title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Generalization of Carey's equality and a theorem on stationary population. | Carey's Equality pertaining to stationary models is well known. In this paper, we have stated and proved a fundamental theorem related to the formation of this Equality. This theorem will provide an in-depth understanding of the role of each captive subject, and their corresponding follow-up duration in a stationary population. We have demonstrated a numerical example of a captive cohort and the survival pattern of medfly populations. These results can be adopted to understand age-structure and aging process in stationary and non-stationary population models. | 25,230,675 | [
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The complete mitochondria genome of Chrysomya pinguis (Diptera: Calliphoridae). | Chrysomya pinguis (Ch. pinguis) belongs to blowfly species of great medical and forensic importance. In this study, we report the complete mitochondrial genome of the Ch. pinguis for species identification. The 38 genes presented in the 15,838 bp circular genome has been found in a typical Metazoan genome, of which there are 23 transfer RNA genes, 13 protein-coding genes and 2 ribosomal RNA genes. In addition, there is a non-coding A + T-rich region between one and another tRNA-Ile. The array of the genes is similar to that discovered in other insects. The overall base compositions of A, G, C and T are 38.72%, 9.86%, 14.07% and 37.35% respectively. This study contributes to the availability of dipteran mitochondrial genomes and provides the first complete mitochondrial genome of Ch. pinguis for entomologists to identify diagnostic regions for species identifications and phylogenetic analysis. | 25,230,700 | [
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The complete mitochondrial genome sequence of an endometrial cancer inbred Donryu rat model. | The Donryu rat strain is a commonly used model for endometrial cancer disease study. We sequenced this rat strain mitochondrial genome for the first time (GenBank Accession No. KM114605). Its mitogenome was 16,307 bp and coding 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. A total of 96 SNPs were examined when compared to reference BN sequence. | 25,230,703 | [
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DUSP28 contributes to human hepatocellular carcinoma via regulation of the p38 MAPK signaling. | DUSP28, a member of the atypical dual‑specificity phosphatase (DUSP) family, is a candidate tumor-related gene in hepatocellular carcinoma (HCC) selected by genome‑wide approach, but its pathological role in HCC has not been elucidated. Here, we report for the first time that DUSP28 is involved in HCC progression. Quantitative real‑time PCR and semi‑quantitative RT-PCR showed notably elevated expression of DUSP28 in HCC specimens compared to that in corresponding adjacent non‑tumor liver. DUSP28 overexpression promoted HCC cell proliferation, colony formation and soft agar colony formation in vitro while DUSP28 knockdown resulted in the opposite effects. Furthermore, the flow cytometric analysis indicated that DUSP28 could lead to an increased population of cancer cells in S phase, with a concomitant decrease of cells in G1 phase. Investigation of the mechanism revealed that DUSP28 could activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Taken together, these data demonstrate that DUSP28 plays a significant role in HCC progression and may be a feasible molecular target for anti-cancer therapy. | 25,230,705 | [
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piRNA identification based on motif discovery. | Piwi-interacting RNA (piRNA) is a class of small non-coding RNAs about 24 to 32 nucleotides long, associated with PIWI proteins, which are involved in germline development, transposon silencing, and epigenetic regulation. Identification of piRNA loci on the genome is very useful for further studies in the biogenesis and function of piRNAs. To accomplish this, we applied the computational biology tool Teiresias to identify motifs of variable length appearing frequently in mouse piRNA and non-piRNA sequences, respectively, and then proposed an algorithm for piRNA identification based on motif discovery, termed "Pibomd" by using these sequence motifs as features in the Support Vector Machine (SVM) algorithm, a sensitivity of 91.48% and a specificity of 89.76% on a mouse test dataset could be achieved, much better results than those reported in previously published algorithms. We also trained an unbalanced SVM classifier (named as "Asym-Pibomd") that provided a higher specificity (96.2%) and a lower sensitivity (72.68%) than Pibomd. Inspite of the predicted ACC being less than that of Pibomd, the predicted ACC (84.44%) of Asym-Pibomd is about ten percent more than that obtained using the k-mer method. Further analysis of the motif positions on the piRNA sequences showed that the piRNA sequences may contain information at the 5'- and/or 3'-end recognized by the piRNA processing apparatus of actual piRNA precursors. Furthermore, this prediction method can be found on a user-friendly web server found at http://app.aporc.org/Pibomd/. | 25,230,731 | [
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Social networking versus facebook advertising to recruit survey respondents: a quasi-experimental study. | Increasingly, social contact and knowledge of other people's attitudes and behavior are mediated by online social media such as Facebook. The main research to which this recruitment study pertains investigates the influence of parents on adolescent alcohol consumption. Given the pervasiveness of online social media use, Facebook may be an effective means of recruitment and intervention delivery. The objective of the study was to determine the efficacy of study recruitment via social networks versus paid advertising on Facebook. We conducted a quasi-experimental sequential trial with response rate as the outcome, and estimates of cost-effectiveness. The target population was parents of 13-17 year old children attending high schools in the Hunter region of New South Wales, Australia. Recruitment occurred via: method (1) social recruitment using Facebook, email-based, social networks, and media coverage followed by method (2) Facebook advertising. Using a range of online and other social network approaches only: method (1) 74 parents were recruited to complete a survey over eight months, costing AUD58.70 per completed survey. After Facebook advertising: method (2) 204 parents completed the survey over four weeks, costing AUD5.94 per completed survey. Participants were representative of the parents recruited from the region's schools using standard mail and email. Facebook advertising is a cost-effective means of recruiting parents, a group difficult to reach by other methods. | 25,230,740 | [
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Repeated oral dosing of TAS-102 confers high trifluridine incorporation into DNA and sustained antitumor activity in mouse models. | TAS-102 is a novel oral nucleoside antitumor agent containing trifluridine (FTD) and tipiracil hydrochloride (TPI). The compound improves overall survival of colorectal cancer (CRC) patients who are insensitive to standard chemotherapies. FTD possesses direct antitumor activity since it inhibits thymidylate synthase (TS) and is itself incorporated into DNA. However, the precise mechanisms underlying the incorporation into DNA and the inhibition of TS remain unclear. We found that FTD-dependent inhibition of TS was similar to that elicited by fluorodeoxyuridine (FdUrd), another clinically used nucleoside analog. However, washout experiments revealed that FTD-dependent inhibition of TS declined rapidly, whereas FdUrd activity persisted. The incorporation of FTD into DNA was significantly higher than that of other antitumor nucleosides. Additionally, orally administered FTD had increased antitumor activity and was incorporated into DNA more effectively than continuously infused FTD. When TAS-102 was administered, FTD gradually accumulated in tumor cell DNA, in a TPI-independent manner, and significantly delayed tumor growth and prolonged survival, compared to treatment with 5-FU derivatives. TAS-102 reduced the Ki-67-positive cell fraction, and swollen nuclei were observed in treated tumor tissue. The amount of FTD incorporation in DNA and the antitumor activity of TAS-102 in xenograft models were positively and significantly correlated. These results suggest that TAS-102 exerts its antitumor activity predominantly due to its DNA incorporation, rather than as a result of TS inhibition. The persistence of FTD in the DNA of tumor cells treated with TAS-102 may underlie its ability to prolong survival in cancer patients. | 25,230,742 | [
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Use of sodium hypochlorite for skin antisepsis before inserting a peripheral venous catheter: a pilot study. | Although it can be prevented, catheter-related bacteremia is common and dangerous. The antiseptics most widely used during insertion of peripheral venous catheters (PVCs) include povidone iodine, alcohol, and chlorhexidine. Another widely used antiseptic is a solution of 0.057 g sodium hypochlorite. This pilot study explored the contamination rate of the PVC tip inserted after skin decontamination with sodium hypochlorite. Culture analysis of the tips of the PVCs inserted into the 42 participants showed 7 (16.7%) colonized catheters. The results of this pilot study suggest taking into serious consideration the assessment of this antiseptic in randomized experimental studies. | 25,230,748 | [
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IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation. | Eosinophils originate in the bone marrow from an eosinophil lineage-committed, IL-5Rα-positive, hematopoietic progenitor (eosinophil progenitor). Indeed, IL-5 is recognized as a critical regulator of eosinophilia and has effects on eosinophil progenitors, eosinophil precursors, and mature eosinophils. However, substantial levels of eosinophils remain after IL-5 neutralization or genetic deletion, suggesting that there are alternative pathways for promoting eosinophilia. In this study, we investigated the contributory role of IL-5 accessory cytokines on the final stages of eosinophil differentiation. IL-5 stimulation of low-density bone marrow cells resulted in expression of a panel of cytokines and cytokine receptors, including several ligand-receptor pairs. Notably, IL-4 and IL-4Rα were expressed by eosinophil precursors and mature eosinophils. Signaling through IL-4Rα promoted eosinophil maturation when IL-5 was present, but IL-4 stimulation in the absence of IL-5 resulted in impaired eosinophil survival, suggesting that IL-4 cooperates with IL-5 to promote eosinophil differentiation. In contrast, CCL3, an eosinophil precursor-produced chemokine that signals through CCR1, promotes terminal differentiation of CCR1-positive eosinophil precursors in the absence of IL-5, highlighting an autocrine loop capable of sustaining eosinophil differentiation. These findings suggest that brief exposure to IL-5 is sufficient to initiate a cytokine cooperative network that promotes eosinophil differentiation of low-density bone marrow cells independent of further IL-5 stimulation. | 25,230,753 | [
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A cross sectional survey examining the association between therapeutic relationships and service user satisfaction in forensic mental health settings. | This small-scale study examines an often neglected patient group (service users in forensic mental health settings). The research investigates their therapeutic relationship with staff and which therapeutic relationship factors are associated with their level of satisfaction with services. A cross sectional survey was undertaken in two medium secure units in the UK with seventy seven participants completing self-report measures examining service user satisfaction with services and their therapeutic relationship with staff. Multiple regression analysis was used to identify the main predictor variables associated with satisfaction with the service provided. The respondents had a generally positive view of services and also of their therapeutic relationships with staff. However, the therapeutic relationship scores were lower than those recorded in community samples. One predictor variable was significantly associated with service user satisfaction; feeling respected and well regarded. The therapeutic relationship domain of being respected and well regarded by staff was identified as the most significant factor among the therapeutic relationship domains when examining the association with satisfaction with services. The important role mental health clinicians play in enabling service users to recognize they are being treated respectfully is noted as service users judge the degree of honesty, caring and interest that staff show in them. Staff also need to be available and accessible while having good listening and information giving skills. The importance of having both positive therapeutic relationships and service user satisfaction in forensic settings is also discussed. | 25,230,757 | [
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Structure and photoluminescence of silver(i) trinuclear halopyrazolato complexes. | Five halogen substituted pyrazolates, 4-chloro-3,5-diisopropylpyrazole (4-Cl-3,5-iPr2pzH), 4-bromo-3,5-diisopropylpyrazole (4-Br-3,5-iPr2pzH), 4-iodo-3,5-diisopropylpyrazole (4-I-3,5-iPr2pzH), 4-chloro-3,5-diphenylpyrazole (4-Cl-3,5-Ph2pzH), and 4-bromo-3,5-diphenylpyrazole (4-Br-3,5-Ph2pzH), were conveniently prepared by halogenation of the appropriate pyrazoles with N-halosuccinimides (NXS) (X = Cl, Br, and I) followed by complexation of the pyrazolate anions with silver(i) nitrate. Single crystal X-ray analysis revealed either dimeric trinuclear {[Ag(μ-4-X-3,5-R2pz)]3}2 (R = iPr, X = Cl, Br, and I) or trinuclear [Ag(μ-4-X 3,5-R2pz)]3 (R = iPr, X = I; R = Ph, X = Cl, R = Ph, X = Br) structures, the latter held together with argentophilic interactions (AgAg interactions) that could also be observed in the Raman spectra. The electronegativity of the halogen substituent could be correlated with the strength of the AgAg interaction and the wavelength of solid-state photoluminescence. All complexes were emissive on UV irradiation at low temperatures, with the colour of emission from the diisopropyl substituted analogues red shifted by the halogens in the order Cl (red) > Br (orange) > I (yellow). Emission from the diphenyl substituted analogues was dominated by the extended aromatic system and was largely invariant to the halogens. | 25,230,795 | [
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Cerebral vasospasm patterns following aneurysmal subarachnoid hemorrhage: an angiographic study comparing coils with clips. | Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) results in significant morbidity due to ischemia. Subarachnoid hematoma evacuation during aneurysm clipping reduces the incidence of vasospasm. However, studies comparing endovascular coiling with open clipping have reported similar rates of spasm. We addressed the question of how coiling produces similar (if not less) vasospasm without the benefit of clot evacuation by evaluating vasospasm patterns among patients with aSAH. We hypothesize that cerebrospinal fluid (CSF) circulation plays a major role in clearing blood breakdown products, and that coiling may preserve CSF flow in the subarachnoid space. A retrospective chart review identified 36 (18 coiled/18 clipped) patients with aSAH who developed angiographic vasospasm. The degree of spasm was quantified using an ordinal scale from 0 (none) to 5 (severe) for 26 anatomic vessel segments evaluated on 164 successive angiograms. Statistical analysis was performed using the Fisher exact test for proportions and the Wilcoxon and Student t tests on ordinal/continuous measures. Quadratic regression was also used as a model for spasm activity versus post-bleed days. In both the coiling and clipping groups the most severely spastic vessels were located adjacent to aneurysm rupture. Perianeurysmal spasm affected all subjects. However, whereas spasm remained largely confined in patients treated by clipping, those who underwent coiling developed stepwise progression distally over time. The distal vasospasm severity scores were higher among subjects treated by coiling, particularly in the most dependent regions of the subarachnoid space. Patients with aSAH treated by endovascular coiling and surgical clipping demonstrate distinct vasospasm patterns. While both initially exhibit perianeurysmal spasm, patients treated by coiling go on to develop stepwise progression distally over time. This finding may reflect dispersion of blood breakdown products along preserved CSF egress pathways in patients treated by endovascular coiling. | 25,230,840 | [
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A new biflavonoid from Solanum dulcamara L. and investigation of anti-hyperglycaemic activity of its fruit extract. | A new biflavone, 6,2',3″,5″,4‴-pentahydroxy-3,7″-biflavone, has been isolated from the fruits of Solanum dulcamara L., in addition to two known compounds, β-sitosterol and stigmasterol. Their structures were established on the basis of UV, IR, 1D, 2D NMR and HR-ESI-MS spectroscopic methods. The anti-hyperglycaemic effect of S. dulcamara was investigated using diabetic rats. The anti-hyperglycaemic activity of the fruit extract of S. dulcamara was presented for the first time in this study. | 25,230,855 | [
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[Study of the effects of high volume hemofiltration on extra vascular lung water and alveolar-arterial oxygen exchange in patients with septic shock]. | To explore the effects of high volume hemofiltration (HVHF) on inflammatory factors, extra vascular lung water and alveolar-arterial oxygen exchange in patients with septic shock. The data of 87 patients with septic shock underwent fluid resuscitation admitted to intensive care unit (ICU) of Shandong Provincial Hospital Affiliated to Shandong University were retrospectively analyzed. According to whether HVHF was used or not, all the patients were divided into fluid resuscitation group (n=41) and HVHF group (n=46). The patients in HVHF group received bedside high volume continuous vein-vein hemofiltration for at least 3 days on the basis of fluid resuscitation. The inflammatory factors, indexes of heart function, hemodynamics monitored by pulse-indicated continuous cardiac output (PiCCO), oxygen exchange, the severity of the disease before and after treatment, and 28-day mortality were compared between the two groups. The relationship between extra-vascular lung water index (EVLWI) and alveolar-arterial oxygen pressure difference (P(A-a)DO₂) was analyzed. (1) After treatment, the serum levels of interleukin-6 (IL-6), procalcitonin (PCT), and N-terminal pro-B-type natriuretic peptide (NT(-pro)BNP) in both group were gradually decreased. The IL-6, PCT, and NT(-pro)BNP on the 3rd day after treatment in HVHF group were significantly lower than those in fluid resuscitation group [IL-6 (μg/L): 34.8 ± 15.8 vs. 63.3 ± 21.2, PCT (μg/L): 7.5 ± 6.4 vs. 17.3 ± 11.2, NT(-pro)BNP (μg/L): 561.8 ± 23.7 vs. 584.3 ± 56.7, P<0.05 or P<0.01]. (2) The hemodynamics indexes were improved after treatment in both groups. The levels of intrathoracic blood volume index (ITBVI), EVLWI and pulmonary vascular permeability index (PVPI) on the 3rd day after treatment in HVHF group were significantly lower than those in fluid resuscitation group [ITBVI (mL/m²): 634.2 ± 125.8 vs. 963.8 ± 321.0, EVLWI (mL/kg): 7.5 ± 2.4 vs. 12.3 ± 4.2, PVPI: 2.2 ± 1.2 vs. 4.2 ± 2.0, all P<0.01]. (3) The levels of PA-aDO₂and arterial blood lactic (Lac) were gradually decreased, and oxygenation index (PaO₂/FiO₂) was gradually increased in both groups. Compared with fluid resuscitation group, the P(A-a)DO₂and Lac on the 3rd and the 7th day were significantly declined[P(A-a)DO₂(mmHg, 1 mmHg=0.133 kPa) on the 3rd day: 252.37 ± 29.45 vs. 270.82 ± 38.07, on the 7th day: 181.08 ± 21.81 vs. 221.02 ± 29.13; Lac (mmol/L) on the 3rd day: 3.17 ± 2.03 vs. 4.07 ± 2.43, on the 7th day: 1.95 ± 0.97 vs. 2.45 ± 1.07, P<0.05 or P<0.01], and the PaO₂/FiO₂on the 7th day was significantly elevated (mmHg: 258 ± 41 vs. 178 ± 34, P<0.01). (4) A significant positive correlation was found between EVLWI and P(A-a)DO₂(r=0.693, P=0.001), with the 95% confident interval (95% CI) 0.617-0.773. (5) The condition was improved after treatment in the two groups. The acute physiology and chronic health evaluationII (APACHEII) scores and sepsis-related organ failure assessment (SOFA) scores on the 7th day after treatment in HVHF group were significantly reduced compared with those in fluid resuscitation group (APACHEII score on the 3rd day: 18.2 ± 7.7 vs. 22.4 ± 8.6, on the 7th day: 8.2 ± 3.8 vs. 17.2 ± 6.8; SOFA score on the 3rd day: 13.6 ± 3.4 vs. 15.8 ± 5.0, on the 7th day: 7.6 ± 3.3 vs. 12.8 ± 3.9, P<0.05 or P<0.01). The 28-day mortality in HVHF group was significantly lower than that in fluid resuscitation group [15.22% (7/46) vs. 34.15% (14/41), χ² = 4.242, P=0.038]. HVHF could decrease blood inflammatory factors, and reduce the vaso-permeability and extra vascular lung water with a result of the improvement of the levels of alveolar- arterial oxygen exchange in patients with septic shock and the prognosis at the same time. | 25,230,859 | [
