title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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A new sunscreen application technique to protect more efficiently from ultraviolet radiation. | UV radiation protection is an important health issue. Sophisticated sunscreen formulations have been developed to improve compliance. However, sunscreen is still inadequately applied, leaving large body areas without effective protection. This study aims to validate a newly developed sunscreen application technique for adults and children. Fifty-eight volunteers were recruited to participate in a monocenter, intraindividual, sequential, comparative study. The covering potential of their currently used sunscreen application technique and of a newly developed systematized application technique (Dose, Apply, Spread) were compared. Evaluation criteria included the amount of product applied, the homogeneity of sunscreen application as measured by the Wood's lamp, and the volunteers' appreciation of the new technique. Fifty-eight volunteers participated in the study: 20 women, 19 men, and 19 children. Respecting the new application technique resulted in a statistically significant (P < 0.05) more evenly spread sunscreen on the different parts of the body and an increase in the amount of product applied. Furthermore, the body surface area covered was significantly increased (P < 0.05), and the new technique was well perceived and accepted by the volunteers. The proposed new application technique ensures that more sunscreen will be used and that it will be applied more evenly. Educational work could help improve the efficient use of sunscreens, therefore providing better UV protection. | 25,215,864 | [
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Spectral-domain optical coherence tomography of emulsified subretinal silicone oil presenting as a macular inverted pseudohypopyon. | The authors present a rare case of an inverted pseudohypopyon due to subretinal emulsified silicone oil in the macula of a patient who underwent pars plana vitrectomy surgery for repair of retinal detachment with proliferative vitreoretinopathy 1 year prior to presentation of this finding. The patient’s predisposing diagnosis is pathologic myopia. | 25,215,873 | [
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Effect of body condition on tissue distribution of perfluoroalkyl substances (PFASs) in Arctic fox (Vulpes lagopus). | Arctic animals undergo large seasonal fluctuations in body weight. The effect of body condition on the distribution and composition of 16 perfluoroalkyl substances (PFASs) was investigated in liver, blood, kidney, adipose tissue, and muscle of Arctic foxes (Vulpes lagopus) from Svalbard (n = 18, age 1-3 years). PFAS concentrations were generally highest in liver, followed by blood and kidney, while lowest concentrations were found in adipose tissue and muscle. Concentrations of summed perfluorocarboxylic acids and perfluoroalkyl sulfonates were five and seven times higher, respectively, in adipose tissue of lean compared to fat foxes. In addition, perfluorodecanoate (PFDA) and perfluoroheptanesulfonate (PFHpS) concentrations in liver, kidney, and blood, and, perfluorononanoate (PFNA) in liver and blood, were twice as high in the lean compared to the fat foxes. The ratio between perfluorooctane sulfonamide (FOSA) and its metabolite perfluorooctanesulfonate (PFOS) was lowest in liver, muscle, and kidney, while significantly higher proportions of FOSA were found in adipose tissue and blood. The results of the present study suggest that toxic potential of exposure to PFAS among other pollutants in Arctic mammals may increase during seasonal emaciation. The results also suggest that body condition should be taken into account when assessing temporal trends of PFASs. | 25,215,880 | [
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Differential reward learning for self and others predicts self-reported altruism. | In social environments, decisions not only determine rewards for oneself but also for others. However, individual differences in pro-social behaviors have been typically studied through self-report. We developed a decision-making paradigm in which participants chose from card decks with differing rewards for themselves and charity; some decks gave similar rewards to both, while others gave higher rewards for one or the other. We used a reinforcement-learning model that estimated each participant's relative weighting of self versus charity reward. As shown both in choices and model parameters, individuals who showed relatively better learning of rewards for charity--compared to themselves--were more likely to engage in pro-social behavior outside of a laboratory setting indicated by self-report. Overall rates of reward learning, however, did not predict individual differences in pro-social tendencies. These results support the idea that biases toward learning about social rewards are associated with one's altruistic tendencies. | 25,215,883 | [
