title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Synthesis and characterization of self-curing hydrophilic bone cements for protein delivery. | New formulations of acrylic bone cements for bone defect reparation, based on self-hardening methyl methacrylate (MMA)/methacrylic acid (MAA), with a high capacity for protein delivery, have been developed. The self-curing formulations were prepared by partial substitution of solid phase PMMA microparticles by newly obtained PMAA microspheres. The PMAA microspheres were prepared by inverse suspension polymerization of their monomer and were cross-linked with N,N'-methylene-bis-acrylamide (MBA) (10-15 wt %) to produce stable systems in contact with aqueous media. PMAA microspheres were loaded with hydrolyzed collagen (HC) as a model protein to simulate bone morphogenetic protein delivery useful for hard tissue reconstruction. Solid phase PMMA microparticles in the formulation were partially substituted by new PMAA-HC microspheres and were characterized to determine viability as an acrylic bone cement in minimally invasive surgery. The incorporation of PMAA-HC microspheres decreased peak temperature by 20°C, which minimized thermal necrotic risk after implantation. Mechanical compression tests revealed a behavior, under dry conditions, close to ISO 5833 standard requirements. However, a drastic drop in mechanical strength, ∼64%, was obtained after 15 days of immersion in simulated physiological conditions (37°C and pH 7.4) and was attributed to water absorption and a subsequent plasticizing effect. The increase in water uptake and retention enhanced the capability for controlled protein delivery. Finally, the biocompatibility of the cements was determined; some toxicity of the material during the first hours of culture incubation was observed. Later, toxicity was observed to decrease due to nonreacted monomer leaching, which ensured the low toxicity of the already polymerized phase. | 25,209,322 | [
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Compound heterozygous PLEC mutations in a patient of consanguineous parentage with epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia. | Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD; OMIM 226670) is an autosomal recessive form of EBS, characterized by skin blistering at birth and delayed onset of muscle dystrophy. Mutations in PLEC, the gene encoding plectin, have been identified to be causal for EBS-MD. We report a case of EBS-MD with diffuse alopecia. Genetic study revealed the patient carrying compound heterozygous mutations in PLEC despite the consanguineous parentage. | 25,209,331 | [
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Cranial morphological diversity of early, middle, and late Holocene Brazilian groups: implications for human dispersion in Brazil. | The history of human occupation in Brazil dates to at least 14 kyr BP, and the country has the largest record of early human remains from the continent. Despite the importance and richness of Brazilian human skeletal collections, the biological relationships between groups and their implications for knowledge about human dispersion in the country have not been properly explored. Here, we present a comprehensive assessment of the morphological affinities of human groups from East-Central, Coastal, Northeast, and South Brazil from distinct periods and test for the best dispersion scenarios to explain the observed diversity across time. Our results, based on multivariate assessments of shape and goodness of fit tests of dispersion and adaptation models, favor the idea that Brazil experienced at least two large dispersion waves. The first dispersive event brought the morphological pattern that characterize Late Pleistocene groups continent-wide and that persisted among East-Central Brazil groups until recently. Within the area covered by our samples, the second wave was probably restricted to the coast and is associated with a distinct morphological pattern. Inland and coastal populations apparently did not interact significantly during the Holocene, as there is no clear signal of admixture between groups sharing the two morphological patterns. However, these results cannot be extended to the interior part of the country (Amazonia and Central Brazil), given the lack of skeletal samples in these regions. | 25,209,335 | [
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"Sliding angulation osteotomy": preliminary report of a novel technique of treatment for chronic radial head dislocation following missed Monteggia injuries. | Neglected anterior radial head dislocation in type I Monteggia lesions leads to restriction of movement, deformity and instability of the affected elbow. If left untreated this leads to a painful arthritic elbow due to secondary degenerative changes. This is a difficult problem to manage and many intra-articular, extra-articular and combined procedures have been described with variable results. We report a new technique of sliding angulation osteotomy for this condition, which allows both lengthening and angulation of the ulna. A novel technique of sliding angulation osteotomy of the proximal ulna was done to achieve reduction of the radial head. Four patients with persistent anterior radial head dislocation were treated at our institution with this technique. All of them had good clinical and radiological outcomes at final follow-up. Sliding angulation osteotomy is a technically simple procedure, which achieves lengthening and angulation of the ulna simultaneously in the sagittal plane and reduces the radial head. | 25,209,346 | [
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Cornelia de Lange syndrome. | Cornelia de Lange syndrome (CdLS; MIM #122470, 300590, 610759, 614701, 300882) is a rare and clinically variable disorder that affects multiple organs. It is characterized by intellectual disability (mild to severe), distinctive facial features, prenatal and postnatal growth retardation, and hirsutism. Congenital anomalies include malformations of the upper limbs, gastrointestinal malformation/rotation, pyloric stenosis, diaphragmatic hernia, heart defects and genitourinary malformations. Gastroesophageal reflux disease is present in almost all patients. In addition to classic forms, milder phenotypes have been reported. To date five genes [NIPBL (Nipped-B-like protein), SMC1A (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of chromosomes 3), RAD21 (human homolog of Schizosaccharomyces pombe radiation sensitive mutant 21) and HDAC8 (histone deacetylase 8)] have been associated with CdLS and mutations of these genes comprise the underlying defect in 70% of the patients. Here, we will provide a brief review of the clinical features of CdLS, summarize the known underlying genetic defects, prenatal and postnatal diagnosis possibilities, and genetic counseling. | 25,209,348 | [
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Potentially functional polymorphisms in the ERCC2 gene and risk of esophageal squamous cell carcinoma in Chinese populations. | ERCC2 is indispensable for nucleotide excision repair pathway, and its functional polymorphisms may be associated with cancer risk. In a large case-control study of 1126 esophageal squamous cell carcinomas (ESCC) patients and 1131 controls, we genotyped two SNPs in ERCC2 (rs238406 G > T and rs13181 T > G) and assessed their associations with ESCC risk. We found a significantly elevated ESCC risk associated with the rs238406 T variant genotypes (adjusted OR = 1.30 and 1.24, 95% CI = 1.02-1.66 and 1.03-1.49 for TG and TG/TT, respectively, compared with GG), particularly in the subgroup of those smoked more than 16 pack-years. Multivariate logistic regression analysis suggested a possible multiplicative gene-environment interaction between rs238406 genotypes and smoking (Pinteraction = 0.026) on ESCC risk. Although no significant risk associations were observed for rs13181, further mini meta-analysis with our and 18 other published studies of 5,012 cases and 8,238 controls found evidence of an association between the rs13181 variant G allele and esophageal cancer risk (TG/GG vs. TT, OR = 1.17; 95% CI = 1.02-1.33). Interestingly, we consistently found a significant correlation between variant genotypes of these two SNPs and ERCC2 mRNA expression. These findings suggest that potentially functional SNPs in ERCC2 may contribute to ESCC risk. | 25,209,371 | [
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Concurrent and longitudinal relationships between cognitive activity, cognitive performance, and brain volume in older adult women. | We investigated (a) cross-sectional associations between cognitive activity, cognitive performance, and MRI measures and (b) longitudinal associations between cognitive activity and change in cognitive performance, using structural equation modeling (SEM). Women's Health Initiative Memory Study (WHIMS) Extension participants who continued annual neuropsychological assessments by telephone and completed a concurrent questionnaire of cognitive activities and MRI scans were included (mean age = 81.4 years; N = 393). Cognitive performance was measured by tests of attention, working memory, verbal fluency, executive function, and memory. Cognitive activity was measured by self-reported participation in a variety of cognitive activities (e.g., reading books, playing games, computer activities; N = 11 items) during the previous 12 months. MRI measures included gray and white matter normal and white matter lesion volumes. SEM demonstrated a significant association between cognitive activity and baseline cognitive performance but not change over 2-3 years. Gray and white matter was associated with cognitive performance but not cognitive activity. All effects remained significant after modeling covariates (age, education, depressive symptoms, WHIMS intervention assignment, and intracranial volume). Cognitive activity benefits current cognitive performance but is not associated with change over 2-3 years. Cognitive activity and MRI volumes are independently associated with cognitive performance, suggesting distinct cognitive and brain reserve constructs. | 25,209,372 | [
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Submandibular artery: bilobed platysma myocutaneous flap for total lower lip reconstruction. | Lower lip reconstruction following cancer resection includes a variety of clinical and microsurgical options. We have developed a myocutaneous flap for full thickness reconstruction with a functioning muscle. In all patients, the submandibular artery was outlined using computerized tomographic angiography and Doppler. The flap was designed after resection. The first lobe was designed to fill the defect and was outlined 90° from the defect margin, with the submandibular artery in the center of the flap. A second lobe was then outlined 90° from the first lobe. The flap was raised along with the platysma muscle and artery, with the first lobe rotated to the lip and the second lobe inset into the first lobe site, permitting neck closure without skin redundancy. From January to May 2012, 17 patients were treated with this flap, and all flaps survived. All of the patients had oral continence at sixteen months, and electromyography documented platysma function. The flap provides single-stage lower lip reconstruction with functional muscle. | 25,209,383 | [
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Effects of metabolic acidosis on intracellular pH responses in multiple cell types. | Metabolic acidosis (MAc), a decrease in extracellular pH (pHo) caused by a decrease in [HCO3 (-)]o at a fixed [CO2]o, is a common clinical condition and causes intracellular pH (pHi) to fall. Although previous work has suggested that MAc-induced decreases in pHi (ΔpHi) differ among cell types, what is not clear is the extent to which these differences are the result of the wide variety of methodologies employed by various investigators. In the present study, we evaluated the effects of two sequential MAc challenges (MAc1 and MAc2) on pHi in 10 cell types/lines: primary-cultured hippocampal (HCN) neurons and astrocytes (HCA), primary-cultured medullary raphé (MRN) neurons, and astrocytes (MRA), CT26 colon cancer, the C2C12 skeletal muscles, primary-cultured bone marrow-derived macrophages (BMDM) and dendritic cells (BMDC), Ink4a/ARF-null melanocytes, and XB-2 keratinocytes. We monitor pHi using ratiometric fluorescence imaging of 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein while imposing MAc: lowering (pHo) from 7.4 to 7.2 by decreasing [HCO3 (-)]o from 22 to 14 mM at 5% CO2 for 7 min. After MAc1, we return cells to the control solution for 10 min and impose MAc2. Using our definition of MAc resistance [(ΔpHi/ΔpHo) ≤ 40%], during MAc1, ∼70% of CT26 and ∼50% of C2C12 are MAc-resistant, whereas the other cell types are predominantly MAc-sensitive. During MAc2, some cells adapt [(ΔpHi/ΔpHo)2 < (ΔpHi/ΔpHo)1], particularly HCA, C2C12, and BMDC. Most maintain consistent responses [(ΔpHi/ΔpHo)2 ≅ (ΔpHi/ΔpHo)1], and a few decompensate [(ΔpHi/ΔpHo)2>(ΔpHi/ΔpHo)1], particularly HCN, C2C12, and XB-2. Thus, responses to twin MAc challenges depend both on the individual cell and cell type. | 25,209,413 | [
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Obesity-stroke paradox and initial neurological severity. | An obesity paradox in patients with stroke has been documented. However, although the initial neurological severity (INS) is generally the most important prognostic factor, the impact of this paradox has not been considered in most previous studies. We sought to investigate the impact of obesity on INS in patients with ischaemic stroke and to investigate whether it is a significant risk factor for short-term outcomes. A total of 2670 patients from Seoul National University Hospital with ischaemic stroke were enrolled from October 2002 to May 2013. Baseline information, including body mass index (BMI) and INS, was collected at admission. Associations between obesity and INS were analysed. In addition, we evaluated the effect of BMI on modified Rankin Scale (mRS) 3 months after stroke onset. Among the 2670 patients, patients whose BMI levels were higher than the chosen reference level had reduced risks of moderate to severe INS (Q2: OR, 0.65; 95% CI 0.49 to 0.87; Q3: OR, 0.48; 95% CI 0.35 to 0.65; Q4: OR, 0.39; 95% CI 0.28 to 0.54; and Q5: 0.31; 95% CI 0.22 to 0.44). In addition, of the 703 patients with available 3-month mRS patients with higher BMI levels seem to have had more favourable outcomes. Such associations disappeared after adjusting for INS. In our study, although obesity was associated with better short-term functional outcomes, INS might be a more important prognostic factor. Therefore, initial status should also be considered when considering an 'obesity paradox' in chronic diseases. | 25,209,415 | [
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Optimal design of clinical trials with biologics using dose-time-response models. | Biologics, in particular monoclonal antibodies, are important therapies in serious diseases such as cancer, psoriasis, multiple sclerosis, or rheumatoid arthritis. While most conventional drugs are given daily, the effect of monoclonal antibodies often lasts for months, and hence, these biologics require less frequent dosing. A good understanding of the time-changing effect of the biologic for different doses is needed to determine both an adequate dose and an appropriate time-interval between doses. Clinical trials provide data to estimate the dose-time-response relationship with semi-mechanistic nonlinear regression models. We investigate how to best choose the doses and corresponding sample size allocations in such clinical trials, so that the nonlinear dose-time-response model can be precisely estimated. We consider both local and conservative Bayesian D-optimality criteria for the design of clinical trials with biologics. For determining the optimal designs, computer-intensive numerical methods are needed, and we focus here on the particle swarm optimization algorithm. This metaheuristic optimizer has been successfully used in various areas but has only recently been applied in the optimal design context. The equivalence theorem is used to verify the optimality of the designs. The methodology is illustrated based on results from a clinical study in patients with gout, treated by a monoclonal antibody. | 25,209,423 | [
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Bone's responses to different designs of implant-supported fixed partial dentures. | This paper explores the biomechanics and associated bone remodeling responses of two different abutment configurations, namely implant-implant-supported versus tooth-implant-supported fixed partial dentures. Two 3D finite element analysis models are created based upon computerized tomography data. The strain energy density induced by occlusal loading is used as a mechanical stimulus for driving the bone remodeling. To measure osseointegration and stability during healing, a resonance frequency analysis is conducted. At the second premolar peri-implant region, overloading resorption around the neck of implant is identified in both the models over the first 12 months. Stress-shielding around the edentulous region is also observed in both the models with a greater resorption rate found in the implant-implant case. The remodeling and resonance frequency analyses reveal that the tooth-implant scheme offers a higher degree of osseointegration. The remodeling procedure is expected to provide prosthodontists with a modeling tool to assess possible long-term clinical outcomes. | 25,209,424 | [
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Emotional assessment of patients with oral lichen planus. | Oral lichen planus is a chronic immune-mediated disease with an estimated prevalence of 0.5-2.5% in the general population. Patients with oral lichen planus are often emotionally unstable and anxious and may develop concomitant systemic disorders. The objective of this study was to evaluate emotional characteristics of patients with oral lichen planus. Two groups were studied: the first group consisted of 48 patients with a diagnosis of oral lichen planus, and the second group consisted of controls without the disease matched for age and gender at a proportion of 1:1. The emotional state of the patients was evaluated using the State-Trait Anxiety Inventory, SF-36 generic quality of life questionnaire, and the Self Reporting Questionnaire-20. The present investigation demonstrated the presence of anxiety and depression in patients with oral lichen planus and a negative impact of the disorder on the patient's quality of life as indicated by impairment of the physical aspect, vitality, mental health, and social aspect domains. This could indicate that associated psychological treatment may be important in the follow-up of these patients. | 25,209,436 | [
