title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Determination of organochlorines, polychlorinated biphenyls and polybrominated diphenyl ethers in human hair: estimation of external and internal exposure. | A novel method was developed for the analysis of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in human hair samples. External contaminants of hair were extracted with acetone under sonication, while washed hair was further hydrolyzed in formic acid and acetone (1:4, v/v) with microwave assisted extraction (MAE) for internal contaminant measurements. Both internal and external extracts were cleaned up with gel permeation chromatography (GPC) and then solid phase extraction (SPE), before analyzed by a large volume injection-gas chromatography-tandem mass spectrometry (LVI-GC-MS/MS) using triple quadruple mass analyzer. Good linearity (R(2)⩾ 0.996) was established within a concentration range between 0.1 and 100 ng mL(-)(1) among all target analytes. The method was validated for accuracy, precision and sensitivity. The developed method is intended to be cost effective and robust for the routine human hair analysis of PCBs, PBDEs and OCPs including acid-labile OCPs. The described method has been applied in pilot biomonitoring study and the preliminary data suggested that the contaminant profiles with the use of partial least-squares analysis discriminant analysis (PLA-DA) could be useful in differentiating external and internal exposure. | 25,113,219 | [
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Systematic review of diplommatinid land snails (Caenogastropoda, Diplommatinidae) endemic to the Palau Islands. (1) Generic classification and revision of Hungerfordia species with highly developed axial ribs. | Diplommatinidae is a family of terrestrial caenogastropod snails that shows extensive species diversity and endemic radiation within the Palau (Belau) Islands. In this paper, we revised the taxonomy of Palauan endemic diplommatinids based on the comparative morphology of shell, operculum, radula, and genitalia. Although the generic classification of Palauan diplommatinids has been confusing, they are currently classified into two genera, Hungerfordia Beddome, 1889 and Palaina Semper, 1865. Palauan diplommatinids of these two genera are primarily distinguished by the radular, genital and operculum morphology. However, shell morphology, on which taxonomy has traditionally been based, does not provide definitive characters for generic identification, because shell shape and sculpture are highly variable within each genus. Although Hungerfordia has long been known as a monotypic genus, the current study redefines the endemic genus to include a wider range of species that were formerly placed in Diplommatina or Palaina. Following species are transferred to Hungerfordia: H. alata (Crosse, 1866) comb. nov.; H. lamellata (Crosse, 1866) comb. nov.; H. pyramis (Crosse, 1866) comb. nov.; H. ringens (Crosse, 1866) comb. nov.; H. polymorpha (Crosse, 1866) comb. nov.; H. inflatula (Crosse, 1866) comb. nov.; H. lutea (Beddome, 1889) comb. nov.; H. aurea (Beddome, 1889) comb. nov.; H. gibboni (Beddome, 1889) comb. nov.; H. crassilabris (Beddome, 1889) comb. nov. Pseudopalaina Moellendorff in Kobelt & Moellendorff, 1898 (synonym nov.) is demoted as a junior synonym of Hungerfordia. Palaina is also redefined based on the internal shell features and operculum morphology, in addition to the external shell characters. Furthermore, Eupalaina Kobelt & Moellendorff, 1898 is restored as a subgenus of Palaina for Palauan species on the basis of a genital character. The taxonomy of Hungerfordia species with highly developed axial ribs is revised. H. pelewensis Beddome, 1889, H. lamellata (Crosse, 1866) comb. nov., and H. alata (Crosse, 1866) comb. nov. are redescribed with new morphological data. Following new taxa are described: H. triplochilus sp. nov., H. expansilabris sp. nov., H. nudicollum sp. nov., H. echinata echinata sp. et subsp. nov., H. echinata tubulispina subsp. nov., H. elegantissima sp. nov., H. goniobasis goniobasis sp. et subsp. nov., H. goniobasis dmasechensis subsp. nov., H. subalata sp. nov., H. pteropurpuroides sp. nov., H. papilio papilio sp. et subsp. nov., H. papilio stenoptera subsp. nov.. | 25,113,222 | [
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Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center. | Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch-Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death ('primary refractoriness'). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML. | 25,113,226 | [
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A low computational cost algorithm for REM sleep detection using single channel EEG. | The push towards low-power and wearable sleep systems requires using minimum number of recording channels to enhance battery life, keep processing load small and be more comfortable for the user. Since most sleep stages can be identified using EEG traces, enormous power savings could be achieved by using a single channel of EEG. However, detection of REM sleep from one channel EEG is challenging due to its electroencephalographic similarities with N1 and Wake stages. In this paper we investigate a novel feature in sleep EEG that demonstrates high discriminatory ability for detecting REM phases. We then use this feature, that is based on spectral edge frequency (SEF) in the 8-16 Hz frequency band, together with the absolute power and the relative power of the signal, to develop a simple REM detection algorithm. We evaluate the performance of this proposed algorithm with overnight single channel EEG recordings of 5 training and 15 independent test subjects. Our algorithm achieved sensitivity of 83%, specificity of 89% and selectivity of 61% on a test database consisting of 2221 REM epochs. It also achieved sensitivity and selectivity of 81 and 75% on PhysioNet Sleep-EDF database consisting of 8 subjects. These results demonstrate that SEF can be a useful feature for automatic detection of REM stages of sleep from a single channel EEG. | 25,113,231 | [
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Chaotic oscillation and random-number generation based on nanoscale optical-energy transfer. | By using nanoscale energy-transfer dynamics and density matrix formalism, we demonstrate theoretically and numerically that chaotic oscillation and random-number generation occur in a nanoscale system. The physical system consists of a pair of quantum dots (QDs), with one QD smaller than the other, between which energy transfers via optical near-field interactions. When the system is pumped by continuous-wave radiation and incorporates a timing delay between two energy transfers within the system, it emits optical pulses. We refer to such QD pairs as nano-optical pulsers (NOPs). Irradiating an NOP with external periodic optical pulses causes the oscillating frequency of the NOP to synchronize with the external stimulus. We find that chaotic oscillation occurs in the NOP population when they are connected by an external time delay. Moreover, by evaluating the time-domain signals by statistical-test suites, we confirm that the signals are sufficiently random to qualify the system as a random-number generator (RNG). This study reveals that even relatively simple nanodevices that interact locally with each other through optical energy transfer at scales far below the wavelength of irradiating light can exhibit complex oscillatory dynamics. These findings are significant for applications such as ultrasmall RNGs. | 25,113,239 | [
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Incidence and risk factors for AIDS-related mortality in HIV patients in China: a cross-sectional study. | To estimate the incidence and risk factors for mortality in HIV-1-infected patients in China. Information on AIDS-related deaths was collected from the Chinese Center for Disease Control and Prevention's Disease Surveillance Information Reporting System and AIDS Prevention and Control Information System. A total of 379,348 HIV cases were recorded in the databases from 2006. Among those, 138,288 patients were reported as having developed AIDS and 72,616 (19%) died of AIDS after data was extracted from the databases in January 2011. Mortality was higher among those patients aged 50 years old or older (AOR: 3.41, CI: 1.47-7.91) who had been infected by intravenous drug use (AOR: 1.65, CI: 1.28-2.14) or blood transfusion/donation (AOR: 2.18: 1.18-3.99). Compared to patients who had not initiated highly active antiretroviral therapy (HAART), those who had initiated HAART were more likely to have a long interval of time between infection confirmation and AIDS-related death. The effective reduction of AIDS mortality could be improved through timely treatment. | 25,113,245 | [
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Impact of transpulmonary thermodilution-based cardiac contractility and extravascular lung water measurements on clinical outcome of patients with Takotsubo cardiomyopathy after subarachnoid hemorrhage: a retrospective observational study. | Takotsubo cardiomyopathy (TCM) is a life-threatening systemic consequence early after subarachnoid hemorrhage (SAH), but precise hemodynamics and related outcome have not been studied. The purpose of this study was to investigate the TCM-induced cardiac function by transpulmonary thermodilution and its impact on clinical outcome of SAH. We retrospectively analyzed 46 consecutive postoperative SAH patients who developed TCM. Patients were divided into two groups of echocardiographic left ventricular ejection fraction (LVEF) < 40% (TCM with left ventricular (LV) dysfunction) and LVEF ≥40% (TCM without LV dysfunction). Cardiac function index (CFI) and extravascular lung water index (ELWI) were monitored by transpulmonary thermodilution, in parallel with serial measurements of echocardiographic parameters and blood biochemical markers. Transpulmonary thermodilution-derived cardiac function index (CFI) was significantly correlated with (LVEF) (r = 0.82, P < 0.0001). The CFI between day 0 to day 7 was significantly lower in patients with LV dysfunction (LVEF <40%) than in patients with LVEF ≥40% (P < 0.05). CFI had a better ability than cardiac output to detect cardiac dysfunction (LVEF < 40%) (area under the curve: 0.85 ± 0.02; P < 0.001). A CFI value of < 4.2 min-1 had a sensitivity of 82% and specificity of 84% for detecting LVEF <40%. The CFI < 4.2 min-1 was associated with delayed cerebral ischemia (DCI) (odds ratio (OR), 2.14; 95% confidence interval (CI), 1.33-2.86; P = 0.004) and poor 3-month functional outcome on modified Rankin Scale of 4-6 (OR, 1.87; 95% CI, 1.06-3.29; P = 0.02). An extravascular lung water index (ELWI) > 14 mL/kg after day 4 increased the risk of poor functional outcome at 3-month follow-up (OR, 2.10; 95% CI, 1.11-3.97; P = 0.04). Prolonged cardiac dysfunction and pulmonary edema increased the risk of DCI and poor 3-month functional outcome in patients with SAH suffering from TCM. Serial measurements of CFI and ELWI by transpulmonary thermodilution may provide an easy bedside method of detecting early changes of the cardiopulmonary function in directing proper post-SAH treatment. | 25,113,260 | [
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Impact locations and concussion outcomes in high school football player-to-player collisions. | Little research has examined concussion outcomes in terms of impact location (ie, the area on the head in which the impact occurred). This study describes the epidemiology of concussions resulting from player-to-player collision in high school football by impact location. National High School Sports-Related Injury Surveillance Study data (2008/2009-2012/2013) were analyzed to calculate rates and describe circumstances of football concussion (eg, symptomology, symptom resolution time, return to play) resulting from player-to-player collisions by impact location (ie, front-, back-, side-, and top-of-the-head). Most concussions resulting from player-to-player collisions occurred from front-of-the-head (44.7%) and side-of-the-head (22.3%) impacts. Number of symptoms reported, prevalence of reported symptoms, symptom resolution time, and length of time to return to play were not associated with impact location. However, a larger proportion of football players sustaining concussions from top-of-the-head impacts experienced loss of consciousness (8.0%) than those sustaining concussions from impacts to other areas of the head (3.5%) (injury proportion ratio 2.3; 95% confidence interval 1.2-4.2; P = .008). Players had their head down at the time of impact in a higher proportion of concussions caused by top-of-the-head impacts (86.4%) than concussions from impacts to other areas of the head (24.0%) (injury proportion ratio 3.6; 95% confidence interval 3.2-4.0; P < .001). Among high school football players who sustained concussions due to player-to-player collisions, concussion outcomes were generally independent of impact location. Recommended strategies for reducing the proportion of top-of-the-head impacts include improved education regarding tackling with proper "head-up" technique. | 25,113,292 | [
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Biology of advanced uveal melanoma and next steps for clinical therapeutics. | Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherapies are reviewed, and next steps in the development of clinical therapeutics are discussed. | 25,113,308 | [
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Versatile Cu(I)/Pd(0) dual catalysis for the synthesis of quaternary α-allylated carbonyl compounds: development, mechanistic investigations and scope. | We report herein a versatile cooperative dual catalysis reaction based on a Cu(I)/Pd(0) system. Mechanistic investigation shows that every component plays a crucial role in determining the reaction outcome. The reaction is successfully extended to various substrates; such as α,β-unsaturated ketones, malonates and coumarins. The strategy tolerates different substitution patterns and affords good yields for each family of substrates. | 25,113,317 | [
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One pot synthesis of nanoscale phase-segregated PdPt nanoarchitectures via unusual Pt-doping induced structural reorganization of a Pd nanosheet into a PdPt nanotent. | Pt-doping of an ultrathin Pd nanosheet results in the unprecedented structural rearrangement of a Pd nanosheet into a PdPt nanotent structure, in which a tripod stands on a triangular nanosheet. Further growth of Pt phase on this nanotent structure is dependent on the presence of surface-stabilizing CO molecules, leading to the formation of two distinct nanoscale phase segregated structures with respective structural features of a popped out Pt facet and an overgrown Pt layer. | 25,113,322 | [
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[Clinical features and prurigo nodularis in nephrogenic pruritus]. | Nephrogenic pruritus (NP) is a well-known associated symptom in patients with chronic renal failure. The aim of the present study was to make a detailed dermatological analysis including distribution of excoriations and their correlation with pruritus characteristics. Data on a total of 17 patients with NP (14 males, mean 65.4 ± SD 14.3 years) were subjected to retrospective analysis. Most of the patients developed NP after start of kidney disease; however, in 20 % of the patients, there was premonitory appearance of the symptom 18 months (median) earlier. A majority of patients reported neuropathic symptom qualities (burning, stinging). In 94.1 % of patients xerosis was present; in 58.8 %, prurigo nodularis. The latter group of patients had a longer duration of pruritus as well as up to 10 years longer duration of renal disease than those without prurigo. Pruritus characteristics of NP show a wide variance without a clear profile that is useful for clinical diagnosis. NP can occur premonitorily, and, if of long duration and with coexistent metabolic diseases, can develop into prurigo. | 25,113,331 | [
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Morphological variation and affinities of the poorly known snake Atractus caxiuana (Serpentes: Dipsadidae) . | Atractus caxiuana was recently described based on three specimens (two males and one female) from the Floresta Nacional de Caxiuanã, municipality of Melgaço, state of Pará, in the eastern portion of the Brazilian Amazon. Apart from the type series, no additional samples are known for the species. In this study, we report new specimens of A. caxiuana, providing new morphological data (meristic, morphometric, pholidosis, colour pattern, and hemipenis) and localities. We relate the variability displayed by the characters analyzed to sexual dimorphism, geographic variation, and ontogeny. Additionally, we provide detailed comparisons with A. collaris and putative sister species, and propose a new species group to accommodate this distinct and possible monophyletic assemblage. | 25,113,336 | [