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[The assessment of ultrasonic measurement of superior vena cava blood flow for the volume responsiveness of patients with mechanical ventilation]. | To approach the evaluative effect of respiratory variation of superior vena cava peak flow velocity measured using transthoracic echocardiography (TTE) on fluid responsiveness in patients with mechanical ventilation. A prospective cohort study was conducted. All mechanical ventilated critically ill patients whose fluid therapy was planned due to hypovolemia in Department of Critical Care Medicine of Beijing Tongren Hospital of Capital Medical University from April 2011 to April 2013 were enrolled. Volume expansion was performed with 500 mL Linger solution within 30 minutes. Patients were classified as responders if pulse pressure variation (PPV) increased ≥ 13% before volume expansion. The respiratory variation in superior vena cava peak velocity was calculated as the difference between maximum and minimum values of velocity in peak A, peak S and peak D over a single respiratory circle, and their variations (ΔA, ΔS, ΔD) were also calculated. The receiver operating characteristic curve (ROC curve) was plotted to assess the evaluative effect of respiratory variation of superior vena cava peak velocity on fluid responsiveness. Twenty-seven patients were enrolled in this study. Volume expansion increased PPV ≥ 13% happened in 14 patients (responders). The velocity of superior vena cava in peak A, peak S, peak D was significantly increased after volume expansion compared with that before volume expansion in responders [peak A (cm/s): 34.6 ± 2.2 vs. 31.3 ± 2.1, t=-2.493, P=0.027; peak S (cm/s): 39.1 ± 1.3 vs. 35.3 ± 2.1, t=-2.564, P=0.024; peak D (cm/s): 28.1 ± 1.2 vs. 23.3 ± 1.4, t=-4.995, P=0.000], but there was no significant difference in ΔA, ΔS and ΔD between before and after volume expansion. The ΔA, ΔS and ΔD were positively correlated with PPV (r=0.040, P=0.854; r=0.350, P=0.074; r=0.749, P=0.000). The area under ROC curve (AUC) of peak S was 0.36 [95% confidence interval (95%CI): 0.11-0.52], but the AUC of ΔS was 0.68 (95%CI 0.47-0.89), the AUC of peak D was 0.41 (95%CI 0.19-0.63), but the AUC of ΔD was 0.95 (95%CI 0.86-1.00), so the aberration rate of superior vena cava in respiration was better than the flow rate in superior vena cava. When the cut-off value of ΔS was 20.7% for predicting fluid responsiveness, the sensitivity was 78.6% and the specificity was 61.5%. When the cut-off value of ΔD was 12.7% for predicting fluid responsiveness, the sensitivity was 92.0% and the specificity was 92.3%. Respiratory variations in superior vena cava peak velocity measured by TTE could assess fluid responsiveness in patients with mechanical ventilation. | 25,230,862 | [
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C5a stimulates the proliferation of breast cancer cells via Akt-dependent RGC-32 gene activation. | Complement system activation contributes to various immune and inflammatory diseases, as well as cancers.However, the role of complement activation in the proliferation of cancer cells is not clear. In the present study, we investigated the consequences of complement activation on the proliferation of breast cancer cells and its possible mechanisms. We focused our study on the potential roles of the anaphylatoxins C3a and C5a in the proliferation of human breast cancer, as two important immune mediators generated after complement activation. Our study revealed that C5a stimulation, but not C3a, enhanced the proliferation of human breast cancer cells in vitro. Moreover, the expression of response gene to complement 32 (RGC-32) was pronounced in breast cancer cells in response to C5a stimulation. Notably, blockade of the C5a receptor markedly reduced the expression of RGC-32 and the proliferation of breast cancer cells stimulated by C5a. Meanwhile, silencing of RGC-32 expression reduced the proliferation of breast cancer cells induced by C5a treatment. Further investigation revealed that Akt activation was involved in C5a-induced RGC-32 expression and breast cancer cell proliferation. In conclusion, the present study indicates that C5a may promote the proliferation of breast cancer cells through Akt1 activation of the RGC-32 gene. | 25,230,890 | [
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Knowledge and use of edible mushrooms in two municipalities of the Sierra Tarahumara, Chihuahua, Mexico. | The Sierra Madre Occidental of Chihuahua in Northern Mexico is inhabited by indigenous Raramuris, mestizos, and other ethnic groups. The territory consists of canyons and ravines with pine, oak and pine-oak forests in the higher plateaus. A great diversity of potentially edible mushrooms is found in forests of the Municipalities of Bocoyna and Urique. Their residents are the only consumers of wild mushrooms in the Northern Mexico; they have a long tradition of collecting and eating these during the "rainy season." However, despite the wide diversity of edible mushrooms that grow in these areas, residents have a selective preference. This paper aims to record evidence of the knowledge and use of wild potentially edible mushroom species by inhabitants of towns in the Sierra Tarahumara of Chihuahua, Mexico. Using a semi-structured technique, we surveyed 197 habitants from seven locations in Urique, Bocoyna, and the Cusarare area from 2010 to 2012. Known fungi, local nomenclature, species consumed, preparation methods, appreciation of taste, forms of preservation, criteria for differentiating toxic and edible fungi, other uses, economic aspects, and traditional teaching were recorded. To identify the recognized species, photographic stimuli of 22 local edible species and two toxic species were used. The respondents reported preference for five species: Amanita rubescens, Agaricus campestris, Ustilago maydis, Hypomyces lactifluorum, and the Amanita caesarea complex. No apparent differences were found between ethnic groups in terms of preference, although mestizos used other species in Bocoyna (Boletus edulis and B. pinophilus). Some different uses of fungi are recognized by respondents, i.e. home decorations, medicine, as food in breeding rams, etc. The studied population shows a great appreciation towards five species, mainly the A. caesarea complex, and an apparent lack of knowledge of nearly 20 species which are used as food in other areas of Mexico. There are no apparent differences among Sierra inhabitants in terms of gender, occupation, or language regarding the recognition and consumption of species. The rejection of certain species is due mainly to fear of poisoning and the traditional selective teaching of families in the mountain communities of the Sierra Tarahumara. | 25,230,891 | [
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Thermogenic brown and beige/brite adipogenesis in humans. | Evidence from rodents established an important role of brown adipose tissue (BAT) in energy expenditure. Moreover, to sustain thermogenesis, BAT has been shown to be a powerful sink for draining and oxidation of glucose and triglycerides from blood. The potential of BAT activity in protection against obesity and metabolic syndrome is recognized. Recently, an unexpected presence and activity of BAT has been found in adult humans. Here we review the most recent research in this field and, specifically, how new findings apply to humans. Moreover, we seek to clarify the underlying biological processes occurring beyond the burst of new nomenclature in the field. The cell type responsible for thermogenesis, the brown adipocyte, arises from complex developmental processes. In addition to 'classical' brown adipocytes, present in developmentally programmed BAT depots, there are brown adipocytes, named 'brite' (from 'brown-in-white') or 'beige', which appear in response to thermogenic stimuli in white fat due to the so-called 'browning' process. Beige/brite cells appear to be important components of BAT depots in adult humans. In addition to the known control of BAT activity by the sympathetic nervous system, metabolic and hormonal signals originating in muscle or liver (e.g. irisin, FGF21) are recognized as activators of BAT and beige/brite adipocytes. | 25,230,914 | [
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Association of left atrial booster-pump function with heart failure symptoms in patients with severe aortic stenosis and preserved left ventricular ejection fraction. | Identification of heart failure (HF) symptoms in patients with severe aortic stenosis (AS) and preserved left ventricular (LV) ejection fraction (EF) is clinically important, but assessment of HF symptoms is challenging. It was recently reported that resting left atrium (LA) functions are related to exercise performance and are also important prognostic markers for patients with HF. The aim of this study was to assess the association of the HF symptoms with LA function in patients with severe AS and preserved LVEF. We retrospectively studied 40 patients with severe AS and preserved LVEF (all ≥50%) who were referred for aortic valve replacement (AVR). LA reservoir (SR-LAs), conduit (SR-LAe), and booster-pump (SR-LAa) functions were determined as the averaged global LA speckle tracking longitudinal strain rate from apical four- and two-chamber views. Twenty patients were symptomatic and 20 asymptomatic. Aortic stenosis severity was similar for the 2 groups. Symptomatic status was associated with age, LV mass index, hemoglobin, B-type natriuretic peptide, LV end-systolic volume index, LVEF, LA volume index, SR-LAs, SR-LAe, and SR-LAa. Importantly, multivariate logistic regression analysis revealed that SR-LAa was the only independent determinant of symptomatic status (OR = 0.242, P = 0.002). Furthermore, significant improvement of SR-LAa was observed along with the reduction in LA volume index and LV mass index after AVR. SR-LAa was found to be associated with the HF symptoms. Characterization of LA booster-pump function may be useful for the assessment of the symptomatic status in patients with severe AS patients and limited physical activity. | 25,230,926 | [
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Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential. | We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P < 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and <1 in 17 patients. Patients ≥65 years old had a lower median Ig titer ratio than did younger patients (P < 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P < 0.05 for both comparisons after adjustment for age). Ig titer ratios of <1 were predominantly noted in patients with serotypes with a thick capsule. In 8 patients with pneumococcal DNA detected in plasma, the three patients with the highest DNA load had the lowest Ig titer ratios. In conclusion, a high antibody response was associated with serotypes with a thin capsule and medium/high invasive potential, although a low antibody response was associated with serotypes with a thick capsule and a high pneumococcal plasma load. | 25,230,937 | [
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Factors associated with severe deep neck space infections: targeting multiple fronts. | To determine factors predictive of a severe deep neck space infection (DNSI), defined as those requiring surgery and/or postoperative intensive care unit (ICU) admission. To specifically examine dental practices and socioeconomic factors that may contribute to the development of a DNSI. Retrospective review. This study was conducted at 2 tertiary care academic referral centers from January 2007 to September 2011. The study was composed of 2 arms: a prospective questionnaire and data collection to identify modifiable risk factors such as dental practices and socioeconomic considerations for a DNSI, and a retrospective review of deep neck space infections to identify commonly associated risk factors predictive of a severe DNSI, requiring surgery and/or postoperative ICU admission. 233 patients were reviewed retrospectively and 25 patients prospectively. Patients with a low level of education (p = 0.03), those living greater than 1 hour from a tertiary care center (p = 0.002), those that have tonsils (p = 0.03), and those with Streptococcus infections (p = 0.03) have an increase risk of developing a severe DNSI. Patients that were smokers (p = 0.02) or had diabetes (p = 0.02), and those that presented with airway compromise (p = 0.03) were more likely to have a prolonged hospital stay. Factors predictive of severe DNSIs are Streptococcus infections, the presence of tonsils, education level, and geographic location. | 25,230,978 | [
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The characteristics of the porcine (Sus scrofa) liver miRNAome with the use of next generation sequencing. | MicroRNAs (miRNAs) are a class of small, noncoding RNAs, which play a vital role in the regulation of gene expression by binding to the 3' untranslated region (3'UTR) of a target mRNA. Despite a significant improvement in the identification of miRNAs in a variety of species, the coverage of the porcine miRNAome is still scarce. To identify porcine miRNAs potentially regulating processes taking place in the liver, we applied next generation sequencing. As a result, we detected 206 distinct miRNAs, of which 68 represented potential novel miRNAs. Among these new miRNAs, there were miRNAs deriving from the opposite arm of a hairpin precursor of already known miRNAs. Moreover, we observed 3' and 5' length and sequence variants, probably constituting so called isomiRs, as well as differentially mapped precursor loci, alternative precursor sequences and clustering of miRNA encoding genes. On the basis of expression levels, reflected by the number of sequence reads, we identified the most abundant miRNAs followed by gene target prediction and pathway analysis. The enriched pathways were connected with cellular and metabolic processes, growth factors as well as enzymatic activity. The obtained results are the first ones to concern the porcine liver miRNAome. Consequently, they will increase the number of known porcine miRNAs and facilitate further research on gene regulation mechanisms as well as biological processes associated with the liver functioning in pigs. | 25,230,983 | [
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Linking bioregulatory systems: reciprocal autonomic activation predicts sleep over 1 year in middle childhood. | This study examined reactivity to social-evaluative stress in the parasympathetic (PNS) and sympathetic (SNS) branches of the autonomic nervous system (ANS) as prospective predictors of sleep in middle childhood. Participants included 339 children (M age = 9 years and 5 months at T1; 54% female; 64% European American, 36% African American). Sleep efficiency, sleep minutes, and variability in sleep onset time were assessed with actigraphy for seven consecutive nights at T1 and 1 year later at T2. Respiratory sinus arrhythmia reactivity (RSAR) and skin conductance level reactivity (SCLR) were assessed in response to a developmentally salient social-evaluative stress task at T1. Controlling for demographic variables and the respective sleep parameter at T1, the interaction between RSAR and SCLR predicted T2 sleep efficiency and sleep minutes. Consistent with the hypothesized role of reciprocal sympathetic activation (higher SCLR) and parasympathetic withdrawal (higher RSAR), higher RSAR predicted higher sleep efficiency and sleep minutes among children with higher SCLR but not lower SCLR. | 25,230,991 | [
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Auras in generalized epilepsy. | We studied the frequency of auras in generalized epilepsy (GE) using a detailed semistructured diagnostic interview. In this cross-sectional study, participants with GE were drawn from the Epilepsy Phenome/Genome Project (EPGP). Responses to the standardized diagnostic interview regarding tonic-clonic (grand mal) seizures were then examined. This questionnaire initially required participants to provide their own description of any subjective phenomena before their "grand mal seizures." Participants who provided answers to these questions were considered to have an aura. All participants were then systematically queried regarding a list of specific symptoms occurring before grand mal seizures, using structured (closed-ended) questions. Seven hundred ninety-eight participants with GE were identified, of whom 530 reported grand mal seizures. Of these, 112 (21.3%) reported auras in response to the open-ended question. Analysis of responses to the closed-ended questions suggested that 341 participants (64.3%) experienced at least one form of aura. Auras typically associated with focal epilepsy were reported by a substantial proportion of EPGP subjects with GE. This finding may support existing theories of cortical and subcortical generators of GE with variable spread patterns. Differences between responses to the open-ended question and closed-ended questions may also reflect clinically relevant variation in patient responses to history-taking and surveys. Open-ended questions may underestimate the prevalence of specific types of auras and may be in part responsible for the underrecognition of auras in GE. In addition, structured questions may influence participants, possibly leading to a greater representation of symptoms. | 25,230,998 | [
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Human polyomavirus 7-associated pruritic rash and viremia in transplant recipients. | Human polyomavirus 7 (HPyV7) is one of 11 HPyVs recently discovered through genomic sequencing technologies. Two lung transplant recipients receiving immunosuppressive therapy developed pruritic, brown plaques on the trunk and extremities showing a distinctive epidermal hyperplasia with virus-laden keratinocytes containing densely packed 36-45-nm icosahedral capsids. Rolling circle amplification and gradient centrifugation testing were positive for encapsidated HPyV7 DNA in skin and peripheral blood specimens from both patients, and HPyV7 early and capsid proteins were abundantly expressed in affected tissues. We describe for the first time that HPyV7 is associated with novel pathogenicity in some immunosuppressed individuals. | 25,231,015 | [
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High-level secretory expression and purification of unhydroxylated human collagen α1(III) chain in Pichia pastoris GS115. | Recombinant collagen and gelatin have been applied in biomedical materials field because of products from genetically engineered microorganisms with improved safety, traceability, reproducibility, and homogeneous quality. To obtain high-level secretory expression of single-chain full-length human collagen α1(III) chain (COL3A1) without the N and C telopeptides, the cDNA coding for the human COL3A1 gene was cloned into the secretory expression vector pPIC9K and integrated into Pichia pastoris GS115. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting analysis of culture supernatant from the recombinant methylotrophic yeast suggested that the unhydroxylated recombinant human COL3A1 (rhCOL3A1) was secreted into the culture medium, and exhibited an apparent molecular mass of approximately 130 kDa, which is 1.4 times higher than the theoretical one. Finally, the unhydroxylated rhCOL3A1 was purified to greater than 90% purity using a four-step approach. In addition, methylthiazolydiphenyl-tetrazolium bromide experiments indicated that low concentration of rhCOL3A1 could promote Baby hamster kidney cell (BHK21) proliferation effectively. The production and purification of rhCOL3A1 described in this study offer a new method for obtaining high level of rhCOL3A1 in relatively pure form, which is suitable for biomedical materials application. | 25,231,012 | [