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How Can Adult Children Influence Parents' Long-Term Care Insurance Purchase Decisions? | Long-term care (LTC) poses a significant strain on public health insurance financing. In response, there is policy interest in bolstering the private long-term care insurance (LTCI) market. Although families are central to LTC provision, their role in LTCI demand remains unclear. The purpose of this study was to obtain in-depth information concerning: (a) How do older parents evaluate the need for LTCI, (b) what role do adult children play? and (c) How do families communicate about parents' LTC preferences and plans, including LTCI purchase? We conducted focus groups with older parents and adult children in diverse markets. Two groups were conducted with older parents who had purchased LTCI and two with parents who had not purchased LTCI. Four groups were conducted with adult children, mixed as to whether their parents had purchased LTCI. Probes were informed by published reasons for purchasing or not purchasing LTCI. We analyzed transcriptions using directed content analysis and constant comparative method. Older parents valued autonomy for themselves and their children. Older parent purchasers regarded LTCI as supporting this value while nonpurchasers perceived limitations. Adult children described unstated expectations that they would care for their parents. Though discussions between parents and children about LTCI were rare, successful influence occurred when children appealed to shared values, specifically avoiding burden and remaining home. Messages that emphasize autonomy over LTC decisions and interventions that start the LTC conversation among families, with attention to shared values, could increase private LTCI uptake. | 25,209,446 | [
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Trends of pre-hospital emergency medical services activity over 10 years: a population-based registry analysis. | The number of requests to pre-hospital emergency medical services (PEMS) has increased in Europe over the last 20 years, but epidemiology of PEMS interventions has little be investigated. The aim of this analysis was to describe time trends of PEMS activity in a region of western Switzerland. Use of data routinely and prospectively collected for PEMS intervention in the Canton of Vaud, Switzerland, from 2001 to 2010. This Swiss Canton comprises approximately 10% of the whole Swiss population. We observed a 40% increase in the number of requests to PEMS between 2001 and 2010. The overall rate of requests was 35/1000 inhabitants for ambulance services and 10/1000 for medical interventions (SMUR), with the highest rate among people aged ≥ 80. Most frequent reasons for the intervention were related to medical problems, predominantly unconsciousness, chest pain respiratory distress, or cardiac arrest, whereas severe trauma interventions decreased over time. Overall, 89% were alive after 48 h. The survival rate after 48 h increased regularly for cardiac arrest or myocardial infarction. Routine prospective data collection of prehospital emergency interventions and monitoring of activity was feasible over time. The results we found add to the understanding of determinants of PEMS use and need to be considered to plan use of emergency health services in the near future. More comprehensive analysis of the quality of services and patient safety supported by indicators are also required, which might help to develop prehospital emergency services and new processes of care. | 25,209,450 | [
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Hydroa vacciniforme with eye involvement: report of two cases. | We herein report two patients with hydroa vacciniforme and concomitant ophthalmic involvement, primarily in the form of keratoconjunctivitis leading to corneal opacity. Awareness of this occasional manifestation may help to prevent severe complications. | 25,209,448 | [
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Understanding Positive Play: An Exploration of Playing Experiences and Responsible Gambling Practices. | This study is one of the first to explore in detail the behaviors, attitudes and motivations of players that show no signs of at-risk or problem gambling behavior (so-called 'positive players'). Via an online survey, 1484 positive players were compared with 209 problem players identified using the Lie/Bet screen. The study identified two distinct groups of positive players defined according to their motivations to play and their engagement with responsible gambling (RG) practices. Those positive players that played most frequently employed the most personal RG strategies. Reasons that positive players gave for gambling were focused on leisure (e.g., playing for fun, being entertained, and/or winning a prize). By contrast, problem gamblers were much more focused upon modifying mood states (e.g., excitement, relaxation, depression and playing when bored or upset). The present study also suggests that online gambling is not, by default, inherently riskier than gambling in more traditional ways, as online gambling was the most popular media by which positive players gambled. Furthermore, most positive players reported that it was easier to stick to their limits when playing the National Lottery online compared to traditional retail purchasing of tickets. Problem players were significantly more likely than positive players to gamble with family and friends, suggesting that, contrary to a popular RG message, social play may not be inherently safer than gambling alone. It is proposed that players (generally) may identify more with the term 'positive play' than the term 'RG' which is frequently interpreted as being aimed at people with gambling problems, rather than all players. | 25,209,455 | [
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International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. | In 2006, WHO published international growth standards for children younger than 5 years, which are now accepted worldwide. In the INTERGROWTH-21(st) Project, our aim was to complement them by developing international standards for fetuses, newborn infants, and the postnatal growth period of preterm infants. INTERGROWTH-21(st) is a population-based project that assessed fetal growth and newborn size in eight geographically defined urban populations. These groups were selected because most of the health and nutrition needs of mothers were met, adequate antenatal care was provided, and there were no major environmental constraints on growth. As part of the Newborn Cross-Sectional Study (NCSS), a component of INTERGROWTH-21(st) Project, we measured weight, length, and head circumference in all newborn infants, in addition to collecting data prospectively for pregnancy and the perinatal period. To construct the newborn standards, we selected all pregnancies in women meeting (in addition to the underlying population characteristics) strict individual eligibility criteria for a population at low risk of impaired fetal growth (labelled the NCSS prescriptive subpopulation). Women had a reliable ultrasound estimate of gestational age using crown-rump length before 14 weeks of gestation or biparietal diameter if antenatal care started between 14 weeks and 24 weeks or less of gestation. Newborn anthropometric measures were obtained within 12 h of birth by identically trained anthropometric teams using the same equipment at all sites. Fractional polynomials assuming a skewed t distribution were used to estimate the fitted centiles. We identified 20,486 (35%) eligible women from the 59,137 pregnant women enrolled in NCSS between May 14, 2009, and Aug 2, 2013. We calculated sex-specific observed and smoothed centiles for weight, length, and head circumference for gestational age at birth. The observed and smoothed centiles were almost identical. We present the 3rd, 10th, 50th, 90th, and 97th centile curves according to gestational age and sex. We have developed, for routine clinical practice, international anthropometric standards to assess newborn size that are intended to complement the WHO Child Growth Standards and allow comparisons across multiethnic populations. Bill & Melinda Gates Foundation. | 25,209,487 | [
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International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. | In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. Bill & Melinda Gates Foundation. | 25,209,488 | [
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Syntheses and biological activities of the proposed structure of apteniol A and its derivatives. | We describe the syntheses of the proposed structure of diphenyl ether oxyneolignan, apteniol A and its derivatives. The diphenyl ether moiety of proposed apteniol A was formed via Ullmann ether synthesis, but the spectral data of the synthesized apteniol A did not agree with that in previous studies. The dimethyl ester derivative of the proposed apteniol A was found to enhance neurite outgrowth in PC12 cells and inhibit antigen-induced degranulation in RBL-2H3 cells. | 25,209,495 | [
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Determination of hydrophobicity of dry-heated wheat starch granules using sucrose fatty acid esters (SFAE). | Sucrose fatty acid esters (SFAE) were adsorbed onto dry-heated (120 °C for 10, 20, 40, 60, and 120 min) wheat starch granules and extracted with ethyl ether in a Soxhlet apparatus without gelatinization of the starch granules. The amount of sucrose in the extracted SFAE was determined by the phenol sulfate method. A gradual increase of the sucrose from 159 to 712 μg, in SFAE per gram of starch, occurred with increasing dry-heating time and demonstrated the increased hydrophobicity of the starch granules. Increase of the SFAE was highly correlated (r = 0.9816) to increase of the oil-binding capacity of the dry-heated wheat starch granules. Non-waxy rice, waxy rice, sweet potato, and potato starch granules also showed higher hydrophobicity after dry-heating by this method. | 25,209,506 | [
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You didn't have to do that: belief in free will promotes gratitude. | Four studies tested the hypothesis that a weaker belief in free will would be related to feeling less gratitude. In Studies 1a and 1b, a trait measure of free will belief was positively correlated with a measure of dispositional gratitude. In Study 2, participants whose free will belief was weakened (vs. unchanged or bolstered) reported feeling less grateful for events in their past. Study 3 used a laboratory induction of gratitude. Participants with an experimentally reduced (vs. increased) belief in free will reported feeling less grateful for the favor. In Study 4, a reduced (vs. increased) belief in free will led to less gratitude in a hypothetical favor scenario. This effect was serially mediated by perceiving the benefactor as having less free will and therefore as being less sincerely motivated. These findings suggest that belief in free will is an important part of being able to feel gratitude. | 25,209,516 | [
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Viewpoint: Re-instating a 'public health' system under universal health care in India. | I examine possibilities for strengthening essential public health functions in the context of India's drive to implement universal health care. In a country where population health outcomes are rooted in social, political, economic, cultural, and ecological conditions, it is important to have a state mediated public health system that can modify the causes of the major public health problems. This calls for strengthening the social epidemiological approach in public health by demarcating public health functions distinct from medical care. This will be a prerequisite for the growth of the public health profession in the country, because it can offer avenues for newly trained professionals within the country to work in 'core' public health. | 25,209,538 | [
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Phytodiversity on fly ash deposits: evaluation of naturally colonized species for sustainable phytorestoration. | Proliferation of fly ash (FA) deposits and its toxicity have become a global concern, which contaminate the ecosystems of our Earth. In this regard, identification of potential plant species for FA deposits' restoration is the main concern. Keeping this view in mind, the present study was conducted to identify potential plant species naturally growing on FA deposits for the restoration purposes. Six intensive surveys were made during 2010-2014 to collect naturally growing plant species during different seasons from two FA deposits in Unchahar of Raebareli district, Uttar Pradesh, India. The plant species having potential for FA deposits' restoration were identified on the basis of their ecological importance, dominance at the study sites and socio-economic importance for rural livelihoods. Typha latifolia L., Cynodon dactylon (L.) Pers., Saccharum spontaneum L., Saccharum bengalense Retz. (syn. Saccharum munja), Prosopis juliflora (Sw.) DC., Ipomoea carnea Jacq. and Acacia nelotica L. are identified as potential plant species for FA deposits' restoration. Furthermore, the characteristics of naturally colonized species can be used for the phytorestoration during a revegetation plan of new FA deposits for multiple benefits. | 25,209,541 | [
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Two novel zeolitic imidazolate frameworks (ZIFs) as sorbents for solid-phase extraction (SPE) of polycyclic aromatic hydrocarbons (PAHs) in environmental water samples. | In this work, two novel zeolitic imidazolate framework (ZIF) materials, ZIF-7 and ZIF-11, were firstly introduced as solid-phase extraction (SPE) sorbents for PAHs efficient extraction and highly sensitive analysis in environmental water samples with high performance liquid chromatography (HPLC) coupled with fluorescence detection. ZIF-7 and ZIF-11 were successfully synthesized and characterized with SEM, FTIR, XRD and water contact angels, exhibiting unique and excellent stability, spatial structure and chemical composition, promising for environmental PAHs efficient enrichment through hydrophobic, π-π and π-complexation interactions. The topology effect on PAHs extraction was compared between ZIF-7 and ZIF-11, considering they have the same composition in metal ion (Zn(2+)) and organic linker, but differing spatial structures: ZIF-7 has a cubic structure, while ZIF-11 is a rhombic dodecahedron. At last, ZIF-11 with markedly better extraction efficiencies was selected for subsequent analysis. Under optimum extraction conditions such as sample volume, extraction time, desorption conditions, volume of organic modifier and salt concentration, a robust and highly efficient method based on ZIF-11 as a novel SPE sorbent has been successfully developed for environmental PAHs analysis. Satisfactory precision and accuracy ranging from 1-2.4 × 10(3) ng L(-1) as well as ultrasensitive detection limits of 0.08-1.6 ng L(-1) have been successfully achieved. Moreover, ZIF-11 extraction also exhibited high recoveries of 82.4-112.7% with relative standard deviations (RSDs) being less than 9% for PAHs in the environmental water samples. Therefore, our novel, convenient and efficient extraction method based on ZIF-11 as a sorbent is promising for applications in future trace-level environmental PAHs analyses. | 25,209,546 | [
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Thermodynamics of water condensation on a primary marine aerosol coated by surfactant organic molecules. | A large subset of primary marine aerosols can be initially (immediately upon formation) treated using an "inverted micelle" model. We study the thermodynamics of heterogeneous water condensation on such a marine aerosol. Its hydrophobic organic coating can be processed by chemical reactions with atmospheric species; this enables the marine aerosol to serve as a nucleating center for water condensation. The most probable pathway of such "aging" involves atmospheric hydroxyl radicals that abstract hydrogen atoms from organic molecules coating the aerosol (first step), the resulting radicals being quickly oxidized by ubiquitous atmospheric oxygen molecules to produce surface-bound peroxyl radicals (second step). Taking these two reactions into account, we derive an expression for the free energy of formation of an aqueous droplet on a marine aerosol. The model is illustrated by numerical calculations. The results suggest that the formation of aqueous droplets on marine aerosols is most likely to occur via Köhler activation rather than via nucleation. The model allows one to determine the threshold parameters necessary for the Köhler activation of such aerosols. Numerical results also corroborate previous suggestions that one can omit some chemical species of aerosols (and other details of their chemical composition) in investigating aerosol effects on climate. | 25,209,578 | [
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Multiple sclerosis in Germany: data analysis of administrative prevalence and healthcare delivery in the statutory health system. | Healthcare-utilization data for multiple sclerosis (MS) are scarce in Germany. The Purpose of the study was to analyse administrative prevalence of MS, medication use and type of specialists involved in MS treatment in the outpatient setting in Bavaria. Pseudonymized claims data from Bavarian Statutory Health Insurance (SHI)-accredited physicians were used. Administrative prevalence of MS was defined as having ≥1 MS diagnosis (International Classification of Diseases, 10th edition, code G35) documented by a neurologist or psychiatrist, or ≥1 prescription for disease-modifying drugs (DMDs)). The administrative prevalence calculated for Bavaria was projected to Germany. DMD prescription and involvement of different specialities in health care service for MS patients was analysed. Administrative prevalence of MS in Bavaria increased from 0.123% to 0.175% of insured persons between 2005 and 2009; when projected, this yielded ~102,000-143,000 patients with MS in the German population. The percentage of patients receiving ≥1 DMD prescription increased from 45.5% to 50.5%. Patients with MS were mainly treated by neurologists in the ambulatory care setting. These results provide important information on the administrative prevalence of MS in Bavaria and on healthcare provision for patients, which is relevant for resource planning in the healthcare sector. | 25,209,585 | [