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World synopsis of described species of the genus Platypygus Loew (Diptera: Mythicomyiidae: Platypyginae). | The taxonomy of the genus Platypygus Loew is summarized, previously described species are reviewed based on examination of types, and a key to known species of the genus worldwide is presented. All previously described species are diagnosed and illustrated. The male genitalia of P. ridibundus (Costa) and female genitalia of P. americanus Melander are described for the first time. Some characters supporting the monophyly of the genus Platypygus are discussed and the Nearctic Cyrtisiopsis americanus (Melander) is restored to its original combination as Platypygus americanus. The type status of Platypygus bellus Loew, P. lativentris Loew, P. pumilio Loew, and P. turkmenorum Paramonov is clarified and a lectotype is selected for Platypygus kurdorum Paramonov and P. tauricus Paramonov. New country records are given for the following species: P. bellus (Greece); P. chrysanthemi (Israel, Jordan); P. kurdorum (Israel, Jordan, Syria); P. limatus (Nepal, Thailand); P. pumilio (Greece, Turkmenistan); P. ridibundus (Cyprus, Israel, Portugal), P. titanomedea (Jordan, Turkey). | 25,113,345 | [
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Description of Culicoides paradoxalis sp. nov. from France and Portugal (Diptera: Ceratopogonidae). | A new species, Culicoides paradoxalis Ramilo and Delécolle (Diptera: Ceratopogonidae), is described from specimens collected in France (Corsica and southeast region) and Portugal. This species resembles Culicoides lupicaris Downes and Kettle, and can be distinguished from this species and from Culicoides newsteadi Austen by its wing pattern, in addition to the absence of spines on the tarsomere 4 of female mid leg. In male, the presence of two appendices on the sternite 9 together with the absence of sensilla coeloconica on the flagellomere 11 is also useful to distinguish these three species. Separation from other members of the Culicoides subgenus is confirmed by the analysis of the Cytochrome Oxidase I (COI) mitochondrial marker. | 25,113,346 | [
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... |
Two new species of scale mites (Acari: Pterygosomatidae) parasitizing Agama agama (Sauria: Agamidae) from Kenya. | Two new species of pterygosomatid mites Pterygosoma garissi sp. nov. and P. fragilis sp. nov. (Acari: Pterygosomatidae) are described from the agamid lizard Agama agama (Sauria: Agamidae) from Kenya. P. garissi sp. nov. is similar to P. annectans Jack, 1962 but in the new species the peripheral setae are slightly expanded apically, 3 pairs of setae are situated on the coxal fields I and and 2 pairs on II coxal fields, all pseudoanal setae are paddle-shaped with minute spicules on the apical part, setae dFIV are absent and lTrIV present. P. fragilis sp. nov. is most closely related to P. garissi sp. nov. but differs by the presence of setae n on the subcapitulum, the hypostome with several denticles at the apex, the fixed cheliceral digit bearing a spinous process, the presence of 8-9 pairs of the peripheral setae, 1-2 pairs of genital setae g, and by the cheliceral shaft 2.1 times longer than the cheliceral base. | 25,113,347 | [
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Review of the genus Dolichosciara Tuomikoski (Diptera, Sciaridae) from China. | The genus Dolichosciara from China is reviewed and 17 species are recognized. Among them, eight new species, D. sparsula sp. nov., D. gracilenta sp. nov., D. oxyacantha sp. nov., D. scrobiculata sp. nov., D. tumidula sp. nov., D. rectospinosa sp. nov., D. multisetosa sp. nov. and D. qingliangfengana sp. nov. are described and seven species, D. ninae (Antonova, 1977), D. megumiae (Sasakawa, 1994), D. orcina (Tuomikoski, 1960), D. semiferruginea (Menzel, 1995), D. hippai Komarova & Vilkamaa, 2006, D. subornata (Mohrig & Menzel, 1994) and D. ornata (Winnertz, 1867) are reported for the first time from China. In addition, geographical distribution of 17 Chinese species are provided, as well as a key to all these Chinese species. This study raises the number of the species of Chinese Dolichosciara from 2 to 17. | 25,113,353 | [
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Endogean and cavernicolous Coleoptera of the Balkans. XII. New species of Paramaurops Jeannel, 1948 (Coleoptera: Staphylinidae: Pselaphinae) from Macedonia. | The new species of the tribe Amauropini, Paramaurops vonickai n. sp. is described from Macedonia. | 25,113,357 | [
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Two interstitial species of the genus Semicytherura (Crustacea: Ostracoda) from Japan, with notes on their microhabitats. | A new interstitial ostracod, Semicytherura uzushio sp. nov., is described from the southwest of Japan, and the details of the carapace characters of Semicytherura mukaishimensis Okubo, 1980 are redescribed. Semicytherura uzushio and S. mukaishimensis live interstitially in the intertidal and infralittoral zones, respectively. They have the smallest carapaces among the known Semicytherura species, comparable to those of other interstitial ostracods. It is thought that most of the small species belonging to this genus have an interstitial life style in marine sediments. | 25,113,360 | [
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Association between fasting serum glucose levels and incidence of colorectal cancer in Korean men: the Korean Cancer Prevention Study-II. | The incidence of colorectal cancer (CRC) is steadily increasing worldwide. Numerous studies have demonstrated that diabetes mellitus is related to an increased risk of CRC; however, the association between impaired fasting glucose and CRC is unclear. Therefore, we evaluated the correlation between fasting serum glucose (FSG) levels and the incidence of CRC, which can be used to develop novel methods for preventing CRC. A total of 175,677 individuals from the Korean Metabolic Syndrome Research Initiative study were enrolled between 2004 and 2011. The incidence of CRC was assessed during a mean follow-up of 4.7 years. Hazard ratios (HR) for CRC according to FSG levels were calculated with the Cox proportional hazard model adjusted for age, sex, body mass index, smoking status, alcohol consumption, and regular exercise. The risk of developing CRC in subjects with high FSG was significant (HR, 1.45; 95% confidence interval [CI], 1.10-1.90), and the risk was higher in men (HR, 1.51; 95% CI, 1.12-2.05). The HR of rectal cancer, but not colon cancer, was significantly higher both in the total population and in men in the high FSG group. The incidence of CRC positively correlated with FSG levels in men. Rectal cancer incidence was especially correlated with high FSG in the site-specific analysis. Therefore, serum glucose levels maybe a potential marker of colorectal cancer. Early detection and intervention for controlling elevated glucose levels may be indicated as a way to prevent carcinogenesis. | 25,113,383 | [
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The advances and perspectives of recombinant protein production in the silk gland of silkworm Bombyx mori. | The silk gland of silkworm Bombyx mori, is one of the most important organs that has been fully studied and utilized so far. It contributes finest silk fibers to humankind. The silk gland has excellent ability of synthesizing silk proteins and is a kind tool to produce some useful recombinant proteins, which can be widely used in the biological, biotechnical and pharmaceutical application fields. It's a very active area to express recombinant proteins using the silk gland as a bioreactor, and great progress has been achieved recently. This review recapitulates the progress of producing recombinant proteins and silk-based biomaterials in the silk gland of silkworm in addition to the construction of expression systems. Current challenges and future trends in the production of valuable recombinant proteins using transgenic silkworms are also discussed. | 25,113,390 | [
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The hidden history of the snowshoe hare, Lepus americanus: extensive mitochondrial DNA introgression inferred from multilocus genetic variation. | Hybridization drives the evolutionary trajectory of many species or local populations, and assessing the geographic extent and genetic impact of interspecific gene flow may provide invaluable clues to understand population divergence or the adaptive relevance of admixture. In North America, hares (Lepus spp.) are key species for ecosystem dynamics and their evolutionary history may have been affected by hybridization. Here we reconstructed the speciation history of the three most widespread hares in North America - the snowshoe hare (Lepus americanus), the white-tailed jackrabbit (L. townsendii) and the black-tailed jackrabbit (L. californicus) - by analysing sequence variation at eight nuclear markers and one mitochondrial DNA (mtDNA) locus (6240 bp; 94 specimens). A multilocus-multispecies coalescent-based phylogeny suggests that L. americanus diverged ~2.7 Ma and that L. californicus and L. townsendii split more recently (~1.2 Ma). Within L. americanus, a deep history of cryptic divergence (~2.0 Ma) was inferred, which coincides with major speciation events in other North American species. While the isolation-with-migration model suggested that nuclear gene flow was generally rare or absent among species or major genetic groups, coalescent simulations of mtDNA divergence revealed historical mtDNA introgression from L. californicus into the Pacific Northwest populations of L. americanus. This finding marks a history of past reticulation between these species, which may have affected other parts of the genome and influence the adaptive potential of hares during climate change. | 25,113,393 | [
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GlycoMaster DB: software to assist the automated identification of N-linked glycopeptides by tandem mass spectrometry. | Glycosylation is one of the most commonly observed post-translational modifications (PTMs) in eukaryotes. It is believed that more than 50% eukaryotic proteins are glycosylated. To reveal the biological functions of protein-linked glycans involved in numerous biological processes, the high-throughput identification of both glycoproteins and the attached glycan structures becomes fundamentally important. Tandem mass spectrometry (MS/MS) is an effective method for glycoproteomic analysis because of its high sensitivity and selectivity. Two experimental approaches exist to obtain MS/MS spectral data of glycopeptides. One consists of isolating glycans from glycopeptides and generating MS/MS spectra of the glycans and peptides separately. The other approach produces spectra directly from intact glycopeptides. The latter approach has the advantage of retaining the glycosylation site information. However, the spectral data cannot be readily analyzed because of the lack of software specifically designed for the identification of intact glycopeptides. To address this need, we developed a novel software tool, GlycoMaster DB, to assist the automated and high-throughput identification of intact N-linked glycopeptides from MS/MS spectra. The software simultaneously searches a protein sequence database and a glycan structure database to find the best pair of peptide and glycan for each input spectrum. GlycoMaster DB can analyze mass spectral data produced with HCD/ETD mixed fragmentation, where HCD spectra are used to identify glycans and ETD spectra are used to determine peptide sequences. When only HCD spectra are available, GlycoMaster DB can still help to identify the glycans, and a list of possible peptide sequences are reported according to the accurate precursor mass and the N-linked glycopeptide sequon. GlycoMaster DB is freely accessible at http://www-novo.cs.uwaterloo.ca:8080/GlycoMasterDB . | 25,113,421 | [
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Dehydrative cross-coupling reactions of allylic alcohols with olefins. | The direct dehydrative activation of allylic alcohols and subsequent cross-coupling with alkenes by using palladium catalyst containing a phosphoramidite ligand is described. The activation of the allyl alcohol does not require stoichiometric additives, thus allowing clean, waste-free reactions. The scope is demonstrated by application of the protocol to a series allylic alcohols and vinyl arenes, leading to variety of 1,4-diene products. Based on kinetic studies, a mechanism is proposed that involves a palladium hydride species that activates the allyl alcohol to form the allyl intermediate. | 25,113,437 | [
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Rubisco catalytic properties optimized for present and future climatic conditions. | Because of its catalytic inefficiencies, Rubisco is the most obvious target for improvement to enhance the photosynthetic capacity of plants. Two hypotheses are tested in the present work: (1) existing Rubiscos have optimal kinetic properties to maximize photosynthetic carbon assimilation in existing higher plants; (2) current knowledge allows proposal of changes to kinetic properties to make Rubiscos more suited to changed conditions in chloroplasts that are likely to occur with climate change. The catalytic mechanism of Rubisco results in higher catalytic rates of carboxylation being associated with decreased affinity for CO2, so that selection for different environments involves a trade-off between these two properties. The simulations performed in this study confirm that the optimality of Rubisco kinetics depends on the species and the environmental conditions. In particular, environmental drivers affecting the CO2 availability for carboxylation (Cc) or directly shifting the photosynthetic limitations between Rubisco and RuBP regeneration determine to what extend Rubisco kinetics are optimally suited to maximize CO2 assimilation rate. In general, modeled values for optimal kinetic reflect the predominant environmental conditions currently encountered by the species in the field. Under future climatic conditions, photosynthetic CO2 assimilation will be limited by RuBP-regeneration, especially in the absence of water stress, the largest rise in [CO2] and the lowest increases in temperature. Under these conditions, the model predicts that optimal Rubisco should have high Sc/o and low kcat(c). | 25,113,451 | [
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Review of the Eulamprotes wilkella species-group based on morphology and DNA barcodes, with descriptions of new taxa (Lepidoptera, Gelechiidae). | The Eulamprotes wilkella species-group is revised based on morphological characters and on DNA barcodes of the mtCOI (Cytochrome c Oxidase 1) gene. Adult morphology combined with sequence information for 9 species supports the existence of 12 species, 7 of which are described as new to science: E. mirusella Huemer & Karsholt sp. nov. (France), E. baldizzonei Karsholt & Huemer sp. nov. (Italy, Slovenia, Croatia), E. atrifrontella Karsholt & Huemer sp. nov. (Turkey), E. wieseri Huemer & Karsholt sp. nov. (Kyrgizia), E. altaicella Huemer & Karsholt sp. nov. (Russia: Altai, Buryatia, Tuva Republic), E. kailai Karsholt & Huemer sp. nov. (Kazakhstan, Kyrgizia, Russia: Buryatia, Tuva Republic) and E. gemerensis Elsner sp. nov. (Slovakia). E. buvati Leraut, 1991 syn. nov. is synonymized with E. ochricapilla (Rebel, 1903). | 25,113,469 | [
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New records of Recent Brachiopoda from the Red Sea with a description of a new species . | A revised checklist of 14 Recent brachiopod species from Egypt and the Sudan in the Red Sea has been compiled. New records of Minutella minuta (Cooper), Thecidellina blochmanni Dall and Argyrotheca somaliensis Cooper are described and a new species Argyrotheca cooperi is erected for specimens with few but very strong costae. The new records support earlier suggestions that the affinities of the Red Sea brachiopod fauna are with those of the Mediterranean and Indo-Pacific areas. | 25,113,473 | [
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Revision of the genus Ortopla Walker, [1859] with description of two new species from Southeast Asia (Lepidoptera, Noctuidae, Pantheinae). Revision of Pantheinae, contribution X. | The pantheine genus Ortopla Walker, [1859] 1858 is revised. Two new species, Ortopla witti sp. n. from the Philippines and O. longiuncus sp. n. from Nepal, Vietnam, Thailand, Myanmar and South China are described. The name O. commutanda Warren, 1891 (syn. n.) is synonymised with O. iarbasalis Walker, [1859] 1858. The distribution of species in East Asia is clarified. A checklist of the genus Ortopla is presented. Imagines, male and female genitalia of all species are illustrated. | 25,113,477 | [
