0.2924255,
0.184565,
-0.1595647,
-0.1585796,
0.2124801,
-0.3064421,
-0.2798445,
0.09642852,
0.07121907,
-0.2506487,
0.2486808,
0.2273212,
0.1902058,
0.3421895,
-0.06868506,
-0.1808538,
-0.5259154,
0.1707054,
-0.2208509,
-0.06360567,
0.201417,
0.169035,
-0.106861,
0.068... |
The effects of Andrographis paniculata (Burm.f.) Nees extract and diterpenoids on the CYP450 isoforms' activities, a review of possible herb-drug interaction risks. | Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction. | 25,156,015 | [
-0.3404988,
-0.04639237,
-0.1305637,
0.06131379,
0.2170566,
-0.1210379,
-0.1658372,
0.3803465,
0.08129667,
-0.09522253,
-0.05266821,
-0.0949446,
-0.009271116,
-0.1963566,
-0.3744875,
0.1170842,
-0.5515639,
0.47767,
0.08662,
0.3454577,
0.2934297,
0.3598484,
-0.3074642,
0... |
[Is there overuse of neuroimaging procedures in patients with chronic migraine? An study in a Health Area in Asturias, Spain]. | There is a general perception of neuroimaging procedures overuse, mainly of CT scan, in patients with headache in Spain. To analyze the use of neuroimaging techniques, mainly CT scan as it is of free access in our region, in routine clinical practice in patients with chronic migraine (CM). We reviewed the medical records of a consecutive series of women diagnosed as CM in our headache clinic. The data on consumption of neuroimaging procedures were collected at all levels (emergency department, inpatient ward and neurologic outpatient consultation). We included 139 women with CM. A total of 106 patients (76%) had at least one CT brain scan. Twenty-eight patients (20%) had 2 or more CT scans. In 6 of these patients (21%) there was a clinical reason for repeating the studies, while there was no reason in the remaining 22 (79%). MRI had been carried out in our headache clinic in 59 patients (42%). In 43 (73%) MRI was normal, in 9 (15%) the MRI showed nonspecific lesions in the white matter and in 7 patients (11%) MRI studies were abnormal. There was no direct relationship between MRI lesion and CM. There were 15 patients with CM (11%) without any neuroimaging study. We could not find a real overuse of neuroimaging techniques in patients with CM in our health area. | 25,156,024 | [
-0.4024677,
0.1176392,
0.04480594,
0.1151157,
0.02654899,
-0.2336127,
-0.5935608,
-0.359268,
-0.2919163,
-0.3122471,
-0.06959399,
0.2885132,
-0.2088468,
-0.2212068,
-0.4666545,
-0.3558647,
-0.2964908,
0.3927153,
-0.386861,
-0.1392724,
-0.1688084,
-0.09105433,
-0.2153725,
... |
Breech-strike on mulesed, clipped and unmulesed Merino ewes and hoggets in south-eastern Australia. | Compare breech-strike on Merino ewes and hoggets that were mulesed, had breech and tail clips applied ('clipped') or left unmulesed and treated strategically with long-acting insecticide. A cohort study on two farms in southern Victoria. Three treatment groups were established at lamb marking in 2008 and 2009 on each farm. The unmulesed group was treated with a long-acting insecticide in early spring. The prevalence of breech-strike and key risk factors, including presence of dag, urine stain and breech wrinkle, were compared between groups. Breech-strike was detected from October to December on 1.9% and 7.2% of mulesed, and on 14.8% and 12.5% of clipped ewes, respectively, on each farm. Thus, clipped ewes had a relative risk of breech-strike 7.8- and 1.7-fold that of mulesed ewes. Unmulesed ewes treated with insecticide had similar or less breech-strike compared with mulesed ewes (3.4% and 1.4%), but significantly more dag, stain and breech wrinkle. From January, breech-strike on unprotected unmulesed ewes was 8.5% and 2.8%, compared with 3.5% and 0% on mulesed ewes. Early-season treatment of unmulesed sheep prevented most breech-strikes during spring and early summer on both hoggets and breeding ewes, confirming it as a short- to medium-term option for the control of breech-strike. Some benefits were associated with the use of clips but, to control breech-strike, clipped sheep should be treated the same as unmulesed sheep. Genetic selection to reduce the prevalence of dag will be required for future strategies to control breech-strike on Merino sheep in south-eastern Australia. | 25,156,054 | [
0.2108308,
0.2959924,
-0.02661073,
-0.2651283,
0.3274393,
-0.2431349,
-0.1666423,
-0.3685958,
0.1262796,
-0.1430357,
0.06522527,
-0.2846611,
0.1969445,
-0.05715531,
-0.05493657,
0.2510495,
-0.4946597,
0.29701,
0.3255458,
-0.3403381,
0.3852617,
0.4375588,
-0.2667017,
0.1... |
Production and citation of cochrane systematic reviews: a bibliometrics analysis. | To evaluate the production and utilization of Cochrane systematic reviews(CSRs) and to analyze its influential factors, so as to improve the capacity of translating CSRs into practice. All CSRs and protocols were retrieved from the Cochrane Library ISSUE 2, 2011 and citation data were retrieved from SCI database. Citation analysis was used to analyze the situation of CSRs production and utilization. CSR publication had grown from an annual average of 32 to 718 documents. Only one developing country was among the ten countries with the largest amount of publications. High income countries accounted for 83% of CSR publications and 90.8% of cited counts. 34.7% of CSRs had a cited count of 0, while only 0.9% had been cited more than 50 times. Highly cited CSRs were published in England, Australia, Canada, USA and other high income countries. The countries with a Cochrane center or a Cochrane methodology group had a greater capability of CSRs production and citing than others. The CSRs addressing the topics of diseases were more than those targeted at public health issues. There was a big gap in citations of different interventions even for the same topic. The capability of CSR production and translation grew rapidly, but varied among countries and institutions, which was affected by several factors such as the capability of research, the resourcesand the applicability of the evidence. It is important to improve evidence translation through educating, training and prioritizing the problems based on real demands of end user. This article is protected by copyright. All rights reserved. | 25,156,081 | [
-0.1579692,
0.1636535,
0.2231859,
0.009244972,
0.001608203,
0.03751846,
-0.1444007,
-0.16515,
0.06919403,
-0.1296163,
-0.01499139,
-0.1927406,
-0.02383358,
0.3879717,
0.02878058,
0.09796578,
0.08537345,
-0.1464333,
-0.3014366,
0.08553716,
-0.004969813,
0.2964073,
-0.01092... |
Interclonal gradient of virulence in the Pseudomonas aeruginosa pangenome from disease and environment. | The population genomics of Pseudomonas aeruginosa was analysed by genome sequencing of representative strains of the 15 most frequent clonal complexes in the P. aeruginosa population and of the five most common clones from the environment of which so far no isolate from a human infection has been detected. Gene annotation identified 5892-7187 open reading frame (ORFs; median 6381 ORFs) in the 20 6.4-7.4 Mbp large genomes. The P. aeruginosa pangenome consists of a conserved core of at least 4000 genes, a combinatorial accessory genome of a further 10 000 genes and 30 000 or more rare genes that are present in only a few strains or clonal complexes. Whole genome comparisons of single nucleotide polymorphism synteny indicated unrestricted gene flow between clonal complexes by recombination. Using standardized acute lettuce, Galleria mellonella and murine airway infection models the full spectrum of possible host responses to P. aeruginosa was observed with the 20 strains ranging from unimpaired health following infection to 100% lethality. Genome comparisons indicate that the differential genetic repertoire of clones maintains a habitat-independent gradient of virulence in the P. aeruginosa population. | 25,156,090 | [
-0.09829896,
-0.4784423,
-0.0769921,
-0.1029001,
-0.07436271,
0.02909549,
0.08904412,
-0.07665741,
-0.1602432,
-0.189618,
-0.08348016,
0.07220723,
-0.02551676,
-0.2210041,
-0.2236823,
-0.1083768,
-0.3002532,
-0.01782957,
0.1740632,
-0.2221741,
0.2620189,
0.226716,
0.01197... |
A technique to ensure the reproducibility of a cast post and core. | The post-and-core pattern duplication technique is a simple, cost-effective, and accurate method of ensuring the reproducibility of a cast post and core. An acrylic resin pattern is fabricated for an endodontically treated tooth. The post portion of the pattern is duplicated with a polyvinyl siloxane impression material in the lower compartment of a container. The core portion is then duplicated with a polyether impression material in the upper compartment. After the original pattern has been retrieved, the duplicate resin pattern is fabricated in the provided space. This technique will improve efficiency if damage or loss of the pattern or the actual cast post and core occurs. | 25,156,094 | [
-0.3393782,
0.8066446,
-0.01289903,
0.04304744,
0.0902096,
-0.09649453,
-0.02817098,
0.1627716,
0.5859343,
0.04390422,
-0.04438107,
0.1075158,
-0.1085102,
0.1330268,
-0.2940657,
-0.0660818,
-0.05310084,
-0.02949197,
-0.336439,
-0.2786135,
0.1102274,
0.2647975,
0.2721305,
... |
Kinesiographic study of masticatory movements in denture wearers with normal and resorbed denture-bearing areas. | An unfavorable denture-bearing area could compromise denture retention and stability, limit mastication, and possibly alter masticatory motion. The purpose of this study was to evaluate the masticatory movements of denture wearers with normal and resorbed denture-bearing areas. Completely edentulous participants who received new complete dentures were selected and divided into 2 groups (n=15) according to the condition of their denture-bearing areas as classified by the Kapur method: a normal group (control) (mean age, 65.9 ± 7.8 years) and a resorbed group (mean age, 70.2 ± 7.6 years). Masticatory motion was recorded and analyzed with a kinesiographic device. The patients masticated peanuts and Optocal. The masticatory movements evaluated were the durations of opening, closing, and occlusion; duration of the masticatory cycle; maximum velocities and angles of opening and closing; total masticatory area; and amplitudes of the masticatory cycle. The data were analyzed by 2-way ANOVA and the Tukey honestly significant difference post hoc test (α=.05). The group with a resorbed denture-bearing area had a smaller total masticatory area in the frontal plane and shorter horizontal masticatory amplitude than the group with normal denture-bearing area (P<.05). Denture wearers with resorbed denture-bearing areas showed reduced jaw motion during mastication. | 25,156,095 | [
0.03615102,
0.2385465,
-0.1245931,
0.0630038,
0.08964533,
-0.6732754,
-0.005408385,
0.1390109,
-0.1493693,
-0.5833065,
0.1051945,
0.02859566,
-0.2812581,
-0.05217587,
-0.7341552,
-0.08180102,
-0.5982472,
0.2034309,
-0.3707515,
-0.5968452,
-0.1511315,
-0.03118377,
0.157528... |
Bridle procedure combined with a subtalar implant: a case series and review of the literature. | The bridle procedure is a tritendon anastomosis between the tibialis posterior, peroneus longus, and tibialis anterior, utilized in the treatment of drop foot. Concerned about the potential for acquired flatfoot deformity following the bridle procedure, the authors hypothesized that placing a sinus tarsi implant would prevent this potential sequela. Over a 10-year period, 15 patients (16 feet) were treated with a bridle procedure for drop foot, and 9 of these feet also had a subtalar arthroereisis implanted; 8 patients (9 feet) positively responded to requests for long-term follow-up evaluation and returned for subjective evaluation with the American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot Scale and Short Form (SF)-36 forms and objective clinical and radiographic measurements. At an average follow-up of 61 months, the 8 patients (9 feet) who returned for long-term evaluation maintained a plantigrade foot, were able to dorsiflex above neutral both actively and passively, and did not develop a flatfoot deformity at long-term follow-up. There were no significant differences between those who had a sinus tarsi implant (6 feet) and those who did not (3 feet). Although 7 of the 9 feet evaluated in this study wore a brace preoperatively, none continued to use a brace after surgery. The major complaints were occasional pain at the subtalar arthroereisis site and a feeling that the great toe was dragging. The bridle procedure provided excellent outcomes in patients with drop foot, with patients achieving long-term success in being free from brace wear. The ability to actively dorsiflex the foot during gait was also restored, reestablishing a normal heel-to-toe gait pattern. Therapeutic, Level IV: Case series. | 25,156,098 | [
-0.2831801,
0.1827265,
-0.1985314,
-0.08148466,
0.1505121,
-0.3401268,
-0.2546287,
0.07344179,
-0.2397215,
-0.1435738,
0.03980241,
-0.4702478,
-0.06647623,
-0.2733713,
-0.3232493,
-0.3652035,
0.02193068,
-0.08391392,
-0.009744169,
-0.06920325,
-0.4580201,
-0.05760946,
-0.... |