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Long-term Outcome of Peripherally Implanted Venous Access Ports in the Forearm in Female Cancer Patients. | The aim of this retrospective study was to analyze the long-term outcome of peripherally implanted venous access ports in the forearm at our institution in a female patient collective. Between June 2002 and May 2011, a total of 293 female patients with an underlying malignancy had 299 forearm ports implanted in our interventional radiology suite. The mean age of the cohort was 55 ± 12 years (range 26-81 years). The majority of women suffered from breast (59.5 %) or ovarian cancer (28.1 %). Complications were classified as infectious complications, thrombotic and nonthrombotic catheter dysfunction (dislocation of the catheter or port chamber, fracture with/without embolization or kinking of the catheter, port occlusion), and others. We analyzed a total of 90,276 catheter days in 248 port systems (47 patients were lost to follow-up). The mean device service interval was 364 days per catheter (range 8-2,132, median 223 days, CI 311-415, SD 404). Sixty-seven early (≤ 30 days from implantation) or late complications (>30 days) occurred during the observation period (0.74/1,000 catheter days). Common complications were port infection (0.18/1,000 days), thrombotic dysfunction (0.12/1,000 days), and skin dehiscence (0.12/1,000 days). Nonthrombotic dysfunction occurred in a total of 21 cases (0.23/1,000 days) and seemed to cumulate on the venous catheter entry site on the distal upper arm. Peripherally implanted venous access ports in the forearm are a safe alternative to chest or upper-arm ports in female oncology patients. Special attention should be paid to signs of skin dehiscence and nonthrombotic dysfunction, especially when used for long-term treatment. | 25,209,595 | [
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The risk for depression in patients with ankylosing spondylitis: a population-based cohort study. | Depression is frequent in ankylosing spondylitis (AS) patients. However, epidemiological data about the potential increase in risk are lacking. This study compares the rate of doctor-diagnosed depression in a well defined cohort of AS patients to the general population seeking care. The Skåne Healthcare Register comprises healthcare data of each resident in Region Skåne, Sweden (population 1.2 million), including ICD-10 diagnoses. Using physician coded consultation data from years 1999 to 2011, we calculated depression consultation rates for all AS patients. We obtained standardized depression-rate ratios by dividing the observed depression rate in AS patients by the expected rate based on the corresponding age- and sex-specific rates of depression in the general population seeking care. A ratio > 1 equals a higher rate of depression among AS patients. The AS cohort consisted of 1738 subjects (65% men) with a mean age of 54 years. The reference population consisted of 967,012 subjects. During the 13-year observation period 10% (n = 172) of the AS cohort had a doctor-diagnosed depression compared to 6% (n = 105) to be expected. The standardized estimate of depression-rate ratio was 1.81 (95% confidence interval 1.44 to 2.24) in women men and 1.49 (1.20 to 1.89) in men. The rate of doctor-diagnosed depression is increased about 80% in female and 50% in male AS patients. Future challenges are to timely identify and treat the AS patients who suffer from depression. | 25,209,603 | [
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Predicting the Time Course of Individual Objects with MEG. | To respond appropriately to objects, we must process visual inputs rapidly and assign them meaning. This involves highly dynamic, interactive neural processes through which information accumulates and cognitive operations are resolved across multiple time scales. However, there is currently no model of object recognition which provides an integrated account of how visual and semantic information emerge over time; therefore, it remains unknown how and when semantic representations are evoked from visual inputs. Here, we test whether a model of individual objects--based on combining the HMax computational model of vision with semantic-feature information--can account for and predict time-varying neural activity recorded with magnetoencephalography. We show that combining HMax and semantic properties provides a better account of neural object representations compared with the HMax alone, both through model fit and classification performance. Our results show that modeling and classifying individual objects is significantly improved by adding semantic-feature information beyond ∼200 ms. These results provide important insights into the functional properties of visual processing across time. | 25,209,607 | [
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Influence of ofloxacin on photosystems I and II activities of Microcystis aeruginosa and the potential role of cyclic electron flow. | Pollution with antibiotics poses a great risk to aquatic ecosystems. Although some toxic effects of antibiotics on photosystem II (PSII) have been documented, their toxicity to photosystem I (PSI) is still unclear. In this study, effects of ofloxacin on activities of both PSI and PSII of Microcystis aeruginosa (Kützing) Kützing were investigated. Exposure to 0.1 mg L(-)(1) ofloxacin led to increases in contents of chlorophyll a and carotenoids and photosynthetic activity of M. aeruginosa. PSI activity and its electron transport were not affected by 0.1 mg L(-)(1) ofloxacin. When M. aeruginosa was exposed to ≥10 mg L(-)(1) ofloxacin, the electron transport rates of PSI and PSII, the yield of cyclic electron flow (CEF) and the contribution of linear electron flow (LEF) to PSI decreased whereas Y(NA) (limitation of donor side of PSI) and Y(NO) (the quantum yield of non-regulated energy dissipation in PSII) significantly increased. CEF had a significant contribution to alleviating the inhibitory effect of ofloxacin on PSI of M. aeruginosa treated with low concentrations of ofloxacin. The protective role CEF for tolerance of PSI to the toxicity of ofloxacin decreased with increasing ofloxacin concentration. | 25,209,631 | [
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Global burden of dental condition among children in nine countries participating in an international oral health promotion programme, 2012-2013. | The Live.Learn.Laugh. phase 2 programme is a unique global partnership between FDI World Dental Federation and Unilever Oral Care which aims to provide measurable improvement of oral health on a global scale through encouraging twice-daily brushing with a fluoride toothpaste. It was based on international recommendations using the principles of health promotion within school for the implementation of preventive health strategies. This paper is an overview of the dental caries condition of children from 2012 to 2013 in nine countries included in four World Health Organisation (WHO) regions. A cross-sectional study was conducted in each country before the implementation of health-promotion measures focused on twice-daily toothbrushing with fluoride toothpaste. The sample was based on stratified sampling according to the WHO pathfinder recommendations. From a total of 7,949 children examined, there were 517 children (1-2 years of age), 1,667 preschool children (3-5 years of age) and 5,789 schoolchildren (6-13 years of age). The prevalence and severity of primary dental caries, early childhood caries and temporary dental caries were described using decayed, filled teeth (dft), permanent decayed, missing, filled teeth (DMFT) indices and the significant caries index (SCI). The major findings were a high prevalence of caries, identification of high-risk groups and inequality in the distribution of the severity of dental conditions. Aggregated data from this overview should provide justification for implementing an oral health programme. The main point is the need to retain and expand the community fluoridation programme as an effective preventive measure. At the individual level, the aggregated data identify the need for more targeted efforts to reach children early - especially among specific high-risk groups. | 25,209,648 | [
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Immune functions of platelets. | This review collects evidence about immune and inflammatory functions of platelets from a clinician's point of view. A focus on clinically relevant immune functions aims at stimulating further research, because the complexity of platelet immunity is incompletely understood and not yet translated into patient care. Platelets promote chronic inflammatory reactions (e.g. in atherosclerosis), modulate acute inflammatory disorders such as sepsis and other infections (participating in the host defense against pathogens), and contribute to exacerbations of autoimmune conditions (like asthma or arthritis). It would hence be obsolete to restrict a description of platelet functions to thrombosis and haemostasis--platelets clearly are the most abundant cells with immune functions in the circulation. | 25,209,670 | [
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Alpha-synuclein binds to the inner membrane of mitochondria in an α-helical conformation. | The human alpha-Synuclein (αS) protein is of significant interest because of its association with Parkinson's disease and related neurodegenerative disorders. The intrinsically disordered protein (140 amino acids) is characterized by the absence of a well-defined structure in solution. It displays remarkable conformational flexibility upon macromolecular interactions, and can associate with mitochondrial membranes. Site-directed spin-labeling in combination with electron paramagnetic resonance spectroscopy enabled us to study the local binding properties of αS on artificial membranes (mimicking the inner and outer mitochondrial membranes), and to evaluate the importance of cardiolipin in this interaction. With pulsed, two-frequency, double-electron electron paramagnetic resonance (DEER) approaches, we examined, to the best of our knowledge for the first time, the conformation of αS bound to isolated mitochondria. | 25,209,675 | [
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The Utility of the WHO ICD-10-AM Pastoral Intervention Codings Within Religious, Pastoral and Spiritual Care Research. | The World Health Organization (WHO) 'Pastoral Intervention Codings' were first released in 2002 as part of the 'International Statistical Classification of Diseases and Related Health Problems' (WHO 2002). The purpose of the WHO pastoral intervention codings (colloquially abbreviated as 'WHO-PICs') was to record and account for the religious, pastoral and/or spiritual interventions of chaplains and volunteers providing care to patients and other clients experiencing religious and/or spiritual health and well-being issues. The intent of such WHO codings was to provide information in five areas: statistical, research, clinical, education and policy. The purpose of this paper predominantly accounts for research although it does intersect and relate to other WHO priorities. Over the past 10 years, research by the current and associated authors to test the efficacy of the WHO-PICs has been implemented in a number of different health and welfare contexts that have engaged chaplaincy personnel. In summary, while the WHO-PICs are yet to be more widely utilized internationally, the codings have largely proven to be valuable indices appropriate to a variety of contexts. Research utilizing the WHO-PICs, however, has also revealed the necessity for a number of changes and inclusions to be implemented. Recommendations concerning the future utilisation of the WHO-PICs are made, as are recommendations for these codings to be further developed and promoted by the WHO, so as to more accurately record religious, pastoral and spiritual interventions. | 25,209,684 | [
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Individual phenolic response and peroxidase activity in peel of differently sun-exposed apples in the period favorable for sunburn occurrence. | Extreme weather events like high solar radiation can cause stress in apple fruits (Malus domestica Borkh.). The aim of the study was to make a screening of individual phenols and peroxidase activity in apple peel as a response to sunburn and different sun-exposures in the period when weather conditions are suitable for sunburn occurrence. Apple fruits of 'Golden Delicious' and 'Braeburn' were sampled. Fruit temperature and color were measured prior HPLC-MS(2) and peroxidase activity analyses. Sunburned peel was darker and more yellow-red in comparison to healthy peel, which appeared yellow-green. Fruit temperature, total as well as individual flavonols and dihydrochalcones, total hydroxycinnamics and perixodase activity were highest in sunburned peel in comparison with healthy sun-exposed peel, furthermore both were different than shaded sides of both fruits and peel of apples inside the tree crown; moreover in sunburned peel dihydrochalcones were determined for the first time. Chlorogenic acid was up to 2.5 times higher, 3-hydroxy-phloretin-2'-O-xyloglucoside was up to 10 times higher and quercetin-3-galactoside was up to 33 times higher in sunburned peel, comparing to shaded sided peels. Flavanols did not show a distinct pattern. A deeper insight in phenolic response against environmental stress caused by high solar radiation and high air temperatures has been made. | 25,209,696 | [
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Pustular secondary syphilis: report of three cases and review of the literature. | Pustular syphilis is an extremely rare manifestation of secondary syphilis. Failure to recognize the disease can have devastating consequences. We present three patients with pustular syphilis as the primary manifestation of secondary syphilis. Patient 1 was initially diagnosed by Venereal Disease Research Laboratory (VDRL) test (titers 1 : 32) and confirmed by enzyme immunoassay (EIA) for Treponema pallidum. Patient 2 was screened for syphilis by VDRL (titers 1 : 64), yielding a positive result, and tested negative for HIV. Secondary syphilis was confirmed by EIA. In Patient 3, a diagnosis of secondary syphilis was established by VDRL (titers 1 : 128) and EIA. Treponema pallidum was detected by dark field microscopy in three patients. Testing for HIV infection was negative in all patients. Diagnosis in secondary syphilis remains challenging because of the diversity of clinical presentations. The most commonly observed cutaneous presentation is a generalized, non-pruritic, papulosquamous eruption varying from pink to violaceous to brown, with mucous membrane involvement. The diagnostic methods used to identify secondary syphilis are the same as those used to diagnose other stages of syphilitic infection. The persistence of syphilis in both developed and underdeveloped regions highlights the importance of considering syphilitic infection in the setting of a cutaneous pustular eruption, especially one that fails to respond to standard therapy. Testing for other sexually transmitted diseases, including HIV, should be performed in all patients diagnosed with syphilis. | 25,209,699 | [
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Context-dependent latent inhibition in preweanling rats. | Preexposure to a conditioned stimulus (CS) usually weakens conditioning, an effect known as latent inhibition. Similar to other learning interference effects, latent inhibition has been characterized as context-dependent, which means that the magnitude of this effect can be attenuated by changing the context between the different phases of the procedure (e.g., preexposure and conditioning). Latent inhibition has been found with a variety of procedures in infant rats, but the few studies that examined the context-dependency of this phenomenon during this ontogenetic period found no context-change effect. The present study explored the context-dependency of latent inhibition during infancy using a conditioned taste aversion preparation and employing contexts enriched with distinctive odors to increase the possible efficacy of the context manipulation. Experiment 1 showed that three preexposures to the CS (saccharin) were sufficient to retard conditioning to the same CS, although this effect was also observed in a control group preexposed to an alternative taste stimulus (saline), in comparison with a non-preexposed control group. In Experiment 2a, the CS-preexposure effect was found to be specific to the preexposed CS when the number of preexposures was increased. This effect was revealed as context-dependent in Experiment 2b, since it was attenuated by changing the context between preexposure and conditioning. The present result is consistent with recent studies showing the context-dependency of extinction in preweanling rats, thus demonstrating these animals' capacity to learn about context early on in their development. | 25,209,712 | [
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Extremely 'vanadiphilic' multiply metal-resistant and halophilic aerobic anoxygenic phototrophs, strains EG13 and EG8, from hypersaline springs in Canada. | Two pinkish peach-colored strains of obligately aerobic phototrophic bacteria, EG13 and EG8, were isolated from a saline spring effluent stream in west central Manitoba, Canada. The strains possessed bacteriochlorophyll a incorporated into a typical purple bacterial light-harvesting complex 1 (870 nm) and reaction center (801 nm). Analysis of 16S rRNA gene sequences indicated 100% identity among the isolates and 99% similarity to Roseovarius tolerans EL-172(T). The strains were physiologically well adapted to high salinity (0-22%), fluctuating pH (7-12) and temperature (7-40 °C) of the exposed hypersaline stream of East German Creek. EG8 and EG13 were also highly resistant to the toxic metal(loid) oxyanions tellurite, selenite and metavanadate (≥1000 μg/ml each). Most intriguingly, growth and pigment production of EG13 on glutamate minimal medium was stimulated by 1000-10000 μg/ml of sodium metavanadate compared to metal-free conditions. Phylogenetic analysis and phenotypic properties such as pigment composition and morphology indicate close relatedness to Roseovarius genus. | 25,209,747 | [