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The male and larvae of Nigritothrips longistylosus (Thysanoptera, Thripidae) with observations on its biology. | The male and larvae of Nigritothrips longistylosus (Priesner) are described for the first time. The life cycle, seasonal abundance, natural enemies and host plant relationships are described. This is the first record of this species from the Iberian Peninsula. | 25,113,493 | [
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Two new species of the leafhopper genus Anidiocerus (Hemiptera: Cicadellidae: Idiocerinae) from China. | Two new species of Anidiocerus from China, A. brevispinus Xue & Zhang sp. nov. and A. longimus Xue & Zhang sp. nov. are described and illustrated, and A. variabilis Maldonado-Capriles, 1976 is placed as a senior synonym of A. flavidus Cai & Shen, 1998, syn. nov. A redescription of the genus is provided together with a checklist and key for the separation of males. | 25,113,491 | [
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XI-011 enhances cisplatin-induced apoptosis by functional restoration of p53 in head and neck cancer. | Head and neck cancer (HNC), one of the most common cancers worldwide, frequently involves mutation of the TP53 gene and dysregulation of the p53 pathway. Overexpression of MDM2 or MDM4 inactivates the tumor-suppressive function of p53. Restoration of p53 function that counteracts these p53 repressors can lead to in vivo tumor regression. Therefore, the present study assessed the ability of the small molecule p53 activator XI-011 (NSC146109) to induce apoptosis in HNC by restoring p53 function. We tested the effects of XI-011 treatment in HNC cell lines, either individually or in combination with cisplatin and assessed growth suppression, cell cycle arrest, and apoptosis. The drug effects on in vivo growth of HNC cells were examined in mice xenograft model. XI-011 exerted the highest growth suppression in tumor cells that overexpress MDM4, in which p53 is degraded. XI-011 treatment downregulated MDM4 mRNA and protein levels, and upregulated expression of proapoptotic genes and promoted apoptosis, in a dose-dependent manner. The apoptotic response was blocked by inhibition of p53 or expression of MDM4, demonstrating that the effects of XI-011 depend on p53 and MDM4. In combination treatments, XI-011 acted synergistically with cisplatin to inhibit growth of HNC cells in vitro and in vivo. MDM4 inhibition and functional restoration of p53 by XI-011 effectively enhanced cisplatin-induced cytotoxicity in HNC cells, an activity that suggests a promising strategy for treating HNC. | 25,113,507 | [
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The critical role of the operating conditions on the Fenton oxidation of 2-chlorophenol: assessment of PCDD/Fs formation. | This work assesses the influence of the operating conditions H2O2 dose (20 or 100% of the stoichiometric amount), temperature (20 or 70°C), and the presence of chloride in the oxidation medium in the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during Fenton treatment of aqueous samples of 2-chlorophenol, 2-CP, one of the strongest precursor of PCDD/Fs. After 4h of oxidation in the experiments carried out with 20% H2O2 chlorinated phenoxyphenols and biphenyls, which are intermediates in PCDD/Fs formation, as well as PCDD/Fs were observed, resulting in concentrations 11 times higher than in the untreated sample. Additionally, when NaCl was also present in the reaction medium, PCDD/Fs were formed at higher extent, with a total concentration 74.4 times higher than in the untreated 2-CP solution. Results depicted a preferential formation of PCDFs over PCDDs, with dominance of lower chlorinated PCDD/Fs (tetra and penta-PCDD/Fs). Besides, the formation of the most toxic PCDD/Fs congeners (2,3,7,8-PCDD/Fs) was not favored under the operating conditions used in this work. | 25,113,517 | [
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The effects of dexmedetomidine administration on the pulmonary artery pressure and the transpulmonary pressure gradient after the bidirectional superior cavopulmonary shunt. | The hemodynamic effects of dexmedetomidine (DEX) on pulmonary artery pressure (PAP) are not fully understood in patients with a single-ventricle physiology. The objective of this retrospective study was to characterize the effect of perioperative DEX infusion on PAP and the transpulmonary pressure gradient after a bidirectional superior cavopulmonary shunt (BCPS) operation. We retrieved physiologic data including the heart rate, incidence of cardiac pacing, systolic and diastolic arterial blood pressure (ABP), and superior vena cava (SVC) and inferior vena cava (IVC) pressures from the medical records of all patients <12 months of age who underwent a BCPS operation. Patients with an additional Norwood or Damus-Kaye-Stansel procedure, those with additional pulmonary blood flow, and those without both a SVC and an IVC catheter were excluded from the present study. Following the BCPS operation, the SVC pressure is equivalent to the PAP. Similarly, the IVC pressure is equivalent to the common atrial pressure (CAP). Accordingly, we can directly assess the transpulmonary pressure gradient, defined as the difference between the PAP and the CAP, using simultaneous SVC and IVC pressure measurements. Twenty-nine patients were included in the present study. We did not find any increase in the PAP, CAP, PAP/systolic ABP ratio, or the transpulmonary pressure gradient as of 6 h after admission to the intensive care unit when the patients were treated with DEX infusion at a median (interquartile ranges) dose of 0.6 mcg/kg/h (0.4, 0.64 mcg/kg/h). We concluded that the administration of DEX to children with a single-ventricle physiology is acceptable. | 25,113,519 | [
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Development of a charge adjustment model for cardiac catheterization. | A methodology that would allow for comparison of charges across institutions has not been developed for catheterization in congenital heart disease. A single institution catheterization database with prospectively collected case characteristics was linked to hospital charges related and limited to an episode of care in the catheterization laboratory for fiscal years 2008-2010. Catheterization charge categories (CCC) were developed to group types of catheterization procedures using a combination of empiric data and expert consensus. A multivariable model with outcome charges was created using CCC and additional patient and procedural characteristics. In 3 fiscal years, 3,839 cases were available for analysis. Forty catheterization procedure types were categorized into 7 CCC yielding a grouper variable with an R (2) explanatory value of 72.6%. In the final CCC, the largest proportion of cases was in CCC 2 (34%), which included diagnostic cases without intervention. Biopsy cases were isolated in CCC 1 (12%), and percutaneous pulmonary valve placement alone made up CCC 7 (2%). The final model included CCC, number of interventions, and cardiac diagnosis (R (2) = 74.2%). Additionally, current financial metrics such as APR-DRG severity of illness and case mix index demonstrated a lack of correlation with CCC. We have developed a catheterization procedure type financial grouper that accounts for the diverse case population encountered in catheterization for congenital heart disease. CCC and our multivariable model could be used to understand financial characteristics of a population at a single point in time, longitudinally, and to compare populations. | 25,113,520 | [
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A randomized controlled trial of an internet-based therapist-assisted indicated preventive intervention for prolonged grief disorder. | This trial assessed the feasibility, acceptability, tolerability, and efficacy of an Internet-based therapist-assisted cognitive-behavioral indicated prevention intervention for prolonged grief disorder (PGD) called Healthy Experiences After Loss (HEAL). Eighty-four bereaved individuals at risk for PGD were randomized to either an immediate treatment group (n = 41) or a waitlist control group (n = 43). Assessments were conducted at four time-points: prior to the wait-interval (for the waitlist group), pre-intervention, post-intervention, 6 weeks later, and 3 months later (for the immediate group only). Intent-to-treat analyses indicated that HEAL was associated with large reductions in prolonged grief (d = 1.10), depression (d = .71), anxiety (d = .51), and posttraumatic stress (d = .91). Also, significantly fewer participants in the immediate group met PGD criteria post-intervention than in the waitlist group. Pooled data from both groups also yielded significant reductions and large effect sizes in PGD symptom severity at each follow-up assessment. The intervention required minimal professional oversight and ratings of satisfaction with treatment and usability of the Internet interface were high. HEAL has the potential to be an effective, well-tolerated tool to reduce the burden of significant pre-clinical PGD. Further research is needed to refine HEAL and to assess its efficacy and mechanisms of action in a large-scale trial. | 25,113,524 | [
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Quality of life among people living with hypertension in a rural Vietnam community. | To respond to growing prevalence of hypertension in Vietnam, it is critical to have an in-depth understanding about quality of life (QOL) among people living with hypertension and related factors. This study aimed to measure QOL among hypertensive people in a rural community in Vietnam, and its association with socio-demographic characteristics and factors related to treatment. This study was conducted in a rural community located 60 km from Ho Chi Minh City. Face-to-face interviews were conducted among 275 hypertensive people aged 50 years and above using WHOQOL-BREF questionnaire. Descriptive statistics were used to examine mean scores of quality of life. Cronbach's alpha coefficient and Pearson's correlation coefficient were applied to estimate the internal consistency, and the level of agreement between different domains of WHOQOL-BREF, respectively. Independent T-test and ANOVA test followed by multiple linear regression analyses were used to measure the association between QOL domains and independent variables. Both overall WHOQOL-BREF and each domain had a good internal consistency, ranging from 0.65 to 0.88. The QOL among hypertensive patients was found moderate in all domains, except for psychological domain that was fairly low (mean = 49.4). Backward multiple linear regressions revealed that being men, married, attainment of higher education, having physical activities at moderate level, and adherence to treatment were positively associated with QOL. However, older age and presence of co-morbidity were negatively associated with QOL. WHOQOL-BREF is a reliable instrument to measure QOL among hypertensive patients. The results revealed low QOL in psychological domain and inequality in QOL across socio-demographic characteristics. Given the results, encouraging physical activities and strengthening treatment adherence should be considered to improve QOL of hypertensive people, especially for psychological aspect. Actions to improve QOL among hypertensive patients targeted towards women, lower educated and unmarried patients are needed in the setting. | 25,113,528 | [
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A semi-empirical approach to analyze the activities of cylindrical radioactive samples using gamma energies from 185 to 1764 keV. | This work suggests a method for determining the activities of cylindrical radioactive samples. The self-attenuation factor was applied for providing the self-absorption correction of gamma rays in the sample material. The experimental measurement of a (238)U reference sample and the calculation using the MCNP5 code allow obtaining the semi-empirical formulae of detecting efficiencies for the gamma energies ranged from 185 to 1764keV. These formulae were used to determine the activities of the (238)U, (226)Ra, (232)Th, (137)Cs and (40)K nuclides in the IAEA RGU-1, IAEA-434, IAEA RGTh-1, IAEA-152 and IAEA RGK-1 radioactive standards. The coincidence summing corrections for gamma rays in the (238)U and (232)Th series were applied. The activities obtained in this work were in good agreement with the reference values. | 25,113,537 | [
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Single-cell transcriptome in the identification of disease biomarkers: opportunities and challenges. | Single cell transcriptome defined as the entire RNA or polyadenylated products of RNA polymerase II on a cell can describe the gene regulation networks responsible for physiological functions, behaviours, and phenotypes in response to signals and microenvironmental changes. Single cell transcriptome/sequencing has the special power to investigate small groups of differentiating cells, circulating tumour cells, or tissue stem cells. A large number of factors may influence the extent of single-cell heterogeneity within a system. It is the opportunity that the single-cell sequencing can be used for the identification of genetic changes in rare cells, e.g. cancer and tissue stem cells, in clinical samples. The methodologies of single-cell sequencing have been improved and developed with the increase of the understanding and attention. The clinical research and application of the single cell sequencing analysis are expected to identify and validate disease-specific biomarkers, network biomarkers, dynamic network biomarkers. The single cell research and value will be also dependent upon the understanding of genomic heterogeneity, planning and design of study protocol, representative of selected and targeted cells, and sensitivity and repeatability of the methodology. The single cell sequencing can be used to develop new diagnostics, monitor disease progresses, measure responses to therapies, and predict the prognosis of patients, although there are still a large number of challenges and difficulties to be faced. It would be more values and specificities of the single cell sequencing to integrate with the function of cells, organs, and systems of the body, the clinical phenotypes of patients, and the description of clinical bioinformatics. | 25,113,546 | [
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Impact of xylan on synergistic effects of xylanases and cellulases in enzymatic hydrolysis of lignocelluloses. | Supplementation of xylanase (XYL) has been found to synergistically improve the performance of cellulases (CEL) in the hydrolysis of lignocelluloses. However, the effect of xylan on the synergistic effects of XYL and CEL is still unclear. In this work, the effect of xylan on the synergy between CEL and XYL was investigated. Xylan content in corn stover was generally a good indicator of the degree of the synergism between CEL and XYL. Strongest synergism was observed in the hydrolysis of cellulose in corn stover with the highest xylan contents. A more evident synergistic effect of CEL in xylan hydrolysis was observed in the substrates with low original xylan content. It was also found that the ratio of cellulose to xylan in substrates correlated to the synergism between the two types of enzymes. The results indicated that supplementation of XYL with CEL was most effective in the hydrolysis of corn stover with the highest xylan content. For efficient enzymatic hydrolysis of lignocelluloses, both cellulases and xylanase were important because cellulose and xylan coved each other and these enzymes could improve their performance each other in the hydrolysis of cellulose and xylan in lignocelluloses. | 25,113,551 | [
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What can genes tell us about the relationship between education and health? | We use genome wide data from respondents of the Health and Retirement Study (HRS) to evaluate the possibility that common genetic influences are associated with education and three health outcomes: depression, self-rated health, and body mass index. We use a total of 1.7 million single nucleotide polymorphisms obtained from the Illumina HumanOmni2.5-4v1 chip from 4233 non-Hispanic white respondents to characterize genetic similarities among unrelated persons in the HRS. We then used the Genome Wide Complex Trait Analysis (GCTA) toolkit, to estimate univariate and bivariate heritability. We provide evidence that education (h(2) = 0.33), BMI (h(2) = 0.43), depression (h(2) = 0.19), and self-rated health (h(2) = 0.18) are all moderately heritable phenotypes. We also provide evidence that some of the correlation between depression and education as well as self-rated health and education is due to common genetic factors associated with one or both traits. We find no evidence that the correlation between education and BMI is influenced by common genetic factors. | 25,113,566 | [