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Novel mucosal DNA-MVA HIV vaccination in which DNA-IL-12 plus cholera toxin B subunit (CTB) cooperates to enhance cellular systemic and mucosal genital tract immunity. | Induction of local antiviral immune responses at the mucosal portal surfaces where HIV-1 and other viral pathogens are usually first encountered remains a primary goal for most vaccines against mucosally acquired viral infections. Exploring mucosal immunization regimes in order to find optimal vector combinations and also appropriate mucosal adjuvants in the HIV vaccine development is decisive. In this study we analyzed the interaction of DNA-IL-12 and cholera toxin B subunit (CTB) after their mucosal administration in DNA prime/MVA boost intranasal regimes, defining the cooperation of both adjuvants to enhance immune responses against the HIV-1 Env antigen. Our results demonstrated that nasal mucosal DNA/MVA immunization schemes can be effectively improved by the co-delivery of DNA-IL-12 plus CTB inducing elevated HIV-specific CD8 responses in spleen and more importantly in genital tract and genito-rectal draining lymph nodes. Remarkably, these CTL responses were of superior quality showing higher avidity, polyfunctionality and a broader cytokine profile. After IL-12+CTB co-delivery, the cellular responses induced showed an enhanced breadth recognizing with higher efficiency Env peptides from different subtypes. Even more, an in vivo CTL cytolytic assay demonstrated the higher specific CD8 T-cell performance after the IL-12+CTB immunization showing in an indirect manner its potential protective capacity. Improvements observed were maintained during the memory phase where we found higher proportions of specific central memory and T memory stem-like cells T-cell subpopulations. Together, our data show that DNA-IL-12 plus CTB can be effectively employed acting as mucosal adjuvants during DNA prime/MVA boost intranasal vaccinations, enhancing magnitude and quality of HIV-specific systemic and mucosal immune responses. | 25,215,887 | [
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Comparison of hepatocellular carcinoma miRNA expression profiling as evaluated by next generation sequencing and microarray. | MicroRNA (miRNA) expression profiling has proven useful in diagnosing and understanding the development and progression of several diseases. Microarray is the standard method for analyzing miRNA expression profiles; however, it has several disadvantages, including its limited detection of miRNAs. In recent years, advances in genome sequencing have led to the development of next-generation sequencing (NGS) technologies, which significantly advance genome sequencing speed and discovery. In this study, we compared the expression profiles obtained by next generation sequencing (NGS) with the profiles created using microarray to assess if NGS could produce a more accurate and complete miRNA profile. Total RNA from 14 hepatocellular carcinoma tumors (HCC) and 6 matched non-tumor control tissues were sequenced with Illumina MiSeq 50-bp single-end reads. Micro RNA expression profiles were estimated using miRDeep2 software. As a comparison, miRNA expression profiles for 11 out of 14 HCCs were also established by microarray (Agilent human microRNA microarray). The average total sequencing exceeded 2.2 million reads per sample and of those reads, approximately 57% mapped to the human genome. The average correlation for miRNA expression between microarray and NGS and subtraction were 0.613 and 0.587, respectively, while miRNA expression between technical replicates was 0.976. The diagnostic accuracy of HCC, p-value, and AUC were 90.0%, 7.22×10(-4), and 0.92, respectively. In summary, NGS created an miRNA expression profile that was reproducible and comparable to that produced by microarray. Moreover, NGS discovered novel miRNAs that were otherwise undetectable by microarray. We believe that miRNA expression profiling by NGS can be a useful diagnostic tool applicable to multiple fields of medicine. | 25,215,888 | [
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Roles of calcium/calmodulin-dependent kinase II in long-term memory formation in crickets. | Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a key molecule in many systems of learning and memory in vertebrates, but roles of CaMKII in invertebrates have not been characterized in detail. We have suggested that serial activation of NO/cGMP signaling, cyclic nucleotide-gated channel, Ca(2+)/CaM and cAMP signaling participates in long-term memory (LTM) formation in olfactory conditioning in crickets, and here we show participation of CaMKII in LTM formation and propose its site of action in the biochemical cascades. Crickets subjected to 3-trial conditioning to associate an odor with reward exhibited memory that lasts for a few days, which is characterized as protein synthesis-dependent LTM. In contrast, animals subjected to 1-trial conditioning exhibited memory that lasts for only several hours (mid-term