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Mechanisms of nanosized titanium dioxide-induced testicular oxidative stress and apoptosis in male mice. | Due to the increased application of titanium dioxide nanoparticles (TiO₂ NPs) in the food industry and daily life, their potential toxic effects in humans and animals have been investigated. However, very few studies have focused on testicular oxidative stress and/or apoptosis. In order to understand the possible molecular mechanisms of testicular lesions following exposure to TiO₂ NPs, male mice were exposed to 2.5, 5, or 10 mg/kg body weight TiO₂ NPs for 90 consecutive days. Testicular oxidative stress and apoptosis were then evaluated, and the testicular mRNA expression of several genes and their proteins involved in oxidative stress and/or apoptosis was investigated. TiO₂ NPs entered Sertoli cells and caused severe testicular oxidative damage and/or apoptosis, accompanied by excessive production of reactive oxygen species and peroxidation of lipids, proteins and DNA as well as a significant reduction in antioxidant capacity. Furthermore, exposure to TiO₂ NPs resulted in the up-regulation of caspase-3, Nrbp2, and cytochrome c expression, and caused down-regulation of SOD, CAT, GPx, GST, GR, Cyp1b1, Car3, Bcl-2, Acaa2, and Axud1 expression in mouse testis. TiO₂ NPs entered Sertoli cells via the blood-testis barrier and were deposited in mouse seminiferous cord and/or Sertoli cells, causing oxidative damage and apoptosis. | 25,209,749 | [
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Identification of an antigenic domain in the N-terminal region of avian hepatitis E virus (HEV) capsid protein that is not common to swine and human HEVs. | The antigenic domains located in the C-terminal 268 amino acid residues of avian hepatitis E virus (HEV) capsid protein have been characterized. This region shares common epitopes with swine and human HEVs. However, epitopes in the N-terminal 338 amino acid residues have never been reported. In this study, an antigenic domain located between amino acids 23 and 85 was identified by indirect ELISA using the truncated recombinant capsid proteins as coating antigens and anti-avian HEV chicken sera as primary antibodies. In addition, this domain did not react with anti-swine and human HEV sera. These results indicated that the N-terminal 338 amino acid residues of avian HEV capsid protein do not share common epitopes with swine and human HEVs. This finding is important for our understanding of the antigenicity of the avian HEV capsid protein. Furthermore, it has important implications in the selection of viral antigens for serological diagnosis. | 25,209,807 | [
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Paramyxovirus-based production of Rift Valley fever virus replicon particles. | Replicon-particle-based vaccines combine the efficacy of live-attenuated vaccines with the safety of inactivated or subunit vaccines. Recently, we developed Rift Valley fever virus (RVFV) replicon particles, also known as nonspreading RVFV (NSR), and demonstrated that a single vaccination with these particles can confer sterile immunity in target animals. NSR particles can be produced by transfection of replicon cells, which stably maintain replicating RVFV S and L genome segments, with an expression plasmid encoding the RVFV glycoproteins, Gn and Gc, normally encoded by the M-genome segment. Here, we explored the possibility to produce NSR with the use of a helper virus. We show that replicon cells infected with a Newcastle disease virus expressing Gn and Gc (NDV-GnGc) were able to produce high levels of NSR particles. In addition, using reverse genetics and site-directed mutagenesis, we were able to create an NDV-GnGc variant that lacks the NDV fusion protein and contains two amino acid substitutions in, respectively, Gn and HN. The resulting virus uses a unique entry pathway that facilitates the efficient production of NSR in a one-component system. The novel system provides a promising alternative for transfection-based NSR production. | 25,209,808 | [
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[CLOVES syndrome: a malformational syndrome closely resembling Proteus syndrome]. | CLOVES syndrome (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal nevi, Skeletal anomalies) is a sporadic malformational syndrome that has recently been described (mutation of PIK3CA), with asymmetric body hypertrophy, lipomatous hamartoma of the trunk and numerous malformations. We report a case of CLOVES syndrome initially diagnosed as Proteus syndrome, revealed by infection of a dorsal lipomatous hamartoma. The patient presented with both right lower limb hypertrophy and capillary and venous-lymphatic malformations, associated with dorsal capillary malformations, left cervico-facial hypertrophy, and cervical epidermal hamartoma, all of which are consistent with Proteus syndrome. Imaging of the dorsal lipomatous hamartoma associated with capillary as well as underlying venous-lymphatic malformations and syringomyelia resulted in subsequent correction of the earlier diagnosis of Proteus syndrome to that of CLOVES syndrome. Several malformational syndromes are associated with tissue hypertrophy, hamartoma and vascular malformations. Diagnosis of CLOVES syndrome may be delayed due to its fairly close phenotypic similarity to Proteus syndrome. Nevertheless, the prognosis and complications differ. Our case underlines the importance of considering a diagnosis of CLOVES syndrome in the presence of lipomatous hamartoma with hemi-hypertrophy and epidermal hamartoma, in order to enable adequate follow-up with specific monitoring for the possible complications associated with this disease. | 25,209,813 | [
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An Outbreak of Porcine Reproductive and Respiratory Syndrome Virus in Switzerland Following Import of Boar Semen. | An outbreak of porcine reproductive and respiratory syndrome virus (PRRSV) occurred in November 2012 in Switzerland (CH), traditionally PRRSV-free. It was detected after a German boar stud informed a semen importer about the detection of PRRSV during routine monitoring. Tracing of semen deliveries revealed 26 Swiss sow herds that had used semen from this stud after its last negative routine monitoring and 62 further contact herds. All herds were put under movement restrictions and examined serologically and virologically. As a first measure, 59 sows from five herds that had previously been inseminated with suspicious semen were slaughtered and tested immediately. Investigations in the stud resulted in 8 positive boars with recent semen deliveries to CH (Seven with antibodies and virus, one with antibodies only). In one boar out of six tested, virus was detected in semen. Of the 59 slaughtered sows, five from three herds were virus-positive. In one herd, the virus had spread, and all pigs were slaughtered or non-marketable animals euthanized. In the remaining herds, no further infections were detected. After confirmatory testings in all herds 3 weeks after the first examination gave negative results, restrictions were lifted in January 2013, and Switzerland regained its PRRSV-free status. The events demonstrate that import of semen from non-PRRS-free countries--even from negative studs--poses a risk, because monitoring protocols in boar studs are often insufficient to timely detect an infection, and infections of sows/herds occur even with low numbers of semen doses. The outbreak was eradicated successfully mainly due to the high disease awareness of the importer and because immediate actions were taken before clinical or laboratory diagnosis of a single case in the country was made. To minimize the risk of an introduction of PRRSV in the future, stricter import guidelines for boar semen have been implemented. | 25,209,832 | [
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Relationship and factor structure in multisystem neurodegeneration in Parkinson's disease. | Parkinson's disease (PD) is a multisystem neurodegenerative disease. We aimed to identify the relationship and factor structure among its different features. Motor, olfactory and cognitive function, and cardiac sympathetic denervation were evaluated in 125 patients with PD using the Unified Parkinson's Disease Rating Scale (UPDRS) part III score, odor stick identification test for the Japanese (OSIT-J), Mini-Mental State Examination (MMSE), and [(123) I] meta-iodobenzylguanidine (MIBG) cardiac scintigraphy (heart-to-mediastinum (H/M) ratio). Pearson's correlation and multiple regression analysis were used to evaluate the association among the four measures with age, gender, and disease duration as the covariates. Exploratory factor analysis was used to identify the underlying factor structure among the measures and covariates. Pearson's correlation and multiple regression analysis showed correlations between OSIT-J score and MIBG H/M ratio, OSIT-J and MMSE scores, UPDRS part III score and MIBG H/M ratio, UPDRS part III score and disease duration, and MMSE score and age. Factor analysis identified three factors: (i) age and MMSE score; (ii) MIBG H/M ratio and OSIT-J score; and (iii) UPDRS part III score and disease duration. Our results suggest that aging, PD-related pathogenesis, and disease duration underlie the multisystem neurodegeneration present in PD. Moreover, age and disease duration are the major risk factors for cognitive impairment and motor symptoms, respectively. Olfactory impairment and cardiac sympathetic denervation are strongly associated in PD. | 25,209,841 | [
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Phthalates, perfluoroalkyl acids, metals and organochlorines and reproductive function: a multipollutant assessment in Greenlandic, Polish and Ukrainian men. | Numerous environmental contaminants have been linked to adverse reproductive health outcomes. However, the complex correlation structure of exposures and multiple testing issues limit the interpretation of existing evidence. Our objective was to identify, from a large set of contaminant exposures, exposure profiles associated with biomarkers of male reproductive function. In this cross-sectional study (n=602), male partners of pregnant women were enrolled between 2002 and 2004 during antenatal care visits in Greenland, Poland and Ukraine. Fifteen contaminants were detected in more than 70% of blood samples, including metabolites of di(2-ethylhexyl) and diisononyl phthalates (DEHP, DiNP), perfluoroalkyl acids, metals and organochlorines. Twenty-two reproductive biomarkers were assessed, including serum levels of reproductive hormones, markers of semen quality, sperm chromatin integrity, epididymal and accessory sex gland function, and Y:X chromosome ratio. We evaluated multipollutant models with sparse partial least squares (sPLS) regression, a simultaneous dimension reduction and variable selection approach which accommodates joint modelling of correlated exposures. Of the over 300 exposure-outcome associations tested in sPLS models, we detected 10 associations encompassing 8 outcomes. Several associations were notably consistent in direction across the three study populations: positive associations between mercury and inhibin B, and between cadmium and testosterone; and inverse associations between DiNP metabolites and testosterone, between polychlorinated biphenyl-153 and progressive sperm motility, and between a DEHP metabolite and neutral α-glucosidase, a marker of epididymal function. This global assessment of a mixture of environmental contaminants provides further indications that some organochlorines and phthalates adversely affect some parameters of male reproductive health. | 25,209,848 | [
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Expression and localization of a UT-B urea transporter in the human bladder. | Facilitative UT-B urea transporters have been shown to play an important role in the urinary concentrating mechanism. Recent studies have now suggested a link between UT-B allelic variation and human bladder cancer risk. UT-B1 protein has been previously identified in the bladder of various mammalian species, but not yet in humans. The aim of the present study was to investigate whether any UT-B protein was present in the human bladder. First, RT-PCR results confirmed that UT-B1 was strongly expressed at the RNA level in the human bladder, whereas UT-B2 was only weakly present. Initial Western blot analysis confirmed that a novel UT-B COOH-terminal antibody detected human UT-B proteins. Importantly, this antibody detected a specific 40- to 45-kDa UT-B signal in human bladder protein. Using a peptide-N-glycosidase F enzyme, this bladder UT-B signal was deglycosylated to a core 30-kDa protein, which is smaller than the predicted size for UT-B1 but similar to many proteins reported to be UT-B1. Finally, immunolocalization experiments confirmed that UT-B protein was strongly expressed throughout all urothelium layers except for the apical membrane of the outermost umbrella cells. In conclusion, these data confirm the presence of UT-B protein within the human bladder. Further studies are now required to determine the precise nature, regulation, and physiological role of this UT-B. | 25,209,859 | [
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Evaluation of bone repair of critical size defects treated with simvastatin-loaded poly(lactic-co-glycolic acid) microspheres in rat calvaria. | Statins are hypolipemiant drugs with osteoinductive effect. We evaluated the potential of simvastatin loaded into poly(lactic-co-glycolic acid) (PLGA) microspheres to heal critical size defects in rat calvaria. PLGA scaffolds (50:50 ratio) were synthesized as pure membranes or as microspheres loaded with 2.5% simvastatin. Critical size defects (5-mm diameter) were created in the parietal bone of 3-month-old male Wistar rats; they were either left filled with blood clot (C group), covered with a PLGA membrane (M group) or with PLGA microspheres loaded with simvastatin (MSI group) or not (MM group), and then covered with the PLGA membrane. The defects were evaluated after 30 or 60 days by light and electron microscopy, immunohistochemistry for osteopontin (OPN), bone sialoprotein (BSP) and osteoadherin (OSAD), and immunocytochemistry for OPN. Scanning electron microscopy showed that the calvarial defects treated with MSI were almost completely healed after 60 days, while groups M and C presented less bone formation, whereas the bone matrix formed into the defects of MSI group was more organized and mature. The immunolabeling for OPN and BSP on the matrix in groups C and M showed typical areas of primary bone unlike the MSI that presented weak labeling at the formed area. In the MSI group, there was an intense immunostaining for OSAD in osteoid, as well as in osteocyte cytoplasm. The immunocytochemistry showed intense labeling for OPN with homogeneous distribution in the interfibrillar spaces in all groups after 30 days and after 60 days; however, while C and M groups exhibited similar aspect, the MSI specimens showed weak labeling. The ultrastructural evaluation showed the interaction between the biomaterial and the surrounding tissue where some cells established intimate contact with microspheres. The repair of critical size bone defects was accelerated and enhanced by the implantation of simvastatin-loaded PLGA microspheres. | 25,209,881 | [
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Specific language impairment in language-minority children from low-income families. | Recent evidence suggests that specific language impairment (SLI) might be secondary to general cognitive processing limitations in the domain of executive functioning. Previous research has focused almost exclusively on monolingual children with SLI and offers little evidence-based guidance on executive functioning in bilingual children with SLI. Studying bilinguals with SLI is important, especially in the light of increasing evidence that bilingualism can bring advantages in certain domains of executive functioning. To determine whether executive functioning represents an area of difficulty for bilingual language-minority children with SLI and, if so, which specific executive processes are affected. This cross-cultural research was conducted with bilingual children from Luxembourg and monolingual children from Portugal who all had Portuguese as their first language. The data from 81 eight-year-olds from the following three groups were analysed: (1) 15 Portuguese-Luxembourgish bilinguals from Luxembourg with an SLI diagnosis; (2) 33 typically developing Portuguese-Luxembourgish bilinguals from Luxembourg; and (3) 33 typically developing Portuguese-speaking monolinguals from Portugal. Groups were matched on first language, ethnicity, chronological age and socioeconomic status, and they did not differ in nonverbal intelligence. Children completed a battery of tests tapping: expressive and receptive vocabulary, syntactic comprehension, verbal and visuospatial working memory, selective attention and interference suppression. The bilingual SLI group performed equally well compared with their typically developing peers on measures of visuospatial working memory, but had lower scores than both control groups on tasks of verbal working memory. On measures of selective attention and interference suppression, typically developing children who were bilingual outperformed their monolingual counterparts. For selective attention, performance of the bilingual SLI group did not differ significantly from the controls. For interference suppression the bilingual SLI group performed significantly less well than typically developing bilinguals but not monolinguals. This research provides further support to the position that SLI is not a language-specific disorder. The study indicates that although bilingual children with SLI do not demonstrate the same advantages in selective attention and interference suppression as typically developing bilinguals, they do not lag behind typically developing monolinguals in these domains of executive functioning. This finding raises the possibility that bilingualism might represent a protective factor against some of the cognitive limitations that are associated with SLI in monolinguals. | 25,209,889 | [