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Robotic single-site hysterectomy: two institutions' preliminary experience. | To evaluate the feasibility, safety and peri- and postoperative outcomes of robotic single-site hysterectomy for gynaecological diseases. We studied 45 patients who underwent robotic single-site hysterectomy for benign and malignant disease at two institutions during May 2012-June 2013. We evaluated whether any correlation exists between BMI, patient's height, uterine size, operative time and blood loss, comparing the outcomes between the two centres. The mean operative and console times were 134 ± 36 and 93 ± 29 min, respectively, with no significant difference between the centres (p = 0.09; p = 0.08). The mean intra-operative blood losses were 53 ± 45 and 33 ± 44 ml, respectively (p = 0.15). We observed a low rate of complications. Robotic single-site hysterectomy is feasible and safe and allows for optimal postoperative pain control and improved cosmetic results. This technique also seems to be successful in obese patients and in patients with a large uterine size. | 25,231,021 | [
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The ratio of acetate-to-glucose oxidation in astrocytes from a single 13C NMR spectrum of cerebral cortex. | The (13) C-labeling patterns in glutamate and glutamine from brain tissue are quite different after infusion of a mixture of (13) C-enriched glucose and acetate. Two processes contribute to this observation, oxidation of acetate by astrocytes but not neurons, and preferential incorporation of α-ketoglutarate into glutamate in neurons, and incorporation of α-ketoglutarate into glutamine in astrocytes. The acetate:glucose ratio, introduced previously for analysis of a single (13) C NMR spectrum, provides a useful index of acetate and glucose oxidation in the brain tissue. However, quantitation of relative substrate oxidation at the cell compartment level has not been reported. A simple mathematical method is presented to quantify the ratio of acetate-to-glucose oxidation in astrocytes, based on the standard assumption that neurons do not oxidize acetate. Mice were infused with [1,2-(13) C]acetate and [1,6-(13) C]glucose, and proton decoupled (13) C NMR spectra of cortex extracts were acquired. A fit of those spectra to the model indicated that (13) C-labeled acetate and glucose contributed approximately equally to acetyl-CoA (0.96) in astrocytes. As this method relies on a single (13) C NMR spectrum, it can be readily applied to multiple physiologic and pathologic conditions. Differences in (13) C labeling of brain glutamate and glutamine have been attributed to metabolic compartmentation. The acetate:glucose ratio, introduced for description of a (13) C NMR (nuclear magnetic resonance) spectrum, is an index of glucose and acetate oxidation in brain tissue. A simple mathematical method is presented to quantify the ratio of acetate-to-glucose oxidation in astrocytes from a single NMR spectrum. As kinetic analysis is not required, the method is readily applicable to analysis of tissue extracts. α-KG = alpha-ketoglutarate; CAC = citric acid cycle; GLN = glutamine; GLU = glutamate. | 25,231,025 | [
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Rehabilitation of irradiated patients with chemically modified and conventional SLA implants: five-year follow-up. | The aim of this study is to evaluate the clinical and radiological parameters of standard SLA surface implants compared to chemically modified hydrophilic SLActive implants in irradiated patients after the initial 12-month loading period up to 5 years. Twenty patients with a mean age of 61·1 years were treated with dental implants after ablative surgery and radio-chemotherapy of oral cancer. All patients were non-smokers. The placement of 102 implants (50 SLA, 52 SLActive) was performed bilaterally according to a split-mouth design. Mean crestal bone changes were evaluated using standardised orthopantomographies and clinical parameters. Data were analysed using a Kaplan-Meier curve, Mann-Whitney U-test and two-factorial non-parametric analysis. The average observation period was 60 months. The amount of bone loss at the implant shoulder of SLA implants was mesial and distal 0·7 mm. The SLActive implants displayed a bone loss of mesial 0·6 mm as well as distal 0·7 mm after 5 years. Two SLA implants were lost before loading. One patient lost five implants due to recurrence of a tumour. The overall cumulative 12-month, 3-year and 5-year survival rate of SLA implants was 92%, 80% and 75·8% and of SLActive implants 94·2%, 78·8% and 74·4%, respectively. Eighteen implants were considered lost because the patients had died. Sandblasted acid-etched implants with or without a chemically modified surface can be used in irradiated patients with a high predictability of success. Lower implant survival rates in patients with irradiated oral cancer may be associated with systemic effects rather than peri-implantitis. | 25,231,029 | [
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Association of physical properties and maintenance of sterility of primary teeth in human tooth bank. | This study was carried out to evaluate the sterility and structural integrity of stored primary teeth in artificial saliva over a storage period of 12 weeks (3 months) in human tooth bank (HTB). A total of 80 freshly extracted teeth were taken and were categorized into four groups of 20 each. The samples were stored at 4°C for 12 weeks (3 months) in the refrigerator. During their storage time of 3 months, they were repetitively evaluated for their sterility, enamel hardness, calcium and phosphate solubility and color stability at regular intervals of 3 weeks. That teeth stored in artificial saliva maintained their sterility throughout the storage time of 12 weeks, but changes in their physical and chemical properties occurred with an increase in storage time. Storage time not more than 9 weeks is recommended for deciduous teeth to be stored in artificial saliva in a HTB. | 25,231,034 | [
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Obsessive compulsive disorder in dental setting. | Globally, 20% of children and adolescents suffer from a disabling psychologic illness. Among these, Obsessive Compulsive Disorder (OCD) is listed by the World Health Organization (WHO) as one of the 10 most disabling conditions, with prevalence rates of OCD in children ranging between 1 to 3%. Pediatric dentists are in a unique position to diagnose psychological problems in children and adolescents due to their ongoing relationship with children and their parents that starts at a very early age. Timely diagnosis of psychological illness can result in early intervention as well as better patient management for the dentist too. The purpose of this case report is to highlight a case of OCD in an adolescent girl diagnosed in a dental setting. | 25,231,042 | [
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Type III B dens invaginatus: diagnostic and clinical considerations using 128-slice computed tomography. | Endodontic therapy is successful only when thorough knowledge of root canal morphology is understood. Dens invaginatus is malformation of teeth resulting from invagination of tooth before biological mineralization occurs. It is clinically significant with an early pulpal involvement and chronic periapical lesion, which are often associated with this anomaly. The present case report describes a 13-year-old female patient who reported to our institution with complaint of pain and swelling in the right maxillary region. Intraoral examination revealed Ellis Type II fracture of right maxillary central incisor and normal appearing right maxillary lateral incisor. On radiographic examination right maxillary, lateral incisor roots are morphologically altered with an immature apex and a large periradicular lesion. Conventional radiographs help in the assessment of complex root morphology, but certain limitations pertaining to detail of complexity needs for the use of more advance imaging modalities. Complex anatomic variations can best be diagnosed with the use of computed tomography (CT). A combined endodontic and surgical treatment was performed followed by postobturation CT images which were reviewed as axial slices and in volume rendering multiplanar reconstruction. The scope of using spiral CT in the endodontic diagnosis and treatments is increasing as it provides better resolution than other methods. | 25,231,045 | [
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What makes people sick? Burmese refugee children's perceptions of health and illness. | Understanding children's perceptions of health and illness is important for health promotion so that age-appropriate health care services and preventative health programs can be developed. In this article, we discuss the perceptions and experiences of health and illness among refugee children, their health knowledge and ways they regain their health when ill. In-depth interviewing and the drawing methods were employed. Twelve Burmese refugee children, aged between 8 and 12 years, were interviewed individually. The children were knowledgeable about what keeps them healthy and what makes them ill, yet they had difficulties in providing appropriate explanations. The children employed more of the professional model in their attempt to understand health and illness. This may be due to the acculturation process that the children have absorbed in their new homeland. This article contributes to limited literature on the health of refugee children. Our results may be used for the implementation of specific health education/promotion programs for refugee children. Our findings are also useful for the provision of sensitive health care for children of refugee backgrounds in Australia and elsewhere. | 25,231,057 | [
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Role of the conformational flexibility of evodiamine in its binding to protein hosts: a comparative spectroscopic and molecular modeling evaluation with rutaecarpine. | Spectroscopic studies combined with computational analysis indicate the inherent conformational flexibility of the β-carbolin derivative evodiamine (EVD) featured with diverse pharmacological activities. Qualitative evaluation of the circular dichroism (CD) spectra of EVD enantiomers complemented with quantum chemical calculations reveals a chiral exciton signature that can be assigned to the folded, L-shaped conformation of the molecule. Changes of the exciton couplet measured in different solvents and the near-UV CD profile upon binding to human serum albumin (HSA) refer to the structural adaptability of EVD. The enantioselectivity of EVD-HSA interaction is demonstrated showing the binding preference of the (R)-enantiomer. Comparison of experimental and calculated CD spectra of various conformers of EVD as well as the results of molecular docking data suggest that the (R)-antipode is accomodated within the IIA subdomain of HSA in ridge-tile conformation. Rutaecarpine (RTC), the close congener of EVD, forms much tighter association complexes both with HSA and α1-acid glycoprotein. In contrast to EVD, the nearly planar geometry of the indoloquinazoline ring system of RTC allows its stacked dimeric binding to the HSA. | 25,231,059 | [
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Gene network analysis: from heart development to cardiac therapy. | Networks offer a flexible framework to represent and analyse the complex interactions between components of cellular systems. In particular gene networks inferred from expression data can support the identification of novel hypotheses on regulatory processes. In this review we focus on the use of gene network analysis in the study of heart development. Understanding heart development will promote the elucidation of the aetiology of congenital heart disease and thus possibly improve diagnostics. Moreover, it will help to establish cardiac therapies. For example, understanding cardiac differentiation during development will help to guide stem cell differentiation required for cardiac tissue engineering or to enhance endogenous repair mechanisms. We introduce different methodological frameworks to infer networks from expression data such as Boolean and Bayesian networks. Then we present currently available temporal expression data in heart development and discuss the use of network-based approaches in published studies. Collectively, our literature-based analysis indicates that gene network analysis constitutes a promising opportunity to infer therapy-relevant regulatory processes in heart development. However, the use of network-based approaches has so far been limited by the small amount of samples in available datasets. Thus, we propose to acquire high-resolution temporal expression data to improve the mathematical descriptions of regulatory processes obtained with gene network inference methodologies. Especially probabilistic methods that accommodate the intrinsic variability of biological systems have the potential to contribute to a deeper understanding of heart development. | 25,231,088 | [
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Sphingosine kinase 1 (Sphk1) negatively regulates platelet activation and thrombus formation. | Sphingosine 1-phosphate (S1P) is a powerful regulator of platelet formation. Enzymes generating S1P include sphingosine kinase 1. The present study thus explored the role of sphingosine kinase 1 in platelet formation and function. Activation-dependent platelet integrin αIIbβ3 activation and secretion of platelets lacking functional sphingosine kinase 1 (sphk1(-/-)) and of wild-type platelets (sphk1(+/+)) were determined utilizing flow cytometry and chronolume luciferin assay. Cytosolic Ca(2+) activity ([Ca(2+)]i) and aggregation were measured using fura-2 fluorescence and aggregometry, respectively. In vitro platelet adhesion and thrombus formation were evaluated using a flow chamber with shear rates of 1,700 s(-1). Activation-dependent increase of [Ca(2+)]i, degranulation (release of alpha and dense granules), integrin αIIbβ3 activation, and aggregation were all significantly increased in sphk1(-/-) platelets compared with sphk1(+/+) platelets. Moreover, while platelet adhesion and thrombus formation under arterial shear rates were significantly augmented in Sphk1-deficient platelets, bleeding time and blood count were unaffected in sphk1(-/-) mice. In conclusion, sphingosine kinase 1 is a powerful negative regulator of platelet function counteracting degranulation, aggregation, and thrombus formation. | 25,231,106 | [
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Placental mesenchymal stem cells of fetal origin deposit epigenetic alterations during long-term culture under serum-free condition. | Fetal placental mesenchymal stem cells (fPMSCs) have shown promising cell therapy potentials. However, their genetic and epigenetic stability during in vitro propagation has not been well studied. We thus interrogated the methylation alterations and tumorigenicity of fPMSCs after in vitro expansion using serum-free medium. The properties of fPMSCs cultured in a serum-free medium at passage 3 and passage 8 were ascertained by determining their MSC markers, proliferative capacity, chromosomal stability, activity of global DNA methyltransferases and methylation profile. Their potential of malignant transformation was also evaluated in a severe combined immunodeficiency (SCID) murine model. The fPMSCs could maintain their MSC characteristics but quickly reached a senescent state of proliferation during in vitro expansion. 246 genes with differential DNA methylation of promoters were identified, along with a significantly downregulated global DNA methyltransferase activity. The genes associated with aging and tumorigenesis had a significantly demethylated tendency over in vitro propagation. However, the deposition of epigenetic alterations did not translate into malignant transformation in SCID mice. The fPMSCs cultured in serum-free medium have a tendency to deposit methylation modifications over in vitro expansion, therefore the detection of genetic and/or epigenetic alterations is necessary for fPMSCs before they are employed for clinical uses. | 25,231,124 | [
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Gleason drift in the NIHR ProtecT study. | There is increasing evidence of Gleason score (GS) drift in prostatic core biopsies during the last two decades. The ProtecT study is a randomized controlled study and provides an excellent cohort to study the effect of time, prostate-specific antigen (PSA) level, perineural invasion, tumour length and age on GS. The ProtecT study recruited men in the United Kingdom between 1999 and 2010. The Gleason scores were grouped into four categories ≤ 3 + 3, 3 + 4, 4 + 3 and ≥ 4 + 4 for analysis. Data from England between 2000 and 2012 were also available. A total of 3282 biopsies containing cancer were analysed. For each year of the ProtecT study, the odds of being diagnosed with a higher GS category increased by 4.9%. Higher GS was also associated with perineural invasion, increasing tumour length, age and PSA level. While biopsy GS from England was incomplete, it also showed a marked decrease in GS five and six tumours during the same period. There was GS drift from 3 + 3 to 3 + 4 with time in the ProtecT study, but there appeared to be no significant change in percentage of GS 4 + 3 or higher. This drift was less dramatic when compared to GS in the rest of England. | 25,231,130 | [
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The 24-year clinical performance of porcelain laminate veneer restorations bonded with a two-liquid silane primer and a tri-n-butylborane-initiated adhesive resin. | This report describes the bonding technique and clinical course of porcelain laminate veneer restorations applied to discolored maxillary incisors and canines. The patient was an 18-year-old woman, and tooth reduction was limited to the enamel. Laminate veneer restorations were made with a feldspathic porcelain material (Cosmotech Porcelain). After try-in, enamel surfaces were etched with 65% phosphoric acid gel, and a tri-n-butylborane-initiated resin (Super-Bond C&B) was applied as a bonding agent. The inner surface of the restorations was etched with 5% hydrofluoric acid gel (HF Gel) and treated with a two-liquid silane primer (Porcelain Liner M), after which the Super-Bond resin was applied. Each restoration was seated with a dual-activated composite luting agent (Cosmotech Composite). After 24 years and 8 months, the restorations are functioning satisfactorily. The luting system and bonding technique described in this report are an option for seating laminate veneer restorations made of silica-based tooth-colored ceramics. | 25,231,150 | [
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New suture materials for midline laparotomy closure: an experimental study. | Midline laparotomy closure carries a significant risk of incisional hernia. This study examines the behavior of two new suture materials, an elastic material, polyurethane (PUe), and a barbed polydioxanone (PDXb) suture thread in a rabbit model of midline incision closure. Three 2-cm midline incisions were made in 68 New Zealand White rabbits. The incisions were closed by running suture using four 3/0 threads: polypropylene (PP) (Surgipro®, Covidien), PUe (Assuplus®, Assut Europe), PDX (Assufil®, Assut Europe) or PDXb (Filbloc®, Assut Europe). Animals in each suture group were euthanized 3 weeks and 6 months after surgery. Histological sections of the tissue-embedded sutures were subjected to morphological, collagen expression, macrophage response and uniaxial tensiometry studies. No signs of wound dehiscence or complications were observed. At 3 weeks, all sutures were surrounded by connective tissue composed mainly of collagen III. PUe showed greater collagen I expression than the other sutures. All sutures elicited a macrophage response that diminished from 3 weeks to 6 months (p < 0.001). This response was similar for the non-reabsorbable sutures (PP and PUe) yet PDXb showed a significantly greater response than the other reabsorbable suture (PDX) at 3 weeks (p < 0.01). At this early time point, the tensile strength of PUe was similar to that of control intact tissue (p > 0.05). Three weeks after surgery, PUe revealed more collagen I deposition than the remaining materials and this translated to a similar biomechanical behavior to linea alba, that could avoid the appearance of short term dehiscences and thus reduce the incidence of incisional hernia. PDXb provides no additional advantages in their behavior regarding PDX suture. | 25,231,161 | [