memory, MTM). Injection of a CaMKII inhibitor prior to 3-trial conditioning impaired 1-day memory retention but not 1-hour memory retention, suggesting that CaMKII participates in LTM formation but not in MTM formation. Animals injected with a cGMP analogue, calcium ionophore or cAMP analogue prior to 1-trial conditioning exhibited 1-day retention, and co-injection of a CaMKII inhibitor impaired induction of LTM by the cGMP analogue or that by the calcium ionophore but not that by the cAMP analogue, suggesting that CaMKII is downstream of cGMP production and Ca(2+) influx and upstream of cAMP production in biochemical cascades for LTM formation. Animals injected with an adenylyl cyclase (AC) activator prior to 1-trial conditioning exhibited 1-day retention. Interestingly, a CaMKII inhibitor impaired LTM induction by the AC activator, although AC is expected to be a downstream target of CaMKII. The results suggest that CaMKII interacts with AC to facilitate cAMP production for LTM formation. We propose that CaMKII serves as a key molecule for interplay between Ca(2+) signaling and cAMP signaling for LTM formation, a new role of CaMKII in learning and memory. | 25,215,889 | [
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Level IB nodal involvement in oropharyngeal carcinoma: implications for submandibular gland-sparing intensity-modulated radiotherapy. | Submandibular gland-sparing intensity-modulated radiotherapy (SMG-sparing IMRT) has been proposed to reduce xerostomia following head and neck irradiation. However, the safety of this practice has been questioned. Data from a large surgical series of oropharyngeal carcinoma patients were extracted to identify clinicopathological correlates for submandibular involvement and to create a risk stratification scheme to guide decision making to refine selection guidelines for SMG-sparing IMRT. Clinicopathologic analysis. The medical records of 153 consecutive patients with squamous cell carcinoma of the oropharynx treated by primary surgery and neck dissection were reviewed. Univariate and multivariate analysis was performed with logistic regression to identify factors predictive of submandibular involvement. Recursive partitioning was used to develop risk stratification schemas based on preoperative data alone and in combination with pathologic data to guide treatment decisions in the definitive and postoperative settings, respectively. Submandibular (level IB) nodal dissection was performed in 119 heminecks (85 ipsilateral and 17 contralateral). The incidence of submandibular involvement was 18%. Young age, T3-4 disease, N2b-3 disease, and perineural invasion were identified as risk factors for submandibular nodal involvement on multivariate analysis (P < .01). Three distinct risk groups for submandibular involvement were identified: age >60 years and N0-2a disease (low risk, 2%), age ≤60 years and T1-2N2b-3 (intermediate risk, 16%), age ≤60 years and T3-4N2b-3 disease (high risk, 57%). These data provide assurances that SMG-sparing IMRT can reasonably be offered to appropriately selected patients. Risk stratification schemas were successfully developed for SMG-sparing IMRT in both the definitive and adjuvant settings. | 25,215,891 | [
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Nuclear factor kappa B and cyclo-oxygenase-2: two concordant players in psoriasis pathogenesis. | Nuclear factor kappa B (NFκB) is a key regulatory element in a variety of immune and inflammatory pathways, cellular proliferation, differentiation and apoptosis. Cyclo-oxygenase 2 (COX2) is one of the downstream targets of NFκB. The current work aimed to explore the possible role of NFκB and COX2 in psoriasis pathogenesis through their immunohistochemical (IHC) expression in skin biopsies of this disease and correlating this expression with clinico-pathological parameters of studied cases. 103 subjects were studied; including 58 cases with psoriasis vulgaris (lesional and perilesional skin) and 45 normal, age- and gender-matched subjects, as a control group. NFκB and COX2 expressions were evaluated using standard IHC techniques. NFκB and COX2 were upregulated in psoriasis lesional skin compared to perilesional (p < 0.001 for both) and control skin (p < 0.001 for both). Higher NFκB and COX2 H scores were significantly associated with absent granular cell layer (p = 0.02 for both), severe degree of perivascular inflammatory infiltrate (p = 0.03 and 0.002, respectively) and thin suprapapillary epidermis (p = 0.003 and 0.006, respectively). Significant positive correlation was noted between NFκB and COX2 H scores in epidermis (r = 0.41, p = 0.02) and dermis (r = 0.6, p = 0.04) of lesional skin. Significant positive correlation between NFκB H score and PASI score (r = 0.38, p = 0.04) and between COX2 H score and PASI score (r = 0.52, p < 0.001) were detected in lesional epidermis. In conclusion, both NFκB and COX2 play a role in the pathogenesis of chronic plaque psoriasis. This may open an avenue for research for new therapeutic modalities based on their inhibition. | 25,215,902 | [