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Associations between thyroid autoantibody status and abnormal pregnancy outcomes in euthyroid women. | We investigated whether thyroid autoantibody status influences pregnancy outcomes in euthyroid women, by comparing abnormal pregnancy outcome rates between those who tested positive for thyroid autoantibodies (Ab+) and those who tested autoantibody-negative (Ab-). Euthyroid pregnant women (n=7,641) underwent tests for serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). The subjects were divided into 4 groups according to thyroid antibody status: TPOAb-/TgAb- (92.9%); TPOAb+/TgAb- (3.2%); TPOAb-/TgAb+ (2.0%); and TPOAb+/TgAb+ (1.9%). The incidence rates of the following abnormal pregnancy outcomes were compared among the 4 groups and analyzed by Fisher's exact test: gestational diabetes, gestational hypertension, placenta previa, placental abruption, premature rupture of fetal membrane (PROM), intrauterine growth restriction, fetal distress, fetal anomalies, stillbirth, preterm birth, and low birth weight. Among the 4 groups, there were no significant differences in age, gestational age, or in the incidence rates of abnormal pregnancy outcomes, except for PROM and low birth weight. The highest incidence rates for PROM and low birth weight were in the TPOAb-/TgAb+ and TPOAb+/TgAb+ subjects, respectively. TgAb positivity and TPOAb positivity were associated with PROM and low birth weight, respectively. Underlying factors that govern the association between thyroid autoantibodies and PROM and low birth weight require further investigation. | 25,209,893 | [
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Conditional shared confidentiality in mental health care. | Because of the development towards community care, care providers not only exchange information in a team, but increasingly also in networks. This is a challenge to confidentiality. The ethical question is how care providers can keep information about the care receiver confidential, whilst at the same time exchanging information about that care receiver in a team or network? Can shared confidentiality be extended from a team to a network? To clarify this question, the article refers to the advice of an expert ethics committee in mental health care. The advice regards exchange of information in a network as a further step in enhancing collaboration among care providers. Therefore, the good and evident practice of shared confidentiality in a team can be extended to a network if the same conditions are met. First, the care providers participate in a clearly defined and identifiable team or network. Secondly, they have a shared care responsibility. Thirdly, they have a duty of confidentiality. Fourth, they dialogue with the care receiver and obtain his or her consent. Finally, they apply the filter of relevance. Hence, conditional shared confidentiality is an ethical justification for the exchange of information in a team or network. | 25,209,901 | [
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Phylogenetic Analysis of Canine Parvovirus VP2 Gene in China. | In this study, a total of 37 samples (58.0%) were found through PCR assay to be positive for canine parvovirus (CPV) of 66 suspected faecal samples of dogs collected from various cities throughout China. Eight CPV isolates could be obtained in the CRFK cell line. The sequencing of the VP2 gene of CPV identified the predominant CPV strain as CPV-2a (Ser297Ala), with two CPV-2b (Ser297Ala). Sequence comparison revealed homologies of 99.3-99.9%, 99.9% and 99.3-99.7% within the CPV 2a isolates, within the CPV 2b isolates and between the CPV 2a and 2b isolates, respectively. In addition, several non-synonymous and synonymous mutations were also recorded. The phylogenetic tree revealed that most of the CPV strains from different areas in China were located in the formation of a large branch, which were grouped together along with the KU143-09 strain from Thailand and followed the same evolution. In this study, we provide an updated molecular characterization of CPV 2 circulation in China. | 25,209,922 | [
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Early-life exposure to climate change impairs tropical shark survival. | Sharks are one of the most threatened groups of marine animals worldwide, mostly owing to overfishing and habitat degradation/loss. Although these cartilaginous fish have evolved to fill many ecological niches across a wide range of habitats, they have limited capability to rapidly adapt to human-induced changes in their environments. Contrary to global warming, ocean acidification was not considered as a direct climate-related threat to sharks. Here we show, for the first time, that an early ontogenetic acclimation process of a tropical shark (Chiloscyllium punctatum) to the projected scenarios of ocean acidification (ΔpH = 0.5) and warming (+4°C; 30°C) for 2100 elicited significant impairments on juvenile shark condition and survival. The mortality of shark embryos at the present-day thermal scenarios was 0% both at normocapnic and hypercapnic conditions. Yet routine metabolic rates (RMRs) were significantly affected by temperature, pH and embryonic stage. Immediately after hatching, the Fulton condition of juvenile bamboo sharks was significantly different in individuals that experienced future warming and hypercapnia; 30 days after hatching, survival rapidly declined in individuals experiencing both ocean warming and acidification (up to 44%). The RMR of juvenile sharks was also significantly affected by temperature and pH. The impact of low pH on ventilation rates was significant only under the higher thermal scenario. This study highlights the need of experimental-based risk assessments of sharks to climate change. In other words, it is critical to directly assess risk and vulnerability of sharks to ocean acidification and warming, and such effort can ultimately help managers and policy-makers to take proactive measures targeting most endangered species. | 25,209,942 | [
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TOKYO criteria 2014 for transpapillary biliary stenting. | It is difficult to carry out meta-analyses or to compare the results of different studies of biliary stents because there is no uniform evaluation method. Therefore, a standardized reporting system is required. We propose a new standardized system for reporting on biliary stents, the 'TOKYO criteria 2014', based on a consensus among Japanese pancreatobiliary endoscopists. Instead of stent occlusion, we use recurrent biliary obstruction, which includes occlusion and migration. The time to recurrent biliary obstruction was estimated using Kaplan-Meier analysis with the log-rank test. We can evaluate both plastic and self-expandable metallic stents (uncovered and covered). We also propose specification of the cause of recurrent biliary obstruction, identification of complications other than recurrent biliary obstruction, indication of severity, measures of technical and clinical success, and a standard for clinical care. Most importantly, the TOKYO criteria 2014 allow comparison of biliary stent quality across studies. Because blocked stents can be drained not only using transpapillary techniques but also by an endoscopic ultrasonography-guided transmural procedure, we should devise an evaluation method that includes transmural stenting in the near future. | 25,209,944 | [
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Effects of loratadine and cetirizine on serum levels of neuropeptides in patients with chronic urticaria. | H1-receptor inhibiting drugs, namely loratadine and cetirizine, were frequently used in treatment of chronic urticaria. Urticarial weal and flare reactions, a neurogenic reflex due to neuropeptides, were reported to be more effectively inhibited by cetirizine than loratadine. The aim of this study was to determine and compare the effects of systemic loratadine and cetirizine treatments on serum levels of selected neuropeptides in chronic urticaria. Treatment groups of either systemic loratadine or cetirizine (10 mg/d), consisting of 16 and 22 patients, respectively, were included. Serum levels of stem cell factor (SCF), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), and substance P (SP) were detected before and after one week of treatment with antihistamines. Serum NPY and VIP levels were significantly decreased when compared before and after treatment with antihistamines (P < 0.001 and P < 0.01, respectively). SCF and NGF values were also decreased after antihistamine treatment (P < 0.05). Post-treatment levels of CGRP were significantly higher compared with pretreatment values, while no significant difference was detected between pre and post treatment levels of SP. Cetirizine was significantly more effective than loratadine on lowering serum levels of SCF among the other neuropeptides. Systemic loratadine and cetirizine treatments in patients with chronic urticaria precisely caused variations in serum levels of neuropeptides. The predominant effect of cetirizine compared to loratadine on reducing serum SCF levels might be explained with anti-inflammatory properties of cetirizine. | 25,209,952 | [
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Revisiting yeast trehalose metabolism. | Establishing the function of trehalose in yeast cells has led us, over the years, through a long path-from simple energy storage carbohydrate, then a stabilizer and protector of membranes and proteins, through a safety valve against damage caused by oxygen radicals, up to regulator of the glycolytic path. In addition, trehalose biosynthesis has been proposed as a target for novel drugs against several pathogens. Since this pathway is entirely absent in mammalian cells and makes use of highly specific enzymes, trehalose metabolism might be an interesting target for the development of novel therapies. In this review, we want to address some recent points investigated about trehalose metabolism in Saccharomyces cerevisiae, focusing mainly on the mechanism by which this simple disaccharide protects against stress and on the enzymes involved in its synthesis and breakdown. We believe that these concepts are of great importance for medical and biotechnological applications. | 25,209,979 | [
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Fetal inhibition of inflammation improves disease phenotypes in harlequin ichthyosis. | Harlequin ichthyosis (HI) is a severe skin disease which leads to neonatal death in ∼50% of cases. It is the result of mutations in ABCA12, a protein that transports lipids required to establish the protective skin barrier needed after birth. To better understand the life-threatening newborn HI phenotype, we analysed the developing epidermis for consequences of lipid dysregulation in mouse models. We observed a pro-inflammatory signature which was characterized by chemokine upregulation in embryonic skin which is distinct from that seen in other types of ichthyosis. Inflammation also persisted in grafted HI skin. To examine the contribution of inflammation to disease development, we overexpressed interleukin-37b to globally suppress fetal inflammation, observing considerable improvements in keratinocyte differentiation. These studies highlight inflammation as an unexpected contributor to HI disease development in utero, and suggest that inhibiting inflammation may reduce disease severity. | 25,209,981 | [
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Factors associated with a delay in seeking HIV/AIDS treatment in São Paulo, Brazil. | This quantitative cross-sectional study of HIV/AIDS patients (N = 1,520) in São Paulo evaluated factors associated with a delay in seeking care. Analysis included Chi square tests and multiple logistic regression. Care was sought at the AIDS stage in 56.7 % (861) of patients, and 48.2 % (732) had a CD4 count ≤350 cells/mm(3); 9 % (136) delayed seeking care for 6 months or more after a positive HIV test. Women sought medical care earlier after testing (odds ratio (OR) = 1.79; P = 0.0227), but were already symptomatic (OR = 1.90; P = 0.0004). Partners of seropositive patients (OR = 3.92; P = 0.0000) also sought care symptomatic. Reasons for late presentation for care were non-acceptance of HIV diagnosis (OR = 24.56; P = 0.0000), treatment refusal (OR = 55.34; P = 0.0000), and physical disability (OR = 1.90; P = 0.0414). Necessary strategies for HIV treatment and prevention include improved education and access to services. | 25,210,003 | [
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Discovery of a highly selective PLD2 inhibitor (ML395): a new probe with improved physiochemical properties and broad-spectrum antiviral activity against influenza strains. | Further chemical optimization of the halopemide-derived family of dual phospholipase D1/2 (PLD1/2) inhibitors afforded ML395 (VU0468809), a potent, >80-fold PLD2 selective allosteric inhibitor (cellular PLD1, IC50 >30,000 nM; cellular PLD2, IC50 =360 nM). Moreover, ML395 possesses an attractive in vitro DMPK profile, improved physiochemical properties, ancillary pharmacology (Eurofins Panel) cleaner than any other reported PLD inhibitor, and has been found to possess interesting activity as an antiviral agent in cellular assays against a range of influenza strains (H1, H3, H5 and H7). | 25,210,004 | [
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Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies. | This report provides a survival update at a follow-up of >5 years (5.5-6 years) for patients with advanced melanoma who previously received ipilimumab in phase II clinical trials. Safety and efficacy data following ipilimumab retreatment are also reported. Patients who previously received ipilimumab 0.3, 3, or 10 mg/kg in one of six phase II trials (CA184-004, CA184-007, CA184-008, CA184-022, MDX010-08, and MDX010-15) were eligible to enroll in the companion study, CA184-025. Upon enrollment, patients initially received ipilimumab retreatment, extended maintenance therapy, or were followed for survival only. Overall survival (OS) rates were evaluated in patients from studies CA184-004, CA184-007, CA184-008, and CA184-022. Safety and best overall response during ipilimumab retreatment at 10 mg/kg were assessed in study CA184-025. Five-year OS rates for previously treated patients who received ipilimumab induction at 0.3, 3, or 10 mg/kg were 12.3%, 12.3%-16.5%, and 15.5%-28.4%, respectively. Five-year OS rates for treatment-naive patients who received ipilimumab induction at 3 or 10 mg/kg were 26.8% and 21.4%-49.5%, respectively. Little to no change in OS was observed from year 5 up to year 6. The objective response rate among retreated patients was 23%. Grade 3/4 immune-related adverse events occurred in 25%, 5.9%, and 13.2% of retreated patients who initially received ipilimumab 0.3, 3, and 10 mg/kg, with the most common being observed in the skin (4.2%, 2.9%, 3.8%) and gastrointestinal tract (12.5%, 2.9%, 3.8%), respectively. At a follow-up of 5-6 years, ipilimumab continues to demonstrate durable, long-term survival in a proportion of patients with advanced melanoma. In some patients, ipilimumab retreatment can re-establish disease control with a safety profile that is comparable with that observed during ipilimumab induction. Further studies are needed to determine the contribution of ipilimumab retreatment to OS. NCT00162123. | 25,210,016 | [
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Unannounced in situ simulation of obstetric emergencies: staff perceptions and organisational impact. | To describe how unannounced in situ simulation (ISS) was perceived by healthcare professionals before and after its implementation, and to describe the organisational impact of ISS. Ten unannounced ISS involving all staff were scheduled March-August 2007. Questionnaire surveys on staff perceptions were conducted before (2003-2006) and after (2007-2008) implementation of unannounced ISS. Information from the debriefing sessions following each ISS constituted a proxy measure of the organisational impact of the ISS. Five out of ten of the unannounced ISS scheduled were conducted. Twenty-three members of the staff at work on a scheduled day for ISS were randomly selected to participate. Questionnaires before implementation revealed that 137/196 (70%) of staff members agreed or strongly agreed that ISS was a good idea and 52/199 (26%) thought it likely to be stressful and unpleasant. Questionnaires completed after implementation showed significantly more staff members, 135/153 (89%), thought ISS was a good idea. A significantly higher amount of staff members 50/153 (33%) found it to be stressful and unpleasant, and among midwives, 15/59 (25%) were anxious about ISS, whereas none of the obstetricians reported this. Information obtained through debriefing sessions generated learning points. The number of staff members with a positive perception of multiprofessional unannounced ISS increased after implementation; however, one-third considered ISS to be stressful and unpleasant and midwives more frequently so. The specific perception of ISS by each healthcare profession should be taken into account when planning ISS. The information from the debriefing sessions showed that implementation of ISS had an impact as it provided information required for organisational changes. | 25,210,023 | [
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Massive thermal acceleration of the emergence of primordial chemistry, the incidence of spontaneous mutation, and the evolution of enzymes. | Kelvin considered it unlikely that sufficient time had elapsed on the earth for life to have reached its present level of complexity. In the warm surroundings in which life first appeared, however, elevated temperatures would have reduced the kinetic barriers to reaction. Recent experiments disclose the profound extent to which very slow reactions are accelerated by elevated temperatures, collapsing the time that would have been required for early events in primordial chemistry before the advent of enzymes. If a primitive enzyme, like model catalysts and most modern enzymes, accelerated a reaction by lowering its enthalpy of activation, then the rate enhancement that it produced would have increased automatically as the environment cooled, quite apart from any improvements in catalytic activity that arose from mutation and natural selection. The chemical events responsible for spontaneous mutation are also highly sensitive to temperature, furnishing an independent mechanism for accelerating evolution. | 25,210,030 | [
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Introduction to the thematic minireview series on enzyme evolution. | In this thematic minireview series, the JBC presents five provocative articles on Enzyme Evolution. The reviews discuss stimulating concepts that include the emergence of primordial catalysts at temperatures that were considerably warmer than present day ones and the impact of the cooling environment on the evolution of catalytic fitness and the preservation of catalysis-promoting conformational dynamics. They also discuss the use of Urzymes or invariant modules in enzyme superfamilies as paradigms for understanding the evolution of catalytic efficiency and specificity, the use of bioinformatics approaches to understand the roles of substrate ambiguity and catalytic promiscuity as drivers of evolution, and the challenges associated with assigning catalytic function as the number of superfamily members grows rapidly. | 25,210,045 | [