A dually located multi-HMG-box protein of Aspergillus nidulans has a crucial role in conidial and ascospore germination. | Seven HMG-box proteins of Aspergillus nidulans have been identified in the genomic databases. Three of these have the characteristics of non-specific DNA-binding proteins. One of these, AN1267 (HmbB), comprises one canonical HMG-box in its C-terminus and upstream of the canonical box two structurally related boxes, to be called Shadow-HMG-boxes. This protein defines, together with the Podospora anserina mtHMG1, a clade of proteins present in the Pezizomycotina, with orthologues in some of the Taphrinomycotina. HmbB localizes primarily to the mitochondria but occasionally in nuclei. The deletion of the cognate gene results in a number of pleiotropic effects, including those on hyphal morphology, sensitivity to oxidative stress, absence of sterigmatocystin production and changes in the profile of conidial metabolites. The most striking phenotype of deletion strains is a dramatic decrease in conidial and ascospore viability. We show that this is most likely due to the protein being essential to maintain mitochondrial DNA in spores. | 25,156,107 | [
-0.02428905,
-0.2047158,
-0.1568411,
-0.5912763,
-0.09561048,
0.1199926,
0.09129351,
-0.2205726,
0.2028124,
-0.313147,
-0.2044361,
-0.2097665,
0.1345531,
0.02503845,
-0.426612,
0.4165618,
-0.4025776,
-0.1909072,
0.02383806,
-0.04502743,
0.3217147,
0.3077093,
-0.006730301,... |
Molecular mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene on HL-60 leukemia cells. | The aim of this work was to investigate the mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene (1) on HL-60 human leukemia cells. While inactive against noncancerous cells, 1 provoked a concentration-dependent decrease in viable tumor cells, primarily via apoptosis, as evidenced by analysis of cell morphology, activation of caspases 3 and 7, increased DNA fragmentation, and externalization of phosphatidylserine. Necrosis was observed only at the highest tested concentration (4 μM). Compound 1 interfered with the cell cycle, causing an accumulation of cells in the G1 /G0 phase. Interaction of 1 with dsDNA and ssDNA was observed by differential pulse voltammetry and confirmed by hyperchromicity in the UV/Vis spectra of dsDNA, with an interaction constant of 2×10(4) M(-1). Both the organic analogue 1,1,2-triphenylbut-1-ene (2) and ferrocene were inactive against cancer and noncancer cell lines and did not react with DNA. These results reinforce the idea that the hybrid strategy of conjugating ferrocene to the structure of tamoxifen derivatives is advantageous in finding new substances with antineoplastic activity. | 25,156,124 | [
-0.4275932,
0.1026222,
-0.0143817,
-0.09393995,
0.1274931,
-0.1300866,
0.07361063,
-0.1123746,
0.2287783,
0.3839321,
-0.3208085,
0.379695,
-0.4283773,
-0.007707753,
-0.771875,
-0.2595733,
-0.324627,
-0.07195222,
-0.1408081,
0.505608,
0.6516113,
0.3415205,
-0.2038071,
0.... |
Capability of new bone formation with a mixture of hydroxyapatite and beta-tricalcium phosphate granules. | The aim of this experimental study was to test a mixture of hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP) granules inserted in cranial defects in rabbits, by the evaluation of the hard tissues volume, new bone formation, and residual graft after 4 and 8 weeks. Two defects of 8 mm diameter were created at the calvarial bone of 24 Japanese white rabbits for a total of 48 defects. Four groups were created: defects filled with a mixture of HA and beta-TCP granules (test A), defects filled with HA alone (test B), defects filled with beta-TCP (test C), and empty defects (control). Hard tissues volume (remaining graft + new bone) was evaluated by μ-CT and new bone (NB) and remaining graft (RG) percentages were evaluated by histomorphometry. The animals were sacrificed at 4 or 8 weeks postoperatively. The test groups A, B, and C showed a significant higher total volume compared with controls at 4 and 8 weeks (P < 0.05). Regarding the percentages of NB and RG at 4 and 8 weeks, no significant differences were detected (P > 0.05). When comparing 4 and 8 weeks, test group A showed a significant increase in new bone formation. At both 4 and 8 weeks, no group showed significant differences in NB (P > 0.05). At 8 weeks, test group B had more RG than test group A. The novel mixture could maintain the volume of the grafted area compared with that with intervention, and in a similar way compared with HA. | 25,156,136 | [
-0.09746494,
0.212608,
-0.09035165,
-0.1018517,
-0.1551434,
-0.4409973,
-0.08134298,
0.08342334,
0.1569681,
-0.02724152,
0.04299146,
0.157384,
-0.2967658,
-0.1865951,
-0.7754692,
-0.200276,
-0.1589082,
0.05641809,
0.2970018,
0.03654688,
0.1270462,
0.2255653,
0.1534768,
... |
Corneal abnormalities early in the course of Fuchs' endothelial dystrophy. | Corneas with advanced Fuchs' endothelial dystrophy that require endothelial keratoplasty manifest anterior corneal structural and cellular abnormalities that have been associated with visual deficits before and after endothelial keratoplasty. In this study, we determined the onset of these abnormalities in the course of the disease. Cross-sectional study. Sixty-three eyes (39 subjects) with a range of severity of Fuchs' dystrophy and 25 eyes (13 subjects) with normal corneas. All corneas were examined using slit-lamp biomicroscopy, ultrasonic pachymetry, and confocal microscopy. The clinical grade of Fuchs' dystrophy was assessed according to the presence and extent of guttae and clinically evident edema and was categorized as mild (grades 1 and 2), moderate (grades 3 and 4), or advanced (grades 5 and 6). Normal corneas were devoid of any central guttae (grade 0). Corneal backscatter (haze) was measured from the confocal image light intensity profile. Stromal cell density and number and the presence of abnormal subepithelial cells were determined from confocal images. Comparisons between groups were made by using generalized estimating equation models. Anterior corneal backscatter, stromal cell density and number, presence of subepithelial cells, and central corneal thickness. Anterior corneal backscatter was 18% to 67% higher in eyes with moderate and advanced Fuchs' dystrophy compared with normal eyes (P ≤ 0.003); a similar trend was noted in mild Fuchs' dystrophy eyes compared with normal eyes (P = 0.08). Stromal cell density and the absolute number of stromal cells in the anterior 10% of the stroma were approximately 20% and 27% lower, respectively, in Fuchs' dystrophy (regardless of severity) compared with normal (P < 0.001). Abnormal subepithelial cells were visible in 9%, 19%, and 30% of corneas with mild, moderate, and advanced Fuchs' dystrophy, respectively. Only corneas with advanced Fuchs' dystrophy were thicker than normal (P < 0.001). Anterior corneal cellular and structural abnormalities begin early in the course of Fuchs' dystrophy, before the onset of clinically evident edema. The chronicity of these changes can explain their incomplete resolution after endothelial keratoplasty, and understanding the onset of these may help to determine the optimal time to intervene to achieve best outcomes. | 25,156,138 | [
0.01048251,
-0.06182687,
-0.2255278,
-0.2599132,
0.2428358,
-0.2587357,
0.1116158,
0.2359194,
0.2120761,
0.04383318,
-0.08083519,
-0.4458994,
-0.5776437,
-0.1129916,
0.1547338,
0.03403581,
-0.3713916,
-0.04107594,
0.1004139,
0.04472706,
0.05861597,
0.5536441,
0.06046367,
... |
Simulation in the Internet age: the place of web-based simulation in nursing education. An integrative review. | The objective of this article was to review the literature on utilisation and place of Web-based simulation within nursing education. Web-based simulation combines electronic multimedia options with a central video or virtual world to produce interactive learning activities mediated by the learner. An integrative review. A search was conducted of healthcare databases between 2000 and 2014 and of Internet sources for hosted simulation programs in nursing. Eighteen primary programs were identified for inclusion. A strategy for integrative review was adopted in which studies were identified, filtered, classified, analysed and compared. Of 18 programs, two game-based programs were identified which represented a 'virtual world' in which students could simultaneously or individually immerse themselves in a character role-play. However, most programs (n=10) taught an aspect of procedural patient care using multimedia (e.g. video, audio, graphics, quiz, text, memo). Time-limited sequences, feedback and reflective activities were often incorporated. Other studies (n=8) taught interpersonal communication skills or technical skills for equipment use. Descriptive study outcomes indicated ease of program use, strong satisfaction with learning and appreciation of program accessibility. Additionally, four studies reported significant improvements in knowledge post-intervention. Web-based simulation is highly acceptable to students and appears to provide learning benefits that align with other simulation approaches and it augments face-to-face teaching. Web-based simulation is likely to have a major place in nursing curricula in the next decade, yet further research is necessary to objectively evaluate learner outcomes and to justify its use. | 25,156,144 | [
-0.2511936,
0.0371634,
-0.3379029,
-0.1964902,
0.02331865,
0.0515517,
0.2387157,
-0.2720978,
-0.06773793,
0.03890127,
0.09276949,
0.2705797,
-0.2983686,
-0.3635893,
-0.09843805,
-0.202476,
-0.2249642,
0.3014174,
-0.2308513,
-0.4697096,
0.4106453,
0.1668714,
-0.1308602,
... |
Substrate binding activates the designed triple mutant of the colicin E7 metallonuclease. | The nuclease domain of colicin E7 (NColE7) cleaves DNA nonspecifically. The active center is a Zn(2+)-containing HNH motif at the C-terminus. The N-terminal loop is essential for the catalytic activity providing opportunity for allosteric modulation of the enzyme. To identify the key residues responsible for the structural integrity of NColE7, a virtual alanine scan was performed on a semiempirical quantum chemical level within the 25 residue long N-terminal sequence (446-470). Based on the calculations the T454A/K458A/W464A-NColE7 triple mutant (TKW) was expressed and purified. According to the agarose gel electrophoresis experiments and linear dichroism spectra the catalytic activity of the TKW mutant decreased in comparison with wild-type NColE7. The distorted structure and weakened Zn(2+) binding may account for this as revealed by circular dichroism spectra, mass spectrometry, fluorescence-based thermal analysis and isothermal microcalorimetric titrations. Remarkably, the substrate induced the folding of the mutant protein. | 25,156,149 | [
-0.2555187,
0.01328095,
-0.4914758,
-0.02792859,
-0.1031391,
-0.06148491,
-0.06575985,
0.2724994,
0.2357753,
0.09616456,
0.09783013,
0.2520903,
0.1604583,
-0.293386,
-0.5408042,
0.1504298,
-0.7686283,
0.07693151,
-0.3005622,
0.07857852,
0.1395096,
0.0695454,
0.01937811,
... |
Multifaceted interplay between lipophilicity, protein interaction and luminescence parameters of non-intercalative ruthenium(II) polypyridyl complexes controlling cellular imaging and cytotoxic properties. | Here, we examine the photophysical properties of five ruthenium(II) complexes comprising two 4,7-diphenyl-1,10-phenanthroline (dip) ligands and functionalized bipyridine (R₁bpy-R₂, where R₁= H or CH3, R₂= H, CH₃, COO⁻,4-[3-(2-nitro-1H-imidazol-1-yl)propyl] or 1,3-dicyclohexyl-1-carbonyl-urea) towards development of luminescence probes for cellular imaging. These complexes have been shown to interact with albumin and the formed adducts exhibited up to eightfold increase in the luminescence quantum yield as well as the average lifetime of emission. It was demonstrated that they cannot bind to DNA through the intercalation mode and its luminescence in the presence of DNA is quenching. Cell viability experiments indicated that all complexes possess significant dose-dependent cytotoxicity (with IC₅₀ 5-19 μM) on 4T1 breast cancer cell line and their anti-proliferative activity correlates very well with their lipophilicity. Cellular uptake was studied by measuring the ruthenium content in cells using ICP-MS technique. As expected, the better uptake is directly related to higher lipophilicity of doubly charged ruthenium complexes while uptake of monocationic one is much lower in spite of the highest lipophilicity. Additionally staining properties were assessed using flow cytometry and fluorescence microscopy. These experiments showed that complex with 1,3-dicyclohexyl-1-carbonyl-urea substituent exhibits the best staining properties in spite of the lowest luminescence quantum yield in buffered solution (pH 7.4). Our results point out that both the imaging and cytotoxic properties of the studied ruthenium complexes are strongly influence by the level of internalization and protein interaction. | 25,156,150 | [
-0.2644176,
-0.1454572,
0.09333046,
0.1105638,
-0.03829535,
0.01527286,
-0.1128784,
-0.07526726,
0.4278124,
0.2740333,
-0.1273783,
0.1614405,
-0.2786885,
-0.06418926,
-0.7462519,
-0.193036,
-0.2650558,
0.1791348,
-0.09972052,
0.1253559,