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Adding insult to injury: The development of psychosocial stress in Ontario wind turbine communities. | Though historically dismissed as not-in-my-backyard (NIMBY) attitudes, reports of psychosocial stress linked to wind energy developments have emerged in Ontario, Canada. While the debate and rhetoric intensify concerning whether wind turbines 'actually' cause 'health' effects, less sincere attention has been given to the lived experience and mental well-being of those near turbines. Drawing on theories of environmental stress, this grounded theory, mixed-method (n = 26 interviews; n = 152 questionnaires) study of two communities in 2011 and 2012 traces how and why some wind turbine community residents suffer substantial changes to quality of life, develop negative perceptions of 'the other' and in some cases, experience intra-community conflict. Policy-related forces, along with existing community relationships may help explain much of these differences between communities. We suggest a move beyond debating simply whether or not 'annoyance' represents a 'health impact' and instead focus on ways to minimize and attenuate these feelings of threat (risk) and stress at the community level. | 25,113,568 | [
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A stair-climbing test for measuring mechanical efficiency of ambulation in adults with chronic stroke. | Mechanical efficiency can assess motor performance in individuals with physical disabilities. The purpose was to determine the utility of predicting it from heart rate (HR) during a self-paced stair-climbing test in adults with chronic hemiparesis after stroke and to determine the minimal detectable change of net mechanical efficiency (MEnet) measured by this exercise. First, 15 subjects with chronic hemiparesis participated in a validation study (A) and then 28 took part in a repeatability study (B). In study A the MEnet was calculated from external work and oxygen uptake above rest (dVO2), as directly measured and as predicted from body weight and increase in heart rate (dHR). In study B, predicted dVO2 was used to obtain MEnet for duplicate stair-climbing tests (T1, T2) with >30 min rest between. Measured MEnet was closely related to predicted MEnet (r = 0.97, p < 0.001). In study B predicted MEnet for T2 and T1 were closely related (r = 0.91, ICC = 0.90). With a minimal detectable change of 0.6% (0.053 of average MEnet score of 10.4%), MEnet values from the stair-climbing test seem sufficiently meaningful to estimate ambulatory ability and its changes with interventions or walking aids in adults with hemiparesis. Ambulatory ability can be estimated from mechanical efficiency, obtained from a 5-min stair-climbing test utilizing a 4-step stair, to measure external work, and the change in heart rate above rest to estimate the metabolic cost of the task. A change of > 0.6% in mechanical efficiency by this stair-climbing test indicates a significant change in ambulatory ability of persons with hemiparesis. | 25,113,573 | [
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An algorithm for score aggregation over causal biological networks based on random walk sampling. | We recently published in BMC Systems Biology an approach for calculating the perturbation amplitudes of causal network models by integrating gene differential expression data. This approach relies on the process of score aggregation, which combines the perturbations at the level of the individual network nodes into a global measure that quantifies the perturbation of the network as a whole. Such "bottom-up" aggregation relates the changes in molecular entities measured by omics technologies to systems-level phenotypes. However, the aggregation method we used is limited to a specific class of causal network models called "causally consistent", which is equivalent to the notion of balance of a signed graph used in graph theory. As a consequence of this limitation, our aggregation method cannot be used in the many relevant cases involving "causally inconsistent" network models such as those containing negative feedbacks. In this note, we propose an algorithm called "sampling of spanning trees" (SST) that extends our published aggregation method to causally inconsistent network models by replacing the signed relationships between the network nodes by an appropriate continuous measure. The SST algorithm is based on spanning trees, which are a particular class of subgraphs used in graph theory, and on a sampling procedure leveraging the properties of specific random walks on the graph. This algorithm is applied to several cases of biological interest. The SST algorithm provides a practical means of aggregating nodal values over causally inconsistent network models based on solid mathematical foundations. We showed its utility in systems biology, where the nodal values can be perturbation amplitudes of protein activities or gene differential expressions, while the networks can be models of cellular signaling or expression regulation. Since the SST algorithm is based on general graph-theoretical considerations, it is scalable to arbitrary graph sizes and can potentially be used for performing quantitative analyses in any context involving signed graphs. | 25,113,603 | [
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Developmental profiles of GFAP-positive astrocytes in sheep cerebellum. | Astroglial account for the largest glial population in the brain and play a variety of vital functions in the development of the central nervous system (CNS). An immunohistochemical study was performed in 19 ovine foetuses ranging from 2 to 5 months of gestation, one newborn lamb and three adult sheep. Using the anit-glial fibrillary acidic protein (GFAP) marker, several variations were found in the degree of GFAP positive (GFAP+) astrocyte distribution between the different zones in the cerebellum of sheep during brain development. Our study indicates that the first appearance of astrocytes from restricted zones in the cerebellum occurs around the eighth week of gestation. Bergmann cells were found to be present from around the 15th week of gestation onwards. Our findings suggest that the maturation of astrocytes begins in the caudal parts of the cerebellum, developing from their initial ventral regions to spread first to dorsal regions radially within the white matter, then followed by the more rostral parts of the cerebellum. Astrocytes were also found to proliferate in the vermis before appearing in the cerebellar hemispheres. | 25,113,608 | [
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Acoustic reflectors are visible in the right heart during radiofrequency ablation of varicose veins. | Cerebrovascular events have been noted after foam sclerotherapy for varicose veins. One hypothesis is migration of microemboli to the brain through a cardiac septal defect. The aim of this study was to identify whether acoustic reflectors are found in the right side of the heart during radiofrequency ablation of varicose veins, as neurological events are not reported during these procedures. Transthoracic echocardiography was performed during local anaesthetic radiofrequency ablation (VNUS ClosureFast) of the great saphenous vein in 14 patients. An apical view was captured at the start of the procedure, during each cycle of heating and at 1 min post-treatment. Patients were monitored for 1 h. Video loops were read by an independent cardiologist. The presence of acoustic reflectors was classified as: 0 = absent, 1 = occasional, 2 = stream, 3 = complete opacification. Loops were of diagnostic quality in 11/14 (79%) patients. After the second cycle of heating, acoustic reflectors moving through the right heart were seen in 5/11 (45%) patients. These were classified as grade 1 in four patients and grade 2 in one patient. No acoustic reflectors were seen in the left heart. No neurological symptoms were reported. Acoustic reflectors in the right heart are a common finding during radiofrequency ablation of varicose veins. Considering the prevalence of cardiac septal defects (17%), more neurological events would be expected if these particles were indeed responsible for these events. Further work is required to elicit the mechanisms underlying neurological complications following sclerotherapy. | 25,113,612 | [
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Systematic review and meta-analysis on the efficacy of selective laser trabeculoplasty in open-angle glaucoma. | Selective laser trabeculoplasty (SLT) is a relatively new type of laser used in treating open-angle glaucoma (OAG) and is reported to be equally efficacious to a first-line medication and argon laser trabeculoplasty (ALT). We summarize available evidence for considering SLT as an alternative treatment in OAG through systematic review and meta-analysis. Among OAG patients who range from newly diagnosed to those on maximally tolerated medical therapy, SLT results in a 6.9-35.9% intraocular pressure (IOP) reduction. Complications are rare and include an IOP spike requiring surgery, persistent macular edema, and corneal haze and thinning. Meta-analysis of randomized, controlled trials shows that SLT is non-inferior to ALT and medication in IOP reduction and also in achieving treatment success. Number of medications reduction is similar between SLT and ALT. More robust evidence is needed to determine its efficacy as a repeated procedure. | 25,113,610 | [
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The gene expression profile of cumulus cells reveals altered pathways in patients with endometriosis. | The objective of this experimental study was to compare the global gene expression profile of CC of mature oocytes in 18 patients with severe endometriosis and CC in 18 control patients affected by a severe male factor. For each group, the CC were pooled, RNA was extracted and a microarray performed. For validating the microarray, a quantitative real-time PCR was performed in the CC of an independent set of patients with endometriosis (n = 5) and controls (n = 7). 595 differentially expressed genes (320 down-regulated, 275 up-regulated, p < 0.05, fold change ≥1.5) were identified. The most significant changes were observed in genes involved in the chemokine signaling and cell-cell or cell-extracellular matrix adhesion pathways. Several genes of these pathways were down-regulated in endometriosis. Individual RT-PCR assays confirmed the microarray for ten genes. Several genes involved in the chemokine mediated-signaling pathway and in the functional cross-talk between CC and the oocyte are down-regulated in endometriosis CC. The impairment of these processes could explain the reduction of oocyte competence in endometriosis. This preliminary knowledge could be the starting point for a more detailed elucidation of the relationship between endometriosis and oocyte competence. | 25,113,618 | [
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A semi-probabilistic modelling approach for the estimation of dietary exposure to phthalates in the Belgian adult population. | In this study, a semi-probabilistic modelling approach was applied for the estimation of the long-term human dietary exposure to phthalates--one of world's most used families of plasticisers. Four phthalate compounds were considered: diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), benzylbutyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP). Intake estimates were calculated for the Belgian adult population and several subgroups of this population for two considered scenarios using an extended version of the EN-forc model. The highest intake rates were found for DEHP, followed by DnBP, BBP and DEP. In the Belgian adult population, men and young adults generally had the highest dietary phthalate intake estimates. Nevertheless, predicted dietary intake rates for all four investigated phthalates were far below the corresponding tolerable daily intake (TDI) values (i.e. P99 intake values were 6.4% of the TDI at most), which is reassuring because adults are also exposed to phthalates via other contamination pathways (e.g. dust ingestion and inhalation). The food groups contributing most to the dietary exposure were grains and grain-based products for DEP, milk and dairy products for DnBP, meat and meat products or grains and grain-based products (depending on the scenario) for BBP and meat and meat products for DEHP. Comparison of the predicted intake results based on modelled phthalate concentrations in food products with intake estimates from other surveys (mostly based on measured concentrations) showed that the extended version of the EN-forc model is a suitable semi-probabilistic tool for the estimation and evaluation of the long-term dietary intake of phthalates in humans. | 25,113,625 | [
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Experimental investigation of the 2D ion beam profile generated by an ESI octopole-QMS system. | In this paper, we have employed an ion imaging approach to investigate the behavior of ions exiting from a quadrupole mass spectrometer (QMS) system that employs a radio frequency octopole ion guide before the QMS. An in-vacuum active pixel detector (Timepix) is employed at the exit of the QMS to image the ion patterns. The detector assembly simultaneously records the ion impact position and number of ions per pixel in every measurement frame. The transmission characteristics of the ion beam exiting the QMS are studied using this imaging detector under different operating conditions. Experimental results confirm that the ion spatial distribution exiting the QMS is heavily influenced by ion injection conditions. Furthermore, ion images from Timepix measurements of protein standards demonstrate the capability to enhance the quality of the mass spectral information and provide a detailed insight in the spatial distribution of different charge states (and hence different m/z) ions exiting the QMS. | 25,113,629 | [
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Prostaglandin D2-supplemented "functional eicosanoid testing and typing" assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study. | Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. Using the "functional eicosanoid testing and typing" (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14-2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD. | 25,113,638 | [
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A simple and sensitive fluorescence based biosensor for the determination of uric acid using H2O2-sensitive quantum dots/dual enzymes. | A novel optical detection system consisting of combination of uricase/HRP-CdS quantum dots (QDs) for the determination of uric acid in urine sample is described. The QDs was used as an indicator to reveal fluorescence property of the system resulting from enzymatic reaction of uricase and HRP (horseradish peroxidase), which is involved in oxidizing uric acid to allaintoin and hydrogen peroxide. The hydrogen peroxide produced was able to quench the QDs fluorescence, which was proportional to uric acid concentration. The system demonstrated sufficient activity of uricase and HRP at a ratio of 5U:5U and pH 7.0. The linearity of the system toward uric acid was in the concentration range of 125-1000 µM with detection limit of 125 µM. | 25,113,659 | [
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Examining the link between adolescent brain development and risk taking from a social-developmental perspective (reprinted). | The adolescent age period is often characterized as a health paradox because it is a time of extensive increases in physical and mental capabilities, yet overall mortality/morbidity rates increase significantly from childhood to adolescence, often due to preventable causes such as risk taking. Asynchrony in developmental time courses between the affective/approach and cognitive control brain systems, as well as the ongoing maturation of neural connectivity are thought to lead to increased vulnerability for risk taking in adolescence. A critical analysis of the frequency of risk taking behaviors, as well as mortality and morbidity rates across the lifespan, however, challenges the hypothesis that the peak of risk taking occurs in middle adolescence when the asynchrony between the different developmental time courses of the affective/approach and cognitive control systems is the largest. In fact, the highest levels of risk taking behaviors, such as alcohol and drug use, often occur among emerging adults (e.g., university/college students), and highlight the role of the social context in predicting risk taking behavior. Moreover, risk taking is not always unregulated or impulsive. Future research should broaden the scope of risk taking to include risks that are relevant to older adults, such as risky financial investing, gambling, and marital infidelity. In addition, a lifespan perspective, with a focus on how associations between neural systems and behavior are moderated by context and trait-level characteristics, and which includes diverse samples (e.g., divorced individuals), will help to address some important limitations in the adolescent brain development and risk taking literature. | 25,113,660 | [