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Extracellular matrix modulates the biological effects of melatonin in mesenchymal stem cells. | Both self-renewal and lineage-specific differentiation of mesenchymal stem cells (MSCs) are triggered by their in vivo microenvironment including the extracellular matrix (ECM) and secreted hormones. The ECM may modulate the physiological functions of hormones by providing binding sites and by regulating downstream signaling pathways. Thus, the purpose of this study was to evaluate the degree of adsorption of melatonin to a natural cell-deposited ECM and the effects of this interaction on the biological functions of melatonin in human bone marrow-derived MSCs (BM-MSCs). The fibrillar microstructure, matrix composition, and melatonin-binding affinity of decellularized ECM were characterized. The cell-deposited ECM improved melatonin-mediated cell proliferation by 31.4%, attenuated accumulation of intracellular reactive oxygen species accumulation, and increased superoxide dismutase (SOD) mRNA and protein expression. Interaction with ECM significantly enhanced the osteogenic effects of melatonin on BM-MSCs by increasing calcium deposition by 30.5%, up-regulating osteoblast-specific gene expression and down-regulating matrix metalloproteinase (MMP) expression. The underlying mechanisms of these changes in expression may involve intracellular antioxidant enzymes, because osteoblast-specific genes were down-regulated, whereas MMP expression was up-regulated, in the presence of SOD-specific inhibitors. Collectively, our findings indicate the importance of native ECM in modulating the osteoinductive and antioxidant effects of melatonin and provide a novel platform for studying the biological actions of growth factors or hormones in a physiologically relevant microenvironment. Moreover, a better understanding of the enhancement of MSC growth and osteogenic differentiation resulting from the combination of ECM and melatonin could improve the design of graft substitutes for skeletal tissue engineering. | 25,210,047 | [
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Thiazolidinedione-induced lipid droplet formation during osteogenic differentiation. | Chronic administration of the insulin-sensitising drugs, thiazolidinediones (TZDs), results in low bone mineral density and 'fatty bones'. This is thought to be due, at least in part, to aberrant differentiation of progenitor mesenchymal stem cells (MSCs) away from osteogenesis towards adipogenesis. This study directly compared the effects of rosiglitazone, pioglitazone, and netoglitazone treatment on osteogenesis and adipogenesis in MSCs derived from subcutaneous (SC) or visceral (PV) white adipose tissue. MSCs were isolated from adipose tissue depots of male Wistar rats and characterised using flow cytometry. The effects of TZD treatment on osteogenic and adipogenic differentiation were assessed histologically (day 14) and by quantitative PCR analysis (Pparγ2 (Pparg2), Ap2 (Fabp4), Adipsin (Adps), Msx2, Collagen I (Col1a1), and Alp) on days 0, 7, and 10. Uniquely, lipid droplet formation and mineralisation were found to occur concurrently in response to TZD treatment during osteogenesis. Compared with SC MSCs, PV MSCs were more prone to lipid accumulation under controlled osteogenic and adipogenic differentiation conditions. This study demonstrated that the extent of lipid accumulation is dependent on the nature of the Ppar ligand and that SC and PV MSCs respond differently to in vitro TZD treatment, suggesting that metabolic status can contribute to the adverse effects associated with TZD treatment. | 25,210,048 | [
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Multilocus sequence typing of Mycobacterium xenopi. | Mycobacterium xenopi is an opportunistic mycobacterial pathogen of increasing clinical importance. Surveillance of M. xenopi is hampered by the absence of tools for genotyping and molecular epidemiology. In this study, we describe the development and evaluation of an effective multilocus sequence typing strategy for M. xenopi. | 25,210,065 | [
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Contemporary inter-hospital transfer patterns for the management of acute coronary syndrome patients: findings from the EPICOR study. | The EPICOR observational study was designed to describe antithrombotic strategies in a broad acute coronary syndrome (ACS) population; it also included information on inter-hospital transfers and institutional resources. EPICOR enrolled 10,568 consecutively discharged patients with ST-elevation (STE) or non-STE (NSTE) ACS in 555 centres in 20 countries across Europe and Latin America. Patients were categorized as non-transferred, transferred in from another hospital and then discharged, or transferred out to a second hospital but discharged from their initial hospital after transfer back. Two-thirds of ACS patients were non-transferred, of which only 14% were hospitalized at a centre without a catheterization laboratory, and one-third were transferred in or transferred out. Almost all transferred out patients were transferred out to a hospital with catheterization facilities, most often for primary/urgent/rescue (78%) or planned catheterization (18%) in STE myocardial infarction (STEMI), and primary/urgent/rescue (44%) or planned (43%) catheterization in NSTE-ACS. Transferred in patients were more likely to have a STEMI (60%) than non-transferred (44%) and transferred out patients (36%). In STEMI patients, time from symptom onset to catheterization was shorter in non-transferred patients (median 3.5 h vs. 5.9 h for transferred in and 6.3 h for transferred out). In NSTE-ACS, cardiac markers were positive in 66% of non-transferred patients versus 78% and 82% in transferred in and transferred out, respectively. The lack of on-site 24/7 facilities or the availability of more advanced care are frequent reasons for inter-hospital transfer in ACS. Further follow-up of these patients will help to determine whether these practice patterns affect outcome. | 25,210,075 | [
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Preterm delivery among first-time Mexico-born mothers: a binational population-based comparison of deliveries in California and Mexico. | While studies have attributed the favourable birth outcomes of Mexico-born mothers in the USA to a 'healthy immigrant effect' that confers protection to immigrants, a comparison of immigrants with the source population in Mexico has been lacking. We compared preterm delivery (PTD) rates of Mexico-born immigrants who delivered in California with Mexico-born women who delivered in Mexico (WIMX) and with a subgroup who delivered in the five top immigrant sending states in Mexico. Using 2009 birth records, we selected all live-born singletons of primiparous WIMX (699 129) and immigrants in California (33 251). We examined the unadjusted and adjusted association between place of delivery and any PTD (<37 weeks gestation), including PTD subcategories (early, moderate, late), using relative risks (RR) and 95% CIs. Multivariate models controlled for demographic and health system characteristics. PTD rates were higher among immigrants in California (6.7%) than WIMX (5.8%) and compared to women in the sending states (5.5%). The unadjusted risk of any PTD (RR=1.17 (1.12 to 1.22)), early/moderate PTD (<34 weeks gestation; RR=1.27 (1.18 to 1.38)) and late PTD (34-36 weeks; RR=1.14 (1.08 to 1.19)) was higher for immigrants than for WIMX and remained higher when controlling for age, education and healthcare variables. Birth weight <1500 g was also higher among immigrants (RR=1.27 (1.14 to 1.44)). Similar patterns were observed when comparing women in the sending states. We found no evidence of a 'healthy immigrant effect'. Further research must assess the comparability of gestational-age data in Mexican and Californian birth certificates. | 25,210,076 | [
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Assessing protective factors for sexually violent offending with the SAPROF. | The Structured Assessment of Protective Factors for violence risk (SAPROF) has recently been developed as a risk assessment tool to focus solely on protective factors for (sexual) violence risk. Research on protective factors for sexual offending is very limited and most risk assessment tools for adult sexual offenders do not incorporate protective factors. The current study investigates the applicability and predictive validity of the SAPROF for forensic psychiatric patients who have sexually offended. For a sample of 83 hands-on sexual offenders, risk assessments were carried out retrospectively with the SAPROF, the Historical Clinical Risk Management-20 (HCR-20) and the Sexual Violence Risk-20 (SVR-20). Results show good interrater reliability and negative correlations between the SAPROF and both risk tools. Predictive validities of the SAPROF protective factors for reconvictions of general and sexual violence were good for short-term (1-3 year) as well as for long-term follow-up (15 year). Moreover, the SAPROF remained a statistically significant predictor of future violence and sexual violence even after controlling for the HCR-20 and the SVR-20. Implications of these findings and recommendations for future research are discussed. | 25,210,106 | [
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Heterologous immunological effects of early BCG vaccination in low-birth-weight infants in Guinea-Bissau: a randomized-controlled trial. | Bacillus Calmette-Guérin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia. Within a randomized trial in LBW infants in Guinea-Bissau of early BCG vs the usual postponed BCG, a subgroup was bled 4 weeks after randomization. Levels of interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured from whole-blood assays stimulated with innate agonists to Toll-like receptor (TLR)-2, -4 or -7/8, or purified protein derivative (PPD). Among 467 infants, BCG significantly increased the in vitro cytokine responses to purified protein derivative of Mycobacterium tuberculosis (PPD), as expected. BCG was also associated with increased responses to heterologous innate stimulation, particularly of the cytokines IL-1β, IL-6, TNF-α, and IFN-γ. Four weeks after immunization, BCG-vaccinated infants have a significantly increased production of cytokines upon heterologous challenge, particularly T helper cell type 1 polarizing and typically monocyte-derived pro-inflammatory cytokines. BCG may accelerate the development of the neonatal immune system, mediating comprehensive protection against infections and mortality. | 25,210,141 | [
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Unraveling the complexity of lipid body organelles in human eosinophils. | Lipid-rich organelles are common in many cell types. In cells, such as adipocytes, these organelles are termed LDs, whereas in other cells, such as leukocytes, they are called LBs. The study of leukocyte LBs has attracted attention as a result of their association with human diseases. In leukocytes, such as eosinophils, LB accumulation has been documented extensively during inflammatory conditions. In these cells, LBs are linked to the regulation of immune responses by compartmentalization of several proteins and lipids involved in the control and biosynthesis of inflammatory mediators (eicosanoids). However, it has been unclear how diverse proteins, including membrane-associated enzymes involved in eicosanoid formation, incorporate into LBs, especially if the internal content of LBs is assumed to consist solely of stores of neutral lipids, as present within adipocyte LDs. Studies of the formation, function, and ultrastructure of LBs in eosinophils have been providing insights pertinent to LBs in other leukocytes. Here, we review current knowledge of the composition and function of leukocyte LBs as provided by studies of human eosinophil LBs, including recognitions of the internal architecture of eosinophil LBs based on 3D electron tomographic analyses. | 25,210,147 | [
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Modulation of alpha power at encoding and retrieval tracks the precision of visual short-term memory. | Our ability to hold information in mind is strictly limited. We sought to understand the relationship between oscillatory brain activity and the allocation of resources within visual short-term memory (VSTM). Participants attempted to remember target arrows embedded among distracters and used a continuous method of responding to report their memory for a cued target item. Trial-to-trial variability in the absolute circular accuracy with which participants could report the target was predicted by event-related alpha synchronization during initial processing of the memoranda and by alpha desynchronization during the retrieval of those items from VSTM. Using a model-based approach, we were also able to explore further which parameters of VSTM-guided behavior were most influenced by alpha band changes. Alpha synchronization during item processing enhanced the precision with which an item could be retained without affecting the likelihood of an item being represented per se (as indexed by the guessing rate). Importantly, our data outline a neural mechanism that mirrors the precision with which items are retained; the greater the alpha power enhancement during encoding, the greater the precision with which that item can be retained. | 25,210,151 | [
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Population interactions between parietal and primary motor cortices during reach. | Neural interactions between parietal area 2/5 and primary motor cortex (M1) were examined to determine the timing and behavioral correlates of cortico-cortical interactions. Neural activity in areas 2/5 and M1 was simultaneously recorded with 96-channel microelectrode arrays in three rhesus monkeys performing a center-out reach task. We introduce a new method to reveal parietal-motor interactions at a population level using partial spike-field coherence (PSFC) between ensembles of neurons in one area and a local field potential (LFP) in another. PSFC reflects the extent of phase locking between spike times and LFP, after removing the coherence between LFPs in the two areas. Spectral analysis of M1 LFP revealed three bands: low, medium, and high, differing in power between movement preparation and performance. We focus on PSFC in the 1-10 Hz band, in which coherence was strongest. PSFC was also present in the 10-40 Hz band during movement preparation in many channels but generally nonsignificant in the 60-200 Hz band. Ensemble PSFC revealed stronger interactions than single cell-LFP pairings. PSFC of area 2/5 ensembles with M1 LFP typically rose around movement onset and peaked ∼500 ms afterward. PSFC was typically stronger for subsets of area 2/5 neurons and M1 LFPs with similar directional bias than for those with opposite bias, indicating that area 2/5 contributes movement direction information. Together with linear prediction of M1 LFP by area 2/5 spiking, the ensemble-LFP pairing approach reveals interactions missed by single neuron-LFP pairing, demonstrating that cortico-cortical communication can be more readily observed at the ensemble level. | 25,210,154 | [
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Regular-spiking cells in the presubiculum are hyperexcitable in a rat model of temporal lobe epilepsy. | Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy, characterized by recurrent seizures originating in the temporal lobes. Here, we examine TLE-related changes in the presubiculum (PrS), a less-studied parahippocampal structure that both receives inputs from and projects to regions affected by TLE. We assessed the state of PrS neurons in TLE electrophysiologically to determine which of the previously identified cell types were rendered hyperexcitable in epileptic rats and whether their intrinsic and/or synaptic properties were altered. Cell types were characterized based on action potential discharge profiles followed by unsupervised hierarchical clustering. PrS neurons in epileptic animals could be divided into three major groups comprising of regular-spiking (RS), irregular-spiking (IR), and fast-adapting (FA) cells. RS cells, the predominant cell type encountered in PrS, were the only cells that were hyperexcitable in TLE. These neurons were previously identified as sending long-range axonal projections to neighboring structures including medial entorhinal area (MEA), and alterations in intrinsic properties increased their propensity for sustained firing of action potentials. Frequency and amplitude of both spontaneous excitatory and inhibitory synaptic events were reduced. Further analysis of nonaction potential-dependent miniature currents (in tetrodotoxin) indicated that reduction in excitatory drive to these neurons was mediated by decreased activity of excitatory neurons that synapse with RS cells concomitant with reduced activity of inhibitory neurons. Alterations in physiological properties of PrS neurons and their ensuing hyperexcitability could entrain parahippocampal structures downstream of PrS, including the MEA, contributing to temporal lobe epileptogenesis. | 25,210,155 | [
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Common features of mucosal and peripheral antibody responses elicited by candidate HIV-1 vaccines in rhesus monkeys. | Human immunodeficiency virus type 1 (HIV-1) vaccines that elicit protective antibody responses at mucosal sites would be highly desirable. Here, we report that intramuscular immunization of candidate HIV-1 vaccine vectors and purified Env proteins elicited potent and durable humoral immune responses in colorectal mucosa in rhesus monkeys. The kinetics, isotypes, functionality, and epitope specificity of these mucosal antibody responses were similar to those of peripheral responses in serum. These data suggest a close immunological relationship between mucosal and systemic antibody responses following vaccination in primates. | 25,210,178 | [