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Laparoscopic microwave ablation of human liver tumours using a novel three-dimensional magnetic guidance system. | Accurate antenna placement is essential for effective microwave ablation (MWA) of lesions. Laparoscopic targeting is made particularly challenging in liver tumours by the needle's trajectory as it passes through the abdominal wall into the liver. Previous optical three-dimensional guidance systems employing infrared technology have been limited by interference with the line of sight during procedures. The aim of this study was to evaluate a newly developed magnetic guidance system for laparoscopic MWA of liver tumours in a pilot study. Thirteen patients undergoing laparoscopic MWA of liver tumours gave consent to their participation in the study and were enrolled. Lesion targeting was performed using the InnerOptic AIM™ 3-D guidance system to track the real-time position and orientation of the antenna and ultrasound probe. A total of 45 ablations were performed on 34 lesions. The median number of lesions per patient was two. The mean ± standard deviation lesion diameter was 18.0 ± 9.2 mm and the mean time to target acquisition was 3.5 min. The first-attempt success rate was 93%. There were no intraoperative or immediate postoperative complications. Over an average follow-up of 7.8 months, one patient was noted to have had an incomplete ablation, seven suffered regional recurrences, and five patients remained disease-free. The AIM™ guidance system is an effective adjunct for laparoscopic ablation. It facilitates a high degree of accuracy and a good first-attempt success rate, and avoids the line of site interference associated with infrared systems. | 25,231,167 | [
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Full-genome identification and characterization of NBS-encoding disease resistance genes in wheat. | Host resistance is the most economical, effective and ecologically sustainable method of controlling diseases in crop plants. In bread wheat, despite the high number of resistance loci that have been cataloged to date, only few have been cloned, underlying the need for genomics-guided investigations capable of providing a prompt and acute knowledge on the identity of effective resistance genes that can be used in breeding programs. Proteins with a nucleotide-binding site (NBS) encoded by the major plant disease resistance (R) genes play an important role in the responses of plants to various pathogens. In this study, a comprehensive analysis of NBS-encoding genes within the whole wheat genome was performed, and the genome scale characterization of this gene family was established. From the recently published wheat genome sequence, we used a data mining and automatic prediction pipeline to identify 580 complete ORF candidate NBS-encoding genes and 1,099 partial-ORF ones. Among complete gene models, 464 were longer than 200 aa, among them 436 had less than 70 % of sequence identity to each other. This gene models set was deeply characterized. (1) First, we have analyzed domain architecture and identified, in addition to typical domain combinations, the presence of particular domains like signal peptides, zinc fingers, kinases, heavy-metal-associated and WRKY DNA-binding domains. (2) Functional and expression annotation via homology searches in protein and transcript databases, based on sufficient criteria, enabled identifying similar proteins for 60 % of the studied gene models and expression evidence for 13 % of them. (3) Shared orthologous groups were defined using NBS-domain proteins of rice and Brachypodium distachyon. (4) Finally, alignment of the 436 NBS-containing gene models to the full set of scaffolds from the IWGSC's wheat chromosome survey sequence enabled high-stringence anchoring to chromosome arms. The distribution of the R genes was found balanced on the three wheat sub-genomes. In contrast, at chromosome scale, 50 % of members of this gene family were localized on 6 of the 21 wheat chromosomes and ~22 % of them were localized on homeologous group 7. The results of this study provide a detailed analysis of the largest family of plant disease resistance genes in allohexaploid wheat. Some structural traits reported had not been previously identified and the genome-derived data were confronted with those stored in databases outlining the functional specialization of members of this family. The large reservoir of NBS-type genes presented and discussed will, firstly, form an important framework for marker-assisted improvement of resistance in wheat, and, secondly, open up new perspectives for a better understanding of the evolution dynamics of this gene family in grass species and in polyploid systems. | 25,231,182 | [
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Differential impact of unrecognised brain infarction on stroke outcome in non-valvular atrial fibrillation. | There has been little information regarding the impact of unrecognised brain infarctions (UBIs) on stroke outcome in patients with non-valvular atrial fibrillation (NVAF). By using volumetric analysis of ischaemic lesions, we evaluated the potential impact of UBIs on clinical outcome according to their presence and categorised type. This study enrolled 631 patients with NVAF having no clinical stroke history. UBIs were categorised into three types as territorial, lacunar, or subcortical. We collected stroke severity, functional outcome at three months, and the total volume of UBIs and acute infarction lesions. We investigated the association between clinical outcome and the type or volume of UBI, using a linear mixed model and logistic regression analysis. UBIs were detected in 285 (45.2 %) patients; territorial UBIs were observed in 24.4 % of patients (154/631), lacunar UBIs in 25 % (158/631), and subcortical UBIs in 15.7 % (99/631). Although initial stroke severity was not different between patients with UBIs and those without, those with UBIs had less improvement during hospitalisation, leading to poorer outcome at three months. Among the three types of UBIs, only territorial UBIs were associated with poor outcome, especially in patients with relatively smaller acute infarction volume. UBIs, in particular, territorial UBIs, may be considered as predictors for poor outcome after ischaemic stroke in patients with NVAF. Our results suggest that the impact of UBIs on clinical outcome differs according to the type of UBIs and the acute stroke severity. | 25,231,184 | [
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Clinicopathologic characteristics of breast cancer in BRCA-carriers and non-carriers in women 35 years of age or less. | Breast cancer diagnosed in women 35 years of age or less accounts for <2% of all breast cancer cases. Clinical and pathologic characteristics of early onset breast cancer are not well defined in BRCA mutation carriers and non-carriers. 194 women diagnosed with breast cancer at 35 years of age or less who had BRCA1/2 mutation testing were included in the study. Logistic regression models were fit to determine the associations between clinical variables and BRCA status. Thirty-two (17%) and 12 (6%) patients had BRCA1 and BRCA2 mutations, respectively. BRCA1-carriers had a higher likelihood of a positive family history (FH) of breast and/or ovarian cancer (P = 0.001), or first-degree relatives diagnosed with breast cancer at <50 years old (P = 0.001) compared to non-carriers. BRCA2-carriers were more likely to have a FH of male breast cancer compared to noncarriers (P = 0.02). Among BRCA2-carriers, the age at first full-term pregnancy was younger in ER-negative cases compared with ERpositive cases (19.5 vs. 28.5 years old; P = 0.01). BRCA1-carriers with a later age at menarche were more likely to have a later stage at diagnosis (P = 0.04). Non-carriers with a lower BMI were more likely to have lymph node involvement (P = 0.03). Several associations were identified between reproductive risk factors or BMI and disease characteristics. Further characterization may result in a better understanding of the trends in young onset breast cancer in BRCA-carriers and non-carriers. | 25,231,195 | [
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Directional hearing: from biophysical binaural cues to directional hearing outdoors. | When insects communicate by sound, or use acoustic cues to escape predators or detect prey or hosts they have to localize the sound in most cases, to perform adaptive behavioral responses. In the case of particle velocity receivers such as the antennae of mosquitoes, directionality is no problem because such receivers are inherently directional. Insects equipped with bilateral pairs of tympanate ears could principally make use of binaural cues for sound localization, like all other animals with two ears. However, their small size is a major problem to create sufficiently large binaural cues, with respect to both interaural time differences (ITDs, because interaural distances are so small), but also with respect to interaural intensity differences (IIDs), since the ratio of body size to the wavelength of sound is rather unfavorable for diffractive effects. In my review, I will only shortly cover these biophysical aspects of directional hearing. Instead, I will focus on aspects of directional hearing which received relatively little attention previously, the evolution of a pressure difference receiver, 3D-hearing, directional hearing outdoors, and directional hearing for auditory scene analysis. | 25,231,204 | [
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Detection of gastric precancerous conditions in daily clinical practice: a nationwide survey. | The burden of gastric precancerous conditions and factors associated with their detection have not been fully investigated in community-based settings. Little is known about adherence to Sydney system for histopathology of gastric biopsies. We aimed to investigate what really happens in clinical practice with regard to the detection of gastric atrophy and intestinal metaplasia in dyspeptic patients. We performed a nationwide survey of 979 consecutive patients (50-65 years old) with dyspeptic symptoms, examined at 24 gastrointestinal endoscopy units throughout Italy. Clinical information was collected from questionnaires; a standard bioptic mapping was performed in each unit, biopsies from each patient were analyzed by histopathology performed according to daily clinical practice in each local histopathology center. Separate descriptions of antral and corporal biopsies were included in 679 pathology reports (69%), whereas Sydney system was applied in 324 reports (33%). Gastric atrophy without intestinal metaplasia (GA) and gastric atrophy with intestinal metaplasia (GIM) were detected in 322 (33%) patients. The full adherence to Sydney system significantly increased the probability of detecting GIM (OR 9.6, 95% CI 5.5-16.7), GA (OR 1.92, 95% CI 1.07-3.44), and either of the conditions (OR 6.67, 95% CI 4.36-10.19). This nationwide survey showed that in one-third of dyspeptic patients, gastric precancerous conditions are detected. In daily routine practice, only 1/3 of histology reports were worked out adhering to Sydney system showing that international guidelines are poorly observed in clinical practice. This may represent a critical element for surveillance strategies for gastric cancer. | 25,231,208 | [
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Lacrimal disorders and surgery: historical perspectives. | The history and evolution of lacrimal surgeries has been a fascinating journey. And yet, as we move forward on this path in time, it appears not to have attracted students in sufficient numbers. This article provides a comprehensive history of surgical interventions for lacrimal disorders spanning the ancient and medieval eras as well as its snapshot in modern times. The article also acquaints the readers with both lacrimal surgeons of the early days and important treatises on lacrimal surgery that together contributed to its advancement. | 25,231,209 | [
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Gluten-free dough-making of specialty breads: Significance of blended starches, flours and additives on dough behaviour. | The capability of different gluten-free (GF) basic formulations made of flour (rice, amaranth and chickpea) and starch (corn and cassava) blends, to make machinable and viscoelastic GF-doughs in absence/presence of single hydrocolloids (guar gum, locust bean and psyllium fibre), proteins (milk and egg white) and surfactants (neutral, anionic and vegetable oil) have been investigated. Macroscopic (high deformation) and macromolecular (small deformation) mechanical, viscometric (gelatinization, pasting, gelling) and thermal (gelatinization, melting, retrogradation) approaches were performed on the different matrices in order to (a) identify similarities and differences in GF-doughs in terms of a small number of rheological and thermal analytical parameters according to the formulations and (b) to assess single and interactive effects of basic ingredients and additives on GF-dough performance to achieve GF-flat breads. Larger values for the static and dynamic mechanical characteristics and higher viscometric profiles during both cooking and cooling corresponded to doughs formulated with guar gum and Psyllium fibre added to rice flour/starch and rice flour/corn starch/chickpea flour, while surfactant- and protein-formulated GF-doughs added to rice flour/starch/amaranth flour based GF-doughs exhibited intermediate and lower values for the mechanical parameters and poorer viscometric profiles. In addition, additive-free formulations exhibited higher values for the temperature of both gelatinization and retrogradation and lower enthalpies for the thermal transitions. Single addition of 10% of either chickpea flour or amaranth flour to rice flour/starch blends provided a large GF-dough hardening effect in presence of corn starch and an intermediate effect in presence of cassava starch (chickpea), and an intermediate reinforcement of GF-dough regardless the source of starch (amaranth). At macromolecular level, both chickpea and amaranth flours, singly added, determined higher values of the storage modulus, being strengthening effects more pronounced in presence of corn starch and cassava starch, respectively. | 25,231,269 | [
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Effects of semi-group housing and floor type on pododermatitis, spinal deformation and bone quality in rabbit does. | The most common housing system for reproduction rabbits, individual cage housing on a wire floor, is increasingly scrutinized because of its potential detrimental impact on animal welfare. We compared three types of housing: (1) individual cage housing on a wire floor (3952 cm2/doe, maximum roof height 63 cm, one 1000 cm2 plastic footrest/doe), (2) semi-group housing on a wire floor (5000 cm2/doe, roofless, one 1000 cm2 plastic footrest/doe) and (3) the same semi-group housing, but with a fully plastic slatted floor. In all housing systems, does had free access to an elevated platform. In the semi-group housing pens, four does were housed communally during 21 days of the reproduction cycle (to allow more space for locomotion and to increase opportunities for social contact), and individually during the other 21 days of the cycle (to minimize doe-doe and doe-kit aggression that peaks around kindling). In all, 24 Hycole does were included per system. The does entered the experiment at 203 days of age (after their first parity). The experiment consisted of four reproductive cycles, ending at 369 days of age. Pododermatitis was scored in cycles 1, 2 and 4. At the end of the 4th cycle the does were euthanized and X-rays were taken to assess spinal deformation. Tibia and femur length, width and cortical thickness were determined and bone strength was assessed using a shear test, as a measure of bone quality. Although severe pododermatitis was absent, the prevalence of plantar hyperkeratosis (hair loss and callus formation) at the end of the 4th cycle was much greater on the wire floor (65% and 68% for semi-group housing and individual cages, respectively) than on the plastic floor (5%, P<0.0001), even though the wire floors were equipped with a plastic footrest known to decrease hyperkeratosis. In contrast to our expectations, semi-group housing did not affect the prevalence of spinal deformations (P>0.10), but in line with our expectations bone quality was affected favourably by semi-group housing. The tibial cortex (and to a lesser extent the femoral cortex) was thicker in semi-group housing than in individual cages (1.45, 1.46 and 1.38 mm for semi-group housing on wire, semi-group housing on plastic and individual housing on wire, respectively, P=0.045). What this increase in cortical thickness means in terms of doe welfare requires further study, as it may reflect an increase in activity resulting either from increased space for locomotion, or from fleeing aggressive pen mates. | 25,231,283 | [
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Crystal structure of herpes simplex virus 2 gD bound to nectin-1 reveals a conserved mode of receptor recognition. | Herpes simplex virus 1 (HSV-1) and HSV-2 are among the most prevalent human pathogens. Both viruses can recognize, via the surface envelope glycoprotein D (gD), human nectin-1 as a functional receptor. Previous studies have successfully elucidated the molecular basis of the binding between HSV-1 gD and nectin-1 by cocrystallography. Despite a high sequence identity between HSV-1 and HSV-2 gDs, the atomic intermolecule details for the HSV-2-gD/nectin-1 interaction remain elusive. Here, we report the crystal structures of both the unbound and the nectin-1-bound HSV-2 gDs. The free-gD structure expectedly comprises an IgV-like core and the surface-exposed terminal extensions as observed in its HSV-1 counterpart but lacks traceable electron densities for a large portion of the terminal elements. These terminal residues were clearly traced in the complex structure as a definitive loop in the N terminus and an α-helix in the C terminus, thereby showing a conserved nectin-1-binding mode as reported for HSV-1 gD. The interface residues in nectin-1 were further mutated and tested for the gD interaction by surface plasmon resonance. The resultant binding patterns were similar for HSV-1 and HSV-2 gDs, further supporting a homologous receptor-binding basis by the two viruses for nectin-1. These data, together with a cell-based fusion assay showing a cross-inhibition of the gD/nectin-1-mediated cell-cell fusion by soluble HSV-1 and HSV-2 gDs, provided solid structural and functional evidence that HSV-1 and HSV-2 recognize nectin-1 via the same binding mode. Finally, we also demonstrated that nectin-1 I80 is an important residue involved in gD interaction. Despite intensified studies, a detailed picture of the molecular features in the HSV-2-gD/nectin-1 interaction remains unavailable. Previous work focused on HSV-1 gD, which folds into an IgV-like core with large terminal extensions and utilizes the extension elements to engage nectin-1. Here, we report the crystal structures of HSV-2 gD in both the free and the nectin-1-bound forms. The atomic intermolecule details for HSV-2-gD/nectin-1 interaction are clearly presented. The observed binding mode is identical to that reported for its HSV-1 counterpart. This structural observation was further supported by our comparative functional assays showing that nectin-1 mutations similarly affect the ligand-receptor interaction of both virus gDs. Taken together, we provide comprehensive structural and functional data demonstrating a conserved receptor-binding mode between HSV-1 and HSV-2 for nectin-1. Our results also indicate that the tropism difference between the two viruses likely arises from aspects other than the gD/nectin-1 binding features. | 25,231,300 | [