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The ASEAN economic community and medical qualification. | In the regional movement toward ASEAN Economic Community (AEC), medical professions including physicians can be qualified to practice medicine in another country. Ensuring comparable, excellent medical qualification systems is crucial but the availability and analysis of relevant information has been lacking. This study had the following aims: 1) to comparatively analyze information on Medical Licensing Examinations (MLE) across ASEAN countries and 2) to assess stakeholders' view on potential consequences of AEC on the medical profession from a Thai perspective. To search for relevant information on MLE, we started with each country's national body as the primary data source. In case of lack of available data, secondary data sources including official websites of medical universities, colleagues in international and national medical student organizations, and some other appropriate Internet sources were used. Feasibility and concerns about validity and reliability of these sources were discussed among investigators. Experts in the region invited through HealthSpace.Asia conducted the final data validation. For the second objective, in-depth interviews were conducted with 13 Thai stakeholders, purposely selected based on a maximum variation sampling technique to represent the points of view of the medical licensing authority, the medical profession, ethicists and economists. MLE systems exist in all ASEAN countries except Brunei, but vary greatly. Although the majority has a national MLE system, Singapore, Indonesia, and Vietnam accept results of MLE conducted at universities. Thailand adopted the USA's 3-step approach that aims to check pre-clinical knowledge, clinical knowledge, and clinical skills. Most countries, however, require only one step. A multiple choice question (MCQ) is the most commonly used method of assessment; a modified essay question (MEQ) is the next most common. Although both tests assess candidate's knowledge, the Objective Structured Clinical Examination (OSCE) is used to verify clinical skills of the examinee. The validity of the medical license and that it reflects a consistent and high standard of medical knowledge is a sensitive issue because of potentially unfair movement of physicians and an embedded sense of domination, at least from a Thai perspective. MLE systems differ across ASEAN countries in some important aspects that might be of concern from a fairness viewpoint and therefore should be addressed in the movement toward AEC. | 25,215,908 | [
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Barriers to health care among people with disabilities who are members of underserved racial/ethnic groups: a scoping review of the literature. | Understanding barriers to health care access experienced by people with disabilities who are members of underserved racial/ethnic groups is key to developing interventions to improve access. To conduct a scoping review of the literature to examine the published literature on barriers to health care access for people with disabilities who are members of underserved racial/ethnic groups. Articles cited in MEDLINE, PsycINFO, and CINAHL between the year 2000 and June 19, 2013. In addition, table of contents of 4 journals and the reference lists of the included article were reviewed for potentially relevant titles. Studies examining barriers to health care access among adults aged 18-64 with disabilities who are members of an underserved racial/ethnic group were included. Two reviewers screened abstracts, screened each full-text article and extracted data, and discrepancies were resolved by consensus. Ten studies were identified that met all inclusion criteria. The most frequently described barriers were uninsurance, language, low education level, and no usual source of care. Barriers to health care access related to race or ethnicity (6 studies) and disability (1 study) were observed less often than those related to socioeconomic status or health care systems factors (9 studies). Our findings reflect a critical gap in the literature. Greater attention is needed to subgroup differences including race, ethnicity, and culture within the population of people with disabilities. | 25,215,920 | [