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HBZ stimulates brain-derived neurotrophic factor/TrkB autocrine/paracrine signaling to promote survival of human T-cell leukemia virus type 1-Infected T cells. | Brain-derived neurotrophic factor (BDNF) is a neurotrophin that promotes neuronal proliferation, survival, and plasticity. These effects occur through autocrine and paracrine signaling events initiated by interactions between secreted BDNF and its high-affinity receptor, TrkB. A BDNF/TrkB autocrine/paracrine signaling loop has additionally been implicated in augmenting the survival of cells representing several human cancers and is associated with poor patient prognosis. Adult T-cell leukemia (ATL) is a fatal malignancy caused by infection with the complex retrovirus human T-cell leukemia virus type 1 (HTLV-1). In this study, we found that the HTLV-1-encoded protein HBZ activates expression of BDNF, and consistent with this effect, BDNF expression is elevated in HTLV-1-infected T-cell lines compared to uninfected T cells. Expression of TrkB is also higher in HTLV-1-infected T-cell lines than in uninfected T cells. Furthermore, levels of both BDNF and TrkB mRNAs are elevated in peripheral blood mononuclear cells (PBMCs) from ATL patients, and ATL patient sera contain higher concentrations of BDNF than sera from noninfected individuals. Finally, chemical inhibition of TrkB signaling increases apoptosis in HTLV-1-infected T cells and reduces phosphorylation of glycogen synthase kinase 3β (GSK-3β), a downstream target in the signaling pathway. These results suggest that HBZ contributes to an active BDNF/TrkB autocrine/paracrine signaling loop in HTLV-1-infected T cells that enhances the survival of these cells. Infection with human T-cell leukemia virus type 1 (HTLV-1) can cause a rare form of leukemia designated adult T-cell leukemia (ATL). Because ATL patients are unresponsive to chemotherapy, this malignancy is fatal. As a retrovirus, HTLV-1 integrates its genome into a host cell chromosome in order to utilize host factors for replication and expression of viral proteins. However, in infected cells from ATL patients, the viral genome is frequently modified to block expression of all but a single viral protein. This protein, known as HBZ, is therefore believed to modulate cellular pathways necessary for the leukemic state and the chemotherapeutic resistance of the cell. Here we provide evidence to support this hypothesis. We found that HBZ promotes a BDNF/TrkB autocrine/paracrine signaling pathway that is known to enhance the survival and chemotherapeutic resistance of other types of cancer cells. It is possible that inhibition of this pathway may improve treatments for ATL. | 25,210,182 | [
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Characterization of a broadly neutralizing monoclonal antibody that targets the fusion domain of group 2 influenza A virus hemagglutinin. | Due to continuous changes to its antigenic regions, influenza viruses can evade immune detection and cause a significant amount of morbidity and mortality around the world. Influenza vaccinations can protect against disease but must be annually reformulated to match the current circulating strains. In the development of a broad-spectrum influenza vaccine, the elucidation of conserved epitopes is paramount. To this end, we designed an immunization strategy in mice to boost the humoral response against conserved regions of the hemagglutinin (HA) glycoprotein. Of note, generation and identification of broadly neutralizing antibodies that target group 2 HAs are rare and thus far have yielded only a few monoclonal antibodies (MAbs). Here, we demonstrate that mouse MAb 9H10 has broad and potent in vitro neutralizing activity against H3 and H10 group 2 influenza A subtypes. In the mouse model, MAb 9H10 protects mice against two divergent mouse-adapted H3N2 strains, in both pre- and postexposure administration regimens. In vitro and cell-free assays suggest that MAb 9H10 inhibits viral replication by blocking HA-dependent fusion of the viral and endosomal membranes early in the replication cycle and by disrupting viral particle egress in the late stage of infection. Interestingly, electron microscopy reconstructions of MAb 9H10 bound to the HA reveal that it binds a similar binding footprint to MAbs CR8020 and CR8043. The influenza hemagglutinin is the major antigenic target of the humoral immune response. However, due to continuous antigenic changes that occur on the surface of this glycoprotein, influenza viruses can escape the immune system and cause significant disease to the host. Toward the development of broad-spectrum therapeutics and vaccines against influenza virus, elucidation of conserved regions of influenza viruses is crucial. Thus, defining these types of epitopes through the generation and characterization of broadly neutralizing monoclonal antibodies (MAbs) can greatly assist others in highlighting conserved regions of hemagglutinin. Here, we demonstrate that MAb 9H10 that targets the hemagglutinin stalk has broadly neutralizing activity against group 2 influenza A viruses in vitro and in vivo. | 25,210,195 | [
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Trailing or paradoxical growth of Aspergillus flavus exposed to caspofungin is independent of genotype. | There are limited data on in vitro susceptibility testing of echinocandins against Aspergillus species. The objective of this study was to describe the phenotypes of Aspergillus flavus observed on exposure to caspofungin in vitro and to test whether these phenotypes were associated with A. flavus genotypes. The caspofungin MICs of 37 A. flavus clinical isolates collected from 14 patients with invasive aspergillosis were determined using Etest assays. Caspofungin MICs ranged from 0.012 to 0.064 mg l(-1); the modal MIC was 0.023 mg l(-1) and the MIC₅₀ and MIC₉₀ were 0.032 and 0.064 mg l(-1), respectively. A clear end point was noted in 24 (65 %) isolates, whereas seven (19 %) displayed a trailing effect and six (16 %) showed paradoxical growth when exposed to caspofungin. In these A. flavus isolates, the absence of a significant population structure or genetic differentiation indicated that trailing or paradoxical growth phenotypes were independent of microsatellite genotype. | 25,210,202 | [
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0.043449... |
In vitro activities of amphotericin B deoxycholate and liposomal amphotericin B against 604 clinical yeast isolates. | We determined the in vitro antifungal activity of liposomal amphotericin B (L-AmB) against 604 clinical yeast isolates. Amphotericin B deoxycholate (D-AmB) was tested in parallel against all the isolates. Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 method. Overall, L-AmB was highly active against the isolates (mean MIC, 0.42 µg ml(-1); MIC90, 1 µg ml(-1); 97.2 % of MICs were ≤1 µg ml(-1)) and comparable to D-AmB (mean MIC, 0.48 µg ml(-1); MIC90, 1 µg ml(-1); 97.3 % of MICs were ≤1 µg ml(-1)). The in vitro activity of D-AmB and L-AmB was correlated (R(2) = 0.61; exp(b), 2.3; 95 % CI, 2.19-2.44, P<0.001). Candida albicans (mean MICs of D-AmB and L-AmB, 0.39 µg ml(-1) and 0.31 µg ml(-1), respectively) and Candida parapsilosis (mean MICs of D-AmB and L-AmB, 0.38 µg ml(-1) and 0.35 µg ml(-1), respectively) were the species most susceptible to the agents tested, while Candida krusei (currently named Issatchenkia orientalis) (mean MICs of D-AmB and L-AmB, 1.27 µg ml(-1) and 1.13 µg ml(-1), respectively) was the least susceptible. The excellent in vitro activity of L-AmB may have important implications for empirical treatment approaches and support its role in treatment of a wide range of invasive infections due to yeasts. | 25,210,203 | [
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Video endoscopic oro-nasal visualisation of the anterior wall of maxillary sinus: a new technique. | The anterior wall of the maxillary sinus represents a blind spot in maxillary sinus endoscopic surgery because of the absence of proper visualisation and instrumentation to reach it. The aim of this study was to validate a new approach through the oral cavity into the nose with a flexible video endoscope (oro-nasal endoscopic approach; ONEA) to visualise the entire anterior maxillary wall including the anteromedial angle. We started from a dried bone cadaver model, and then dissected fresh-frozen cadavers. The maxillary sinus was explored with a rigid and a flexible endoscope entering from the nose. Next, a flexible endoscope was introduced through the mouth and back up through the choana, it accessed the maxillary middle antrostomy, entering inside the sinus and looking at the anterior wall. A small ruler inserted inside the sinus demonstrated all the angles visualised. The new ONEA technique allows complete visualisation of the anterior wall of the maxillary sinus with inspection of all blind spots. It is therefore possible to detect lesions that would normally not be visible with a normal rigid endoscope. We demonstrate the validity of a novel technique that allows visualisation of the infero-medial angle of the anterior wall of the maxillary sinus. | 25,210,220 | [
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Repositioning template for mandibular reconstruction with fibular free flaps: an alternative technique to pre-plating and virtual surgical planning. | Oral malignancies involving the mandibular bone require a complex reconstructive plan. Mandibular reconstruction with a fibular free flap is currently considered the best choice for functional and aesthetic rehabilitation after oncological surgery. This flap can be modelled with multiple osteotomies and can provide bone, muscle and skin for composite reconstruction. One of the most delicate aspects of mandibular reconstruction is the technique of bone modelling; the risk of prolonging the period of ischaemia and not restoring the correct maxillomandibular and occlusal relationships can ultimately lead to a higher rate of complications as well as poor aesthetic and functional results. Recently, there has been rising interest in virtual surgical planning and computer-assisted mandibular reconstruction in pre-operative planning; however, this is not always possible because of the costs involved and the set-up time for the entire procedure. In this paper, we present a simple and inexpensive technique for fibular free flap modelling and repositioning after segmental resection of the mandible; the technique entails the pre-operative preparation of a resin repositioning template on a stereolithographic model. This technique has been successfully applied in four cases: two cases underwent resection involving only the mandibular body, one case involving the mandibular body and symphysis and one case in which a ramus to ramus resection was performed. In this preliminary report, we show that the resin repositioning template is an easy, safe and useful tool for mandibular reconstruction with a fibular free flap. | 25,210,223 | [
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Cerebellar haemorrhage mimicking acute peripheral vestibulopathy: the role of the video head impulse test in differential diagnosis. | Dizziness and vertigo without neurological signs are typically due to a peripheral vestibular disease. Although the most common causes are benign, differential diagnosis must include potentially life-threatening central diseases such as cerebrovascular pathologies. A systemic clinical approach needs a careful work-up, bedside examination and appropriate instrumental investigation. The head impulse test (HIT) allows qualitative clinical assessment of canalar function; it has some limitations such as subjective evaluation, mainly in patients with a spontaneous nystagmus. A new device has been recently developed consisting of an infrared video camera (video-HIT) to provide quantitative instrumental assessment of the high-frequency vestibular-ocular reflex (VOR) gain. By reporting a case of cerebellar haemorrhage mimicking an acute peripheral vestibulopathy, the authors suggest that video-HIT may be considered a useful tool in differential diagnosis between vestibular neuritis and cerebellar vascular disease in patients with severe acute vertigo without central signs. | 25,210,225 | [
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Diagnostic efficacy and importance of fine-needle aspiration cytology of thyroid nodules. | Fine-needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules is an easy and cost-effective method. The increase in malignancy rates of the excised nodules due to the high sensitivity and specificity rates of the FNAC is remarkable. The aim of this study was to assess the effectiveness of FNAC in the evaluation of thyroid nodules by comparing the results with histopathologic evaluation and comparing the consistency of the results with the literature. In this study, 1607 FNACs of 1333 patients which were classified according to the Bethesda system and 126 histopathological evaluations obtained from this group were evaluated. The mean age of the patients was 51.24 (range: 17-89, 17% male and 83% female). The sensitivity, specificity, positive and negative predictive values, and accuracy rates were evaluated. The sensitivity was 87.1% and specificity was 64.6%. The positive and negative predictive value and accuracy rates were 76.1%, 79.5%, and 77.3%, respectively. In our study, the evaluation of thyroid FNAC samples with Bethesda system highly correlated with the results of histopathological diagnosis. However, combination of additional and advanced diagnostic methods such as immunocytochemical studies and molecular pathology techniques enhance the prognostic value of FNAC in patients with atypia of undetermined significance or follicular lesion of undetermined significance, lesions suspicious for malignancy, and suspected follicular neoplasm. | 25,210,233 | [
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Anaplastic myeloma presenting as mandibular swelling: Diagnosis by cytology. | Multiple myeloma is a disease resulting from clonal proliferation of plasma cells. A disease of the elderly, jaw lesions are seen in 14% of patients affected with myeloma. Rarely the oral and maxillofacial lesions can be the first manifestation of the disease. We report the case of a 75-year-old man who presented with mandibular swelling. Fine-needle aspiration cytology was done from the swelling and smears were suggestive of anaplastic myeloma, which is a rare and aggressive variant of myeloma. The diagnosis of a plasmacytoma was confirmed by biopsy. Further workup of the patient revealed osteolytic lesions in skull, M band in electrophoresis and evidence of renal failure. Peripheral smear and bone marrow findings were also consistent with myeloma. | 25,210,245 | [
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A rare case of temporal arteritis with rheumatoid arthritis and interstitial lung disease mimicking pulpo-periodontal pathology. | A 75-year-old male patient was planned for dental treatment due to pain of suspected pulpo-periodontal origin in relation to right maxillary first molar. Careful evaluation revealed the pain to be non-odontogenic in nature and led to the diagnosis of temporal arteritis with rheumatoid arthritis along with interstitial lung disease (ILD). Characteristic findings of temporal arteritis include headache, jaw claudication, visual loss, and constitutional symptoms (malaise, fever, weight loss, loss of appetite). Temporal artery biopsy (TAB) remains the gold standard for diagnosis. Additional diagnostic tests include blood tests (ESR, CRP). This article reports and discusses how the orofacial manifestations can lead to misdiagnosis of temporal arteritis. Hence, temporal arteritis should be included in the differential diagnosis of orofacial pain in the elderly especially to prevent complications like vision loss. | 25,210,275 | [
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Communication of radiation risk in nuclear medicine: Are we saying the right thing? | The radiation risk arising from nuclear medicine investigations represents a small but manageable risk to patients and it needs to be effectively communicated to them. Frequently in the culture of "doctor knows best," patients trust their doctors to do whatever is right and appropriate and leave it to them to worry about any attendant risks associated with any tests involving the use of radiation. The benefit to the patient of having a speedier diagnosis and a further guide to management may not be effectively communicated in a comprehensive, timely and professional manner. In this article, we address the issue of communication of radiation risk and benefits to patients and the basis for such information. While there are different ways of communicating radiation risk, we recognize that certain basic parameters are absolutely essential for patients to enable them to make an informed choice about undergoing a nuclear medicine investigation under the direction of a well-trained and qualified individual. | 25,210,276 | [
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Exploring the role of technitium-99m dimercaptosuccinyl acid (V) scan in medullary carcinoma thyroid patients with postoperative persistent hypercalcitoninemia in the era of positron emission tomography-computerized tomography. | Many radio-pharmaceuticals have been used over the years to localize the recurrences in patients with medullary carcinoma thyroid (MCT), including iodine-131-metaiodobenzylguanidine, thallium-201, technitium-99m dimercaptosuccinyl acid [Tc-99m DMSA (V)], Tc-99m methoxyisobutylisonitril, Tc-99 ethylenediamine diacetic acid/hydrazinonicotinyl-Tyr (3)-octreotide, and In-111 diethylenetriaminepenta-acetic acid-octreotide with varying sensitivities and specificities. The aim of this study is to explore the role of Tc-99m DMSA (V) scan in MCT patients with postoperative persistent hypercalcitoninemia in the positron emission tomography-computerized tomography (PET-CT) era. A retrospective review of 53 patients with proven sporadic MCT, who presented to our institution over a period 28 years from 1985 to 2012, was performed. Patients with persistently elevated levels of serum calcitonin (>150 pg/ml) were initially evaluated by a DMSA scan if conventional imaging failed to localize any focus of disease. Our study showed that the postoperative levels of serum calcitonin significantly correlated with the overall survival of our patients and can possibly serve as a good prognostic marker. Tc-99m DMSA (V) scans demonstrated a sensitivity of 75%, specificity of 56%, a positive predictive value of 50%, and a negative predictive value of 80% in detecting metastasis in postoperative persistent hypercalcitoninemia. Our study showed that Tc-99m DMSA (V) scanning is an affordable and a reasonably sensitive imaging agent for localization of recurrent/metastatic disease. PET-CT seems to be a useful complementary tool and needs to be kept in the armamentarium for diagnosis of recurrence especially in cases of discordance between Tc-99m DMSA (V) scan and the serum calcitonin levels. | 25,210,279 | [