0.2474232,
0.2076187,
0.09501978,
... |
Home blood pressure and cardiovascular outcomes in patients during antihypertensive therapy: primary results of HONEST, a large-scale prospective, real-world observational study. | This study aimed to investigate the relationship between on-treatment morning home blood pressure (HBP) and incidence of cardiovascular events using data from the Home Blood Pressure Measurement With Olmesartan Naive Patients to Establish Standard Target Blood Pressure (HONEST) study, a prospective observational study of 21 591 outpatients with essential hypertension (mean age, 64.9 years; women, 50.6%) enrolled between 2009 and 2010 at clinics and hospitals in Japan. They received olmesartan-based treatment throughout. The primary end point was major cardiovascular events. After a mean follow-up period of 2.02 years, cardiovascular events occurred in 280 patients (incidence, 6.46/1000 patient-years). The risk for the primary end point was significantly higher in patients with on-treatment morning HBP ≥145 to <155 mm Hg (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.12-2.99) and ≥155 mm Hg (HR, 5.03; 95% CI, 3.05-8.31) than <125 mm Hg and with on-treatment clinic blood pressure ≥150 to <160 mm Hg (HR, 1.69; 95% CI, 1.10-2.60) and ≥160 mm Hg (HR, 4.38; 95% CI, 2.84-6.75) than <130 mm Hg. Morning HBP associated with minimum risk was 124 mm Hg by spline regression analysis. Cardiovascular risk was increased in patients with morning HBP ≥145 mm Hg and clinic blood pressure <130 mm Hg (HR, 2.47; 95% CI, 1.20-5.08) compared with morning HBP <125 mm Hg and clinic blood pressure <130 mm Hg. In conclusion, it is essential to control morning HBP to <145 mm Hg, even in patients with controlled clinic blood pressure. http://www.umin.ac.jp/ctr/index.htm. UMIN Clinical Trials Registry, trial No. UMIN000002567. | 25,156,169 | [
-0.05537322,
0.3763887,
-0.2494084,
-0.3008778,
-0.1042948,
-0.2162229,
-0.1301161,
-0.05079879,
0.2354592,
-0.4835042,
0.0729539,
0.3331389,
0.3446447,
-0.0884385,
-0.6394731,
-0.06277835,
-0.1178775,
0.5108348,
0.09024352,
0.1168686,
-0.1504009,
0.03262369,
-0.1631356,
... |
New agar microspheres for the separation and purification of natural products. | A new type of agar chromatography media has been prepared with a yield over 80% using a water-in-oil emulsion technique. These microspheres have regular spherical shapes and particle diameters in the range 40-165 μm (average ∼90 μm). Cross-linking of the resulting agar microspheres with epichlorohydrin and 1,4-butanediol diglycidyl ether enhanced their mechanical and thermal stability. The alkaline conditions used during the cross-linking reaction also decreased the content of ionized sulfate groups of the polysaccharide, thus reducing the nonspecific adsorption of positively charged molecules. The cross-linked agar microspheres were functionalized with (i) branched poly(ethyleneimine) to obtain a stationary phase useful for the separation of proteins in an anion-exchange mode and (ii) with poly-β-cyclodextrin enabling direct isolation and purification of puerarin from a crude extract of Radix puerariae. Using a 23.5 mL column loaded with 20 mg extract (0.85 mg/mL gel), puerarin with a purity of 96% was recovered with a yield of 86%. | 25,156,195 | [
-0.3784863,
0.3983201,
0.2498108,
-0.07180237,
0.2331289,
-0.09985074,
-0.2429191,
-0.07569516,
0.3270657,
0.1586319,
0.01702676,
-0.09499869,
-0.1054583,
-0.02687552,
-0.2768025,
0.1189464,
-0.4107551,
0.0473881,
0.1061769,
0.1484103,
0.515883,
0.03482265,
-0.1063324,
... |
Validation of the LupusPRO in Chinese patients from Hong Kong with systemic lupus erythematosus. | LupusPRO is a disease-targeted, patient-reported outcome (PRO) measure that was developed and validated for assessment of quality of life in US patients with systemic lupus erythematosus (SLE). We present results of adapting the LupusPRO into Chinese and testing its psychometric properties in Chinese patients with SLE. LupusPRO was translated into "traditional" Chinese, followed by pretesting among native Cantonese Chinese speakers. The translation version was revised based on the feedback obtained. The Chinese language LupusPRO tool was administered along with a generic PRO tool (the Short Form 36 health survey [SF-36]) to ethnic Chinese SLE patients. At the same time, demographic information, clinical data, disease activity (Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]), and damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]) were obtained. We performed confirmatory factor analysis of the Chinese LupusPRO and evaluated internal consistency reliability, as well as convergent and criterion validity. Among the 463 SLE patients (95% women) with a mean ± SD age of 42.3 ± 13.5 years, the mean ± SD physician global assessment score was 0.48 ± 0.45, the mean ± SD SELENA-SLEDAI score was 2.9 ± 3.0, and the mean ± SD SDI score was 0.7 ± 1.2. Results of factor analysis conformed to the original LupusPRO model with only minor modifications. The reliability of the LupusPRO domains ranged from 0.60-0.94. LupusPRO domains had correlations as expected with the corresponding SF-36 domains. A significant but weak correlation with disease activity was noted for criterion validity as expected. The Chinese language LupusPRO has fair psychometric properties and may be used in SLE clinical trials. | 25,156,199 | [
0.01465475,
0.09465002,
0.2546684,
0.0368821,
-0.1234101,
-0.1500122,
-0.2237535,
0.2425639,
0.3166994,
-0.02779294,
0.07233981,
-0.1203152,
0.05413716,
-0.1091416,
0.3408793,
-0.06153652,
-0.155843,
-0.1698738,
-0.1403516,
0.3735943,
-0.2608152,
0.3099846,
-0.277903,
-... |
Small RNA deep sequencing identifies novel and salt-stress-regulated microRNAs from roots of Medicago sativa and Medicago truncatula. | Small 21- to 24-nucleotide (nt) ribonucleic acids (RNAs), notably the microRNA (miRNA), are emerging as a posttranscriptional regulation mechanism. Salt stress is one of the primary abiotic stresses that cause the crop losses worldwide. In saline lands, root growth and function of plant are determined by the action of environmental salt stress through specific genes that adapt root development to the restrictive condition. To elucidate the role of miRNAs in salt stress regulation in Medicago, we used a high-throughput sequencing approach to analyze four small RNA libraries from roots of Zhongmu-1 (Medicago sativa) and Jemalong A17 (Medicago truncatula), which were treated with 300 mM NaCl for 0 and 8 h. Each library generated about 20 million short sequences and contained predominantly small RNAs of 24-nt length, followed by 21-nt and 22-nt small RNAs. Using sequence analysis, we identified 385 conserved miRNAs from 96 families, along with 68 novel candidate miRNAs. Of all the 68 predicted novel miRNAs, 15 miRNAs were identified to have miRNA*. Statistical analysis on abundance of sequencing read revealed specific miRNA showing contrasting expression patterns between M. sativa and M. truncatula roots, as well as between roots treated for 0 and 8 h. The expression of 10 conserved and novel miRNAs was also quantified by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The miRNA precursor and target genes were predicted by bioinformatics analysis. We concluded that the salt stress related conserved and novel miRNAs may have a large variety of target mRNAs, some of which might play key roles in salt stress regulation of Medicago. | 25,156,209 | [
-0.1090331,
0.1584388,
0.07821783,
-0.07410146,
0.1552794,
-0.197855,
-0.3952701,
-0.1168458,
0.06021411,
-0.7247371,
-0.02915143,
0.01416763,
0.1160194,
-0.1730508,
-0.01740217,
-0.00985873,
-0.1286866,
0.5317501,
0.1515222,
-0.1196755,
0.2929576,
0.1517674,
-0.02688433,... |
Gender differences and patterns of cardiovascular risk factors in Type 1 and Type 2 diabetes: a population-based analysis from a Scottish region. | To explore the gender differences, along with the relationships between BMI, glycaemic control, cardiovascular risk factors and the prevalence of diabetes complications, in a representative population-based group of people with Type 1 and Type 2 diabetes. Data were obtained from general practices in Ayrshire and Arran, Scotland for 15 351 patients. In the cohort with Type 1 diabetes, after adjustment for age, men had a significantly lower BMI (P = 0.007) and significantly lower total cholesterol (P = 0.005), HDL-cholesterol (P = 2.5*10(-17)) and HbA1c levels (P = 0.003) than women. By contrast, men had higher blood pressure, both systolic (P = 0.034) and diastolic (P = 0.0003), and higher non-fasting triglyceride levels (P = 0.001). Men with Type 1 diabetes had a higher prevalence of neuropathy (P = 0.021). Among people with Type 2 diabetes, men had a significantly lower BMI (P = 4.26*10(-37)), and significantly lower total cholesterol (P = 2.96*10(-62)) and HDL-cholesterol levels (P = 8.25*10(-141)) but higher non-fasting triglyceride levels (P = 0.0002). In Type 2 diabetes, men had a higher prevalence of ischaemic heart disease (P = 1.66*10(-25)), stroke (P = 0.002) and peripheral vascular disease (P = 1.68*10(-12)), while women were older (P = 4.83*10(-23)), heavier and had a higher prevalence of hypertension (P = 5.32*10(-12)). More people with Type 2 diabetes were on lipid-lowering treatment (84.7 vs 52.4%; P = 5.51*10(-8)) than were those with Type 1 diabetes. The prevalence of retinopathy was higher among non-smokers thank smokers in people with both Type 1 and Type 2 diabetes (Type 1, P = 0.016; Type 2, P = 0.001). The study shows gender differences between Type 1 and 2 diabetes that are of clinical significance and require further investigation. Follow-up of the patients included in the present study should give us much greater understanding of the importance of gender in the development of metabolic abnormalities and diabetes complications. | 25,156,218 | [
-0.1097363,
0.01092708,
-0.4951421,
-0.4295747,
-0.1369714,
-0.444407,
0.04697426,
0.001698416,
0.09512416,
-0.1987207,
0.1074411,
0.3564025,
0.09785012,
-0.1837044,
0.1200974,
-0.2551051,
-0.2420832,
0.2051648,
-0.006003563,
0.1384881,
-0.3043211,
0.5056906,
-0.183724,
... |
Variation in malariometric and red cell indices in children in the Mount Cameroon area following enhanced malaria control measures: evidence from a repeated cross-sectional study. | Following enhanced malaria control measures, such as nationwide free distribution of insecticide-treated bed nets (ITN) by the government of Cameroon, its impact on malariometric and red cell indices in children ≤14 years in Muea, in the Mount Cameroon area was evaluated. Two cross-sectional studies were conducted during the malaria transmission season (March-July) in 2006 (baseline) and 2013 (follow-up), respectively. The investigative methods included the use of a questionnaire to assess ITN use and coverage, clinical evaluation and laboratory investigations. Blood sample collected from each child was used for the preparation of blood films for detection of malaria parasites and density as well as full blood count determination using standard procedures and also an automated haematology analyzer. The majority of children (81.5%) possessed an ITN in 2013. The proportion of effective users of ITN increased significantly from 20.9% (CI = 17.3-25%) in 2006 to 35.2% (CI = 31-39.7%) in 2013. The highest relative risk reduction in prevalence during the follow-up study was observed in malaria anaemia (79%, CI = 58.0-69.1% [69.1 to 14.5%]), followed by gametocytaemia (71.6%, CI = 58.9-80.3% [25.6 to 7.3%]), anaemia (64%, CI = 58.0-69.1% [80.1 to 28.9%]), and malaria parasitaemia (57.2%, CI = 51.4-62.3% [85.4 to 36.6%]). In the baseline survey, the prevalence of splenomegaly was significantly highest (χ2 = 18.3, P <0.001) in the youngest group of children while in the follow-up study, it was highest in the oldest (χ2 = 6.03, P = 0.049). The overall prevalence of mild, moderate and severe anaemia in the study population at baseline (59.6, 14.9, 6.3%) decreased significantly (P <0.001) to 24.4, 2.7 and 1.3%, respectively during the follow-up with the highest relative risk reduction in prevalence occurring in moderate anaemia (82.1%, CI = 67.3-90.2% [14.9 to 2.7%]). Microcytic anaemia also decreased significantly (P <0.001) from 56 to 7.7% during the follow-up survey. Following interventions, anaemia (moderate to severe) was a more sensitive measure to changes in malaria exposure and children between 11-14 years of age experienced a significant increase in malaria-related morbidity. | 25,156,237 | [
-0.002789608,
0.04422523,
0.3571248,
-0.06290332,
0.008023715,
-0.08377247,
0.05006773,
-0.06126286,
-0.0934894,
-0.0780936,
0.1464539,
-0.009932403,
0.08815293,
0.1907331,
-0.5196639,
0.01477531,
-0.1815527,
-0.1711265,
-0.08506063,
0.2779098,
0.02113279,
0.2538381,
-0.2... |