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Bone substitute first or screws first? A biomechanical comparison of two operative techniques for tibial-head depression fractures. | The aim of this study was to investigate a drillable and injectable bone substitute (calcium phosphate cement) and the operative technique enabled by the drillable option in a new biomechanical fracture model for tibial depression fractures in synthetic bones. Lateral depression fractures of the tibial plateau (AO 41-B2, Schatzker III) were created in a biomechanical fracture model in three different synthetic bones (Sawbone 3401, Synbone 1110/1116). Reproducible fractures were generated employing Synbone 1110, which exhibited a comparable strength to human osteoporotic bones and was used for the further experiments. After reduction of the fractures, the stabilization was performed with two different operative techniques. In group 1, first an osteosynthesis with four screws was performed and then the metaphyseal defect was filled up with calcium phosphate cement (Norian drillable). In group 2, initially the filling up with Norian drillable was done enabling a complete filling of the defect, followed by placing of the screws. Displacement under cyclic loading with 250 N for 3,000 cycles, stiffness, and maximum load in load-to-failure tests were determined. A comparison of the two operative techniques of stabilization showed a distinctly lower displacement and higher stiffness for group 2 when the defect was filled up first. For the maximum load, no significant differences could be demonstrated. A complete filling of the defect by first applying the calcium phosphate cement significantly reduces the secondary loss of reduction of the depression fracture fragment under cyclic loading with a clinically relevant partial weight bearing. The beneficial effects of drillable calcium phosphate cement may also be transferable to defects other than tibial-head depression fractures. | 25,113,667 | [
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A taxonomic revision of South African Sharphydrus, with the description of two new species (Coleoptera: Dytiscidae: Bidessini). | Sharphydrus Omer-Cooper, 1958 is one of two endemic bidessine genera currently recognised from South Africa. Here Sharphydrus brincki sp. nov. and Sharphydrus kamiesbergensis sp. nov. are described from the Cederberg and Gydopas areas of the Western Cape, and the high Kamiesberg of the Northern Cape respectively, doubling the known species of this genus. It is shown that S. brincki sp. nov. has been included under S. capensis (Omer-Cooper, 1955) in the past, but that these are quite distinct taxa, differing in the extent of their elytral keels and male genitalia. Sharphydrus species are inhabitants of pools in seasonally fluctuating rivers, the new species described here occurring in areas which are somewhat transitional between fynbos and karoo biomes. An updated key is presented to Sharphydrus species, together with data on the distribution and ecology of known species, and a discussion of the status of the genus within the Bidessini. | 25,113,675 | [
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Cambarus (C.) hatfieldi, a new species of crayfish (Decapoda:Cambaridae) from the Tug Fork River Basin of Kentucky, Virginia and West Virginia, USA. | Cambarus (Cambarus) hatfieldi is a stream-dwelling crayfish that appears to be endemic to the Tug Fork River system of West Virginia, Virginia, and Kentucky. Within this region, it is prevalent in all major tributaries in the basin as well as the Tug Fork River's mainstem. The new species is morphologically most similar to Cambarus sciotensis and Cambarus angularis. It can be differentiated from C. sciotensis by its squamous, subtrinagular chelae compared to the elongate triangular chelae of C. sciotensis; its shorter palm length/palm depth ratio (1.9) compared to C. sciotensis (2.3); and a smaller areola length/total carapace length ratio (30.4% vs.36.5% respectively). Cambarus hatfieldi can be differentiated from C. angularis by its smaller areola length/total carapace length ratio (30.4% vs. 36.7% respectively); a smaller rostrum width/rostral length ratio (59.4% vs. 67.2% respectively); its rounded abdominal pleura as compared to the subtruncated pleura of C. angularis; the length of the central projection and mesial process of C. hatfieldi which both extend to the margin of the gonopod shaft or slightly beyond the margin compared to the central projection of C. sciotensis and C. angularis where both extend well beyond the margin of the gonopod shaft. | 25,113,694 | [
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An update of the blow flies (Diptera: Calliphoridae) of the Galápagos Islands, and first record of Chrysomya rufifacies (Macquart) from mainland Ecuador. | Seven species of Calliphoridae are reported from the Galápagos Islands, Ecuador: Lucilia pionia (Walker), L. setosa (James), L. deceptor (Curran), L. eximia (Wiedemann), Cochliomyia macellaria (Fabricius), Chrysomya albiceps (Wiedemann), and Chrysomya megacephala (Fabricius). Lucilia eximia is newly recorded from the islands. Lucilia sp. near pionia is recorded from the island of Española. The distribution and collection records of these species are discussed and listed, and a key to their identification is provided. Chrysomya rufifacies (Macquart) is reported for the first time from mainland Ecuador and the identification of this species is outlined. | 25,113,695 | [
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Two new species of Aaptos (Demospongiae, Hadromerida) from Brazil (western Atlantic). | Twenty-one species of Aaptos Gray, 1867 are known world-wide, of which only three were reported from Brazil. Two new species of this genus are here described from the Brazilian coast (Potiguar Basin, Northeastern Brazil): A. hajdui sp. nov. and A. potiguarensis sp. nov. Both possess only one category of strongyloxeas and one of styles, although both with wide size variation, suggesting that the diagnosis of the genus should be revised. Previous Brazilian records of A. aaptos have their status re-evaluated here, and only three species of the genus can be considered valid in Brazil: A. glutinans, A. hajdui sp. nov. and A. potiguarensis sp. nov. | 25,113,704 | [
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Structure and photoluminescence studies of CeO2·CuAlO2 mixed metal oxide fabricated by co-precipitation method. | A novel mixed metal oxide, CeO2·CuAlO2 was fabricated by co-precipitation method in aqueous medium. CeO2·CuAlO2 was characterized by XRD, SEM, EDS, TEM, FTIR and PL spectra. The optical properties of the nanoparticles were studied by photoluminescence (PL) spectra. PL spectra at different excitations were recorded. The composite showed emission in UV, visible and NIR region depending on the excitation wavelength. The special spectral feature observed for this composite is that it showed six emission bands at 364, 409, 434, 448, 465 and 481 nm when excited at 298 nm. The green and red emissions observed at 512 and 669 nm are originated from cubic CeO2 phase when excited at 450 nm. The PL spectra were found to be dependent on excitation wavelength violating Kasha's rule. The X-ray diffraction reveals a cubic CeO2 phase and hexagonal CuAlO2 phase. EDS spectra revealed the presence of cerium (Ce), copper (Cu), aluminum (Al) and oxygen (O) elements. The particle size of the CeO2·CuAlO2 mixed oxide was estimated using Scherrer's formula, which was found to be in the range of 17.2-34.2 nm. The TEM image showed particles are almost uniform size of approximately 15-50 nm with spherical morphology. | 25,113,734 | [
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A murine model of neurofibromatosis type 2 that accurately phenocopies human schwannoma formation. | Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disorder resulting from germline mutations in the NF2 gene. Bilateral vestibular schwannomas, tumors on cranial nerve VIII, are pathognomonic for NF2 disease. Furthermore, schwannomas also commonly develop in other cranial nerves, dorsal root ganglia and peripheral nerves. These tumors are a major cause of morbidity and mortality, and medical therapies to treat them are limited. Animal models that accurately recapitulate the full anatomical spectrum of human NF2-related schwannomas, including the characteristic functional deficits in hearing and balance associated with cranial nerve VIII tumors, would allow systematic evaluation of experimental therapeutics prior to clinical use. Here, we present a genetically engineered NF2 mouse model generated through excision of the Nf2 gene driven by Cre expression under control of a tissue-restricted 3.9kbPeriostin promoter element. By 10 months of age, 100% of Postn-Cre; Nf2(flox/flox) mice develop spinal, peripheral and cranial nerve tumors histologically identical to human schwannomas. In addition, the development of cranial nerve VIII tumors correlates with functional impairments in hearing and balance, as measured by auditory brainstem response and vestibular testing. Overall, the Postn-Cre; Nf2(flox/flox) tumor model provides a novel tool for future mechanistic and therapeutic studies of NF2-associated schwannomas. | 25,113,746 | [
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Radical irradiation of extracranial oligometastases. | Advances in radiotherapy planning and delivery have been used to treat patients with limited metastatic disease. With these techniques, high rates of treated metastasis control and low toxicity have been reported. Some patients have long disease-free intervals after radiotherapy similar to those seen after surgical resection. Ongoing studies will determine the benefit of these irradiation techniques to treat limited metastases, identify appropriate candidates, and assist in integrating these treatments into management strategies for specific diseases. | 25,113,765 | [
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Long non-coding RNAs in cancer: implications for personalized therapy. | Long non-coding RNAs (lncRNAs, pseudogenes and circRNAs) have recently come into light as powerful players in cancer pathogenesis and it is becoming increasingly clear that they have the potential of greatly contributing to the spread and success of personalized cancer medicine. In this concise review, we briefly introduce these three classes of long non-coding RNAs. We then discuss their applications as diagnostic and prognostic biomarkers. Finally, we describe their appeal as targets and as drugs, while pointing out the limitations that still lie ahead of their definitive entry into clinical practice. | 25,113,790 | [
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7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease. | The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ≤ 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. | 25,113,794 | [
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Different regions of bovine deep digital flexor tendon exhibit distinct elastic, but not viscous, mechanical properties under both compression and shear loading. | Tendons in different locations function in unique, and at times complex, in vivo loading environments. Specifically, some tendons are subjected to compression, shear and/or torsion in addition to tensile loading, which play an important role in regulating tendon properties. To date, there have been few studies evaluating tendon mechanics when loaded in compression and shear, which are particularly relevant for understanding tendon regions that experience such non-tensile loading during normal physiologic function. The objective of this study was to evaluate mechanical responses of different regions of bovine deep digital flexor tendons (DDFT) under compressive and shear loading, and correlate structural characteristics to functional mechanical properties. Distal and proximal regions of DDFT were evaluated in a custom-made loading system via three-step incremental stress-relaxation tests. A two-relaxation-time solid linear model was used to describe the viscoelastic response. Results showed large differences in the elastic behavior between regions: distal region stresses were 4-5 times larger than proximal region stresses during compression and 2-3 times larger during shear. Surprisingly, the viscous (i.e., relaxation) behavior was not different between regions for either compression or shear. Histological analysis showed that collagen and proteoglycan in the distal region distributed differently from the proximal region. Results demonstrate mechanical differences between two regions of DDFT under compression and shear loading, which are attributed to variations of composition and microstructural organization. These findings deepen our understanding of structure-function relationships of tendon, particularly for tissues adapted to supporting combinations of tension, compression, and shear in physiological loading environments. | 25,113,805 | [
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Molecular revision of the genus Wallaceina. | This work is focused on the molecular revision of the genus Wallaceina established in the very twilight of the classical morphotype-based approach to classification of the Trypanosomatidae. The genus was erected due to the presence of a unique variant of endomastigotes. In molecular phylogenetic studies four described species of Wallaceina were shown to be extremely close to each other and to some other undescribed isolates clustered within Leishmaniinae clade, while three recently included species formed a separate clade. Our results of morphological and molecular phylogenetic analyses demonstrated that all Leishmaniinae-bound wallaceinas are just different isolates of the same species that we rename back to Crithidia brevicula Frolov, Malysheva, 1989. To accommodate former Wallaceina spp. phylogenetically distant from the genus Crithidia, we propose a new generic name Wallacemonas Kostygov et Yurchenko, 2014. | 25,113,831 | [
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Vessel caliber--a potential MRI biomarker of tumour response in clinical trials. | Our understanding of the importance of blood vessels and angiogenesis in cancer has increased considerably over the past decades, and the assessment of tumour vessel calibre and structure has become increasingly important for in vivo monitoring of therapeutic response. The preferred method for in vivo imaging of most solid cancers is MRI, and the concept of vessel-calibre MRI has evolved since its initial inception in the early 1990s. Almost a quarter of a century later, unlike traditional contrast-enhanced MRI techniques, vessel-calibre MRI remains widely inaccessible to the general clinical community. The narrow availability of the technique is, in part, attributable to limited awareness and a lack of imaging standardization. Thus, the role of vessel-calibre MRI in early phase clinical trials remains to be determined. By contrast, regulatory approvals of antiangiogenic agents that are not directly cytotoxic have created an urgent need for clinical trials incorporating advanced imaging analyses, going beyond traditional assessments of tumour volume. To this end, we review the field of vessel-calibre MRI and summarize the emerging evidence supporting the use of this technique to monitor response to anticancer therapy. We also discuss the potential use of this biomarker assessment in clinical imaging trials and highlight relevant avenues for future research. | 25,113,840 | [