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Elephant endotheliotropic herpesviruses EEHV1A, EEHV1B, and EEHV2 from cases of hemorrhagic disease are highly diverged from other mammalian herpesviruses and may form a new subfamily. | A family of novel endotheliotropic herpesviruses (EEHVs) assigned to the genus Proboscivirus have been identified as the cause of fatal hemorrhagic disease in 70 young Asian elephants worldwide. Although EEHV cannot be grown in cell culture, we have determined a total of 378 kb of viral genomic DNA sequence directly from clinical tissue samples from six lethal cases and two survivors. Overall, the data obtained encompass 57 genes, including orthologues of 32 core genes common to all herpesviruses, 14 genes found in some other herpesviruses, plus 10 novel genes, including a single large putative transcriptional regulatory protein (ORF-L). On the basis of differences in gene content and organization plus phylogenetic analyses of conserved core proteins that have just 20% to 50% or less identity to orthologues in other herpesviruses, we propose that EEHV1A, EEHV1B, and EEHV2 could be considered a new Deltaherpesvirinae subfamily of mammalian herpesviruses that evolved as an intermediate branch between the Betaherpesvirinae and Gammaherpesvirinae. Unlike cytomegaloviruses, EEHV genomes encode ribonucleotide kinase B subunit (RRB), thymidine kinase (TK), and UL9-like origin binding protein (OBP) proteins and have an alphaherpesvirus-like dyad symmetry Ori-Lyt domain. They also differ from all known betaherpesviruses by having a 40-kb large-scale inversion of core gene blocks I, II, and III. EEHV1 and EEHV2 DNA differ uniformly by more than 25%, but EEHV1 clusters into two major subgroups designated EEHV1A and EEHV1B with ancient partially chimeric features. Whereas large segments are nearly identical, three nonadjacent loci totaling 15 kb diverge by between 21 and 37%. One strain of EEHV1B analyzed is interpreted to be a modern partial recombinant with EEHV1A. Asian elephants are an endangered species whose survival is under extreme pressure in wild range countries and whose captive breeding populations in zoos are not self-sustaining. In 1999, a novel class of herpesviruses called EEHVs was discovered. These viruses have caused a rapidly lethal hemorrhagic disease in 20% of all captive Asian elephant calves born in zoos in the United States and Europe since 1980. The disease is increasingly being recognized in Asian range countries as well. These viruses cannot be grown in cell culture, but by direct PCR DNA sequence analysis from segments totaling 15 to 30% of the genomes from blood or necropsy tissue from eight different cases, we have determined that they fall into multiple types and chimeric subtypes of a novel Proboscivirus genus, and we propose that they should also be classified as the first examples of a new mammalian herpesvirus subfamily named the Deltaherpesvirinae. | 25,231,303 | [
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The conserved disulfide bond within domain II of Epstein-Barr virus gH has divergent roles in membrane fusion with epithelial cells and B cells. | Epstein-Barr virus (EBV) infects target cells via fusion with cellular membranes. For entry into epithelial cells, EBV requires the herpesvirus conserved core fusion machinery, composed of glycoprotein B (gB) and gH/gL. In contrast, for B cell fusion it requires gB and gH/gL with gp42 serving as a cell tropism switch. The available crystal structures for gH/gL allow the targeted analysis of structural determinants of gH to identify functional regions critical for membrane fusion. Domain II of EBV gH contains two disulfide bonds (DBs). The first is unique for EBV and closely related gammaherpesviruses. The second is conserved across the beta- and gammaherpesviruses and is positioned to stabilize a putative syntaxin-like bundle motif. To analyze the role of these DBs in membrane fusion, gH was mutated by amino acid substitution of the DB cysteines. Mutation of the EBV-specific DB resulted in diminished gH/gL cell surface expression that correlated with diminished B cell and epithelial cell fusion. In contrast, mutation of the conserved DB resulted in wild-type-like B cell fusion, whereas epithelial cell fusion was greatly reduced. The gH mutants bound well to gp42 but had diminished binding to epithelial cells. Tyrosine 336, located adjacent to cysteine 335 of the conserved DB, also was found to be important for DB stabilization and gH/gL function. We conclude that the conserved DB has a cell type-specific function, since it is important for the binding of gH to epithelial cells initiating epithelial cell fusion but not for fusion with B cells and gp42 binding. EBV predominantly infects epithelial and B cells in humans, which can result in EBV-associated cancers, such as Burkitt and Hodgkin lymphoma, as well as nasopharyngeal carcinoma. EBV is also associated with a variety of lymphoproliferative disorders, typically of B cell origin, observed in immunosuppressed individuals, such as posttransplant or HIV/AIDS patients. The gH/gL complex plays an essential but still poorly characterized role as an important determinant for EBV cell tropism. In the current studies, we found that mutants in the DB C278/C335 and the neighboring tyrosine 336 have cell type-specific functional deficits with selective decreases in epithelial cell, but not B cell, binding and fusion. The present study brings new insights into the gH function as a determinant for epithelial cell tropism during herpesvirus-induced membrane fusion and highlights a specific gH motif required for epithelial cell fusion. | 25,231,307 | [
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Comparative genome analysis of four elephant endotheliotropic herpesviruses, EEHV3, EEHV4, EEHV5, and EEHV6, from cases of hemorrhagic disease or viremia. | The genomes of three types of novel endotheliotropic herpesviruses (elephant endotheliotropic herpesvirus 1A [EEHV1A], EEHV1B, and EEHV2) associated with lethal hemorrhagic disease in Asian elephants have been previously well characterized and assigned to a new Proboscivirus genus. Here we have generated 112 kb of DNA sequence data from segments of four more types of EEHV by direct targeted PCR from blood samples or necropsy tissue samples from six viremic elephants. Comparative phylogenetic analysis of nearly 30 protein-encoding genes of EEHV5 and EEHV6 show that they diverge uniformly by nearly 20% from their closest relatives, EEHV2 and EEHV1A, respectively, and are likely to have similar overall gene content and genome organization. In contrast, seven EEHV3 and EEHV4 genes analyzed differ from those of all other EEHVs by 37% and have a G+C content of 63% compared to just 42% for the others. Three strains of EEHV5 analyzed clustered into two partially chimeric subgroups EEHV5A and EEHV5B that diverge by 19% within three small noncontiguous segments totaling 6.2 kb. We conclude that all six EEHV types should be designated as independent species within a proposed new fourth Deltaherpesvirinae subfamily of mammalian herpesviruses. These virus types likely initially diverged close to 100 million years ago when the ancestors of modern elephants split from all other placental mammals and then evolved into two major branches with high- or low-G+C content about 35 million years ago. Later additional branching events subsequently generated three paired sister taxon lineages of which EEHV1 plus EEHV6, EEHV5 plus EEHV2, and EEHV4 plus EEHV3 may represent Asian and African elephant versions, respectively. One of the factors threatening the long-term survival of endangered Asian elephants in both wild range countries and in captive breeding populations in zoos is a highly lethal hemorrhagic herpesvirus disease that has killed at least 70 young Asian elephants worldwide. The genomes of the first three types of EEHVs (or probosciviruses) identified have been partially characterized in the preceding accompanying paper (L. K. Richman, J.-C. Zong, E. M. Latimer, J. Lock, R. C. Fleischer, S. Y. Heaggans, and G. S. Hayward, J. Virol. 88:13523-13546, 2014, http://dx.doi.org/10.1128/JVI.01673-14). Here we have used PCR DNA sequence analysis from multiple segments of DNA amplified directly from blood or necropsy tissue samples of six more selected cases of hemorrhagic disease to partially characterize four other types of EEHVs from either Asian or African elephants. We propose that all six types and two chimeric subtypes of EEHV belong to multiple lineages of both AT-rich and GC-rich branches within a new subfamily to be named the Deltaherpesvirinae, which evolved separately from all other mammalian herpesviruses about100 million years ago. | 25,231,309 | [
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Vibration on board and health effects. | There is only limited knowledge of the exposure to vibrations of ships' crews and their risk of vibration-induced health effects. Exposure to hand-arm vibrations from the use of vibrating tools at sea does not differ from that in the land-based trades. However, in contrast to most other work places, seafarers are also exposed to vibrations to the feet when standing on vibrating surfaces on board. Anecdotal reports have related the development of "white feet" to local exposure to vibration, e.g. in mining, but this connection has not been investigated in the maritime setting. As known from studies of the health consequences of whole body vibrations in land-transportation, such exposure at sea may affect ships' passengers and crews. While the relation of back disorders to high levels of whole body vibration has been demonstrated among e.g. tractor drivers, there are no reported epidemiological evidence for such relation among seafarers except for fishermen, who, however, are also exposed to additional recognised physical risk factors at work. The assessment and reduction of vibrations by naval architects relates to technical implications of this impact for the ships' construction, but has limited value for the estimation of health risks because they express the vibration intensity differently that it is done in a medical context. | 25,231,326 | [
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Assessment of intelligence quotient among schoolchildren of fishermen community of Kutch, Gujarat, India. | The aim of the study was to assess the intelligence quotient of fishermen school children of Kutch, Gujarat, India. A descriptive cross-sectional study was conducted among 8 to 10 years old school children living in Kutch District, Gujarat, India, from January to February 2013. Seguin Form Board Test was used to assess the intelligence quotient (IQ) level of children. Means of groups were compared by independent student t-test. Stepwise multiple linear regression was used to identify predictors for IQ. The mean average timing taken by fishermen school children to complete the test was 30.64 ± 4.97. Males had significantly lower mean timing scores than females (p < 0.05). Participants with severe dental fluorosis, low socio-economic status (SES), lower education level of both mother and father and those who were overweight had significantly higher mean timing scores for average category. The present study suggested a low IQ among fishermen school children community of Kutch, Gujarat, India. The major factors which influenced their IQ were dental fluorosis, low SES, low education level of parents and high body mass index. | 25,231,330 | [
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In Candida albicans hyphae, Sec2p is physically associated with SEC2 mRNA on secretory vesicles. | Candida albicans hyphae grow in a highly polarized fashion from their tips. This polarized growth requires the continuous delivery of secretory vesicles to the tip region. Vesicle delivery depends on Sec2p, the Guanine Exchange Factor (GEF) for the Rab GTPase Sec4p. GTP bound Sec4p is required for the transit of secretory vesicles from the trans-Golgi to sites of polarized growth. We previously showed that phosphorylation of Sec2p at residue S584 was necessary for Sec2p to support hyphal, but not yeast growth. Here we show that on secretory vesicles SEC2 mRNA is physically associated with Sec2p. Moreover, we show that the phosphorylation of S584 allows SEC2 mRNA to dissociate from Sec2p and we speculate that this is necessary for Sec2p function and/or translation. During hyphal extension, the growing tip may be separated from the nucleus by up to 15 μm. Transport of SEC2 mRNA on secretory vesicles to the tip localizes SEC2 translation to tip allowing a sufficient accumulation of this key protein at the site of polarized growth. | 25,231,350 | [
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Chronic traumatic encephalopathy: clinical-biomarker correlations and current concepts in pathogenesis. | Chronic traumatic encephalopathy (CTE) is a recently revived term used to describe a neurodegenerative process that occurs as a long term complication of repetitive mild traumatic brain injury (TBI). Corsellis provided one of the classic descriptions of CTE in boxers under the name "dementia pugilistica" (DP). Much recent attention has been drawn to the apparent association of CTE with contact sports (football, soccer, hockey) and with frequent battlefield exposure to blast waves generated by improvised explosive devices (IEDs). Recently, a promising serum biomarker has been identified by measurement of serum levels of the neuronal microtubule associated protein tau. New positron emission tomography (PET) ligands (e.g., [18 F] T807) that identify brain tauopathy have been successfully deployed for the in vitro and in vivo detection of presumptive tauopathy in the brains of subjects with clinically probable CTE. Major academic and lay publications on DP/CTE were reviewed beginning with the 1928 paper describing the initial use of the term CTE by Martland. The major current concepts in the neurological, psychiatric, neuropsychological, neuroimaging, and body fluid biomarker science of DP/CTE have been summarized. Newer achievements, such as serum tau and [18 F] T807 tauopathy imaging, are also introduced and their significance has been explained. Recent advances in the science of DP/CTE hold promise for elucidating a long sought accurate determination of the true prevalence of CTE. This information holds potentially important public health implications for estimating the risk of contact sports in inflicting permanent and/or progressive brain damage on children, adolescents, and adults. | 25,231,386 | [
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Raising the bar for antineoplastic agents: how to choose threshold values for superiority trials in advanced solid tumors. | To establish the concept of minimum clinically meaningful outcome (mCMO) of treatment in advanced solid tumors, to establish its threshold and evaluate how many superiority trials of new antineoplastic agents pass this threshold. We chose overall survival as the primary indicator of patient benefit. Four conceptually different types of treatment effect can be identified in OS curves: HR, gains in median OS, proportional, and absolute increases at long-term OS. We postulated threshold levels for these four parameters defining the mCMO and set the bar at three different levels of required benefit: high, medium, and low. The postulated values were then studied by comparing our thresholds with the actual results of the pivotal superiority phase III trials on new drugs reporting on mature OS data. Forty-three trials on 35,419 patients in 12 cancer types on 23 novel agents met these criteria. Only two trials reached the postulated "high" thresholds for HR and median OS. The number of "positive trials" increased to eight and 15 when the bar was lowered to the "medium" and "low" levels, respectively. The same analysis was done for proportional and absolute increases in long-term OS. No trial satisfied the criteria for long-term benefit, whereas only two and nine trials satisfied both parameters for the "medium and low" required benefit levels, respectively. All four OS-related parameters contribute to define the mCMO. If the bar for the mCMO is raised too much, positive trials are exceptional. | 25,231,398 | [
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A Phase I, dose-finding study in patients with advanced solid malignancies of the oral γ-secretase inhibitor PF-03084014. | To estimate the maximum tolerated dose (MTD) for continuous oral administration of the γ-secretase inhibitor PF-03084014, determine the recommended phase II dose (RP2D), and evaluate safety and preliminary activity in patients with advanced solid tumors. This open-label, phase I study consisted of a dose-finding portion based on a 3+3 design, followed by an expansion cohort. PF-03084014 was administered orally, twice daily (BID) for 21 continuous days. Tested doses ranged from 20 to 330 mg BID. In the expansion cohort, patients were to receive the estimated MTD or a lower dose of PF-03084014. A total of 64 patients received treatment. The MTD was estimated to be 220 mg BID. The RP2D was determined to be 150 mg BID, based on the better safety profile versus the 220-mg BID dose, given comparable NOTCH-related target inhibition. The most common treatment-related adverse events were diarrhea, nausea, fatigue, hypophosphatemia, vomiting, rash, and decreased appetite, which were generally mild to moderate in severity. One patient with advanced thyroid cancer had a complete response, and five of seven response-evaluable patients with desmoid tumor achieved a partial response (71.4% objective response rate). Tumor responses were mostly durable, ranging from 1.74+ to 24+ months. PF-03084014 demonstrated a generally dose-dependent pharmacokinetic profile at doses ranging from 20 to 330 mg BID. Consistent downmodulation of NOTCH-related HES4 gene expression was observed in peripheral blood from all evaluable patients. Further development of PF-03084014 for the treatment of patients with advanced solid tumors is warranted and currently under evaluation. | 25,231,399 | [
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Ecology of grazing lawns in Africa. | Grazing lawns are a distinct grassland community type, characterised by short-stature and with their persistence and spread promoted by grazing. In Africa, they reveal a long co-evolutionary history of grasses and large mammal grazers. The attractiveness to grazers of a low-biomass sward lies in the relatively high quality of forage, largely due to the low proportion of stem material in the sward; this encourages repeat grazing that concomitantly suppresses tall-grass growth forms that would otherwise outcompete lawn species for light. Regular grazing that prevents shading and maintains sward quality is thus the cornerstone of grazing lawn dynamics. The strong interplay between abiotic conditions and disturbance factors, which are central to grazing lawn existence, can also cause these systems to be highly dynamic. Here we identify differences in growth form among grazing lawn grass species, and assess how compositional differences among lawn types, as well as environmental variables, influence their maintenance requirements (i.e. grazing frequency) and vulnerability to degradation. We also make a clear distinction between the processes of lawn establishment and lawn maintenance. Rainfall, soil nutrient status, grazer community composition and fire regime have strong and interactive influences on both processes. However, factors that concentrate grazing pressure (e.g. nutrient hotspots and sodic sites) have more bearing on where lawns establish. Similarly, we discuss the relevance of enhanced rates of nitrogen cycling and of sodium levels to lawn maintenance. Grazer community composition and density has considerable significance to grazing lawn dynamics; not all grazers are adapted to foraging on short-grass swards, and differences in body size and relative mouth dimensions determine which species are able to convert tall-grass swards into grazing lawns under different conditions. Hence, we evaluate the roles of different grazers in lawn dynamics, as well as the benefits that grazer populations derive from having access to grazing lawns. The effects of grazing lawns can extend well beyond their borders, due to their influence on grazer densities, behaviour and movements as well as fire spread, intensity and frequency. Variation in the area and proportion of a landscape that is grazing lawn can thus have a profound impact on system dynamics. We provide a conceptual model that summarises grazing lawn dynamics, and identify a rainfall range where we predict grazing lawns to be most prevalent. We also examine the biodiversity associated with grazing lawn systems, and consider their functional contribution to the conservation of this biodiversity. Finally, we assess the utility of grazing lawns as a resource in a rangeland context. | 25,231,416 | [
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Carotid Elongation Does Not Affect Angiographic Results of Mechanical Thrombectomy in Acute Stroke. | New techniques have substantially raised recanalization rates of mechanical thrombectomy in acute ischemic stroke in the last few years with initial prospective trials reporting good neurological outcome in up to 58 % of the cases. However some recent reports questioning the benefit of endovascular therapy have initiated a discussion about the importance of patient-selection. The purpose of this study was to investigate whether an elongation of the carotid artery affects the angiographic outcome of the recanalization procedure in middle cerebral artery (MCA)-occlusions. The data of 54 patients with occlusions of the M1-segment who underwent mechanical thrombectomy were included. The lengths of the carotid arteries were measured using preinterventional computed tomography (CT)-angiograms. To take individual patient's height into account these lengths were divided by the length of the spine from the tip of the dens to the bottom of the th3 vertebral body (referred to as carotid-to-spine (CS)-Ratio). Angiographic results were scored according to the modified thrombolysis in cerebral infarction (mTICI)-score. Recanalization with mTICI ≥ 2b was achieved in 83.3 %. The mean CS-Ratio was 1.32 ± 0.13. There was a significant correlation between the CS-Ratio and the age of the patients. There were no significant differences in the CS-Ratios of occlusions that were successfully recanalized and those that were not. Neither were there significant correlations of the CS-Ratio and the length of procedure or the number of deployments of the stentretrievers. In this retrospective analysis we report that carotid elongation does not affect angiographic results of mechanical thrombectomy in acute stroke. | 25,231,427 | [