Efficiency of irrigation water application in sugarcane cultivation in Pakistan. | Diminishing irrigation water supplies are threatening the sustainability of irrigated agriculture in Pakistan. Within the context of dwindling water resources and low agricultural water productivity, it is imperative to improve efficiency in agricultural production and to make efficient use of available water resources. This study employs a non-parametric approach to estimate the extent of technical and irrigation water efficiency in sugarcane cultivation in Pakistan. The mean technical efficiency score is 0.96 for tube-well owners whereas it is 0.94 for water buyers. The mean irrigation water efficiency score is 0.86 for tube-well owners whereas it is 0.72 for water buyers. We find that across all farms, 59% of the tube-well owners and 45% of the water buyers are fully technically efficient, whereas only 36% of the tube-well owners and 30% of the water buyer are fully efficient in irrigation water use. This study finds that sugarcane growers are operating at fairly high technical efficiency levels. But, there is considerable potential to improve irrigation water efficiency. This study proposes expanding the role of agricultural extension services from merely agronomic grounds to guide farmers to undertake cost benefit analysis of the available production technology, would help achieve higher efficiency levels. | 25,156,252 | [
0.003703092,
0.130537,
0.205548,
-0.1499564,
-0.3016908,
-0.2815065,
-0.1760037,
-0.003425577,
-0.03321555,
-0.1565729,
0.06581497,
-0.05156688,
-0.4898624,
0.1156949,
0.1265475,
0.04289077,
-0.2112613,
0.3506699,
-0.4282146,
-0.1905855,
0.1668165,
0.4529818,
0.1070422,
... |
Quantitative risk assessment of haemolytic and uremic syndrome linked to O157:H7 and non-O157:H7 Shiga-toxin producing Escherichia coli strains in raw milk soft cheeses. | Shiga-toxin producing Escherichia coli (STEC) strains may cause human infections ranging from simple diarrhea to Haemolytic Uremic Syndrome (HUS). The five main pathogenic serotypes of STEC (MPS-STEC) identified thus far in Europe are O157:H7, O26:H11, O103:H2, O111:H8, and O145:H28. Because STEC strains can survive or grow during cheese making, particularly in soft cheeses, a stochastic quantitative microbial risk assessment model was developed to assess the risk of HUS associated with the five MPS-STEC in raw milk soft cheeses. A baseline scenario represents a theoretical worst-case scenario where no intervention was considered throughout the farm-to-fork continuum. The risk level assessed with this baseline scenario is the risk-based level. The impact of seven preharvest scenarios (vaccines, probiotic, milk farm sorting) on the risk-based level was expressed in terms of risk reduction. Impact of the preharvest intervention ranges from 76% to 98% of risk reduction with highest values predicted with scenarios combining a decrease of the number of cow shedding STEC and of the STEC concentration in feces. The impact of postharvest interventions on the risk-based level was also tested by applying five microbiological criteria (MC) at the end of ripening. The five MCs differ in terms of sample size, the number of samples that may yield a value larger than the microbiological limit, and the analysis methods. The risk reduction predicted varies from 25% to 96% by applying MCs without preharvest interventions and from 1% to 96% with combination of pre- and postharvest interventions. | 25,156,259 | [
-0.1709456,
0.07002266,
0.2103771,
0.123946,
0.0996803,
-0.1335191,
0.2973621,
0.08352901,
0.05246667,
-0.4071965,
-0.1787453,
0.1455732,
0.01009197,
0.03816516,
-0.6514828,
-0.07309099,
-0.2014775,
0.1466631,
0.1570262,
-0.432936,
0.03491145,
0.4858691,
-0.1813312,
-0.... |
Process development for recovery of vanadium and nickel from an industrial solid waste by a leaching-solvent extraction technique. | A process for recovering V(V) and Ni(II) from an industrial solid waste using sulfuric acid leaching, solvent extraction, precipitation and crystallization has been developed. The leaching parameters investigated were time, temperature and H2SO4 concentration. To quantify the linear and interaction coefficients a 2(3) full factorial experimental design was used. Regression equations for the extraction of V(V) and Ni(II) were determined and the adequacy of these equations was tested by Student's t-Test. More than 98% of both V(V) and Ni(II) were extracted in 90 min using 1.35 M H2SO4 at 40 °C. In addition, solvent extraction of V(V) with LIX 84-I in kerosene from the acidic leach liquor bearing 10.922 g/L V(V) and 18.871 g/L of Ni(II) was investigated. V(V) was extracted selectively using 40% LIX 84-I followed by stripping with NH4OH solution. McCabe-Thiele plots at O:A = 2:3 with 40% LIX 84-I and O:A = 3:1 with 15% (v/v) NH4OH showed two and three theoretical stages are needed for quantitative extraction and stripping of V(V), respectively. Ni(II) was selectively recovered from the V(V) free raffinate by adding ammonium oxalate at 60 °C. The purity of different products such as ammonium vanadate, nickel oxalate and nickel oxide obtained during the processes were analyzed and confirmed from the XRD studies. | 25,156,262 | [
-0.1146685,
-0.002236434,
-0.07536414,
-0.1415869,
0.1941622,
-0.1608241,
-0.3641662,
0.1919601,
-0.2557181,
0.005315204,
0.06777047,
0.3344829,
-0.26569,
0.1366333,
-0.4021212,
-0.1807591,
-0.1076837,
-0.1151492,
0.006751406,
0.467669,
0.203265,
0.3612504,
-0.4523691,
... |
Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII. | The transmembrane isoforms of carbonic anhydrase (hCA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this paper, we present a new class of C-glycosides incorporating the methoxyaryl moiety, that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. The glycosides have been prepared by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. We also present the inhibition profile of our new glycomimetics, against four isozymes of carbonic anhydrase comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor associated isozymes). In this study, per-O-acetylated glycoside 4, 6 and deprotected compounds 7, 9, 10 and 12 were identified as potent and highly selective inhibitors of hCA IX and XII. These results confirm that attaching carbohydrate moieties to CA methoxyaryl pharmacophore improves and enhances its inhibitory activity. These CA inhibitors have developmental potential to selectively target cancer cells, leading to cell death. | 25,156,300 | [
-0.1941828,
0.2259047,
-0.2107486,
-0.04320663,
0.2628509,
-0.1614235,
-0.2973963,
0.4487226,
-0.07915073,
0.06211242,
-0.05849682,
0.2031375,
0.04274393,
-0.3963771,
-0.1579935,
0.1485022,
-0.6580753,
-0.001464507,
-0.03314218,
0.04984607,
0.1743822,
0.2331304,
-0.457048... |
Shogaol-huprine hybrids: dual antioxidant and anticholinesterase agents with β-amyloid and tau anti-aggregating properties. | Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. Herein, we describe the design and synthesis of a novel class of shogaol-huprine hybrids, purported to hit several key targets involved in Alzheimer's disease. The hybrids have been tested in vitro for their inhibitory activity against human acetylcholinesterase and butyrylcholinesterase and antioxidant activity (ABTS.+, DPPH and Folin-Ciocalteu assays), and in intact Escherichia coli cells for their Aβ42 and tau anti-aggregating activity. Also, their brain penetration has been assessed (PAMPA-BBB assay). Even though the hybrids are not as potent AChE inhibitors or antioxidant agents as the parent huprine Y and [4]-shogaol, respectively, they still exhibit very potent anticholinesterase and antioxidant activities and are much more potent Aβ42 and tau anti-aggregating agents than the parent compounds. Overall, the shogaol-huprine hybrids emerge as interesting brain permeable multitarget anti-Alzheimer leads. | 25,156,301 | [
0.08608302,
0.1541839,
0.2075498,
-0.1479496,
-0.04214724,
-0.2365879,
-0.2601057,
0.1133032,
0.08734351,
0.08025421,
0.1444338,
0.2526442,
0.16125,
-0.07278002,
-0.5284195,
0.3459121,
-0.6984654,
0.2628857,
-0.08724243,
0.1997057,
0.2777943,
-0.07515612,
-0.05009089,
-... |
How are previous physical activity and self-efficacy related to future physical activity and self-efficacy? | Self-efficacy (SE) has been found to be a robust predictor of success in achieving physical activity (PA) goals. While much of the current research has focused on SE as a trait, SE as a state has received less attention. Using day-to-day measurements obtained over 84 days, we examined the relationship between state SE and PA. Postmenopausal women (n = 71) participated in a 12-week PA intervention administered via cell phone and monitored their daily PA using a pedometer. At the end of each day, they reported their state SE and number of steps. Using a longitudinal model, state SE was found to be a robust predictor of PA even after accounting for trait SE and other covariates. The findings offer insights about the temporal relationship between SE and PA over the course of an intervention, which can be of interest to researchers and intervention designers. | 25,156,312 | [
-0.01320212,
0.1154742,
-0.3285138,
-0.2371717,
-0.261895,
-0.2234317,
-0.03330416,
0.04731393,
-0.0627991,
-0.2869386,
0.01234456,
-0.03150593,
0.008505737,
-0.3888777,
-0.5233383,
0.09514792,
-0.1838462,
0.1232093,
0.07935467,
0.1452391,
-0.04956662,
0.06895526,
-0.1905... |
The therapeutic alliance in a naturalistic psychiatric setting: temporal relations with depressive symptom change. | Numerous studies have reported associations between the therapeutic alliance and depressive symptom improvement in outpatient samples. However, little is known regarding the temporal relationship between the alliance and symptom change among relatively severely depressed patients receiving treatment in naturalistic, psychiatric hospital settings. Adult patients with major depression (n = 103) receiving combined cognitive behavioral therapy and pharmacological treatment at a psychiatric hospital completed repeated assessments of the therapeutic alliance and depressive symptoms, as well as a pretreatment assessment of their expectation of symptom improvement. Results indicated that the alliance and treatment outcome expectancies significantly predicted subsequent depressive symptom change. However, in a model in which prior symptom change and treatment outcome expectancies were statistically controlled, the alliance-outcome association was rendered nonsignificant. The alliance was significantly associated with prior symptom improvement. Findings highlight the importance of controlling for plausible third variable and temporal confounds to minimize biased estimates of alliance-outcome associations in future studies. Overall, results were more consistent with the alliance being a consequence, rather than a cause, of symptom change. Finally, findings contribute to a growing body of evidence supporting the role of treatment outcome expectancies in predicting symptom improvement, even within our relatively severely depressed sample. | 25,156,322 | [
0.05081168,
0.3525024,
-0.4506238,
-0.2129759,
0.2216428,
-0.1605482,
-0.2153044,
0.07888645,
-0.07083756,
-0.08813408,
0.1765284,
0.3843136,
-0.1060126,
-0.5515048,
-0.01001507,
0.2318429,
-0.09620689,
0.2115602,
0.1138272,
0.06018431,
-0.218434,
0.2275316,
-0.09766021,
... |
The GAVI Alliance and the 'Gates approach' to health system strengthening. | Lauded for getting specific health issues onto national and international agendas and for their potential to improve value for money and outcomes, public-private global health initiatives (GHIs) have come to dominate global health governance. Yet, they have also been criticised for their negative impact on country health systems. In response, disease-specific GHIs have, somewhat paradoxically, appropriated the aim of health system strengthening (HSS). This article critically analyses this development through an ethnographic case study of the GAVI Alliance, which funds vaccines in poor countries. Despite GAVI's self-proclaimed 'single-minded' focus on vaccines, HSS support is fronted as a key principle of GAVI's mission. Yet, its meaning remains unclear and contested understandings of the health systems agenda abound, reflecting competing public health ideologies and professional pressures within the global health field. Contrary to broader conceptualisations of HSS that emphasise social and political dimensions, GAVI's HSS support has become emblematic of the so-called 'Gates approach' to global health, focused on targeted technical solutions with clear, measurable outcomes. In spite of adopting rhetoric supportive of 'holistic' health systems, GHIs like GAVI have come to capture the global debate about HSS in favour of their disease-specific approach and ethos. | 25,156,323 | [
-0.1605643,
0.1162307,
-0.01101652,
-0.2929982,
0.1825718,
-0.1663773,
-0.1047091,
-0.1019025,
-0.2902293,
-0.19923,
0.04475177,
0.07780035,
-0.1996376,
-0.1279085,
-0.3344184,
-0.1526843,
-0.2376375,
0.1650698,
-0.2027282,
-0.2757897,
0.1275465,
0.01493124,
-0.2751191,
... |