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Task specificity of attention training: the case of probability cuing. | Statistical regularities in our environment enhance perception and modulate the allocation of spatial attention. Surprisingly little is known about how learning-induced changes in spatial attention transfer across tasks. In this study, we investigated whether a spatial attentional bias learned in one task transfers to another. Most of the experiments began with a training phase in which a search target was more likely to be located in one quadrant of the screen than in the other quadrants. An attentional bias toward the high-probability quadrant developed during training (probability cuing). In a subsequent, testing phase, the target's location distribution became random. In addition, the training and testing phases were based on different tasks. Probability cuing did not transfer between visual search and a foraging-like task. However, it did transfer between various types of visual search tasks that differed in stimuli and difficulty. These data suggest that different visual search tasks share a common and transferrable learned attentional bias. However, this bias is not shared by high-level, decision-making tasks such as foraging. | 25,113,853 | [
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Control of the single-molecule magnet behavior of lanthanide-diarylethene photochromic assemblies by irradiation with light. | Lanthanide-based extended coordination frameworks showing photocontrolled single-molecule magnet (SMM) behavior were prepared by combining highly anisotropic Dy(III) and Ho(III) ions with the carboxylato-functionalized photochromic molecule 1,2-bis(5-carboxyl-2-methyl-3-thienyl)perfluorocyclopentene (H2 dae), which acts as a bridging ligand. As a result, two new compounds of the general formula [{Ln(III) 2 (dae)3 (DMSO)3 (MeOH)}⋅10 MeOH]n (M=Dy for 1 a and Ho for 2) and two additional pseudo-polymorphs [{Dy(III) 2 (dae)3 (DMSO)3 (H2 O)}⋅x MeOH]n (1 b) and [{Dy(III) 2 (dae)3 (DMSO)3 (DMSO)}⋅x MeOH]n (1 c) were obtained. All four compounds have 2D coordination-layer topologies, in which carboxylate-bridged Ln2 units are linked together by dae(2-) anions into grid-like frameworks. All four compounds exhibited a strong reversible photochromic response to UV/Vis light. Moreover, both 1 a and 2 show field-induced SMM behavior. The slow magnetic relaxation of 1 a is influenced by the photoisomerization reaction leading to the observation of the cross-effect: photocontrolled SMM behavior. | 25,113,868 | [
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Synthesis and bioevaluation of 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic acids as potent xanthine oxidase inhibitors. | A series of 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic acid derivatives (8a-f, 9a-m) were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro. Structure-activity relationship analyses have also been presented. Most of the target compounds exhibited potency levels in the nanomolar range. Compound 9e emerged as the most potent xanthine oxidase inhibitor (IC50 = 5.5 nM) in comparison to febuxostat (IC50 = 18.6 nM). Steady-state kinetics measurements with the bovine milk enzyme indicated a mixed type inhibition with Ki and Ki' values of 0.9 and 2.3 nM, respectively. A molecular modeling study on compounds 9e was performed to gain an insight into its binding mode with xanthine oxidase, and to provide the basis for further structure-guided design of new non-purine xanthine oxidase inhibitors related with 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic acid scaffold. | 25,113,879 | [
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Shadows from the past: the situated meaning of being suicidal among depressed older people living in the community. | Most depressed older people in a suicidal state have mixed feelings, where the wish to live and the wish to die wage a battle. To explore and describe depressed older people's experiences of being suicidal and their search for meaning. Data were collected from 29 participants resident in the Rogaland and Vestfold districts of Norway, by means of individual interviews, after which a thematic analysis was performed. For the participants in this study, the lived experiences of the situated meaning of survival after being suicidal comprised a main theme - "shadows from the past" - and two themes - "feeling that something inside is broken" and "a struggle to catch the light." Mental health-care professionals might be able to reduce the risk of suicide and perturbation by helping depressed older people to explore, resolve, and ultimately come to terms with their unresolved historical issues. Additional valuable strategies in primary care settings include encountering patients frequently, monitoring adherence to care plans, and providing support to address the source of emotional pain and distress. | 25,113,890 | [
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Patient and physician views on the quality of care in inflammatory bowel disease: results from SOLUTION-1, a prospective IG-IBD study. | Remarkable differences in quality of care (QoC) might be observed in different countries, affecting quality of life of inflammatory bowel disease (IBD) patients. The aim of this study was to assess patient and physician perceptions of the QoC in Italy. A multicentre observational study on the quality of care in IBD (SOLUTION-1) was conducted in 36 IG-IBD (Italian Group for Inflammatory Bowel Disease) centres in Italy. The QUOTE-IBD (Quality of Care Through the Patient's Eyes) questionnaire was administered to IBD patients and to the attending physicians. The Quality Impact (QI) score summarises the QUOTE-IBD questionnaire, and a QI >9 is considered satisfactory. Nine-hundred-ninety-two patients and 75 physicians completed the QUOTE-IBD questionnaire. The patients scored the domains of competence (9.47 vs. 8.55) and costs (9.54 vs. 8.26) higher that the physicians, while information (9.31 vs. 9.43) and continuity of care (8.40 vs. 9.01) were scored lower. The QI score was rated worse by physicians with less experience (<12 years) with regard to competence (8.0 vs. 9.01), courtesy (8.12 vs. 10.0) and autonomy (8.97 vs. 10.0). Physicians considered the cost domain unsatisfactory. Healthcare was rated as satisfactory overall for Italian patients and physicians. The physicians underestimate their competence and consider the cost of medical management unsatisfactory. The patients are more critical regarding the continuity of care and information. Country-specific data on QoC allow local governments to allocate resources more effectively. | 25,113,898 | [
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Patchwork structure-function analysis of the Sendai virus matrix protein. | Paramyxoviruses contain a bi-lipidic envelope decorated by two transmembrane glycoproteins and carpeted on the inner surface with a layer of matrix proteins (M), thought to bridge the glycoproteins with the viral nucleocapsids. To characterize M structure-function features, a set of M domains were mutated or deleted. The genes encoding these modified M were incorporated into recombinant Sendai viruses and expressed as supplemental proteins. Using a method of integrated suppression complementation system (ISCS), the functions of these M mutants were analyzed in the context of the infection. Cellular membrane association, localization at the cell periphery, nucleocapsid binding, cellular protein interactions and promotion of viral particle formation were characterized in relation with the mutations. At the end, lack of nucleocapsid binding go together with lack of cell surface localization and both features definitely correlate with loss of M global function estimated by viral particle production. | 25,113,904 | [
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Chronic Δ⁹-tetrahydrocannabinol administration may not attenuate simian immunodeficiency virus disease progression in female rhesus macaques. | Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; Δ(9)-THC dronabinol). Previously, we demonstrated that chronic Δ(9)-THC administration decreases early mortality in male simian immunodeficiency virus (SIV)-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either Δ(9)-THC (0.18-0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic Δ(9)-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4(+)/CD8(+) ratio, were not altered by Δ(9)-THC compared to control females; however, females that received chronic Δ(9)-THC did not gain as much weight as control animals. In addition, Δ(9)-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4(+) and CD8(+) T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic Δ(9)-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic Δ(9)-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of Δ(9)-THC and other cannabinoids on the HIV disease course and their implications for virus transmission. | 25,113,915 | [
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Thrombotic thrombocytopenic purpura presenting with pathologic fracture: a case report. | Thrombotic thrombocytopenic purpura is an acute syndrome with abnormalities in multiple organ systems, which becomes manifest with microangiopathic hemolytic anemia and thrombocytopenia. The hereditary or acquired deficiency of ADAMTS-13 activity leads to an excess of high molecular weight von Willebrand factor multimers in plasma, leading to platelet aggregation and diffuse intravascular thrombus formation, resulting in thrombotic thrombocytopenic purpura. Thrombotic lesions occurring in TTP leads to ischemia and convulsion. Depending on the properties of the bony tissue, fractures are divided into three groups as traumatic, pathological, and stress fractures. A pathologic fracture is a broken bone caused by disease leading to weakness of the bone. This process is most commonly due to osteoporosis, but may also be due to other pathologies such as cancer, infections, inherited bone disorders, or a bone cyst. We herein report a case with a pathologic fracture due to convulsion secondary to thrombotic thrombocytopenic pupura. Thrombotic lesions occurring in TTP may lead to ischemia and convulsion, as in our patient and pathological fractures presented in our case report may occur as a result of severe muscle contractions associated with convulsive activity. Thrombotic thrombocytopenic pupura is a disease that involves many organ systems and thus may have a very wide spectrum of clinical presentations. | 25,113,918 | [
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Biogenetic explanations and emotional reactions to people with schizophrenia and major depressive disorder. | Using population-based data, the relationship between biogenetic causal beliefs and emotional reactions to persons with schizophrenia or depression was examined. Biogenetic attributions elicited either negative emotions alone or pro-social and negative emotions at the same time. Biogenetic attributions seem not helpful for improving emotional reactions to people with mental disorders. | 25,113,926 | [
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Static and rotational intensity modulated techniques for head-neck cancer radiotherapy: a planning comparison. | To compare helical Tomotherapy (HT), two volumetric-modulated arc techniques and conventional fixed-field intensity modulated techniques (S-IMRT) for head-neck (HN) cancers. Eighteen HN patients were considered. Four treatment plans were generated for each patient: HT, S-IMRT optimised with Eclipse treatment planning system and two volumetric techniques using Elekta-Oncentra approach (VMAT) and Varian-RapidArc (RA), using two full arcs. All techniques were optimised to simultaneously deliver 66Gy to PTV1 (GTV and enlarged nodes) and 54Gy to PTV2 (subclinical and electively treated nodes). Comparisons were assessed on several dosimetric parameters and, secondarily, on planned MUs and delivery time. Concerning PTV coverage, significantly better results were found for HT and RA. HT significantly improved the target coverage both compared to S-IMRT and VMAT. No significant differences were found between S-IMRT and volumetric techniques in terms of dose homogeneity. For OARs, all the techniques were able to satisfy all hard constraints; significantly better results were found for HT, especially in the intermediate dose range (15-30 Gy). S-IMRT reached a significantly better OARs sparing with respect to VMAT and RA. No significant differences were found for body mean dose, excepting higher values of V5-V10 for HT. A reduction of planned MUs and delivery treatment time was found with volumetric techniques. The objectives of satisfying target coverage and sparing of critical structures were reached with all techniques. S-IMRT techniques were found more advantageous compared to RA and VMAT for OARs sparing. HT reached the best overall treatment plan quality. | 25,113,943 | [
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Relevance of subcortical visual pathways disruption to visual symptoms in dementia with Lewy bodies. | Visual hallucinations represent a core diagnostic criterion for dementia with Lewy bodies (DLB). We hypothesized that thalamic regions, which are critically involved in the modulation of visual transmission, may be differentially disrupted in DLB as compared to Alzheimer's Disease (AD) and that these deficits could relate to visual dysfunction in DLB patients. Magnetic Resonance and Diffusion Tensor Imaging (DTI) were performed with a 3 T scanner on a sample population of 15 DLB patients, 15 AD patients and 13 healthy volunteers. Regional thalamic micro-structural changes were assessed by parcelling the thalamus based on its connectivity to cortex and to amygdala and by measuring the mean diffusivity (MD) in each connectivity-defined sub-region. Micro-structural grey matter damage associated to higher MD values was found bilaterally in DLB compared to controls in the sub-regions projecting from thalamus to prefrontal and parieto-occipital cortices. Right thalamic sub-region projecting to amygdala and left thalamic sub-region projecting to motor cortex were also affected in DLB compared to controls. Higher MD values were found bilaterally in AD compared to controls in the thalamic sub-regions projecting to temporal cortex. Specific comparison between the two forms of dementia found differences: the sub-regions which project from thalamus to parieto-occipital cortex and to amygdala showed higher MD values in DLB compared to AD patients. In DLB patients, correlation analysis showed a significant correlation between NPI hallucinations item scores and MD values in the right thalamic sub-regions projecting to parietal and occipital cortices. The present study demonstrates how thalamic connectivity alterations between higher and lower visual areas may be relevant in explaining visual hallucinations in DLB. | 25,113,955 | [
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"Someone like us": delivering maternal mental health through peers in two South Asian contexts. | Peer-led psychosocial interventions are one solution to address the great paucity of skilled mental health human resources in South Asia. The aim of this study was to explore peer-delivered care for maternal depression in two diverse contexts in South Asia. The study was carried out in the urban setting of Goa, India and rural setting in Rawalpindi, Pakistan. In total, 61 in-depth interviews (IDIs) and 3 focus group discussions (FGDs), and 38 IDIs and 10 FGDs, were conducted with multiple stakeholders in urban Goa and rural Rawalpindi respectively. We used the framework approach to analyze data. Peers from the same community were the most preferred delivery agents of a community-based psychosocial intervention in both sites. There were contextual similarities and differences between the two sites. Preferred characteristics among peers included local, middle-aged, educated mothers with similar experiences to participants, good communication skills and a good character. Key differences between the two contexts included a greater emphasis on the peer׳s family social standing in rural Rawalpindi and financial incentives as motivators for individual peers in urban Goa. Generalizability of our findings is limited to two specific contexts in a vast and diverse region. Our study demonstrates that peers have the potential to deliver maternal psychosocial interventions in low-income settings. There are contextual differences in the preferred characteristics and motivators between the sites, and these should be carefully considered in program implementation. | 25,113,958 | [