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Spatial distance effects on incremental semantic interpretation of abstract sentences: evidence from eye tracking. | A large body of evidence has shown that visual context information can rapidly modulate language comprehension for concrete sentences and when it is mediated by a referential or a lexical-semantic link. What has not yet been examined is whether visual context can also modulate comprehension of abstract sentences incrementally when it is neither referenced by, nor lexically associated with, the sentence. Three eye-tracking reading experiments examined the effects of spatial distance between words (Experiment 1) and objects (Experiment 2 and 3) on participants' reading times for sentences that convey similarity or difference between two abstract nouns (e.g., 'Peace and war are certainly different...'). Before reading the sentence, participants inspected a visual context with two playing cards that moved either far apart or close together. In Experiment 1, the cards turned and showed the first two nouns of the sentence (e.g., 'peace', 'war'). In Experiments 2 and 3, they turned but remained blank. Participants' reading times at the adjective (Experiment 1: first-pass reading time; Experiment 2: total times) and at the second noun phrase (Experiment 3: first-pass times) were faster for sentences that expressed similarity when the preceding words/objects were close together (vs. far apart) and for sentences that expressed dissimilarity when the preceding words/objects were far apart (vs. close together). Thus, spatial distance between words or entirely unrelated objects can rapidly and incrementally modulate the semantic interpretation of abstract sentences. | 25,215,930 | [
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AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. | Damaged mitochondria are eliminated by mitophagy, a selective form of autophagy whose dysfunction associates with neurodegenerative diseases. PINK1, PARKIN and p62/SQTMS1 have been shown to regulate mitophagy, leaving hitherto ill-defined the contribution by key players in 'general' autophagy. In basal conditions, a pool of AMBRA1 - an upstream autophagy regulator and a PARKIN interactor - is present at the mitochondria, where its pro-autophagic activity is inhibited by Bcl-2. Here we show that, upon mitophagy induction, AMBRA1 binds the autophagosome adapter LC3 through a LIR (LC3 interacting region) motif, this interaction being crucial for regulating both canonical PARKIN-dependent and -independent mitochondrial clearance. Moreover, forcing AMBRA1 localization to the outer mitochondrial membrane unleashes a massive PARKIN- and p62-independent but LC3-dependent mitophagy. These results highlight a novel role for AMBRA1 as a powerful mitophagy regulator, through both canonical or noncanonical pathways. | 25,215,947 | [
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Targeting proapoptotic protein BAD inhibits survival and self-renewal of cancer stem cells. | Emerging evidence suggests that the resistance of cancer stem cells (CSC) to many conventional therapies is one of the major limiting factors of cancer therapy efficacy. Identification of mechanisms responsible for survival and self-renewal of CSC will help design new therapeutic strategies that target and eliminate both differentiated cancer cells and CSC. Here we demonstrated the potential role of proapoptotic protein BAD in the biology of CSC in melanoma, prostate and breast cancers. We enriched CD44(+)/CD24(-) cells (CSC) by tumorosphere formation and purified this population by FACS. Both spheres and CSC exhibited increased potential for proliferation, migration, invasion, sphere formation, anchorage-independent growth, as well as upregulation of several stem cell-associated markers. We showed that the phosphorylation of BAD is essential for the survival of CSC. Conversely, ectopic expression of a phosphorylation-deficient mutant BAD induced apoptosis in CSC. This effect was enhanced by treatment with a BH3-mimetic, ABT-737. Both pharmacological agents that inhibit survival kinases and growth factors that are involved in drug resistance delivered their respective cytotoxic and protective effects by modulating the BAD phosphorylation in CSC. Furthermore, the frequency and self-renewal capacity of CSC was significantly reduced by knocking down the BAD expression. Consistent with our in vitro results, significant phosphorylation of BAD was found in CD44(+) CSC of 83% breast tumor specimens. In addition, we also identified a positive correlation between BAD expression and disease stage in prostate cancer, suggesting a role of BAD in tumor advancement. Our studies unveil the role of BAD in the survival and self-renewal of CSC and propose BAD not only as an attractive target for cancer therapy but also as a marker of tumor progression. | 25,215,949 | [
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Intraoperative examination of sentinel lymph nodes using scrape cytology. | Background. In breast cancer, sentinel lymph node biopsy (SLNB) is widely used to assess the axilla when the nodes appear normal on palpation and ultrasonography. When the sentinel lymph nodes (SLNs) are negative, no further dissection is required. Surgical dissection or radiotherapy of the axilla is indicated for macrometastases, as well as adjuvant therapy for macrometastases and micrometastasic spread.Aim. To determine the accuracy of scrape cytology (SC) for intraoperative examination of the SLNs.Methods. SLNB was performed in 100 patients with early breast cancer in whom the axillary nodes appeared normal on clinical examination and ultrasonography. None of