Subjective cognitive complaints contribute to misdiagnosis of mild cognitive impairment. | Subjective cognitive complaints are a criterion for the diagnosis of mild cognitive impairment (MCI), despite their uncertain relationship to objective memory performance in MCI. We aimed to examine self-reported cognitive complaints in subgroups of the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort to determine whether they are a valuable inclusion in the diagnosis of MCI or, alternatively, if they contribute to misdiagnosis. Subgroups of MCI were derived using cluster analysis of baseline neuropsychological test data from 448 ADNI MCI participants. Cognitive complaints were assessed via the Everyday Cognition (ECog) questionnaire, and discrepancy scores were calculated between self- and informant-report. Cluster analysis revealed Amnestic and Mixed cognitive phenotypes as well as a third Cluster-Derived Normal subgroup (41.3%), whose neuropsychological and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker profiles did not differ from a "robust" normal control group. This cognitively intact phenotype of MCI participants overestimated their cognitive problems relative to their informant, whereas Amnestic MCI participants with objective memory impairment underestimated their cognitive problems. Underestimation of cognitive problems was associated with positive CSF AD biomarkers and progression to dementia. Overall, there was no relationship between self-reported cognitive complaints and objective cognitive functioning, but significant correlations were observed with depressive symptoms. The inclusion of self-reported complaints in MCI diagnostic criteria may cloud rather than clarify diagnosis and result in high rates of misclassification of MCI. Discrepancies between self- and informant-report demonstrate that overestimation of cognitive problems is characteristic of normal aging while underestimation may reflect greater risk for cognitive decline. | 25,156,329 | [
-0.09680526,
0.4106127,
0.066984,
-0.4057891,
0.06126225,
-0.3230719,
-0.4082631,
0.02081333,
0.0387665,
-0.07821522,
-0.2075614,
0.3220854,
0.02631742,
0.007846861,
-0.4001841,
0.201834,
-0.08034379,
0.3021721,
-0.01907812,
0.01010155,
-0.1214172,
0.05213262,
0.1261882,
... |
Detecting reliable cognitive change in individual patients with the MATRICS Consensus Cognitive Battery. | Clinicians often need to evaluate the treatment response of an individual person and to know that observed change is true improvement or worsening beyond usual week-to-week changes. This paper gives clinicians tools to evaluate individual changes on the MATRICS Consensus Cognitive Battery (MCCB). We compare three different approaches: a descriptive analysis of MCCB test-retest performance with no intervention, a reliable change index (RCI) approach controlling for average practice effects, and a regression approach. Data were gathered as part of the MATRICS PASS study (Nuechterlein et al., 2008). A total of 159 people with schizophrenia completed the MCCB at baseline and 4weeks later. Data were analyzed using an RCI and a regression formula establishing confidence intervals. The RCI and regression approaches agree within one point when baseline values are close to the sample mean. However, the regression approach offers more accurate limits for expected change at the tails of the distribution of baseline scores. Although both approaches have their merits, the regression approach provides the most accurate measure of significant change across the full range of scores. As the RCI does not account for regression to the mean and has confidence limits that remain constant across baseline scores, the RCI approach effectively gives narrower confidence limits around an inaccurately predicted average change value. Further, despite the high test-retest reliability of the MCCB, a change in an individual's score must be relatively large to be confident that it is beyond normal month-to-month variation. | 25,156,338 | [
-0.1064972,
0.1842602,
-0.02760276,
-0.3939993,
0.2763186,
-0.234115,
-0.2016724,
-0.1351647,
0.07204431,
-0.02616274,
0.1109437,
0.4137749,
0.06856651,
0.2010796,
-0.1155359,
-0.03433185,
-0.3418253,
0.08234382,
-0.09809022,
0.3005099,
0.1096486,
0.4154212,
0.1795837,
... |
High-performance liquid chromatography LTQ-Orbitrap mass spectrometry method for tomatidine and non-target metabolites quantification in organic and normal tomatoes. | Tomatoes, members of the Solanaceae plant family, produce biologically active secondary metabolites, including glycoalkaloids and aglycons, which may have both adverse and beneficial biological effects. A new liquid chromatography method that utilized LTQ-Orbitrap MS was developed for the analysis of tomatidine, the main aglycon in tomatoes. Recoveries of tomatidine were >98.3% with the relative standard deviations (RSDs) below 6.1%. The limit of detection (LODs) was 0.0003 mg kg(-1). The limit of quantitation (LOQs) is 0.001 mg kg(-1). The linear range was between with 0.0025 and 1 mg kg(-1) with an excellent correlation coefficient (R(2)) equal to 0.9990. Various tomato samples were analyzed and the level of tomatidine in the 11 samples analysed was higher in normal respect to organic tomatoes. The capability of the set-up Full Scan LTQ-Orbitrap MS method allowed us to quantified two non-target analytes. The m/z 1032 was identified as dehydrotomatine, confirmed through accurate mass studies (mass error in ppm equal to 1.5017) meanwhile m/z 902 as (Glc)2-Gal-Tomatidine (β1-Tomatine) (mass error in ppm equal to 2.0719). | 25,156,359 | [
-0.058538,
0.2561485,
-0.02259365,
-0.4160185,
0.1529035,
0.04810806,
0.1704601,
-0.0184828,
-0.05970877,
-0.0969063,
0.2912423,
-0.04296433,
0.137811,
-0.02272779,
-0.3688294,
-0.09621307,
-0.7011576,
-0.01710584,
0.5469521,
-0.2366932,
0.1044008,
0.2289131,
-0.2110484,
... |
Screening nephroprotective compounds from cortex Moutan by mesangial cell extraction and UPLC. | A method for screening nephroprotective compounds in cortex Moutan, a common traditional Chinese medicine (TCM) in treating diabetic nephropathy with renal mesangial cell extraction and ultra performance liquid chromatography technique was described in this paper. We hypothesize that the compounds which bind to cell membranes under pathological conditions may be the bioactive compounds in TCMs. Mesangial cells were cultured in medium containing 5 mM (physiological, NG) or 30 mM (pathological, HG) glucose for 48 h and then incubated with cortex Moutan extract. After the unbound substances were washed off, the cell membrane-bound compounds were dissociated and concentrated by an SPE column. By comparing the chromatograms of NG and HG cultured-cell extractions and cortex Moutan extract, three compounds bound to both NG and HG-cultured mesangial cells were identified as paeoniflorin, pentagalloylglucose (PGG) and paeonol. In vitro studies showed that paeoniflorin, PGG and paeonol reduced the activity of nicotinamide-adenine dinucleotide phosphate oxidase (NADPH) activity, and decreased the level of reactive oxygen species (ROS), transforming growth factor-β1 (TGF-β1) and fibronectin in high glucose cultured mesangial cells. The results indicate that paeonol, paeoniflorin and PGG may be the nephroprotective compounds from cortex Moutan. This study is expected to provide a more reliable and effective method for screening bioactive compounds from the complex TCM systems. | 25,156,360 | [
0.1818845,
0.293175,
0.1275855,
0.1661025,
0.1292434,
0.1443622,
-0.2256468,
0.4065036,
-0.02999913,
0.1063398,
-0.05902093,
0.0006366806,
-0.2479917,
-0.1752058,
-0.4072769,
0.2932682,
-0.1696433,
0.2887567,
0.210771,
0.4245576,
0.3147015,
0.2625823,
-0.2017867,
-0.187... |
Axl receptor blockade protects from invasive pulmonary aspergillosis in mice. | Aspergillus fumigatus is a sporulating fungus found ubiquitously in the environment, which is quickly contained in the immunocompetent host but can cause lethal invasive aspergillosis in the immunocompromised host. We have recently demonstrated that Axl (one member of the Tyro3, Axl, Mertk receptor family) is a key regulator of antiviral immune responses in the lung. In this study, we investigated the role of Axl in antifungal immunity in a model of invasive pulmonary aspergillosis (IPA). In this model, Aspergillus fumigatus conidia were administered into the lungs of neutrophil-depleted mice, and the mice were monitored for survival, lung inflammatory response, and fungal clearance. The lethal effect of IPA was significantly reduced in anti-Axl mAb-treated mice compared with IgG control-treated mice. Targeting Axl significantly inhibited pulmonary inflammation, including the expression of IL-1β, IL-6, TNF-α, and chitinase-like proteins in whole lung. Further, anti-Axl mAb treatment significantly increased M1 macrophages that highly expressed inducible NO synthase and decreased M2 macrophages that expressed Arginase 1 and were found in inflammatory zone protein (Fizz1). More importantly, anti-Axl mAb treatment significantly increased the number of IFN-γ-producing T cells and NK cells compared with the IgG control group during IPA. Together, our results demonstrate that the Axl mAb treatment is protective during invasive aspergillosis in neutropenic mice. Collectively, these data suggest a potential deleterious role for Axl during primary immune responses directed against A. fumigatus and novel therapeutic strategy for IPA. | 25,156,363 | [
0.1013831,
-0.2052374,
0.07014164,
-0.06361248,
0.009125261,
0.1004745,
0.1752734,
0.2750203,
-0.1508607,
-0.2874399,
0.1964019,
-0.0804242,
0.03330783,
-0.124309,
-0.08929811,
0.1161409,
-0.5991786,
0.08858801,
0.06500065,
-0.1043198,
-0.2178323,
0.167261,
-0.289939,
0... |
Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. | Psoriasis is a chronic autoimmune disease affecting the skin and characterized by aberrant keratinocyte proliferation and function. Immune cells infiltrate the skin and release proinflammatory cytokines that play important roles in psoriasis. The Th17 network, including IL-23 and IL-22, has recently emerged as a critical component in the pathogenesis of psoriasis. IL-22 and IL-23 signaling is dependent on the JAK family of protein tyrosine kinases, making JAK inhibition an appealing strategy for the treatment of psoriasis. In this study, we report the activity of SAR-20347, a small molecule inhibitor with specificity for JAK1 and tyrosine kinase 2 (TYK2) over other JAK family members. In cellular assays, SAR-20347 dose dependently (1 nM-10 μM) inhibited JAK1- and/or TYK2-dependent signaling from the IL-12/IL-23, IL-22, and IFN-α receptors. In vivo, TYK2 mutant mice or treatment of wild-type mice with SAR-20347 significantly reduced IL-12-induced IFN-γ production and IL-22-dependent serum amyloid A to similar extents, indicating that, in these models, SAR-20347 is probably acting through inhibition of TYK2. In an imiquimod-induced psoriasis model, the administration of SAR-20347 led to a striking decrease in disease pathology, including reduced activation of keratinocytes and proinflammatory cytokine levels compared with both TYK2 mutant mice and wild-type controls. Taken together, these data indicate that targeting both JAK1- and TYK2-mediated cytokine signaling is more effective than TYK2 inhibition alone in reducing psoriasis pathogenesis. | 25,156,366 | [
0.040589,
-0.3927465,
-0.2290584,
-0.4131656,
0.2424696,
0.215212,
0.1181798,
0.3440085,
0.1494475,
-0.04046704,
0.0243166,
-0.1052572,
0.002632025,
0.3838983,
0.2455124,
0.1421289,
-0.2773678,
0.1148066,
-0.05446856,
0.2551656,
0.2490365,
0.1233239,
-0.1339425,
-0.0785... |
Basophils promote innate lymphoid cell responses in inflamed skin. | Type 2 inflammation underlies allergic diseases such as atopic dermatitis, which is characterized by the accumulation of basophils and group 2 innate lymphoid cells (ILC2s) in inflamed skin lesions. Although murine studies have demonstrated that cutaneous basophil and ILC2 responses are dependent on thymic stromal lymphopoietin, whether these cell populations interact to regulate the development of cutaneous type 2 inflammation is poorly defined. In this study, we identify that basophils and ILC2s significantly accumulate in inflamed human and murine skin and form clusters not observed in control skin. We demonstrate that murine basophil responses precede ILC2 responses and that basophils are the dominant IL-4-enhanced GFP-expressing cell type in inflamed skin. Furthermore, basophils and IL-4 were necessary for the optimal accumulation of ILC2s and induction of atopic dermatitis-like disease. We show that ILC2s express IL-4Rα and proliferate in an IL-4-dependent manner. Additionally, basophil-derived IL-4 was required for cutaneous ILC2 responses in vivo and directly regulated ILC2 proliferation ex vivo. Collectively, these data reveal a previously unrecognized role for basophil-derived IL-4 in promoting ILC2 responses during cutaneous inflammation. | 25,156,365 | [
0.09822871,
-0.1587795,
-0.2717932,
-0.02813244,
0.01886908,
-0.08037052,
-0.0152017,
0.1004345,
0.04749713,
-0.1162545,
-0.0365208,
-0.1748053,
-0.3136904,
-0.1622202,
-0.2970443,
0.03432876,
-0.1849898,
0.1227465,
-0.09381335,
0.003878631,
0.1363967,
0.1911905,
-0.14622... |