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Central hypothyroidism in children. | Central congenital hypothyroidism (CCH) is an underdiagnosed disorder poorly described in childhood and adolescence. Congenital defects in thyroid-stimulating hormone (TSH) synthesis, secretion or bioactivity may lead to a state of 'regulatory' hypothyroidism expressed through aberrantly low or normal TSH levels and low thyroxine (T4), a hormonal pattern undetectable by TSH-based neonatal screening programs for congenital hypothyroidism (CH) implemented in most countries worldwide. CCH is more prevalent than previously thought, reaching 1 in 16,000 neonates in countries consistently identifying CCH through T4-based CH screening strategies. Neonatal detection and early treatment of CCH would prevent the risk of developing mental retardation secondary to late diagnosis of infantile hypothyroidism. CCH is frequently associated with other pituitary defects causing life-threatening situations (like e.g. adrenocorticotropic hormone deficiency) which could benefit from the early detection of CCH, avoiding considerable morbidity and mortality. CCH is not easy to identify clinically, and therefore few children are investigated for the disorder. The current knowledge on the genetic bases of CCH is also scarce. At the hypothalamic level no gene defects causing CCH have yet been identified in humans, but pituitary (thyrotrope)-selective genes encoding the TSH-releasing hormone (TRH) receptor (TRHR), the TSH β-subunit (TSHB) and, recently, the immunoglobulin superfamily factor 1 (IGSF1) are genes involved in isolated central hypothyroidism. Moreover, central hypothyroidism is a complex condition where many regulatory signals are implicated and converge to finely modulate the activity of the hypothalamic-pituitary-thyroid axis. This review focuses on novel pathogenic mechanisms and their implications to understand human CCH and improve the identification and the therapeutic handling of this elusive disease in the pediatric age. | 25,231,446 | [
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Facilitators and barriers to weight loss and weight loss maintenance: a qualitative exploration. | The present study aimed to explore facilitators and barriers to weight loss (WL) and weight loss maintenance (WLM) in women who participated in a primary, 18-week comparative trial that promoted WL with an energy-restricted diet. Twenty-three women participated in seven focus groups conducted by a moderator and co-facilitator using open-ended questions and probes. Focus groups were held in a private room and audio tape-recorded. Tapes were transcribed verbatim and thematic analysis was used to evaluate transcripts for common themes. Accountability to others, social support, planning ahead, awareness and mindfulness of food choices, basic nutrition education, portion control, exercise, and self-motivation were perceived as key facilitators for WL and WLM by women. Identified barriers included life transitions, health status changes, internal factors, environmental pressures, lack of accountability and an absence of social support. Future interventions should address these salient facilitators and barriers to promote sustainable changes in women across their WL and WLM journeys. | 25,231,461 | [
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Production of few-layer phosphorene by liquid exfoliation of black phosphorus. | We report the liquid exfoliation of black phosphorus in N-methyl-2-pyrrolidone to form few-layer phosphorene nanosheets. | 25,231,502 | [
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The neuro-ophthalmology of head trauma. | Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Concussion, a form of mild TBI, might be associated with long-term neurological symptoms. The effects of TBI and concussion are not restricted to cognition and balance. TBI can also affect multiple aspects of vision; mild TBI frequently leads to disruptions in visual functioning, while moderate or severe TBI often causes structural lesions. In patients with mild TBI, there might be abnormalities in saccades, pursuit, convergence, accommodation, and vestibulo-ocular reflex. Moderate and severe TBI might additionally lead to ocular motor palsies, optic neuropathies, and orbital pathologies. Vision-based testing is vital in the management of all forms of TBI and provides a sensitive approach for sideline or post-injury concussion screening. One sideline test, the King-Devick test, uses rapid number naming and has been tested in multiple athlete cohorts. | 25,231,523 | [
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Predictors of nosocomial pneumonia in intracerebral hemorrhage patients: a multi-center observational study. | Nosocomial pneumonia (NP) is a frequent complication among spontaneous intracerebral hemorrhage (sICH) patients. This study was aimed at identifying in-hospital risk factors that predispose sICH patients to NP. We identified 591 consecutive sICH subjects admitted to six tertiary care hospitals between 2008 and 2012. Information regarding patients' demographics, admission data, laboratory tests, medical history, diagnostic imaging, in-hospital treatments, complications, and outcomes were collected. Using a competing risks analysis, we assessed risk factors associated with NP. Mean age of the subjects was 68 years; 51 % were female and 76 % were white. One-hundred sixteen (19.6 %) of the sICH patients had NP. In the univariate analysis, variables including age, non-white race, early hospital admission (<6 h after onset), larger hematoma volume, basal ganglia or intraventricular hemorrhage, multisite hemorrhage, in-hospital aspiration, intubation, nasogastric tube placement, hematoma evacuation, high ICH score, ventricular drainage, and tracheostomy had a positive association with NP. However, in the multivariate analysis, only early hospital admission, in-hospital aspiration, intubation, and tracheostomy remained statistically significant predictors (p < 0.05). For patients who survived hospitalization, the median length-of-stay (LOS) with or without NP was 20.0 and 4.0 days, respectively (p < 0.0001). For patients who did not survive to discharge, the median LOS with or without NP was 10.5 and 2.0 days, respectively (p < 0.001). Independent predictors of NP included early hospital admission, in-hospital aspiration, intubation, and tracheostomy. NP was associated with prolonged hospital LOS. | 25,231,530 | [
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MicroRNA expression profile in exosome discriminates extremely severe infections from mild infections for hand, foot and mouth disease. | Changes of miRNAs in exosome have been reported in different disease diagnosis and provided as potential biomarkers. In this study, we compared microRNA profile in exosomes in 5 MHFMD and 5 ESHFMD as well as in 5 healthy children. Different expression of miRNAs in exosomes across all the three groups were screened using miRNA microarray method. Further validated test was conducted through quantitative real-time PCR assays with 54 exosome samples (18 ESHFMD, 18 MHFMD, and 18 healthy control). The judgment accuracy was then estimated by the receiver operating characteristic (ROC) curve analysis; and the specificity and sensitivity were evaluated by the multiple logistic regression analysis. There were 11 different miRNAs in exosomes of MHFMD and ESHFMD compared to healthy children, of which 4 were up-regulated and 7 were down-regulated. Further validation indicated that the 4 significant differentially expressed candidate miRNAs (miR-671-5p, miR-16-5p, miR-150-3p, and miR-4281) in exosome showed the same changes as in the microarray analysis, and the expression level of three miRNAs (miR-671-5p, miR-16-5p, and miR-150-3p) were significantly different between MHFMD or ESHFMD and the healthy controls. The accuracy of the test results were high with the under curve (AUC) value range from 0.79 to 1.00. They also provided a specificity of 72%-100% and a sensitivity of 78%-100%, which possessed ability to discriminate ESHFMD from MHFMD with the AUC value of 0.76-0.82. This study indicated that the exosomal miRNA from patients with different condition of HFMD express unique miRNA profiles. Exosomal miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping HFMD infections. | 25,231,540 | [
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Long, titanium, cemented stems decreased late periprosthetic fractures and revisions in patients with severe bone loss and previous revision. | Long, cementless, femoral stem revisions are being used with increasing frequency. There is a relative lack of studies of late fractures after cementless implants, particularly in those patients who had a previous stem revision and are at higher risk for periprosthetic fracture after revision. In this paper, we review risk factors for periprosthetic fracture and revisions of long, cementless, locked stems and report implant survival compared with conventional, cemented, long-stem hip revision arthroplasties in such a group of patients. We used data recorded in our institution. Between 1996 and 2002, 85 cementless femoral stem Aura™ (distal locked stem) prostheses were implanted in 85 patients. Of the 85 revisions with long, cementless stems, 32 were performed after one stem revision, 20 after two stem revisions and 12 after three stem revisions. Between 2003 and 2010, 124 femoral revision stems were performed in 124 patients using an extensively long, titanium femoral stem (Ceraver Osteal™). Kaplan-Meier analysis was used to determine implant survival. The Cox regression model was used to study risk factors for reoperation and revision. The increase in stem length corresponded to a mean of 4.5 ± 2.1 femoral canal diameters and was not significantly different (p = 0.02) between the two groups. Cardiopulmonary distress, intraoperative or postoperative complications were not significantly different between the two groups. There was an overall increased risk of pain, periprosthetic fractures and revision for the cementless prostheses compared with the cemented stems. With regard to thigh pain at the last follow-up, most patients (95 %) reported no pain in the cemented group, while 15 % of the cementless group experienced thigh pain under stress and 6 % had incapacitating pain. In the cemented group, stem re-revision was not required in any hip; there was no periprosthetic fracture; five stems had radiological loosening but in the absence of pain were not revised. Among patients of the cementless group, 21 % sustained failure or revision of their interlocked stem with periprosthetic fractures observed in 15 cases; factors which contributed significantly to a higher risk of fracture included the number of previous revisions; the average time between surgery and failure was 3.2 years after one revision, 2.8 years after two revisions, and 1.6 years after three revisions. The long, cementless, locked stem showed more early complications compared with recementing of long-stem prosthesis. We therefore recommend the use of cemented long stems in patients with severe bone loss and previous revision. | 25,231,573 | [
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[Exanthems and fever in travellers returning from the tropics]. | Dengue fever with its subtle rash is today more common than malaria in travellers returning to Europe from the tropics (meta-analysis Geo Sentinel network). Up to 5 % of all safari tourists experience African tick bite fever during or soon after their journey; it is caused by rickettsiae and clinically presents with exanthems, focal necrotizing vasculitis (eschar, tache noir), lymphadenopathy and moderate fever. Typhoid fever is a severe infectious disease is which is difficult to diagnosis at first assessment. The presence of rose spots, which may be found in up to 33 % of patients with typhoid fever, can lead the way to diagnosis. Exanthems can be subtle and may occur weeks after infection without any other distinctive clinical sign. Particular importance in travel medicine has to be paid to acute HIV infection and secondary syphilis after exposition and infection in the tropics. Also the highly contagious infectious diseases of childhood as measles and rubeola have to be taken into account in adults with no or insufficient vaccination after a stay in tropical countries. | 25,231,591 | [
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Detection of biomarkers of pathogenic Naegleria fowleri through mass spectrometry and proteomics. | Emerging methods based on mass spectrometry (MS) can be used in the rapid identification of microorganisms. Thus far, these practical and rapidly evolving methods have mainly been applied to characterize prokaryotes. We applied matrix-assisted laser-desorption-ionization-time-of-flight mass spectrometry MALDI-TOF MS in the analysis of whole cells of 18 N. fowleri isolates belonging to three genotypes. Fourteen originated from the cerebrospinal fluid or brain tissue of primary amoebic meningoencephalitis patients and four originated from water samples of hot springs, rivers, lakes or municipal water supplies. Whole Naegleria trophozoites grown in axenic cultures were washed and mixed with MALDI matrix. Mass spectra were acquired with a 4700 TOF-TOF instrument. MALDI-TOF MS yielded consistent patterns for all isolates examined. Using a combination of novel data processing methods for visual peak comparison, statistical analysis and proteomics database searching we were able to detect several biomarkers that can differentiate all species and isolates studied, along with common biomarkers for all N. fowleri isolates. Naegleria fowleri could be easily separated from other species within the genus Naegleria. A number of peaks detected were tentatively identified. MALDI-TOF MS fingerprinting is a rapid, reproducible, high-throughput alternative method for identifying Naegleria isolates. This method has potential for studying eukaryotic agents. | 25,231,600 | [
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One-pot synthesis of high molecular weight synthetic heteroprotein dimers driven by charge complementarity electrostatic interactions. | Despite the importance of protein dimers and dimerization in biology, the formation of protein dimers through synthetic covalent chemistry has not found widespread use. In the case of maleimide-cysteine-based dimerization of proteins, we show here that when the proteins have the same charge, dimerization appears to be inherently difficult with yields around 1% or less, regardless of the nature of the spacer used or whether homo- or heteroprotein dimers are targeted. In contrast, if the proteins have opposing (complementary) charges, the formation of heteroprotein dimers proceeds much more readily, and in the case of one high molecular weight (>80 kDa) synthetic dimer between cytochrome c and bovine serum albumin, a 30% yield of the purified, isolated dimer was achieved. This represents at least a 30-fold increase in yield for protein dimers formed from proteins with complementary charges, compared to when the proteins have the same charge, under otherwise similar conditions. These results illustrate the role of ionic supramolecular interactions in controlling the reactivity of proteins toward bis-functionalized spacers. The strategy here for effective synthetic dimerization of proteins could be very useful for developing novel approaches to study the important role of protein-protein interactions in chemical biology. | 25,231,623 | [
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Jack of all trades: versatile catechol crosslinking mechanisms. | Catechols play an important role in many natural systems. They are known to readily interact with both organic (e.g., amino acids) and inorganic (e.g., metal ions, metal oxides) compounds, thereby providing a powerful system for protein curing. Catechol crosslinked protein networks, such as sclerotized cuticle and byssal threads of the mussel, have been shown to exhibit excellent mechanical properties. A lot of effort has been devoted to mimicking the natural proteins using synthetic catechol-functionalized polymers. Despite the success in developing catechol-functionalized materials, the crosslinking chemistry of catechols is still a subject of debate. To develop materials with controlled and superior properties, a clear understanding of the crosslinking mechanism of catechols is of vital importance. This review describes the crosslinking pathways of catechol and derivatives in both natural and synthetic systems. We discuss existing pathways of catechol crosslinking and parameters that affect the catechol chemistry in detail. This overview will point towards a rational direction for further investigation of the complicated catechol chemistry. | 25,231,624 | [
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Monoclonal antibodies against all known variants of EspA: development of a simple diagnostic test for enteropathogenic Escherichia coli based on a key virulence factor. | Enteropathogenic Escherichia coli (EPEC) are a major cause of infant diarrhoea in developing countries and a significant public health issue in industrialized countries. Currently there are no simple tests available for the diagnosis of EPEC. Serology of O-antigens is widely used routinely in many laboratories throughout the world, even though it has been known for many years to be an unreliable indicator of EPEC virulence. We have developed a simple, low-cost immunodiagnostic test based on the EspA filament, an essential virulence factor of EPEC and the related enterohaemorrhagic E. coli (EHEC). Using recombinant proteins of the five major variants of EspA as immunogens, we raised a panel of three monoclonal antibodies in mice that detects all variants of the native target in bacterial cultures. The antibodies proved suitable for application in sandwich-type assays, including ELISA and lateral flow immunoassays (LFI). Prototypes for both assays were specific for EPEC and EHEC strains when tested against a panel of control micro-organisms. We have also developed a simple, affordable culture medium, A/E medium, which optimizes expression of EspA allowing improved sensitivity of detection compared with standard Dulbecco's modified Eagle's medium. Together these reagents form the basis of robust, informative tests for EPEC for use especially in developing countries but also for routine screening in any clinical laboratory. | 25,231,626 | [
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Oxidant-antioxidant status in the blood of horses with symptomatic recurrent airway obstruction (RAO). | Systemic oxidative stress in horses with recurrent airway obstruction (RAO) is poorly characterized. The goal of this study was to investigate whether equine RAO is associated with systemic disturbances in the oxidant-antioxidant equilibrium. Seven healthy horses and 7 horses with symptomatic RAO. A prospective study. Healthy and RAO-affected horses were exposed to a 48-hour challenge with moldy hay and straw to induce clinical exacerbation of RAO. Venous blood was collected and the activities of the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in equine erythrocyte lysates were measured. The concentration of thiobarbituric acid-reactive substances (TBARSs) was assessed both in erythrocyte lysates and in plasma. A significant increase in the activities of GPx and SOD was detected in RAO-affected horses compared with the control animals. There was no significant difference between groups in terms of the erythrocyte lysate activities of CAT, GR, or TBARs or the plasma concentration of TBARs. Our results support the hypothesis that RAO in horses is associated with systemic oxidative stress. Future studies are needed to assess whether horses suffering from RAO can benefit from antioxidant supplementation. | 25,231,643 | [