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Pathological mechanisms underlying aneurysmal subarachnoid haemorrhage and vasospasm. | Aneurysmal subarachnoid haemorrhage is a cerebrovascular disease associated with an overall mortality as high as 50%. Delayed ischaemic neurologic deficits are a major contributor to this statistic, as well as the significant morbidity associated with the disease. Studies examining the pathophysiologic events causing these devastating changes in cerebral blood flow have identified several mechanisms which are thought to contribute to the development of delayed ischaemic neurological deficits, perhaps the most damaging of which are increased intracranial pressure and cerebral vasospasm. In addition, the presence of blood in the subarachnoid space can trigger a myriad of reactions resulting in increased capillary permeability, breakdown of the blood-brain barrier, and inflammation in surrounding neural tissue that adds to the devastating effects of haemorrhage. A detailed understanding of the post-haemorrhagic cellular and molecular changes that contribute to the development of cerebral ischaemia and vasospasm is imperative to the formulation of treatment and prevention options for subarachnoid haemorrhage patients. Despite a large body of research within this field, a complete understanding of rupture and vasospasm remains elusive. This study reviews the role of vasoactive substances, such as endothelin-1, as well as the histochemistry and molecular pathology of post-haemorrhage inflammation in the development of vasospasm and cerebral ischaemia. | 25,113,969 | [
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Differential diagnosis of three common Ixodes spp. ticks infesting songbirds of Western Europe: Ixodes arboricola, I. frontalis and I. ricinus. | The three most common Ixodes spp. ticks found on songbirds in Western Europe are Ixodes frontalis, I. arboricola and I. ricinus. As the latter species is a generalist, it shares several avian hosts with the two strictly ornithophilic species. Infestations of the three species can overlap in time and space, implying that tick-borne pathogens maintained by the ornithophilic ticks and their hosts could be bridged by I. ricinus to non-avian hosts. Whereas the endophilic Ixodes arboricola only occurs in cavities, I. frontalis has been collected frequently by flagging methods from understory vegetation, which is also the habitat of the field-dwelling I. ricinus. As the latter two species have rather similar morphological characteristics, they can easily be confused with each other. In this study, we present scanning electron photomicrographs of all developmental stages of I. arboricola and I. frontalis, and provide a differential diagnosis key to distinguish the ornithophilic ticks from I. ricinus. In addition, we interpreted their phylogenetic associations based on mitochondrial 16S rDNA with other Ixodes spp. ticks (I. lividus, I. turdus, I. brunneus, I. vespertilionis, I. trianguliceps, I. hexagonus, I. scapularis). | 25,113,983 | [
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Voltage control of Ca²⁺ permeation through N-type calcium (Ca(V)2.2) channels. | Voltage-gated calcium (Ca(V)) channels deliver Ca(2+) to trigger cellular functions ranging from cardiac muscle contraction to neurotransmitter release. The mechanism by which these channels select for Ca(2+) over other cations is thought to involve multiple Ca(2+)-binding sites within the pore. Although the Ca(2+) affinity and cation preference of these sites have been extensively investigated, the effect of voltage on these sites has not received the same attention. We used a neuronal preparation enriched for N-type calcium (Ca(V)2.2) channels to investigate the effect of voltage on Ca(2+) flux. We found that the EC50 for Ca(2+) permeation increases from 13 mM at 0 mV to 240 mM at 60 mV, indicating that, during permeation, Ca(2+) ions sense the electric field. These data were nicely reproduced using a three-binding-site step model. Using roscovitine to slow Ca(V)2.2 channel deactivation, we extended these measurements to voltages <0 mV. Permeation was minimally affected at these hyperpolarized voltages, as was predicted by the model. As an independent test of voltage effects on permeation, we examined the Ca(2+)-Ba(2+) anomalous mole fraction (MF) effect, which was both concentration and voltage dependent. However, the Ca(2+)-Ba(2+) anomalous MF data could not be reproduced unless we added a fourth site to our model. Thus, Ca(2+) permeation through Ca(V)2.2 channels may require at least four Ca(2+)-binding sites. Finally, our results suggest that the high affinity of Ca(2+) for the channel helps to enhance Ca(2+) influx at depolarized voltages relative to other ions (e.g., Ba(2+) or Na(+)), whereas the absence of voltage effects at negative potentials prevents Ca(2+) from becoming a channel blocker. Both effects are needed to maximize Ca(2+) influx over the voltages spanned by action potentials. | 25,114,024 | [
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Positive psychological states and health behaviors in acute coronary syndrome patients: A qualitative study. | Positive psychological states are linked to superior cardiac outcomes, possibly mediated through increased participation in health behaviors. Trained study staff conducted in-depth semi-structured interviews in the hospital and 3 months later for 34 patients diagnosed with an acute coronary syndrome. These interviews focused on positive psychological states, cardiac health behaviors, and their connection; the interviews were transcribed and independently coded using directed content analysis. Both optimism and positive affect were associated with completion of physical activity and healthy eating in a bidirectional manner. In contrast, gratitude, while common, was infrequently linked to completion of health behaviors. | 25,114,026 | [
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Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis. | Research into Ginkgo biloba has been ongoing for many years, while the benefit and adverse effects of Ginkgo biloba extract EGb761 for cognitive impairment and dementia has been discussed controversially. To discuss new evidence on the clinical and adverse effects of standardized Ginkgo biloba extract EGb761 for cognitive impairment and dementia. MEDLINE, EMBASE, Cochrane, and other relevant databases were searched in March 2014 for eligible randomized controlled trials of Ginkgo biloba EGb761 therapy in patients with cognitive impairment and dementia. Nine trials met our inclusion criteria. Trials were of 22-26 weeks duration and included 2,561 patients in total. In the meta-analysis, the weighted mean differences in change scores for cognition were in favor of EGb761 compared to placebo (-2.86, 95%CI -3.18; -2.54); the standardized mean differences in change scores for activities in daily living (ADLs) were also in favor of EGb761 compared to placebo (-0.36, 95%CI -0.44; -0.28); Peto OR showed a statistically significant difference from placebo for Clinicians' Global Impression of Change (CGIC) scale (1.88, 95%CI 1.54; 2.29). All these benefits are mainly associated with EGb761 at a dose of 240 mg/day. For subgroup analysis in patients with neuropsychiatric symptoms, 240 mg/day EGb761 improved cognitive function, ADLs, CGIC, and also neuropsychiatric symptoms with statistical superiority than for the whole group. For the Alzheimer's disease subgroup, the main outcomes were almost the same as the whole group of patients with no statistical superiority. Finally, safety data revealed no important safety concerns with EGb761. EGb761 at 240 mg/day is able to stabilize or slow decline in cognition, function, behavior, and global change at 22-26 weeks in cognitive impairment and dementia, especially for patients with neuropsychiatric symptoms. | 25,114,079 | [
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The interaction of APOE genotype by age in amnestic mild cognitive impairment: a voxel-based morphometric study. | The apolipoprotein E (APOE) gene has been confirmed as the major genetic risk factor for the conversion of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). The present study was to assess whether there was a specific interaction of APOE by the aging process on brain morphology in aMCI. The analysis of gray matter (GM) voxel-based morphometry was performed in 85 aMCI and 100 healthy controls (HC). A significant interaction of APOE genotype by age on GM volume was found in the left calcarine, the left insula, and the left medial frontal gyrus in aMCI. GM volume in aMCI decreased significantly with ε 2-carriers < ε3/ε3 < ε4-carriers in above brain regions (except the left insula) while there was only a reduced tendency in HC. The multivariate regression analysis showed the well-known negative relationship for ε4-carriers and the positive relationship for ε2-carriers (except the left insula), while no correlations were found for ε3/ε3 between age and GM volumes on above brain regions. Moreover, the reduced GM volumes in the left calcarine and insula correlated with the impairment of visuo-spatial cognition and episodic memory in ε4- and ε2-carriers but not ε3/ε3, respectively. These results suggest that the APOE ε4 and ε2 alleles have the opposing effects on brain morphology across the spectrum of cognitive aging. Moreover, the interaction of APOE by age on brain morphology may accelerate the pathological progression of late-life cognitive decline in aMCI with ε4-carriers and delay the possible conversion from aMCI with ε2-carriers to AD. | 25,114,090 | [
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The interleukin-1β/CXCL1/2/neutrophil axis mediates host protection against group B streptococcal infection. | Previous studies have indicated that group B streptococcus (GBS), a frequent human pathogen, potently induces the release of interleukin-1β (IL-1β), an important mediator of inflammatory responses. Since little is known about the role of this cytokine in GBS disease, we analyzed the outcome of infection in IL-1β-deficient mice. These animals were markedly sensitive to GBS infection, with most of them dying under challenge conditions that caused no deaths in wild-type control mice. Lethality was due to the inability of the IL-1β-deficient mice to control local GBS replication and dissemination to target organs, such as the brain and the kidneys. Moreover, in a model of inflammation induced by the intraperitoneal injection of killed GBS, a lack of IL-1β was associated with selective impairment in the production of the neutrophil chemokines CXCL1 and CXCL2 and in neutrophil recruitment to the peritoneal cavity. Decreased blood neutrophil counts and impaired neutrophil recruitment to the brain and kidneys were also observed during GBS infection in IL-1β-deficient mice concomitantly with a reduction in CXCL1 and CXCL2 tissue levels. Notably, the hypersusceptibility to GBS infection observed in the immune-deficient animals was recapitulated by neutrophil depletion with anti-Gr1 antibodies. Collectively, our data identify a cytokine circuit that involves IL-1β-induced production of CXCL1 and CXCL2 and leads the recruitment of neutrophils to GBS infection sites. Moreover, our data point to an essential role of these cells in controlling the progression and outcome of GBS disease. | 25,114,117 | [
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Role of pathogen-derived cell wall carbohydrates and prostaglandin E2 in immune response and suppression of fish immunity by the oomycete Saprolegnia parasitica. | Saprolegnia parasitica is a freshwater oomycete that is capable of infecting several species of fin fish. Saprolegniosis, the disease caused by this microbe, has a substantial impact on Atlantic salmon aquaculture. No sustainable treatment against saprolegniosis is available, and little is known regarding the host response. In this study, we examined the immune response of Atlantic salmon to S. parasitica infection and to its cell wall carbohydrates. Saprolegnia triggers a strong inflammatory response in its host (i.e., induction of interleukin-1β1 [IL-1β1], IL-6, and tumor necrosis factor alpha), while severely suppressing the expression of genes associated with adaptive immunity in fish, through downregulation of T-helper cell cytokines, antigen presentation machinery, and immunoglobulins. Oomycete cell wall carbohydrates were recognized by fish leukocytes, triggering upregulation of genes involved in the inflammatory response, similar to what is observed during infection. Our data suggest that S. parasitica is capable of producing prostaglandin [corrected] E2 (PGE2) in vitro, a metabolite not previously shown to be produced by oomycetes, and two proteins with homology to vertebrate enzymes known to play a role in prostaglandin biosynthesis have been identified in the oomycete genome. Exogenous PGE2 was shown to increase the inflammatory response in fish leukocytes incubated with cell wall carbohydrates while suppressing genes involved in cellular immunity (gamma interferon [IFN-γ] and the IFN-γ-inducible protein [γ-IP]). Inhibition of S. parasitica zoospore germination and mycelial growth by two cyclooxygenase inhibitors (aspirin and indomethacin) also suggests that prostaglandins may be involved in oomycete development. | 25,114,122 | [
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Chloroquine has a cytotoxic effect on Acanthamoeba encystation through modulation of autophagy. | Encystation of Acanthamoeba castellanii is associated with resistance to chemotherapeutic agents. Blocking the encystation process could potentiate the efficacy of chemotherapeutic agents and biocides. During encystation, autophagy is highly stimulated and required for proper encystation of Acanthamoeba. In this study, the cytotoxic effect of chloroquine, a well-known autophagy-inhibitory drug, was tested in A. castellanii. Chloroquine was able to selectively reduce cell survival during the encystation of A. castellanii. However, A. castellanii trophozoites and mature cysts were resistant to chloroquine. Chloroquine treatment led to an increase in the number and size of lysosomes in encysting cells. Moreover, chloroquine inhibited the degradation of long-lived proteins in the encysting cells. Decreased autophagic flux, indicated by an increased number of lysosomes and decreased degradation of long-lived proteins, may be the mechanism by which cell death is induced by chloroquine in encysting Acanthamoeba. These results suggest a potential novel therapeutic application of chloroquine as an anti-Acanthamoeba drug. Our findings also suggest that targeting autophagy could be a therapeutic strategy against Acanthamoeba infection. | 25,114,131 | [
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J.H. Pons on 'Sympathetic insanity': With an introduction by GE Berrios. | The ancient concept of 'sympathy' originally referred to a putative affinity or force that linked all natural objects together. This notion was later used to explain the manner in which human beings related and felt for each other. A large literature exists on both the physical and psychological definitions of sympathy. Until the nineteenth century the conceptual apparatus of medicine preserved the view that the organs of the human body had a sympathetic affinity for each other. In addition to these 'physiological' (normal) sympathies there were morbid ones which explained the existence of various diseases. A morbid sympathy link also explained the fact that insanity followed the development of pathological changes in the liver, spleen, stomach and other bodily organs. These cases were classified as 'sympathetic insanities'. After the 1880s, the sympathy narrative was gradually replaced by physiological, endocrinological and psychodynamic explanations. The clinical states involved, however, are often observed in hospital practice and constitute the metier of 'consultation-liaison psychiatry'. Hence, it is surprising that historical work on the development of this discipline has persistently ignored the concept of 'sympathetic insanity'. | 25,114,150 | [
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HMBPP-deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vγ2Vδ2 T cells. | Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria ΔactA prfA* and HMBPP-deficient Listeria ΔactA ΔGCPE: prfA* mutant. The HMBPP-deficient ΔGCPE: mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP-deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN-γ and TNF-α and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention. | 25,114,162 | [