The Research Domain Criteria (RDoC): an analysis of methodological and conceptual challenges. | In a bold effort to address the longstanding shortcomings of the Diagnostic and Statistical Manual (DSM) framework for the classification and diagnosis of psychopathology, the National Institute of Mental Health recently launched a research program - the Research Domain Criteria (RDoC) - in the hopes of developing an alternative taxonomic system rooted in dysfunctional brain circuitry. Although the RDoC endeavor has considerable promise, it faces several methodological and conceptual challenges, four of which I address here: (a) an overemphasis on biological units and measures, (b) neglect of measurement error, (c) biological and psychometric limitations of endophenotypes, and (d) the distinction between biological predispositions and their behavioral manifestations. Because none of these challenges is in principle insurmountable, I encourage investigators to consider potential remedies for them. RDoC is a calculated gamble that appears to be worth the risk, but its chances of success will be maximized by a thoughtful consideration of hard-won lessons learned--but frequently forgotten--over the past several decades of psychological and psychiatric research. | 25,156,396 | [
-0.03770812,
0.06476666,
-0.07146829,
-0.1188662,
0.208247,
-0.440798,
-0.1465912,
0.03880907,
-0.008839278,
0.1168256,
0.03268652,
-0.01471604,
-0.07642348,
0.1220521,
-0.5846619,
0.1084073,
-0.1084244,
0.2524381,
0.01268785,
0.00171864,
0.002357649,
0.05581384,
-0.10825... |
Augmenting one-session treatment of children's specific phobias with attention training to positive stimuli. | This study examined the efficacy of combining two promising approaches to treating children's specific phobias, namely attention training and one 3-h session of exposure therapy ('one-session treatment', OST). Attention training towards positive stimuli (ATP) and OST (ATP+OST) was expected to have more positive effects on implicit and explicit cognitive mechanisms and clinical outcome measures than an attention training control (ATC) condition plus OST (ATC+OST). Thirty-seven children (6-17 years) with a specific phobia were randomly assigned to ATP+OST or ATC+OST. In ATP+OST, children completed 160 trials of attention training responding to a probe that always followed the happy face in happy-angry face pairs. In ATC+OST, the probe appeared equally often after angry and happy faces. In the same session, children completed OST targeting their phobic situation/object. Clinical outcomes included clinician, parent and child report measures. Cognitive outcomes were assessed in terms of change in attention bias to happy and angry faces and in danger and coping expectancies. Assessments were completed before and after treatment and three-months later. Compared to ATC+OST, the ATP+OST condition produced (a) significantly greater reductions in children's danger expectancies about their feared situations/object during the OST and at three-month follow-up, and (b) significantly improved attention bias towards positive stimuli at post-treatment, which in turn, predicted a lower level of clinician-rated phobia diagnostic severity three-months after treatment. There were no significant differences between ATP+OST and ATC+OST conditions in clinician, parent, or child-rated clinical outcomes. Training children with phobias to focus on positive stimuli is effective in increasing attention towards positive stimuli and reducing danger expectancy biases. Studies with larger sample sizes and a stronger 'dose' of ATP prior to the OST may reveal promising outcomes on clinical measures for training attention towards positive stimuli. | 25,156,398 | [
-0.2787076,
0.1876891,
-0.2380376,
0.1358624,
0.2355933,
-0.3580485,
-0.2899586,
0.08536021,
0.1978127,
-0.1398875,
-0.07271503,
0.2656994,
-0.1772276,
-0.03974967,
-0.3136122,
-0.02487961,
-0.5554191,
0.1266263,
-0.01236288,
0.1885473,
0.3151714,
0.1691648,
-0.3693528,
... |
Clinical and imaging follow-up after surgical or endovascular treatment in patients with unruptured carotid-ophthalmic aneurysm. | Carotido-ophthalmic aneurysms are complex and their treatment is challenging. Few data are available on patient follow-up after endovascular or surgical treatment. To evaluate outcome of patients with unruptured carotido-ophthalmic aneurysm after endovascular or surgical treatment. This series included 52 consecutive patients in a single center treated for an unruptured carotido-ophthalmic aneurysm at Lille University Hospital between 2000 and 2011. Visual disturbances were present in 5 patients. Treatment option (endovascular or microsurgical) was decided for each patient in a multidisciplinary meeting. We recorded age and the American Society of Anesthesiology score (ASA) before treatment and the modified Rankin Scale score (mRS) at 3 months after treatment. All patients had conventional angiography performed before and immediately after treatment. Long-term imaging follow-up was performed at 3 years after treatment. Treatment was endovascular in 29 patients and microsurgical in 23. The mean follow-up was 4.6 years. Conventional angiograms showed multiple intracranial aneurysms in 26 patients. Age, pre-therapeutic ASA score and mRS score at 3 months after treatment showed no significant difference between microsurgery and endovascular treatment. Imaging follow-up showed aneurysm recurrence after endovascular treatment in 6 patients including 3 with major recurrence that required further treatment by microsurgery. In these 3 major recurrences, the initial conventional angiography demonstrated the origin of the ophthalmic artery at the neck or from the aneurysmal sac in 3 cases. After microsurgery, conventional angiography showed a remnant neck in 2 patients including 1 treated by further endovascular procedure. Endovascular treatment remains the first therapeutic option when the ophthamic artery originates at a distance from the neck, but microsurgery should be considered for large aneurysms with optic nerve compression, or when the ophthalmic artery arises from the neck of the aneurysm. | 25,156,408 | [
0.08789393,
0.04394767,
-0.2020033,
-0.1659174,
0.05761639,
-0.4383101,
-0.09838932,
0.001204315,
0.1726007,
-0.0555802,
0.02309729,
0.007859815,
-0.1644886,
-0.6003996,
-0.4263495,
0.2478442,
-0.3103958,
0.4404876,
0.1574692,
0.2734118,
0.1293128,
0.005284281,
0.03117732... |
Part II: predictors of depression after stroke and impact of depression on stroke outcome: an updated systematic review of observational studies. | We previously published a systematic review in 2005 on factors associated with the development of depression in people with stroke. To update and expand that review to include published data on the impact of depression on stroke outcome. We included all published observational studies (to May 31, 2013) with prospective consecutive recruitment of people with a clinical diagnosis of stroke where an attempt was made to assess the variables associated with, or predictive of, the development of depression. We included data from 23 studies including 18,374 people. Depression after stroke was associated with prestroke depression, more severe neurological deficit and physical disability in the acute phase, and later after stroke. No consistent relationship between depression and demographic parameters or stroke features was identified. The review of the impact of depression on stroke outcome included data from 14 cohorts, including 4498 people, and found that depression was negatively associated with functional outcome in stroke survivors. Early identification of patients at high risk of depression after stroke, those with a history of depression and physical disability after stroke, would enable the early implementation of effective management and prevention strategies for depression. The reciprocal relationship between depression and physical disability highlights the need for interventions that reduce disability after stroke, which may in turn improve mood and overall recovery for an increasingly large number of stroke survivors. | 25,156,411 | [
-0.1413113,
0.1065074,
-0.0689403,
-0.4693099,
-0.03300786,
-0.3099132,
-0.08143304,
0.1699373,
-0.1985563,
-0.03437249,
-0.1624673,
0.2027564,
-0.01517958,
-0.4767746,
-0.04857384,
-0.09615505,
0.09233456,
0.2895749,
-0.00764723,
-0.004893078,
-0.2962947,
0.06542928,
-0.... |
High serum thyrotropin levels are associated with retinal arteriolar narrowing in the general population. | Recent studies have shown associations of hypothyroidism with arterial blood pressure, atherosclerosis, and inflammation. Based on these pathways, there might also be an association between hypothyroidism and retinal arteriolar narrowing (RAN), a marker of microvascular damage from hypertension, atherosclerosis, and inflammation. Against this background, the aim of this study was to investigate the putative association between serum thyrotropin (TSH) levels and RAN defined by arterio-venous ratio (AVR) from static vessel analysis. We used data from 3189 individuals from the second population-based cohort of the Study of Health in Pomerania (SHIP-TREND-0). Thyroid function was defined according to serum TSH and serum diiodothyronine (3,5-T2) levels. Low and high serum TSH levels were defined by the cutoffs 0.3 mIU/L and 3.0 mIU/L. Fundus photography of the central retina was recorded with a nonmydriatic camera, and images were evaluated by one experienced reader. An AVR <0.8 was defined as decreased. Serum TSH levels, low and high TSH, and serum 3,5-T2 levels were associated with AVR by linear regression and with AVR <0.8 by Poisson regression, both adjusted for age, sex, cigarette smoking, alcohol consumption, and intake of beta-blockers. Serum TSH levels were significantly associated with AVR (β=-0.028 [CI -0.049 to -0.007]; p=0.009) and with a decreased AVR <0.8 (relative risk=2.05 [CI 1.13-3.73]; p=0.019). Individuals with high TSH had a 1.43 higher risk for a decreased AVR ([CI 1.04-1.96]; p=0.027) than individuals with serum TSH levels within the reference range. Serum 3,5-T2 levels were also associated with a decreased AVR (relative risk for an increase of 1 nM=0.45 [CI 0.23-0.87]; p=0.017). Our results substantiate evidence for an association between hypothyroidism and RAN. Potential mechanisms explaining this association are long-term hypertension, atherosclerotic processes, and inflammation. | 25,156,414 | [
0.1173153,
-0.5709581,
-0.4513112,
-0.03290635,
0.09405474,
-0.4451221,
0.3145913,
0.2070151,
-0.04182198,
-0.06999971,
-0.0114633,
-0.0922242,
-0.01669705,
-0.1128153,
-0.1326342,
-0.1367552,
-0.5040216,
0.1060527,
0.3032292,
0.3858393,
0.2481436,
0.2580911,
-0.2923302,
... |
Interferons: Success in anti-viral immunotherapy. | The interferons (IFNs) are glycoproteins with strong antiviral activities that represent one of the first lines of host defense against invading pathogens. These proteins are classified into three groups, Type I, II and III IFNs, based on the structure of their receptors on the cell surface. Due to their ability to modulate immune responses, they have become attractive therapeutic options to control chronic virus infections. In combination with other drugs, Type I IFNs are considered as "standard of care" in suppressing Hepatitis C (HCV) and Hepatitis B (HBV) infections, while Type III IFN has generated encouraging results as a treatment for HCV infection in phase III clinical trials. However, though effective, using IFNs as a treatment is not without the need for caution. IFNs are such powerful cytokines that affect a wide array of cell types; as a result, patients usually experience unpleasant symptoms, with a percentage of patients suffering system wide effects. Thus, constant monitoring is required for patients treated with IFN in order to reach the treatment goals of suppressing virus infection and maintaining quality of life. | 25,156,421 | [
0.06237869,
0.1378581,
-0.07399741,
-0.020617,
0.04314475,
-0.15325,
-0.1081286,
0.2051548,
0.143706,
0.02136926,
-0.08055678,
-0.2196465,
-0.1366604,
0.07077309,
-0.388489,
-0.2940999,
0.04976734,
-0.09040573,
0.1737936,
0.08450082,
0.1230374,
0.1132315,
-0.1077769,
-0... |
Effect of dried California Mission figs on mineral status and food replacement. | Figs are a rich source of several different minerals and fibres. We studied the effect of the consumption of dried California Mission figs on mineral and nutrient levels, as well as the effect of the addition of figs to a self-selected habitual diet on dietary patterns. A crossover randomized controlled trial study design in which participants with a mean of age of approximately 56 years were randomly assigned to eat either their usual diet for 5 weeks or to add dried California Mission figs (120 g/d) to their usual diet for 5 weeks, after which they crossed over to the other group for an additional 5 weeks. Six 24 h dietary recalls and four blood samples were obtained from each participant. Loma Linda University School of Public Health, USA. A follow-up study using data collected from eighty-eight American males and females from September to December 2008. Diets reported in the 24 h dietary recall during the fig-supplemented diet period were significantly higher in Ca and K in the dietary and total phase (P value<0·05). Nevertheless, data on mineral levels in the body gathered by means of biochemical analyses from blood samples were nearly the same for both the figs-added and the participants' standard diet. The estimated displacement suggests that eating figs resulted in the elimination of 4% of desserts, 5% of vegetables, 10% of dairy products, 23% of grain products and 168% of beverages from other sources that participants would otherwise consume. Based on 24 h dietary recalls, the daily consumption of figs may increase the intake of several different minerals. However, mineral levels in blood samples were not altered significantly. | 25,156,424 | [