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"Fighting an uphill battle": experience with the HCV triple therapy: a qualitative thematic analysis. | Hepatitis C virus (HCV) infections are a severe burden on public health worldwide, causing mortality rates triple that of the general population. Since 2011, for both therapy-naive and therapy-experienced genotype 1 patients, the first generation of direct acting antivirals (DAAs), i.e., the protease-inhibitors (PI) telaprevir and boceprevir have been added to existing dual therapies. The therapeutic effect of the resulting triple therapy is striking; however, treatment regimens are complex and commonly cause side effects. Little is known of how patients implement therapy in their daily lives, or of how they deal with these effects.This study aims to describe HCV patients' experiences with protease-inhibitor-based triple therapy and their support needs. A qualitative design was used. Patients from three outpatient clinics, with ongoing, completed or discontinued PI treatment experience were recruited using a maximum variation sampling approach. Open-ended interviews were conducted and analyzed using thematic analysis according to Braun & Clarke (Qual Res Psychol 3:77-101, 2006). Thirteen patients participated in the interviews. All described themselves as highly motivated to undergo treatment, since they saw the new therapy as a "real chance" for a cure. However, all later described the therapy period as a struggle. The constitutive theme-"Fighting an uphill battle"- describes the common existential experience of and negative consequences of coping with side effects. The processes that fostered this common experience followed three sub-themes: "encountering surprises", "dealing with disruption" and "reaching the limits of systems". HCV patients undergoing outpatient protease-inhibitor-based triple therapy need systematic support in symptom management. This will require specially trained professionals to advise and support them and their families, and to provide rapid responses to their needs throughout this complex course of therapy. As the generation of DAAs for all genotypes, are expected to have less severe side effects, and many HCV patients require treatment, this knowledge can improve treatment support tremendously, especially for patients who are quite difficult to treat. Furthermore, these findings are helpful to illustrate development in HCV treatment. | 25,231,646 | [
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Personal identity as a form of freedom. | A commentary on "The Ethics of Anonymous Gamete Donation: Is There a Right to Know One's Genetic Origins?" by Inmaculada de Melo-Martín, in the March-April 2014 issue. | 25,231,651 | [
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Circulating progranulin level is associated with visceral fat and elevated liver enzymes: significance of serum progranulin as a useful marker for liver dysfunction. | Progranulin (PRGN) was recently identified as one of the adipokines involved in the development of insulin resistance. Thus, the aim of this study was to explore the importance of PRGN as a novel marker for metabolic diseases in Japanese. A total of 138 subjects were recruited by the Aijinkai Total Health Care Center. Physical examination, blood sample examination and total body CT scan were performed for all participants. Serum PRGN levels were examined in subjects with or without metabolic syndrome and with or without liver enzyme elevation. Association study of serum PRGN levels and regression analysis of the relationship of elevated liver enzymes to representative metabolic parameters were performed. The metabolic syndrome group exhibited older age, and higher BMI, blood pressure, fasting glucose, HbA1c, IRI, HOMA-R, TG, FFA, CRP, AST, ALT, LDH, and ALP, and larger visceral fat area, subcutaneous fat area and visceral fat area/subcutaneous fat area. Serum PRGN concentrations were significantly higher in the metabolic syndrome group than in the non-metabolic syndrome group. Bivariate correlation analysis revealed that serum PRGN concentrations correlated positively and significantly with AST, ALT, LDH, γGTP, ALP, waist circumference and visceral fat area. The group with elevated liver enzymes exhibited higher BMI, blood pressure, IRI, HOMA-R, and PRGN level and larger waist circumference and visceral fat area than the group without them. In logistic regression analysis, visceral fat area and PRGN were significantly predictive of elevated liver enzymes. These results suggest that serum PRGN level as well as visceral fat are associated closely with liver dysfunction. | 25,231,693 | [
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The pumping lid: investigating multi-material 3D printing for equipment-free, programmable generation of positive and negative pressures for microfluidic applications. | Equipment-free pumping is a challenging problem and an active area of research in microfluidics, with applications for both laboratory and limited-resource settings. This paper describes the pumping lid method, a strategy to achieve equipment-free pumping by controlled generation of pressure. Pressure was generated using portable, lightweight, and disposable parts that can be integrated with existing microfluidic devices to simplify workflow and eliminate the need for pumping equipment. The development of this method was enabled by multi-material 3D printing, which allows fast prototyping, including composite parts that combine materials with different mechanical properties (e.g. both rigid and elastic materials in the same part). The first type of pumping lid we describe was used to produce predictable positive or negative pressures via controlled compression or expansion of gases. A model was developed to describe the pressures and flow rates generated with this approach and it was validated experimentally. Pressures were pre-programmed by the geometry of the parts and could be tuned further even while the experiment was in progress. Using multiple lids or a composite lid with different inlets enabled several solutions to be pumped independently in a single device. The second type of pumping lid, which relied on vapor-liquid equilibrium to generate pressure, was designed, modeled, and experimentally characterized. The pumping lid method was validated by controlling flow in different types of microfluidic applications, including the production of droplets, control of laminar flow profiles, and loading of SlipChip devices. We believe that applying the pumping lid methodology to existing microfluidic devices will enhance their use as portable diagnostic tools in limited resource settings as well as accelerate adoption of microfluidics in laboratories. | 25,231,706 | [
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Assessment of the prophylactic role of aspirin and/or clopidogrel on experimentally induced acute myocardial infarction in hypercholesterolemic rats. | Hyperlipidemia is a risk factor for cardiovascular diseases such as acute infarction. Inflammation and platelet activation are critical phenomena in acute myocardial infarction (AMI). The aim of the study was to assess potential protective effects of aspirin and/or clopidogrel on AMI in hypercholesterolemic rats. Forty adult male Wistar rats were divided into five groups (eight rats in each). Group I included normal healthy rats. The other 32 rats were subjected to induction of hypercholesterolemia by high-fat diet for 3 weeks, followed by induction of AMI by subcutaneous injections of isoproterenol (85 mg/kg/day, for 2 days). Rats were divided into the following groups: group II, rats with induced hypercholesterolemia and AMI; group III, hypercholesterolemic rats that received aspirin 30 mg/kg/day orally for 7 days before induction of AMI; group IV, hypercholesterolemic rats that received clopidogrel 10 mg/kg/day orally for 7 days before induction of AMI; and group V, hypercholesterolemic rats treated with both aspirin and clopidogrel in the same doses for 7 days before induction of AMI. Serum levels of pentraxin 3 (PTX3), transforming growth factor-β1 (TGF-β1), creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol and triglycerides were estimated in all rats. Isoproterenol-induced AMI in hypercholesterolemic rats was associated with an increase in serum levels of PTX3, TGF-β1, CK and LDH. Aspirin and/or clopidogrel pretreatment for 1 week led to a reduction of their levels as compared with non-treated rats. However, the reduction caused by combination of aspirin and clopidogrel was more than that caused by each drug separately. Combination of aspirin and clopidogrel could be a therapeutic option for hypercholesterolemic patients to attenuate the complex vascular inflammatory process which is a key step in the setting of AMI. | 25,231,707 | [
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The complete mitochondrial genome of Lota lota (Gadiformes: Gadidae). | In this study, the complete mitochondrial genome (mitogenome) sequence of Lota lota has been determined by long polymerase chain reaction and primer walking methods. The mitogenome is a circular molecule of 16,547 bp in length and contains 37 mitochondrial genes including 13 protein-coding genes, 2 ribosomal RNA (rRNA), 22 transfer RNA (tRNA) and a control region as other bony fishes. Within the control region, we identified the termination-associated sequence domain (TAS), the central conserved sequence block domains (CSB-F and CSB-D), and the conserved sequence block domains (CSB-1, CSB-2 and CSB-3). | 25,231,712 | [
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Complete mitochondrial genome of the Freshwater Whipray Himantura dalyensis. | The complete mitochondrial genome of the Freshwater Whipray Himantura dalyensis is presented in this study. It is 17,693 bp in length and contains 37 genes in typical gene order and transcriptional orientation observed in vertebrates. There were a total of 86 bp short intergenic spacers and 22 bp overlaps in the genome. The overall base composition was 31.4% A, 25.5% C, 13.2% G and 29.9% T. Two start codons (GTG and ATG) and two stop codons (TAG and TAA/T) were found in 13 protein-coding genes. The length of 22 tRNA genes ranged from 68 (tRNA-Cys and tRNA-Ser2) to 75 bp (tRNA-Leu1). The origin of L-strand replication (OL) was found between the tRNA-Asn and tRNA-Cys genes. The base composition of the control region (1940 bp) was similar to the whole mitogenome. | 25,231,718 | [
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Morphology and Molecular Phylogeny of Pseudocyrtohymena koreana n. g., n. sp. and Antarctic Neokeronopsis asiatica Foissner et al., 2010 (Ciliophora, Sporadotrichida), with a Brief Discussion of the Cyrtohymena Undulating Membranes Pattern. | We discovered a new brackish water oxytrichid Pseudocyrtohymena koreana n. g., n. sp. in South Korea and investigated the new species on the basis of morphology, ontogenesis, and 18S rRNA gene sequences. The new genus has the 18 frontal-ventral-transverse cirri of typical oxytrichids with flexible body, cortical granules, Cyrtohymena undulating membranes (UM), and one left and one right marginal cirral row. Ontogenesis of the new species indicated that dorsal kinety anlage 3 stretches within the parental row without any fragmentations (Urosomoida pattern) and exclusively forms all caudal cirri. The new genus is morphologically similar to Cyrtohymena Foissner, 1989, but has the following distinctive features: (i) caudal cirri absent in dorsal kineties 1 and 2 (vs. present in Cyrtohymena); and (ii) dorsal kinety 3 nonfragmented (vs. fragmented in Cyrtohymena). Further, we collected an additional species Neokeronopsis asiatica Foissner et al. 2010, from King George Island, Antarctica, and the species shares the morphology of UM with Cyrtohymena. Herein, we describe the previously unidentified characteristics of N. asiatica (i.e., cortical granules, body flexibility, contractile vacuole, and 18S rRNA gene sequence). In addition, we obtained two 18S rRNA gene sequences from Cyrtohymena muscorum and Parasterkiella thompsoni to expand samples for phylogenetic analysis. Our 18S rRNA gene tree supports the hypothesis that the Cyrtohymena UM pattern might have evolved several times in hypotrichs (e.g., Neokeronopsidae, Oxytrichinae, and Stylonychinae). | 25,231,725 | [
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A comparative ICF-CY-based analysis and cultural piloting of the assessment of preschool children's participation (APCP). | The aim of this study was to assess and compare the content and measurement construct of a new measure, the Assessment of Preschool Children's Participation (APCP), with other participation measures that have previously been linked to the ICF-CY, and pilot the APCP item relevance in a Norwegian context. All meaningful concepts in the APCP were linked to the ICF-CY and compared with the links of eight other preschool measures. The analysis of measurement construct was based on the attending/doing and involvement/engagement dimensions of participation. The pilot study was a survey among 36 parents of typically developing children. Like most measures, the APCP has a relatively high content intensity on recreation and play, but differs by excluding self-care activities and including some learning activities. All instruments use objective indicators to measure participation. The APCP was not among the few that assessed subjective aspects of participation. The APCP items were found highly relevant in a Norwegian context, with the exception of a few organized activities taking place outside home environments. Differences in content and measurement constructs and the cultural equivalence should be considered when selecting a participation instrument for use among preschool children. | 25,231,756 | [
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Impact of inflammatory bowel disease on disability. | Inflammatory bowel disease can impact individuals at a young age, thus compromising their work productivity. Besides the inability to engage in gainful work, the concept of disability also relates to the patients' diminished ability to undertake household and social activities. A literature search was performed of recent literature, and all articles containing information about the impact of inflammatory bowel disease on disability or any work-related outcomes were included. Recent studies suggest that 9 to 19% of inflammatory bowel disease patients suffer from short-term absences from work and 19 to 22% are on long-term disability. Crohn's disease patients reported being more affected by their disease than ulcerative colitis patients. A comparison of results from different studies is difficult due to the lack of consensus on how to define and measure disability. Additional research is needed to better quantify disability in inflammatory bowel disease patients. | 25,231,757 | [
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Preserving residual renal function in dialysis: what we know. | Residual renal function confers a survival benefit among dialysis patients thought to be related to greater volume removal and solute clearance. Whether the presence of residual renal function is protective or merely a marker for better health is not clear. The basic mechanisms governing the decline or persistence of residual renal function are poorly understood and few studies have examined the role of medical therapy in its preservation. Dialysis modality, inflammatory processes often associated with comorbid diseases (including diabetes mellitus and obesity), volume dysregulation, and vitamin D deficiency are predictive of residual renal function decline. We review potential mechanisms for preservation of remaining glomerular filtration rate among chronic dialysis patients. | 25,231,758 | [
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Hormone treatment of children and adolescents with gender dysphoria: an ethical analysis. | In the context of transgender health, most people are not comfortable with allowing a twelve-year-old child with gender dysphoria to elect to undergo gender reassignment surgery. The likelihood is too high that the child would be unable to fully comprehend the scope of a decision that carries significant, permanent consequences, particularly because the decision to surgically change gender is based upon a conception of gender that can fluctuate during adolescent years. Conversely, however, most people would not contend that this fluidity is reason to wholly deny certain medical care such as hormonal treatments to transgender youth, a demographic with extremely high rates of violent behavior, self-harm, and suicide. This paper will explore ethical considerations to this emerging debate of what therapeutic options should be offered to transgender children and adolescents. Pediatric endocrinologists have been treating gender dysphoric adolescents with puberty-suppressing drugs and, to a lesser extent, with cross-sex hormone therapies for more than twenty years. Clinicians and thought leaders have mentioned ethical components of this emerging practice in the few cohort studies and clinical review articles about the subject. However, ethics have generally been a secondary consideration in the medical academic literature. In this paper, I will provide a brief overview of the practice, summarize the current research on hormone treatment for transgender minors, and provide an ethical analysis of the practice. | 25,231,782 | [
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Ensuring Appropriate Care for LGBT Veterans in the Veterans Health Administration. | Within health care systems, negative perceptions of lesbian, gay, bisexual, and transgender persons have often translated into denial of services, denial of visitation rights to same-sex partners, reluctance on the part of LGBT patients to share personal information, and failure of workers to assess and recognize the unique health care needs of these patients. Other bureaucratic forms of exclusion have included documents, forms, and policies that fail to acknowledge a patient's valued relationships because of, for example, a narrow definition of "spouse," "parent," or "family." Bureaucratic exclusion has taken a particularly prominent form in the U.S. military. Until its repeal and termination in 2011, the "Don't Ask, Don't Tell" policy had for eighteen years barred openly gay men and lesbians from serving in the military. Among the effects of DADT is a dearth of information about the number and needs of LGBT service members who transition to the Veterans Health Administration for health care at the end of their military service. The long-standing social stigma against LGBT persons, the silence mandated by DADT, and the often unrecognized bias built into the fabric of bureaucratic systems make the task of creating a welcoming culture in the VHA urgent and challenging. The VHA has accepted a commitment to that task. Its Strategic Plan for fiscal years 2013 through 2018 stipulates that "[v]eterans will receive timely, high quality, personalized, safe, effective and equitable health care irrespective of geography, gender, race, age, culture or sexual orientation." To achieve this goal, the VHA undertook a number of coordinated initiatives to create an environment and culture that is informed, welcoming, positive, and empowering for the LGBT veterans and families whom the agency serves. | 25,231,789 | [
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Harmonic demodulation and minimum enhancement factors in field-enhanced near-field optical microscopy. | Field-enhanced scanning optical microscopy relies on the design and fabrication of plasmonic probes which had to provide optical and chemical contrast at the nanoscale. In order to do so, the scattering containing the near-field information recorded in a field-enhanced scanning optical microscopy experiment, has to surpass the background light, always present due to multiple interferences between the macroscopic probe and sample. In this work, we show that when the probe-sample distance is modulated with very low amplitude, the higher the harmonic demodulation is, the better the ratio between the near-field signal and the interferometric background results. The choice of working at a given n harmonic is dictated by the experiment when the signal at the n + 1 harmonic goes below the experimental noise. We demonstrate that the optical contrast comes from the nth derivative of the near-field scattering, amplified by the interferometric background. By modelling the far and near field we calculate the probe-sample approach curves, which fit very well the experimental ones. After taking a great amount of experimental data for different probes and samples, we conclude with a table of the minimum enhancement factors needed to have optical contrast with field-enhanced scanning optical microscopy. | 25,231,792 | [