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Structure of Toxoplasma gondii coronin, an actin-binding protein that relocalizes to the posterior pole of invasive parasites and contributes to invasion and egress. | Coronins are involved in the regulation of actin dynamics in a multifaceted way, participating in cell migration and vesicular trafficking. Apicomplexan parasites, which exhibit an actin-dependent gliding motility that is essential for traversal through tissues, as well as invasion of and egress from host cells, express only a single coronin, whereas higher eukaryotes possess several isoforms. We set out to characterize the 3-D structure, biochemical function, subcellular localization, and genetic ablation of Toxoplasma gondii coronin (TgCOR), to shed light on its biological role. A combination of X-ray crystallography, small-angle scattering of X-rays, and light scattering revealed the atomic structure of the conserved WD40 domain and the dimeric arrangement of the full-length protein. TgCOR binds to F-actin and increases the rate and extent of actin polymerization. In vivo, TgCOR relocalizes transiently to the posterior pole of motile and invading parasites, independent of actin dynamics, but concomitant to microneme secretory organelle discharge. TgCOR contributes to, but is not essential for, invasion and egress. Taken together, our data point toward a role for TgCOR in stabilizing newly formed, short filaments and F-actin cross-linking, as well as functions linked to endocytosis and recycling of membranes. | 25,114,175 | [
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Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. | SUMOylation is an essential ubiquitin-like modification involved in important biological processes in eukaryotic cells. Identification of small ubiquitin-related modifier (SUMO)-conjugated residues in proteins is critical for understanding the role of SUMOylation but remains experimentally challenging. We have set up a powerful and high-throughput method combining quantitative proteomics and peptide immunocapture to map SUMOylation sites and have analyzed changes in SUMOylation in response to stimuli. With this technique we identified 295 SUMO1 and 167 SUMO2 sites on endogenous substrates of human cells. We further used this strategy to characterize changes in SUMOylation induced by listeriolysin O, a bacterial toxin that impairs the host cell SUMOylation machinery, and identified several classes of host proteins specifically deSUMOylated in response to this toxin. Our approach constitutes an unprecedented tool, broadly applicable to various SUMO-regulated cellular processes in health and disease. | 25,114,211 | [
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Rare earth elements activate endocytosis in plant cells. | It has long been observed that rare earth elements (REEs) regulate multiple facets of plant growth and development. However, the underlying mechanisms remain largely unclear. Here, using electron microscopic autoradiography, we show the life cycle of a light REE (lanthanum) and a heavy REE (terbium) in horseradish leaf cells. Our data indicate that REEs were first anchored on the plasma membrane in the form of nanoscale particles, and then entered the cells by endocytosis. Consistently, REEs activated endocytosis in plant cells, which may be the cellular basis of REE actions in plants. Moreover, we discovered that a portion of REEs was successively released into the cytoplasm, self-assembled to form nanoscale clusters, and finally deposited in horseradish leaf cells. Taken together, our data reveal the life cycle of REEs and their cellular behaviors in plant cells, which shed light on the cellular mechanisms of REE actions in living organisms. | 25,114,214 | [
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Small RNA combination therapy for lung cancer. | MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but their effective delivery to most solid tumors has been difficult. Here, we show that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically engineered mouse model of lung cancer based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a levels in lung tumors, specifically down-regulated miR-34a target genes, and slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene expression and MAPK signaling, increased apoptosis, and inhibited tumor growth. The combination of miR-34a and siRNA targeting Kras improved therapeutic responses over those observed with either small RNA alone, leading to tumor regression. Furthermore, nanoparticle-mediated small RNA delivery plus conventional, cisplatin-based chemotherapy prolonged survival in this model compared with chemotherapy alone. These findings demonstrate that RNA combination therapy is possible in an autochthonous model of lung cancer and provide preclinical support for the use of small RNA therapies in patients who have cancer. | 25,114,235 | [
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Marine ammonia-oxidizing archaeal isolates display obligate mixotrophy and wide ecotypic variation. | Ammonia-oxidizing archaea (AOA) are now implicated in exerting significant control over the form and availability of reactive nitrogen species in marine environments. Detailed studies of specific metabolic traits and physicochemical factors controlling their activities and distribution have not been well constrained in part due to the scarcity of isolated AOA strains. Here, we report the isolation of two new coastal marine AOA, strains PS0 and HCA1. Comparison of the new strains to Nitrosopumilus maritimus strain SCM1, the only marine AOA in pure culture thus far, demonstrated distinct adaptations to pH, salinity, organic carbon, temperature, and light. Strain PS0 sustained nearly 80% of ammonia oxidation activity at a pH as low as 5.9, indicating that coastal strains may be less sensitive to the ongoing reduction in ocean pH. Notably, the two novel isolates are obligate mixotrophs that rely on uptake and assimilation of organic carbon compounds, suggesting a direct coupling between chemolithotrophy and organic matter assimilation in marine food webs. All three isolates showed only minor photoinhibition at 15 µE ⋅ m(-2) ⋅ s(-1) and rapid recovery of ammonia oxidation in the dark, consistent with an AOA contribution to the primary nitrite maximum and the plausibility of a diurnal cycle of archaeal ammonia oxidation activity in the euphotic zone. Together, these findings highlight an unexpected adaptive capacity within closely related marine group I Archaea and provide new understanding of the physiological basis of the remarkable ecological success reflected by their generally high abundance in marine environments. | 25,114,236 | [
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Collective credit allocation in science. | Collaboration among researchers is an essential component of the modern scientific enterprise, playing a particularly important role in multidisciplinary research. However, we continue to wrestle with allocating credit to the coauthors of publications with multiple authors, because the relative contribution of each author is difficult to determine. At the same time, the scientific community runs an informal field-dependent credit allocation process that assigns credit in a collective fashion to each work. Here we develop a credit allocation algorithm that captures the coauthors' contribution to a publication as perceived by the scientific community, reproducing the informal collective credit allocation of science. We validate the method by identifying the authors of Nobel-winning papers that are credited for the discovery, independent of their positions in the author list. The method can also compare the relative impact of researchers working in the same field, even if they did not publish together. The ability to accurately measure the relative credit of researchers could affect many aspects of credit allocation in science, potentially impacting hiring, funding, and promotion decisions. | 25,114,238 | [
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A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs. | The recent success of antibody-drug conjugates (ADCs) in the treatment of cancer has led to a revived interest in microtubule-destabilizing agents. Here, we determined the high-resolution crystal structure of the complex between tubulin and maytansine, which is part of an ADC that is approved by the US Food and Drug Administration (FDA) for the treatment of advanced breast cancer. We found that the drug binds to a site on β-tubulin that is distinct from the vinca domain and that blocks the formation of longitudinal tubulin interactions in microtubules. We also solved crystal structures of tubulin in complex with both a variant of rhizoxin and the phase 1 drug PM060184. Consistent with biochemical and mutagenesis data, we found that the two compounds bound to the same site as maytansine and that the structures revealed a common pharmacophore for the three ligands. Our results delineate a distinct molecular mechanism of action for the inhibition of microtubule assembly by clinically relevant agents. They further provide a structural basis for the rational design of potent microtubule-destabilizing agents, thus opening opportunities for the development of next-generation ADCs for the treatment of cancer. | 25,114,240 | [
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Fractal branching organizations of Ediacaran rangeomorph fronds reveal a lost Proterozoic body plan. | The branching morphology of Ediacaran rangeomorph fronds has no exact counterpart in other complex macroorganisms. As such, these fossils pose major questions as to growth patterns, functional morphology, modes of feeding, and adaptive optimality. Here, using parametric Lindenmayer systems, a formal model of rangeomorph morphologies reveals a fractal body plan characterized by self-similar, axial, apical, alternate branching. Consequent morphological reconstruction for 11 taxa demonstrates an adaptive radiation based on 3D space-filling strategies. The fractal body plan of rangeomorphs is shown to maximize surface area, consistent with diffusive nutrient uptake from the water column (osmotrophy). The enigmas of rangeomorph morphology, evolution, and extinction are resolved by the realization that they were adaptively optimized for unique ecological and geochemical conditions in the late Proterozoic. Changes in ocean conditions associated with the Cambrian explosion sealed their fate. | 25,114,255 | [
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Patterned progression of bacterial populations in the premature infant gut. | In the weeks after birth, the gut acquires a nascent microbiome, and starts its transition to bacterial population equilibrium. This early-in-life microbial population quite likely influences later-in-life host biology. However, we know little about the governance of community development: does the gut serve as a passive incubator where the first organisms randomly encountered gain entry and predominate, or is there an orderly progression of members joining the community of bacteria? We used fine interval enumeration of microbes in stools from multiple subjects to answer this question. We demonstrate via 16S rRNA gene pyrosequencing of 922 specimens from 58 subjects that the gut microbiota of premature infants residing in a tightly controlled microbial environment progresses through a choreographed succession of bacterial classes from Bacilli to Gammaproteobacteria to Clostridia, interrupted by abrupt population changes. As infants approach 33-36 wk postconceptional age (corresponding to the third to the twelfth weeks of life depending on gestational age at birth), the gut is well colonized by anaerobes. Antibiotics, vaginal vs. Caesarian birth, diet, and age of the infants when sampled influence the pace, but not the sequence, of progression. Our results suggest that in infants in a microbiologically constrained ecosphere of a neonatal intensive care unit, gut bacterial communities have an overall nonrandom assembly that is punctuated by microbial population abruptions. The possibility that the pace of this assembly depends more on host biology (chiefly gestational age at birth) than identifiable exogenous factors warrants further consideration. | 25,114,261 | [
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-... |
"Pictures don't lie, seeing is believing": exploring attitudes to the introduction of pictorial warnings on cigarette packs in Ghana. | To compare perceptions of text and pictorial warning labels on cigarette packs among Ghanaian smokers and nonsmokers and to explore their views on the introduction of pictorial warnings in Ghana. Qualitative study involving 12 focus group discussions with 50 smokers and 35 nonsmokers aged 15 years and older in Kumasi, Ghana. Semistructured discussion guides along with visual discussant aids were used to explore the perception, acceptance, and potential use of pictorial warning labels in Ghana. Health warnings combining text and a picture were perceived by both smokers and nonsmokers to communicate health messages more effectively than text-only or picture-only warnings. The effect of text-only warnings was considered limited by low levels of literacy and by the common practice of single stick sales rather than sales of packs. Of the 6 health warnings tested, lung cancer, blindness, stroke, and throat/mouth cancer messages were perceived to have the most impact on smoking behavior, including uptake and quit attempts. Warning labels combining pictures and text have the potential to reduce smoking uptake, increase quit attempts, and reduce smoking appeal among smokers and nonsmokers in Ghana. Measures to prevent single stick sales, or to promote health messages to purchasers of single sticks, are required. | 25,114,265 | [
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... |
Police exposure to infectious agents: an audit of protective policies. | As first responders, police officers may be exposed to infectious agents such as hepatitis viruses and human immunodeficiency virus. Their risk of infection by these viruses can be reduced with training, monitoring and, with some viruses, vaccination. To examine infection prevention policies and practices among police departments and determine provision of vaccination and infection prevention education programmes. A questionnaire sent to all police departments in five counties of south-eastern Pennsylvania to capture information about department size, immunization policies and practices, record keeping, infection prevention education and monitoring of exposures. Ninety-six of 168 departments responded (57%). Among these, policies requiring pre-employment physical examinations were almost universal (95%). Vaccination policies were less common with <15% requiring and 50% recommending hepatitis, tetanus or influenza vaccination for officers. Few departments took action to provide (2%) or cover the cost (21%) of vaccination. Fewer than 12% maintained vaccination records. Education about the risk of infectious agents was offered by 60% of the responding departments, but often just once at the start of employment. Fewer than half of the departments had systems to collect exposure information. Police departments have opportunities to improve policies and practices for infection prevention and control. Accurate documentation of vaccination status is essential to ensure provision of appropriate post-exposure assessment and treatment. Better reporting of exposure will improve understanding of the infection transmission risk, enhancing the ability to offer targeted education and services to officers. | 25,114,270 | [
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... |
Clinical and molecular characterization of a novel PLIN1 frameshift mutation identified in patients with familial partial lipodystrophy. | Perilipin 1 is a lipid droplet coat protein predominantly expressed in adipocytes, where it inhibits basal and facilitates stimulated lipolysis. Loss-of-function mutations in the PLIN1 gene were recently reported in patients with a novel subtype of familial partial lipodystrophy, designated as FPLD4. We now report the identification and characterization of a novel heterozygous frameshift mutation affecting the carboxy-terminus (439fs) of perilipin 1 in two unrelated families. The mutation cosegregated with a similar phenotype including partial lipodystrophy, severe insulin resistance and type 2 diabetes, extreme hypertriglyceridemia, and nonalcoholic fatty liver disease in both families. Poor metabolic control despite maximal medical therapy prompted two patients to undergo bariatric surgery, with remarkably beneficial consequences. Functional studies indicated that expression levels of the mutant protein were lower than wild-type protein, and in stably transfected preadipocytes the mutant protein was associated with smaller lipid droplets. Interestingly, unlike the previously reported 398 and 404 frameshift mutants, this variant binds and stabilizes ABHD5 expression but still fails to inhibit basal lipolysis as effectively as wild-type perilipin 1. Collectively, these findings highlight the physiological need for exquisite regulation of neutral lipid storage within adipocyte lipid droplets, as well as the possible metabolic benefits of bariatric surgery in this serious disease. | 25,114,292 | [
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0.5028766,
0.08840194,
... |
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