-0.1032539,
0.1640929,
-0.2559841,
0.1554203,
-0.02148666,
-0.1307385,
0.02317789,
0.1233147,
0.2112405,
-0.3518786,
0.0353584,
0.1281996,
0.2268067,
0.005588004,
-0.6576371,
-0.3716548,
-0.3012379,
-0.01125078,
0.2021256,
0.01041894,
0.161396,
0.4634358,
-0.3897048,
0.... |
Modulation of tibialis anterior muscle activity changes with upright stance width. | When individuals stand with their feet apart, activation of tibialis anterior (TA) muscle seems to slightly exceed rest levels. In narrow stances, conversely, the stabilization of body lateral sways may impose marked, active demand on ankle inversors/eversors. In this study we investigate how much the modulation in TA activity, associated to center of pressure (COP) lateral sways, changes when stance width reduces. Surface EMG and COP coordinates were collected from 17 subjects at three different stances: feet apart, feet together and tandem. Pearson correlation analysis was applied to check whether the expected greater modulations in TA activity corresponded to a stronger association between fluctuations in EMG amplitude and COP lateral sways. When standing at progressively narrower stances participants showed larger fluctuations in COP lateral sways (p<0.01) and higher EMG-COP association (p<0.01); marked increases in TA activity were only observed in tandem stance (p<0.001). Interestingly, more pronounced modulations in TA activity were observed for subjects showing greater association between EMG amplitude and COP sways in feet together and tandem stance (Pearson R>0.56, p<0.02), though not when standing with feet apart (R=-0.22, p=0.40). These results indicate that the contribution of TA activity to lateral sway control increases for narrower stances. | 25,156,446 | [
-0.05148569,
0.003630597,
0.06605241,
-0.149593,
-0.05418139,
-0.4661996,
-0.3552389,
-0.1888205,
-0.03389679,
-0.3596329,
-0.03909292,
-0.2266557,
-0.1209689,
-0.2523782,
-0.2753929,
-0.1722039,
-0.4476713,
-0.08070663,
-0.2460471,
-0.1840347,
-0.3209398,
-0.06192241,
-0... |
Preclinical trial of a novel surface architecture for improved primary fixation of cementless orthopaedic implants. | A new surface architecture for cementless orthopaedic implants (OsteoAnchor), which incorporates a multitude of tiny anchor features for enhancing primary fixation, was tested in an ovine hemi-arthroplasty pilot study. Test animals were implanted with a hip stem component incorporating the OsteoAnchor surface architecture produced using additive layer manufacturing and control animals were implanted with stems containing a standard plasma sprayed titanium coating. Intra-operative surgeon feedback indicated that superior primary fixation was achieved for the OsteoAnchor stems and rapid return to normal gait and load bearing was observed post-operation. Following a 16-week recovery time, histological evaluation of the excised femurs revealed in-growth of healthy bone into the porous structure of the OsteoAnchor stems. Bone in-growth was not achieved for the plasma sprayed stems. These results indicate the potential for the OsteoAnchor surface architecture to enhance both the initial stability and long term lifetime of cementless orthopaedic implants. | 25,156,456 | [
-0.05912236,
0.3471931,
0.01041999,
-0.1945493,
-0.3419699,
-0.390662,
-0.09044658,
0.1295132,
0.1210916,
-0.1872529,
-0.03703601,
-0.02963889,
0.1403449,
-0.3279444,
-0.2314322,
0.1825874,
-0.1111885,
-0.09588988,
-0.1022246,
-0.1736218,
-0.09654272,
0.4080867,
-0.004850... |
A big-microsite framework for soil carbon modeling. | Soil carbon cycling processes potentially play a large role in biotic feedbacks to climate change, but little agreement exists at present on what the core of numerical soil C cycling models should look like. In contrast, most canopy models of photosynthesis and leaf gas exchange share a common 'Farquhaur-model' core structure. Here, we explore why a similar core model structure for heterotrophic soil respiration remains elusive and how a pathway to that goal might be envisioned. The spatial and temporal variation in soil microsite conditions greatly complicates modeling efforts, but we believe it is possible to develop a tractable number of parameterizable equations that are organized into a coherent, modular, numerical model structure. First, we show parallels in insights gleaned from linking Arrhenius and Michaelis-Menten kinetics for both photosynthesis and soil respiration. Additional equations and layers of complexity are then added to simulate substrate supply. For soils, model modules that simulate carbon stabilization processes will be key to estimating the fraction of soil C that is accessible to enzymes. Potential modules for dynamic photosynthate input, wetting-event inputs, freeze-thaw impacts on substrate diffusion, aggregate turnover, soluble-C sorption, gas transport, methane respiration, and microbial dynamics are described for conceptually and numerically linking our understanding of fast-response processes of soil gas exchange with longer-term dynamics of soil carbon and nitrogen stocks. | 25,156,470 | [
-0.1465252,
0.03696874,
-0.2171633,
-0.1299953,
0.06637733,
-0.3639783,
-0.1893276,
0.3234092,
-0.03171989,
-0.1059966,
-0.09915072,
-0.04742816,
-0.2244449,
0.3045174,
-0.5257335,
-0.03443535,
-0.5315784,
0.04000156,
0.3526027,
-0.1450299,
0.09734593,
0.4593402,
-0.25938... |
Reduction of Leishmania donovani infectivity in whole blood using riboflavin and ultraviolet light. | Leishmaniasis is a vector-borne disease caused by the protozoan parasite Leishmania sp. that is transmitted by sandflies. Travelers to endemic areas, and US military personnel stationed in the Middle East, are at risk for contracting the disease. Whole blood (WB) units were spiked with human monocytes infected with L. donovani amastigotes to a final concentration of approximately 10(5) infected cells/mL. After riboflavin (RB) addition, units were exposed to 80 J/mLRBCs ultraviolet (UV) light. One pretreatment (collected after RB addition) and one posttreatment sample were collected, serially diluted in culture medium, and incubated at 22°C for up to 5 weeks. Parasite viability was determined by microscopic observation for replicating promastigote forms. Mirasol treatment of 3 units of L. donovani-infected WB with RB and UV light resulted in a parasite reduction of 2.3 ± 0.12 log. Partial reduction of L. donovani can be achieved in WB using RB and UV light. This technology may be useful when potential donors are exposed to Leishmania sp. during residence, travel, or military deployment to an endemic area. | 25,156,473 | [
-0.002199262,
-0.1160026,
-0.2657824,
-0.3283384,
0.3043479,
-0.3244073,
0.004308863,
0.01929208,
0.08981585,
-0.2066947,
0.05939284,
0.319075,
0.1082578,
0.1642101,
-0.2991914,
0.1736546,
-0.3779445,
-0.1044737,
-0.128723,
0.2117665,
0.07861179,
0.4162195,
-0.03611367,
... |
Development of β-cyclodextrin-based sustained release microparticles for oral insulin delivery. | Polymeric microparticles have been previously demonstrated to deliver various therapeutic agents efficiently to targeted regions by protecting the drug from harsh gastric milieu of the gastrointestinal tract. In this study, we investigated the hypoglycemic effect of β-cyclodextrin polymeric insulin microparticles in diabetic rats via the oral route of administration. β-cyclodextrin microparticles were prepared by a unique one-step spray-drying technique and stabilized by incorporating enteric retardant polymers in the formulation. The insulin-loaded microparticles had a mean size of 0.8 ± 0.25 μm with a zeta potential of 3.57 + 0.62 mV. As seen with the chromatographic analysis, the drug content in the microparticles was determined to be 94.9 ± 2.77%. RAW macrophage cells showed greater than 80% viability after 24 h of incubation with the insulin and blank microparticles. For the in vitro release study, the microparticles were able to protect the insulin in gastric fluid where no significant release was detected, followed by only 50% release in intestinal fluid for the first 8 h of the study. This was seen to correlate with the in vivo data where 50% glucose inhibition was seen after 8 h of oral administration in diabetic rats. This data suggest that the oral insulin microparticles were able to reduce glucose levels in disease conditions and would be a favorable route of administration to patients as an alternative to daily subcutaneous injections. | 25,156,483 | [
-0.2617592,
0.08909654,
-0.236802,
-0.1697455,
0.1360264,
-0.02762016,
-0.1317641,
0.1226432,
-0.01407824,
-0.1364432,
0.07445686,
-0.5761916,
-0.0360024,
-0.1565201,
-0.368692,
0.07703322,
-0.3495235,
-0.2674461,
0.09779549,
0.1161534,
-0.04318626,
0.06197673,
0.3150148,... |
Associations between bicycling and carotid arterial stiffness in adolescents: The European Youth Hearts Study. | The aim of the study was to investigate the associations between bicycling and carotid arterial stiffness, independent of objectively measured moderate-and-vigorous physical activity. This cross-sectional study included 375 adolescents (age 15.7 ± 0.4 years) from the Danish site of the European Youth Heart Study. Total frequency of bicycle usage was assessed by self-report, and carotid arterial stiffness was assessed using B-mode ultrasound. After adjusting for pubertal status, body height, and objectively measured physical activity and other personal lifestyle and demographic factors, boys using their bicycle every day of the week displayed a higher carotid arterial compliance {standard beta 0.47 [95% confidence interval (CI) 0.07-0.87]} and distension [standard beta 0.38 (95% CI -0.04 to 0.81)]. Boys using their bicycle every day of the week furthermore displayed a lower Young's elastic modulus [standard beta -0.48 (95% CI -0.91 to -0.06)]. Similar trends were observed when investigating the association between commuter bicycling and carotid arterial stiffness. These associations were not observed in girls. Our observations suggest that increasing bicycling in adolescence may be beneficial to carotid arterial health among boys. | 25,156,494 | [
-0.2610565,
0.3784911,
-0.4290836,
0.1143386,
0.03776286,
-0.5104398,
-0.210761,
-0.2013582,
0.03699855,
0.1370377,
0.05108266,
-0.2215075,
0.1024435,
-0.2275191,
-0.239493,
-0.1271446,
-0.5361608,
0.303952,
-0.4641697,
0.1578253,
0.2795864,
0.0184092,
-0.2972589,
0.068... |
Psychological impact of first-trimester prevention for preeclampsia on anxiety. | This study aims to examine whether a first-trimester strategy of secondary prevention for preeclampsia increases anxiety in pregnant women. The anxiety levels of a cohort of women screened for preeclampsia at first trimester were measured by the Spielberg State-Trait Anxiety Inventory (STAI-S) and compared between women screened as low and high risk. In a subgroup of women, the anxiety levels were additionally measured at second and third trimester. A General Linear Model (GLM) for repeated measurements was performed to adjust for potential confounders (age, nulliparity and socio-economic level). A total of 255 women (135 low-risk and 120 high-risk) were evaluated. No differences were found in the mean STAI-S scores between low-risk and high-risk women: 35 (SD 9.9) and 34.6 (SD 10.1); p = 0.77. The proportion of women with high anxiety was not significantly different between groups (28/134 [20.7%] vs 24/120 [20%]; p = 0.88). No differences were found in the subgroups (51 low-risk and 50 high-risk) in which the anxiety levels were also measured at second and third trimester: 35.8 (SD 8.8) vs 35.2 (SD 9.7), p = 0.74, and 37.2 (SD 9.4) vs 35.3 (SD 8.6), p = 0.3. These differences remained non-significant after adjustment for potential confounders. A strategy of first-trimester screening for preeclampsia does not increase maternal anxiety. | 25,156,501 | [
0.2084273,
0.3107744,
-0.1814765,
0.1860505,
0.3265817,
-0.2354737,
-0.05891017,
-0.3879199,
0.09465492,
-0.07447574,
0.01688635,
0.4016411,
-0.1172767,
-0.2821373,
-0.1390935,
0.2448932,
-0.2642814,
0.03089352,
-0.2687769,
0.3505096,
-0.1060841,
0.4802089,
-0.1622424,
... |