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Symmetry restoration and quantumness reestablishment. | A realistic quantum many-body system, characterized by a generic microscopic Hamiltonian, is accessible only through approximation methods. The mean field theories, as the simplest practices of approximation methods, commonly serve as a powerful tool, but unfortunately often violate the symmetry of the Hamiltonian. The conventional BCS theory, as an excellent mean field approach, violates the particle number conservation and completely erases quantumness characterized by concurrence and quantum discord between different modes. We restore the symmetry by using the projected BCS theory and the exact numerical solution and find that the lost quantumness is synchronously reestablished. We show that while entanglement remains unchanged with the particle numbers, quantum discord behaves as an extensive quantity with respect to the system size. Surprisingly, discord is hardly dependent on the interaction strengths. The new feature of discord offers promising applications in modern quantum technologies. | 25,231,796 | [
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-... |
[Mediating effect of self-efficacy in the relationship between anger and functional health of homeless men]. | The purpose of this study was to examine the mediation of self-efficacy in the relationship between anger and the functional health of homeless men in order to provide a basis for planning nursing interventions to improve the functional health of homeless persons. The participants were 137 homeless men who lived in homeless shelters or visited one center serving free meals for homeless persons in Seoul. Data were collected using self-report questionnaires and analyzed with the SPSS-WIN 20.0 program. The instruments were the Functional Health Pattern Screening Assessment Tool (FHPAST), Self-efficacy Scale (SES), and State-trait Anger Expression Inventory-Korean version (STAXI-K). The mean score for functional health was 2.41. Overall self-efficacy was 70.82. state anger was 16.53, trait anger was 19.54, and anger expression was 25.31. There were signigicant correlations among the 3 variables, functional health, self-efficacy, and anger. Also, self-efficacy had a complete mediating effect in the relationship between anger and functional health. Based on the findings of this study, health management programs focusing on anger management and self-efficacy improvement are highly recommended to promote functional health in homeless persons. | 25,231,801 | [
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0.2145743,
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[Factors affecting dementia prevalence in people aged 60 or over: a community based cross-sectional study]. | This study was done to examine the association between body mass index (BMI) and any type of clinical dementia. Participants were 60,321 people over 60 years of age enrolled in the Seoul Dementia Management Project in 2011. K-MMSE was used to classify participants as having a cognitive impairment and the Clinical Dementia Rating or DSM-IV by psychiatrists or neurologists to determine whether participants were in the dementia group or the non-dementia group. Descriptive statistics, chi-square test, and binary logistic regression analysis were performed. In the univariate analysis, age, education level, living with spouse, BMI, alcohol consumption, and exercise were significantly associated with dementia. In multivariable analysis, increasing age was positively associated with dementia, and educational level was negatively associated with dementia. The exercise group had a lower prevalence of dementia than the non-exercise group. The odds ratio of dementia in the over-weight and obese groups compared to the normal group was 0.85 (95% CI 0.60, 0.98) and 0.64 (95%CI 0.46, 0.75), respectively. Results indicate that dementia is negatively associated with increasing BMI in people aged 60 years or older, but a prospective cohort study is needed to elucidate the causal effect relationship between BMI and dementia. | 25,231,804 | [
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-0.1829809... |
[Association between efficiency and quality of health care in South Korea long-term care hospitals: using the data envelopment analysis and matrix analysis]. | Objectives of this study were to investigate the association between efficiency and quality of health care in Long-term Care Hospitals (LTCH) and determine related factors that would enable achievement of both high efficiency and high quality at the same time. Major data sources were the "2012 Korean Assessment of Propriety by Long-term Care Hospitals" obtained from the Health Insurance Review & Assessment Service. Cost variables were supplemented by a National Tax Service accounting document. First, data envelopment analysis was performed by generating efficiency scores for each LTCH. Second, matrix analysis was conducted to ascertain association between efficiency and quality. Lastly, kruskal-wallis and mann-whitney tests were conducted to identify related factors. First, efficiency and quality of care are not in a relationship of trade-offs; thus, LTCH can be confident that high efficiency-high quality can be achieved. Second, LTCH with a large number of beds, longer tenure of medical personnel, and adequate levels of investment were more likely to have improved quality as well as efficiency. It is essential to enforce legal standards appropriate to the facilities, reduce turnover of nursing staff, and invest properly in human resources. These consequences will help LTCH to maintain the balance of high efficiency-high quality in the long-run. | 25,231,807 | [
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0.2414165,
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0.1789764,
0.3427376,
0.1666522,
... |
[Effects of newborn care education for first-time fathers on their knowledge and confidence in newborn care at postpartum one month]. | This study was conducted to identify the effects of newborn care education for fathers on their knowledge and confidence in newborn care at postpartum one month. A nonequivalent control group pretest posttest design was used. The participants were 53 first-time fathers of newborns, 27 in experimental group, and 26 in control group. They were recruited at the nursery of one municipal hospital in Seoul. For the experimental group, a 50-minute education on newborn care using video, verbal education, demonstration and practice were provided prior to discharge. Fathers' knowledge and confidence in newborn care and their satisfaction with the education program were measured at postpartum one month. The fathers in the experimental group showed significantly higher knowledge (t=-4.51, p<.001), and confidence in newborn care (t=-2.29, p=.026) compared to the control group at postpartum one month. Fathers in the experimental group had a satisfaction score of 27.37±2.73 immediately after the education, and 25.30±3.40 at postpartum one month. Results indicate that newborn care education for first-time fathers is an effective method in enhancing the level of knowledge and confidence in newborn care. It can be used in the nursery department before discharge as a useful nursing intervention. | 25,231,808 | [
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0... |
Hill-sachs lesions in shoulders with traumatic anterior instability: evaluation using computed tomography with 3-dimensional reconstruction. | In patients with traumatic anterior shoulder instability, a large Hill-Sachs lesion is a risk factor for postoperative recurrence. However, there is no consensus regarding the occurrence and enlargement of Hill-Sachs lesions. To investigate the influence of the number of dislocations and subluxations on the prevalence and size of Hill-Sachs lesions evaluated by computed tomography (CT) with 3-dimensional reconstruction. Cohort study (diagnosis); Level of evidence, 2. The prevalence and size of Hill-Sachs lesions were evaluated preoperatively by CT in 142 shoulders (30 with primary instability and 112 with recurrent instability) before arthroscopic Bankart repair. First, the prevalence of Hill-Sachs lesions was compared with the arthroscopic findings. Then, the size of Hill-Sachs lesions confirmed by arthroscopy was remeasured using the previous CT data. In addition, the relationship of Hill-Sachs lesions with the number of dislocations and subluxations was investigated. Hill-Sachs lesions were detected in 90 shoulders by initial CT evaluation and were found in 118 shoulders at arthroscopy. The Hill-Sachs lesions missed by initial CT were 15 chondral lesions and 13 osseous lesions. However, all 103 osseous Hill-Sachs lesions were detected by reviewing the CT data. In patients with primary subluxation, the prevalence of Hill-Sachs lesions was 26.7%, and the mean length, width, and depth of the lesions (calculated as a percentage of the diameter of the humeral head) were 9.0%, 5.3%, and 2.1%, respectively, while the corresponding numbers for primary dislocation were 73.3%, 27.7%, 14.8%, and 7.0%, all showing statistically significant differences. Among all 142 shoulders, the corresponding numbers were, respectively, 56.3%, 20.7%, 11.2%, and 4.8% in patients who had subluxations but never a dislocation; 83.3%, 33.4%, 19.1%, and 7.6% in patients with 1 episode of dislocation; and 87.5%, 46.8%, 22.2%, and 10.2% in patients with ≥2 episodes, all showing statistically significant differences. There were no differences in lesion measurements in relation to the number of subluxations. Computed tomography is a useful imaging modality for evaluating Hill-Sachs lesions except for purely cartilaginous lesions. Hill-Sachs lesions were more frequent and larger when the primary episode was dislocation than when it was subluxation. Among patients with recurrent episodes of complete dislocation, the prevalence of Hill-Sachs lesions is increased, and the lesions are larger. | 25,231,817 | [
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Assessment of a Stool Symptom Screener and Understanding the Opioid-Induced Constipation Symptom Experience. | Many patients with chronic opioid-induced constipation (OIC) seek treatment to relieve their symptoms. A symptom screener may be useful in identifying symptomatic OIC patients. The aims of this study were to assess patient understanding of Stool Symptom Screener content and to evaluate how patients described their constipation experience, to better understand the relationship between constipation symptoms and patterns of laxative use. Adult OIC patients were recruited through five clinical sites across the USA. Patients were classified as either frequent or non-frequent laxative users. Patients participated in a semi-structured interview to assess their understanding of a Stool Symptom Screener and to discuss their constipation symptoms and laxative use experience. Interview transcripts were reviewed using content analysis. Descriptive statistics were used to characterize the sample. Sixty-six OIC patients participated: 39 frequent laxative users (mean age 53.3 years) and 27 non-frequent laxative users (mean age 55.5 years). Both patient groups described high levels of symptom burden on the Stool Symptom Screener as well as anecdotally. Both patient groups generally understood the Stool Symptom Screener items and felt the questions were relevant to their symptom experience. Most (95.5%) reported that they could remember their constipation symptoms "easily" over the previous 2 weeks. No qualitative differences were found between frequent and non-frequent laxative users in how they described their OIC symptom experience. OIC patients understood this Stool Symptom Screener, and its content was relevant to this highly symptomatic patient sample. Pain and bloating may be considered as additional symptoms for future versions of the screener. An emerging conceptual model of the OIC experience, laxative use, and symptoms is presented. | 25,231,829 | [
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0.03305632,
0.03080342,
0.1065755,
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0.2099179,
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0.4356455,
0.1437238,
0.02537015,
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0.02666819,
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... |
Metabolic phenotypes of obesity influence triglyceride and inflammation homoeostasis. | We examined the degree of postprandial triglyceride (TG) response over the day, representing a highly dynamic state, with continuous metabolic adaptations, among normal-weight, overweight and obese patients, according to their metabolically healthy or abnormal status. A total of 1002 patients from the CORDIOPREV clinical trial (NCT00924937) were submitted to an oral fat load test meal with 0·7 g fat/kg body weight (12% saturated fatty acids (SFA), 10% polyunsaturated fatty acids (PUFA), 43% monounsaturated fatty acids (MUFA), 10% protein and 25% carbohydrates). Serial blood test analysing lipid fractions and inflammation markers (high-sensitivity C-reactive protein (hs-CRP)) were drawn at 0, 1, 2, 3 and 4 h during postprandial state. We explored the dynamic response according to six body size phenotypes: (i) normal weight, metabolically healthy; (ii) normal weight, metabolically abnormal; (iii) overweight, metabolically healthy; (iv) overweight, metabolically abnormal; (v) obese, metabolically healthy; and (vi) obese, metabolically abnormal. Metabolically healthy patients displayed lower postprandial response of plasma TG and large triacylglycerol-rich lipoproteins (TRLs)-TG, compared with those metabolically abnormal, independently whether or not they were obese (P < 0·001 and P < 0·001, respectively). Moreover, the area under the curve (AUC) of TG and AUC of large TRLs-TG were greater in the group of metabolically abnormal compared with the group of metabolically healthy (P < 0·001 and P < 0·001, respectively). Interestingly, metabolically abnormal subjects displayed higher postprandial response of plasma hs-CRP than did the subgroup of normal, overweight and obese, metabolically healthy patients (P < 0·001). Our findings showed that certain types of the metabolic phenotypes of obesity are more favourable modulating phenotypic flexibility after a dynamic fat load test, through TG metabolism and inflammation homoeostasis. To identify, these phenotypes may be the best strategy for personalized treatment of obesity. | 25,231,836 | [
0.3730806,
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0.2090839,
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0.2438448,
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0.3061041,
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... |
Systemic inflammation induces a profound long term brain cell injury in rats. | The long term impact of neuroflammation induced by systemic inflammation on astroglial transcription factor nuclear factor (NF)-kappaB activation in the sub-region of hippocampus as well as its' association with the ultra-structural changes in brain cells are yet unknow. In this study, rats received 10 mg/kg of lipopolysaccharide (LPS, ip injection) and NF-kappaBp65 expression on the astroglia as well as the neuronal and astroglial ultra-structural changes and/or death and microvasculature damage were assessed with immunofluorescence and transmission electron microscopy respectively up to 16 days after treatment. The results showed that in the CA1 and CA3 region of the hippocampus, the fluorescence intensity of NF-kappaBp65 was increased from day 1 after LPS injection, reaching a peak at day 3, and stayed at higher level when compared to the control up to 16 days after LPS treatment (P<0.05). Electron microscopy studies revealed sustainable substructural alterations, injury or even death of astrocytes, neurons and capillaries even after 16 days post LPS injection. Our study demonstrated that long-term sustainable activation of astroglial NF-kappaB following systemic inflammation was associated with brain cell and microvasculature injury in the sub-region of the hippocampus which ultimately likely results in brain functional impairment. | 25,231,849 | [
0.2063674,
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0.1219442,
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0.4771265,
0.139792,
... |
Attempted suicide in patients with eating disorders. | Suicide is a major cause of mortality for patients with eating disorders (ED), especially for patients with anorexia nervosa. Attempted suicide is also relatively common in patients with anorexia or bulimia nervosa. This study aimed at examining associations between attempted suicide and trait- and state-dependent characteristics in a large clinical population of ED patients. The sample consisted of 1,436 in- and outpatients of the Centre for Eating Disorders of the Ghent University Hospital. Measures of ED symptoms, psychopathology, and personality traits were compared between ED patients with and ED patients without a history of attempted suicide. A history of attempted suicide was found in 11.8% of the ED patients and lifetime suicidal ideation was reported by 43.3%. Multivariate analyses showed that a history of attempted suicide was associated with higher scores on depression, purging symptomatology, early-developed cognitive schemes (impaired autonomy and increased inhibition), and social insecurity. These findings support the increased risk of suicidal behavior in ED. The presence of particular personality traits, of cognitive schemes, and of purging and depressive symptoms should increase vigilance for suicidal behavior. | 25,231,853 | [
0.03110209,
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0.6919481,
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0.03438276,
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0.392419,
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0.1080934,
0.1673612,
-0.1587739,
... |
The relation between diabetes self-efficacy and psychological distress among older adults: do racial and ethnic differences exist? | This study examined racial/ethnic differences in the relationship between diabetes self-efficacy and psychological distress among older adults with diabetes mellitus. Adults aged 60 or older with a diagnosis of diabetes mellitus (N = 3,067) were drawn from the 2009 California Health Interview Survey (CHIS). Hierarchical multiple regression analyses were conducted. After controlling for covariates, African Americans and those with higher levels of diabetes self-efficacy tended to have lower levels of psychological distress. Significant interactions were found in the Hispanic/Latino and Asian groups: The effect of diabetes self-efficacy on psychological distress was greater for Hispanics/Latinos and Asians than non-Hispanic Whites. Findings suggest that diabetes self-efficacy is associated with psychological distress among older diabetic patients and that race/ethnicity moderates the relationship between diabetes self-efficacy and psychological distress. Increasing diabetes self-efficacy will help racial/ethnic minority older patients with diabetes to improve psychological well-being at a greater level. | 25,231,883 | [
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0.1308504,
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Expanded umbilical cord blood T cells used as donor lymphocyte infusions after umbilical cord blood transplantation. | Umbilical cord blood (UCB) is an alternative graft source for hematopoietic stem cell transplantation and has been shown to give results comparable to transplantation with other stem cell sources. Donor lymphocyte infusion (DLI) is an effective treatment for relapsed malignancies after hematopoietic stem cell transplantation. However, DLI is not available after UCB transplantation. In this study, in vitro-cultured T cells from the UCB graft were explored as an alternative to conventional DLI. The main aim was to study the safety of the cultured UCB T cells used as DLI because such cell preparations have not been used in this context previously. We also assessed potential benefits of the treatment. The cultured UCB T cells (UCB DLI) were given to 4 patients with mixed chimerism (n = 2), minimal residual disease (n = 1) and graft failure (n = 1). No adverse reactions were seen at transfusion. Three of the patients did not show any signs of graft-versus-host disease (GVHD) after UCB DLI, but GVHD could not be excluded in the last patient. In the patient with minimal residual disease treated with UCB DLI, the malignant cell clone was detectable shortly before infusion but undetectable at treatment and for 3 months after infusion. In 1 patient with mixed chimerism, the percentage of recipient cells decreased in temporal association with UCB DLI treatment. We saw no certain adverse effects of treatment with UCB DLI. Events that could indicate possible benefits were seen but with no certain causal association with the treatment. | 25,231,890 | [
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0.1355179,
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0.1011333,
0.5794739,
0.2765259,
0.1385812,
-... |
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