the patients with negative SLNs or SLNs with micrometastases only (N1mic, 0.2 - 2 mm) had further axillary dissection. Patients with SLNs containing macrometastases (N1, &gt;2 mm) underwent axillary lymph node dissection. The results of intraoperative cytology were compared with the histopathological findings on examination of serial paraffin-embedded sections of the SLNs.Results. Intraoperative SC identified SLN metastases in 20 patients: 17 had macrometastases and 3 micrometastases. Histopathological examination of the SLNs found macrometastases in 18 patients and micrometastases in 6. SC had a sensitivity of 94% and specificity of 100% for the detection of macrometastases. For micrometastatic spread, the sensitivity and specificity were 50% and 100%, respectively.Conclusion. SC is a rapid, sensitive technique for detection of macrometastases in the SLNs of women with breast cancer. The overall accuracy in identification of any metastatic spread (N1mic, N1) to the SLNs was 85%, rising to 94% in SLNs with macrometastases. | 25,215,952 | [
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Applying the simplest Kochen-Specker set for quantum information processing. | Kochen-Specker (KS) sets are key tools for proving some fundamental results in quantum theory and also have potential applications in quantum information processing. However, so far, their intrinsic complexity has prevented experimentalists from using them for any application. The KS set requiring the smallest number of contexts has been recently found. Relying on this simple KS set, here we report an input state-independent experimental technique to certify whether a set of measurements is actually accessing a preestablished quantum six-dimensional space encoded in the transverse momentum of single photons. | 25,215,966 | [
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Constraining the equation of state of neutron stars from binary mergers. | Determining the equation of state of matter at nuclear density and hence the structure of neutron stars has been a riddle for decades. We show how the imminent detection of gravitational waves from merging neutron star binaries can be used to solve this riddle. Using a large number of accurate numerical-relativity simulations of binaries with nuclear equations of state, we find that the postmerger emission is characterized by two distinct and robust spectral features. While the high-frequency peak has already been associated with the oscillations of the hypermassive neutron star produced by the merger and depends on the equation of state, a new correlation emerges between the low-frequency peak, related to the merger process, and the total compactness of the stars in the binary. More importantly, such a correlation is essentially universal, thus providing a powerful tool to set tight constraints on the equation of state. If the mass of the binary is known from the inspiral signal, the combined use of the two frequency peaks sets four simultaneous constraints to be satisfied. Ideally, even a single detection would be sufficient to select one equation of state over the others. We test our approach with simulated data and verify it works well for all the equations of state considered. | 25,215,972 | [
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Matrix product states for gauge field theories. | The matrix product state formalism is used to simulate Hamiltonian lattice gauge theories. To this end, we define matrix product state manifolds which are manifestly gauge invariant. As an application, we study (1+1)-dimensional one flavor quantum electrodynamics, also known as the massive Schwinger model, and are able to determine very accurately the ground-state properties and elementary one-particle excitations in the continuum limit. In particular, a novel particle excitation in the form of a heavy vector boson is uncovered, compatible with the strong coupling expansion in the continuum. We also study full quantum nonequilibrium dynamics by simulating the real-time evolution of the system induced by a quench in the form of a uniform background electric field. | 25,215,973 | [
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Hindered Gamow-Teller decay to the odd-odd N=Z (62)Ga: absence of proton-neutron T=0 condensate in A=62. | Search for a new kind of superfluidity built on collective proton-neutron pairs with aligned spin is performed studying the Gamow-Teller decay of the T=1, J(π)=0+ ground state of (62)Ge into excited states of the odd-odd N=Z nucleus (62)Ga. The experiment is performed at GSI Helmholtzzentrum für Shwerionenforshung with the (62)Ge ions selected by the fragment separator and implanted in a stack of Si-strip detectors, surrounded by the RISING Ge array. A half-life of T1/2=82.9(14) ms is measured for the (62)Ge ground state. Six excited states of (62)Ga, populated below 2.5 MeV through Gamow-Teller transitions, are identified. Individual Gamow-Teller transition strengths agree well with theoretical predictions of the interacting shell model and the quasiparticle random phase approximation. The absence of any sizable low-lying Gamow-Teller strength in the reported beta-decay experiment supports the hypothesis of a negligible role of coherent T=0 proton-neutron correlations in (62)Ga. | 25,215,980 | [