The effects of word-learning biases on children's concept of angle. | Despite evidence that young children are sensitive to differences in angle measure, older students frequently struggle to grasp this important mathematical concept. When making judgments about the size of angles, children often rely on erroneous dimensions such as the length of the angles' sides. The present study tested the possibility that this misconception stems from the whole-object word-learning bias by providing a subset of children with a separate label to refer to the whole angle figure. Thirty preschoolers (M = 4.86 years, SD = .53) were tested with a pretest-training-posttest design. At pretest, children showed evidence of the whole-object misconception. After training, children who were given a novel-word label for the whole object improved significantly more than those trained on the meaning of "angle" alone. | 25,156,505 | [
-0.1232091,
0.05257773,
-0.3331649,
-0.2888007,
0.4794246,
-0.2228426,
-0.125146,
0.1501054,
0.2245452,
0.06348679,
0.06315044,
0.1838511,
-0.1177103,
-0.2034797,
-0.4138257,
0.09325514,
-0.2958694,
0.2537043,
-0.4581611,
-0.1508981,
0.3289117,
0.04627509,
-0.1619481,
0... |
Effect of a family-centered, secondhand smoke intervention to reduce respiratory illness in indigenous infants in Australia and New Zealand: a randomized controlled trial. | Secondhand smoke (SHS) is a significant cause of acute respiratory illness (ARI) and 5 times more common in indigenous children. A single-blind randomized trial was undertaken to determine the efficacy of a family centered SHS intervention to reduce ARI in indigenous infants in Australia and New Zealand. Indigenous mothers/infants from homes with ≥ 1 smoker were randomized to a SHS intervention involving 3 home visits in the first 3 months of the infants' lives (plus usual care) or usual care. The primary outcome was number of ARI-related visits to a health provider in the first year of life. Secondary outcomes, assessed at 4 and 12 months of age, included ARI hospitalization rates and mothers' report of infants' SHS exposure (validated by urinary cotinine/creatinine ratios [CCRs]), smoking restrictions, and smoking cessation. Two hundred and ninety-three mother/infant dyads were randomized and followed up. Three quarters of mothers smoked during pregnancy and two thirds were smoking at baseline (as were their partners), with no change for more than 12 months. Reported infant exposure to SHS was low (≥ 95% had smoke-free homes/cars). Infant CCRs were higher if one or both parents were smokers and if mothers breast fed their infants. There was no effect of the intervention on ARI events [471 intervention vs. 438 usual care (reference); incidence rate ratio = 1.10, 95% confidence intervals (CI) = 0.88-1.37, p = .40]. Despite reporting smoke-free homes/cars, mothers and their partners continue to smoke in the first year of infants' lives, exposing them to SHS. Emphasis needs to be placed on supporting parents to stop smoking preconception, during pregnancy, and postnatal. | 25,156,527 | [
-0.01747977,
0.4030979,
-0.09758867,
0.1439426,
0.1519057,
0.02685174,
-0.2873705,
-0.2038227,
0.2016928,
0.2722387,
-0.03308227,
0.2161385,
-0.02416052,
-0.03532931,
0.3944356,
-0.2038542,
-0.5012214,
0.1428112,
-0.1627774,
-0.1106676,
-0.2772787,
0.143646,
-0.1936225,
... |
Triggering through Toll-like receptor 2 limits chronically stimulated T-helper type 1 cells from undergoing exhaustion. | Chronic infections result in T-cell exhaustion, a state of functional unresponsiveness. To control the infection, it is important to salvage the exhausted T cells. In this study, we delivered signals through Toll-like receptor 2 (TLR-2) to reinvigorate functionality in chronically activated T-helper type 1 (Th1) cells. This process significantly augmented the expression of T-bet, interferon γ, interleukin 2, and the antiapoptotic molecule Bcl-2, whereas it dampened the display of the exhaustion markers programmed death receptor 1 (PD-1) and lymphocyte activation gene 3 (Lag-3). Additionally, TLR-2 signaling bolstered the ability of chronically stimulated Th1 cells to activate B cells. Finally, the results were substantiated by observing reduced lung pathology upon administration of TLR-2 agonist in the chronic infection model of tuberculosis. These data demonstrated the importance of TLR-2 in rescuing chronically activated Th1 cells from undergoing exhaustion. This study will pave a way for targeting TLR-2 in developing therapeutic strategies to treat chronic diseases involving loss of Th1 cell function. | 25,156,558 | [
0.02483462,
-0.3171887,
-0.1285432,
0.02266734,
-0.00810916,
-0.2986711,
-0.2038915,
0.09888624,
-0.03663649,
-0.002290038,
-0.001062125,
0.3380075,
-0.02864642,
0.4315724,
-0.4572906,
-0.2931134,
0.07956891,
-0.1310873,
-0.1003539,
-0.005718458,
0.1967147,
0.3613681,
-0.... |
Pre-meal tomato (Lycopersicon esculentum) intake can have anti-obesity effects in young women? | The effect of pre-meal tomato intake in the anthropometric indices and blood levels of triglycerides, cholesterol, glucose, and uric acid of a young women population (n = 35, 19.6 ± 1.3 years) was evaluated. During 4 weeks, daily, participants ingested a raw ripe tomato (∼90 g) before lunch. Their anthropometric and biochemical parameters were measured repeatedly during the follow-up time. At the end of the 4 weeks, significant reductions were observed on body weight (-1.09 ± 0.12 kg on average), % fat (-1.54 ± 0.52%), fasting blood glucose (-5.29 ± 0.80 mg/dl), triglycerides (-8.31 ± 1.34 mg/dl), cholesterol (-10.17 ± 1.21 mg/dl), and uric acid (-0.16 ± 0.04 mg/dl) of the participants. The tomato pre-meal ingestion seemed to interfere positively in body weight, fat percentage, and blood levels of glucose, triglycerides, cholesterol, and uric acid of the young adult women that participated in this study. | 25,156,566 | [
0.1985049,
0.0834746,
-0.2085922,
-0.08299548,
0.04951381,
-0.3052422,
-0.1370261,
-0.03581531,
0.07713405,
-0.2085157,
0.06877207,
0.4303295,
0.1375733,
-0.0309404,
-0.7778959,
0.09296689,
-0.1694352,
0.01744084,
0.1699908,
-0.01071261,
-0.0094796,
0.4993404,
-0.4604278,... |
Relationship between clinical improvement and functional gains with clozapine in schizophrenia. | Impairment in psychosocial functioning is a key feature in schizophrenia, but few studies have examined the relationship between improvements in symptoms and functioning. We examined the relationship between change in symptoms and change in functioning in a group of patients with treatment-resistant schizophrenia after 6 and 12 weeks of clozapine treatment. Participants were assessed prior to clozapine and again at 6 and 12-week on the 18-item Brief Psychiatric Rating Scale (BPRS) and the Social and Occupational Functioning Scale (SOFAS). Change scores in BPRS and SOFAS at 6 and 12-week post-clozapine were calculated and the direct relationship was assessed via regression models. Forty-three participants were included in this study; age of sample was 42.1 ± 12.7 years, with 31 (72.1%) male participants. At baseline, the mean BPRS total and SOFAS scores were 46.98 ± 12.86 and 33.07 ± 10.79, respectively. There were significant improvements in BPRS total and SOFAS scores at 6 weeks, but no significant differences between 6 and 12-week assessments. There was no significant change in negative symptoms at both follow-up assessments. At 6-week, change in symptoms was not correlated with change in functioning and while the relationship between change in symptoms and functioning was stronger at 12 weeks, none of the BPRS factors emerged as a significant predictor. The present study found that lower baseline SOFAS score was the most robust predictor for improvements in SOFAS at 6 and 12-weeks. There appears to be a "ceiling" for functional improvements on clozapine, but follow-up studies are needed to examine functional gains beyond 12 weeks. | 25,156,578 | [
0.302461,
0.2230477,
0.0158844,
-0.3257676,
0.003656939,
-0.1318692,
-0.1715783,
0.2084885,
-0.134429,
-0.2922725,
0.10502,
-0.1036103,
-0.06856308,
0.2956764,
0.09579747,
-0.1633609,
-0.377663,
-0.04549766,
0.218068,
0.1113976,
-0.5430997,
0.2396223,
-0.2209616,
-0.251... |
Oxidative cleavage of benzylic C-N bonds under metal-free conditions. | An interesting procedure for the oxidative cleavage of benzylic C-N bonds has been developed. Using TBAI as the catalyst and H2O2 as the oxidant, various benzylamines were transformed into their corresponding aromatic aldehydes in moderate to good yields. Notably, this is the first example of an oxidative cleavage of benzylic C-N bonds under metal-free conditions. | 25,156,588 | [
-0.2780977,
0.0271469,
0.009829139,
0.04494003,
0.02468566,
-0.02943586,
-0.4521098,
0.004583981,
0.1323909,
-0.0364267,
-0.01039933,
0.02570897,
0.1193377,
0.02206516,
-0.1496674,
-0.13346,
-0.5994083,
0.378049,
0.1075725,
0.1365872,
0.1504334,
0.1545309,
-0.2161268,
0... |
Brain structural substrates of cognitive procedural learning in alcoholic patients early in abstinence. | Procedural learning allows for the acquisition of new behavioral skills. Previous studies have shown that chronic alcoholism is characterized by impaired cognitive procedural learning and brain abnormalities affecting regions that are involved in the automation of new cognitive procedures in healthy individuals. The goal of the present study was to investigate the brain structural substrates of cognitive procedural learning in alcoholic patients (ALs) early in abstinence. Thirty-one ALs and 31 control participants (NCs) performed the Tower of Toronto task (4 daily learning sessions, each comprising 10 trials) to assess cognitive procedural learning. We also assessed episodic and working memory, executive functions, and visuospatial abilities. ALs underwent 1.5T structural magnetic resonance imaging. The initial cognitive phase was longer in the AL group than in the NC group, whereas the autonomous phase was shorter. In ALs, the longer cognitive phase was predicted by poorer planning and visuospatial working memory abilities, and by smaller gray matter (GM) volumes in the angular gyrus and caudate nucleus. ALs' planning abilities correlated with smaller GM volume in the angular gyrus. Cognitive procedural learning was impaired in ALs, with a delayed transition from the cognitive to the autonomous phase. This slowdown in the automation of the cognitive procedure was related to lower planning abilities, which may have hampered the initial generation of the procedure to be learned. In agreement with this neuropsychological finding, a persistent relationship was found between learning performance and the GM volumes of the angular gyrus and caudate nucleus, which are usually regarded as markers of planning and initial learning of the cognitive procedure. | 25,156,613 | [
0.07463656,
0.3865125,
-0.0885978,
-0.217623,
-0.01634974,
-0.3865072,
-0.03184055,
-0.2742349,
-0.01295427,
0.370376,
-0.02614441,
0.2254223,
0.01489943,
0.001365417,
-0.2074717,
0.3061703,
-0.2957748,
0.1688202,
-0.1502905,
-0.09622014,
0.08119933,
0.1627176,
-0.0035217... |
Chronic methylphenidate treatment during early life is associated with greater ethanol intake in socially isolated rats. | Methylphenidate (MPH) is a stimulant prescribed to treat attention-deficit/ hyperactivity disorder. Its primary mechanism of action is in the dopamine system, alterations of which are associated with vulnerability to alcohol abuse. There are concerns that juvenile MPH treatment may influence adult drinking behavior. This study examined the interaction of MPH treatment and environmental rearing conditions, which are known to independently influence ethanol (EtOH) drinking behavior, on anxiety-like behavior and vulnerability to alcohol abuse in a juvenile rodent model. Male Sprague-Dawley rats were housed in enriched, standard, or isolated conditions for 4 weeks, starting at postnatal day 21. Rats were concurrently treated with 8 mg/kg/d MPH or saline, delivered via osmotic minipump. Anxiety-like behavior was determined at the end of the treatment session, and 5 weeks later. After MPH treatment, rats were exposed to a 2-bottle choice EtOH drinking procedure that lasted 3 weeks. Early life chronic MPH treatment was associated with greater EtOH intake and greater EtOH preference, but only in socially isolated animals. Isolated animals had greater levels of anxiety-like behavior than standard-housed or enriched animals after 4 weeks of exposure to the housing conditions, a difference that persisted even after all animals had been individually housed for an additional 5 weeks and exposed to EtOH. These results suggest that early life MPH treatment may increase vulnerability to EtOH drinking in adulthood in a subset of the population. Additionally, this study highlights the importance of early rearing condition for establishing long-lasting behavioral phenotypes. Environmental histories should be considered when prescribing MPH treatment to young children. | 25,156,616 | [
-0.3159276,
0.04658482,
-0.4516316,
0.1295597,
0.08579256,
-0.5763325,
-0.4596643,
-0.1442526,
-0.05032765,
-0.14085,
0.165518,
0.3094495,
-0.1335086,
0.0456111,
0.01535678,
0.05435484,
-0.4074852,
0.2973006,
-0.2440952,
0.1196471,
0.1617684,
0.007173415,
0.1519677,
-0.... |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.