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Post-treatment appearances, pitfalls, and patterns of failure in head and neck cancer on FDG PET/CT imaging. | Majority of patients with head and neck cancer are treated with combined treatment regimes such as surgery, radiation therapy, and chemotherapy. The loss of structural symmetry and imaging landmarks as a result of therapy makes post-treatment imaging a daunting task on conventional modalities like computed tomography (CT) scan and magnetic resonance imaging (MRI) as well as on 18 Fluorine-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F FDG PET/CT). Combined multimodality treatment approach causes various tissue changes that give rise to a spectrum of findings on FDG PET/CT imaging, which are depicted in this atlas along with a few commonly encountered imaging pitfalls. The incremental value of FDG PET/CT in detecting locoregional recurrences in the neck as well as distant failures has also been demonstrated. | 25,210,280 | [
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Granulosa cell tumor induced massive recurrence of post hysterectomy leiomyoma. | The authors report a very unusual occurrence of a massive recurrence of leiomyoma from post hysterectomy stump diagnosed on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT). The case also has an additional complexity of granulosa cell tumor (GCT) of ovary probably contributing to the recurrence and massive size. | 25,210,289 | [
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Simultaneous determination of four neuroprotective compounds of Tilia amurensis by high performance liquid chromatography coupled with diode array detector. | Tilia amurensis consists of various compounds, such as flavonoids and terpenoids. A simple and reliable high performance liquid chromatography (HPLC) coupled with the diode array detector (DAD) method has been established for simultaneous determination of epicatechin, nudiposide, lyoniside, and scopoletin isolated from Tilia amurensis. Optimum separations were obtained with a SHISEIDO C18 column by gradient eluton, with 0.1% Trifluoroacetic acid (TFA) water-methanol as the mobile phase. The gradient elution system was completed within 40 minutes. The flow rate and detection wavelength were 1 mL/minute, 205 nm, 250 nm, and 280 nm, respectively. Validation of the analytical method was evaluated by linearity, precision, and the accuracy test. The calibration curve was linear over the established range with R(2) > 0.997. The limit of detection (LOD) and limit of quantification (LOQ) ranged from 0.01-15.20 μg/mL and 0.03-46.06 μg/mL. The method exhibited an intraday and interday precision range of 96.25-105.66% and 93.52-109.92%, respectively (RSD <2.80%). The recoveries and relative standard deviation (RSD) of the four compounds in Tilia amurensis were in the range of 90.42-104.84% and 0.2-2.58%. This developed method was accurate and reliable for the quality evaluation of the four compounds isolated from Tilia amurensis. | 25,210,303 | [
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Qualitative and quantitative analysis of the major constituents in traditional Chinese medicine Danmu injection using LC-ESI-MS(n) and LC-DAD. | Danmu injection, a traditional Chinese medicine (TCM) preparation made from Nauclea officinalis, has been commonly used for the treatment of cold, fever, swelling of throat in China. However, the chemical constituents in Danmu injection have not been clarified yet. a HPLC/DAD/ESI-MS(n) method was developed for qualitative and quantitative analysis of the components in Danmu injection. The chromatographic separation was performed on a Welch Material XB-C18 (4.6mm × 250mm, 5μm) using gradient elution with acetonitrile (A) and water containing 0.1% formic acid (B) as mobile phase at a flow rate of 1.0 ml/min. Twenty-five compounds, including phenolic acid and phenol glycoside, iridous glycoside and glycoalkaloid were identified or tentatively deduced on the base of their retention behaviors, UV absorption, MS and MS(n) data with those elucidated references or literature. In addition, eleven compounds were simultaneously determined by HPLC-DAD, which was validated and successfully applied for determination of major components in Danmu injection. The results suggested that the established qualitative and quantitative method would be a powerful and reliable analytical tool for the characterization of multi-constituent in complex chemical system and quality control of Danmu injection. | 25,210,312 | [
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Antidepressant-like effects of Chaihu-Shugan-San via SAPK/JNK signal transduction in rat models of depression. | Chaihu-Shugan-San (CHSGS), a traditional Chinese medicinal herbal formula, registered in Jingyue Quanshu, has been indicated that oral administration of the extract from it can remit depressive disorder. C-Jun amino-terminal kinase (JNK/SAPK) signal transduction plays a key role in the apoptosis of nerve cells, be reported closely correlated with depression. This study was designed to investigate CHSGS antidepressant-like effects in rat models of depression and probe its possible mechanism. The classical experimental depression model chronic mild unpredictable stress (CMUS) was used to evaluate the antidepressant-like effects of CHSGS. The extracts were administered orally for 14 days, while the parallel positive control was given at the same time using fluoxetine hydrochloride. The expressions of JNK in the hippocampus were detected by real-time fluorescent quantitation PCR and Western blot assay. Intragastric administration of CHSGS for 14 days caused a significant improvement of weight and locomotor activity in the open-field test. In addition, CHSGS treatment inhibited the expressions of JNK in the hippocampus tissue in CMUS rats. CHSGS could obviously improve the depressive state of the model rats and its mechanism may be correlated with regulating the expressions of JNK in the hippocampus. | 25,210,314 | [
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Content determination of the flavonoids in the different parts and different species of Abelmoschus esculentus L. by reversed phase-high performance liquid chromatograph and colorimetric method. | This research will establish the ultraviolet colorimetric method to determine the total flavonoid content in different species and different parts of Abelmoschus esculentus L. We establish the reversed-phase high-performance liquid chromatograph (RP-HPLC) method to determine the content of the three flavonoid glycosides in different species and different parts of the A. esculentus. Adopt the NaNO2-Al (NO3)3-NaOH colorimetric method to determine the total flavonoid content; at the same time, adopt the RP-HPLC method to determine the contents of the three flavonoid glycosides. Using the methods of ultraviolet colorimetry and RP-HPLC, we determined and analyzed the total flavonoid content and the content of the three flavonoid glycosides in different species and different parts of A. esculentus. There are great distribution differences of the total flavonoids and the three flavonoid glycosides in different species and parts of A. esculentus. Among them, the content of the effective constituents in the flower is relatively high, next is in the fruit. In the different species of A. esculentus, the content of the flavonoids of finger relatively high. The HPLC method established in this research is simple and convenient and its results are accurate and reliable. In addition, it has a very good repeatability. The results provided the reference data for the medicinal use of A. esculentus and it can be used in quality analyzing of its effective constituents. | 25,210,315 | [
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Optimization of simultaneous ultrasonic-assisted extraction of water-soluble and fat-soluble characteristic constituents from Forsythiae Fructus Using response surface methodology and high-performance liquid chromatography. | The compounds (+)-pinoresinol-β-glucoside (1) forsythiaside, (2) phillyrin (3) and phillygenin (4) were elucidated to be the characteristic constituents for quality control of Forsythiae Fructus extract by chromatographic fingerprint in 2010 edition of Chinese Pharmacopoeia due to their numerous important pharmacological actions. It is of great interest to extract these medicinally active constituents from Forsythiae Fructus simultaneously. In this study, a new ultrasound-assisted extraction (UAE) method was developed for the simultaneous extraction of biological components 1-4 in Forsythiae Fructus. The quantitative effects of extraction time, ratio of liquid to solid, extraction temperature, and methanol concentration on yield of these four important biological constituents from Forsythiae Fructus were investigated using response surface methodology with Box-Behnken design. The compounds 1-4 extracted by UAE were quantitative analysis by high-performance liquid chromatography-photodiode array detect (HPLC-PAD), and overall desirability (OD), the geometric mean of the contents of four major biological components, was used as a marker to evaluate the extraction efficiency. By solving the regression equation and analyzing 3-D plots, the optimum condition was at extraction temperature 70°C, time 60 min, ratio of liquid to solid 20, and methanol concentration 76.6%. Under these conditions, extraction yields of compounds 1-4 were 2.92 mg/g, 52.10 mg/g, 0.90 mg/g and 0.57 mg/g, respectively, which were in good agreement with the predicted OD values. In order to achieve a similar yield as UAE, soxhlet extraction required at least 6 h and maceration extraction required much longer time of 24 h. Established UAE method has been successfully applied to sample preparation for the quality control of Forsythiae Fructus. Additionally, a quadrupole time-of-flight mass spectrometry was applied to the structural confirmation of analytes from the complex matrices acquired by UAE. The results indicated that UAE is an effective alternative method for extracting bioactive constituents, which may facilitate a deeper understanding of the extract of active constituents in Forsythiae Fructus from the raw material to its extract for providing the theoretical references. | 25,210,317 | [
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0.1936454,
0.3088824,
0.340676,
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-0.5208386,
-0.521... |
Methyl protodioscin induces G2/M cell cycle arrest and apoptosis in A549 human lung cancer cells. | Methyl protodioscin (MPD) is a furostanol bisglycoside with antitumor properties. It has been shown to reduce proliferation, cause cell cycle arrest. The present study elucidates the mechanism underlying MPD's apoptotic effects, using the A549 human lung cancer cell line. The human pulmonary adenocarcinoma cell line A549 was obtained from the Cell Bank of the Animal Experiment Center, North School Region, Sun Yat-Sen University. All of the cells were grown in RPMI 1640 supplemented with 10% fetal calf serum (Hyclone, Logan, UT, USA), penicillin (10,000 U/l), and streptomycin (100 mg/l) at 37°C in a 5% CO2 humidified atmosphere. The induction of apoptosis was observed in flow cytometry and fluorescent staining experiments. MPD showed growth inhibitory effects in A549 cells in a dose- and time-dependent manner. The significant G2/M cell cycle arrest and apoptotic effect were also seen in A549 cells treated with MPD. MPD-induced apoptosis was accompanied by a significant reduction of mitochondrial membrane potential, release of mitochondrial cytochrome c to cytosol, activation of caspase-3, downregulation of Bcl-2, p-Bad, and upregulation of Bax. Our results show that the induction of apoptosis by MPD involves multiple molecular pathways and strongly suggest that Bcl-2 family proteins signaling pathways. In addition, mitochondrial membrane potential, mitochondrial cytochrome c and caspase-3 were also closely associated with MPD-induced apoptotic process in human A549 cells. | 25,210,320 | [
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A rapid identification of four medicinal chrysanthemum varieties with near infrared spectroscopy. | For genuine medicinal material in Chinese herbs; the efficient, rapid, and precise identification is the focus and difficulty in the filed studying Chinese herbal medicines. Chrysanthemum morifolium as herbs has a long planting history in China, culturing high quality ones and different varieties. Different chrysanthemum varieties differ in quality, chemical composition, functions, and application. Therefore, chrysanthemum varieties in the market demands precise identification to provide reference for reasonable and correct application as genuine medicinal material. A total of 244 batches of chrysanthemum samples were randomly divided into calibration set (160 batches) and prediction set (84 batches). The near infrared diffuses reflectance spectra of chrysanthemum varieties were preprocessed by first order derivative (D1) and autoscaling and was built model with partial least squares (PLS). In this study of four chrysanthemum varieties identification, the accuracy rates in calibration sets of Boju, Chuju, Hangju, and Gongju are respectively 100, 100, 98.65, and 96.67%; while the accuracy rates in prediction sets are 100% except for 99.1% of Hangju. The research results demonstrate that the qualitative analysis can be conducted by machine learning combined with near infrared spectroscopy (NIR), which provides a new method for rapid and noninvasive identification of chrysanthemum varieties. | 25,210,325 | [
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0.1047429... |
Beyond goosebumps: does the arrector pili muscle have a role in hair loss? | The arrector pili muscle (APM) consists of a small band of smooth muscle that connects the hair follicle to the connective tissue of the basement membrane. The APM mediates thermoregulation by contracting to increase air-trapping, but was thought to be vestigial in humans. The APM attaches proximally to the hair follicle at the bulge, a known stem cell niche. Recent studies have been directed toward this muscle's possible role in maintaining the follicular integrity and stability. This review summarizes APM anatomy and physiology and then discusses the relationship between the follicular unit and the APM. The potential role of the APM in hair loss disorders is also described, and a model explaining APM changes in hair loss is proposed. | 25,210,331 | [
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Comparative clinical evaluation of transcutaneous electrical nerve stimulator over conventional local anesthesia in children seeking dental procedures: A clinical study. | The aim of this study to evaluate the effectiveness of pain control by employing transcutaneous electrical nerve stimulator (TENS) over conventional injectable local anesthesia for children requiring restorative procedures under rubber dam. The study design considered was the split mouth design, in experiment (right) side, dental procedures under rubber dam was performed under TENS and in control (left) side, dental procedures under rubber dam was performed under conventional injectable local anesthetic (LA). The level of comfort and discomfort experienced during TENS and conventional LA was determined using visual analog scale (VAS) and heart rate. Increase in mean heart rate associated with TENS (0.78%) was significantly less compared to increase in heart rate with administration of conventional local anesthesia (11.78%). In VAS, the mean values for pain indicate that minimum pain was felt with TENS, which was closely followed by LA. TENS can offer many safer and psychological advantages and is a valuable alternative to conventional LA for children. | 25,210,350 | [
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Comparison of the frictional resistance between archwire and different bracket system: An in vitro study. | The purpose of this study is to evaluate the frictional resistance generated by conventional stainless steel, radiance ceramic bracket, self-ligating and composite brackets using a 0.019 × 0.025 stainless steel straight length wires in a 022 slot and to select brackets based on their frictional characteristic. In order to conduct this study, four different types of bracket system were selected of the mclaughlin-bennet-trevesi (MBT) discipline. They are Group 1 - stainless steel, Group 2 - composite bracket Group 3 - (American Orthodontics) radiance ceramic bracket Group 4 - self-ligating bracket (SLB) (Empower). In this study, five maxillary brackets of an arch of each type were used. All brackets are 0.022 × 0.028 in preadjusted edgewise appliance which simulates the dental arch. Five brackets were bonded to a stainless steel bar of dimension 150 mm × 25 mm × 3 mm. The bracket-arch wire units were submitted to mechanical test with an Instron universal testing machine 3365. A testing apparatus or holding jig was designed to hold the bracket during the mechanical test. Each sample was pulled at a speed of 6 mm for 1 min. Descriptive statistical information including mean and standard deviation of maximum friction force was calculated for each bracket wire combination. The SLB has the least friction among the four groups. The ceramic bracket showed the highest friction followed by stainless steel bracket, composite bracket, and SLB. | 25,210,359 | [
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Prevalence of dental caries among school-going children in Namakkal district: A cross-sectional study. | The aim of this study is to determine the prevalence of dental caries in primary teeth among 4-6 years old school going children in the Namakkal District. The study covered a total of 850 school going children in a total of 26 schools in the Namakkal district of Tamil Nadu. The age group selected for this study ranged from 4 to 6 years of age. Each child was examined in their respective schools by one of the four calibrated examiners and decay, missing and filled teeth (dmft) index was recorded along with demographic details. This study was done in September-October 2013 in a span of 1 month duration. Of 850 children examined, 560 (65.88%) children had dental caries. Mean dmft score was 2.86. Prevalence of dental caries was higher in boys (69.6%) than in girls (61.5%). The untreated decay teeth accounted for 92.4%. The prevalence of dental caries among 4-6 years old children is high in the Namakkal district. The need for the creation of dental awareness among children and their primary caregivers is crucial and the need for developing immediate oral health promotion strategies including an increase in school dental health programs is recommended. | 25,210,362 | [
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0.3... |
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