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Microbunching instability in relativistic electron bunches: direct observations of the microstructures using ultrafast YBCO detectors. | Relativistic electron bunches circulating in accelerators are subjected to a dynamical instability leading to microstructures at millimeter to centimeter scale. Although this is a well-known fact, direct experimental observations of the structures, or the field that they emit, remained up to now an open problem. Here, we report the direct, shot-by-shot, time-resolved recording of the shapes (including envelope and carrier) of the pulses of coherent synchrotron radiation that are emitted, and that are a "signature" of the electron bunch microstructure. The experiments are performed on the UVSOR-III storage ring, using electrical field sensitive YBa2Cu3O(7-x) thin-film ultrafast detectors. The observed patterns are subjected to permanent drifts, that can be explained from a reasoning in phase space, using macroparticle simulations. | 25,215,987 | [
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Observation of a disordered bosonic insulator from weak to strong interactions. | We employ ultracold atoms with controllable disorder and interaction to study the paradigmatic problem of disordered bosons in the full disorder-interaction plane. Combining measurements of coherence, transport and excitation spectra, we get evidence of an insulating regime extending from weak to strong interaction and surrounding a superfluidlike regime, in general agreement with the theory. For strong interaction, we reveal the presence of a strongly correlated Bose glass coexisting with a Mott insulator. | 25,215,990 | [
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Atomistic explanation of shear-induced amorphous band formation in boron carbide. | Boron carbide (B4C) is very hard, but its applications are hindered by stress-induced amorphous band formation. To explain this behavior, we used density function theory (Perdew-Burke-Ernzerhof flavor) to examine the response to shear along 11 plausible slip systems. We found that the (0111)/<1101> slip system has the lowest shear strength (consistent with previous experimental studies) and that this slip leads to a unique plastic deformation before failure in which a boron-carbon bond between neighboring icosahedral clusters breaks to form a carbon lone pair (Lewis base) on the C within the icosahedron. Further shear then leads this Lewis base C to form a new bond with the Lewis acidic B in the middle of a CBC chain. This then initiates destruction of this icosahedron. The result is the amorphous structure observed experimentally. We suggest how this insight could be used to strengthen B4C. | 25,215,991 | [
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Revealing the structure of a granular medium through ballistic sound propagation. | We study the propagation of sound through a bidimensional granular medium consisting of photoelastic disks, which are packed into different crystalline and disordered structures. Acoustic sensors placed at the boundaries of the system capture the acoustic signal produced by a local and well-controlled mechanical excitation. By compressing the system, we find that the speed of the ballistic part of the acoustic wave behaves as a power law of the applied force with both exponent and prefactor sensitive to the internal geometry of the contact network. This information, which we are able to link to the force-deformation relation of single grains under different contact geometries, provides enough information to reveal the structure of the granular medium. | 25,216,006 | [
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Inherent variability in the kinetics of autocatalytic protein self-assembly. | In small volumes, the kinetics of filamentous protein self-assembly is expected to show significant variability, arising from intrinsic molecular noise. This is not accounted for in existing deterministic models. We introduce a simple stochastic model including nucleation and autocatalytic growth via elongation and fragmentation, which allows us to predict the effects of molecular noise on the kinetics of autocatalytic self-assembly. We derive an analytic expression for the lag-time distribution, which agrees well with experimental results for the fibrillation of bovine insulin. Our expression decomposes the lag-time variability into contributions from primary nucleation and autocatalytic growth and reveals how each of these scales with the key kinetic parameters. Our analysis shows that significant lag-time variability can arise from both primary nucleation and from autocatalytic growth and should provide a way to extract mechanistic information on early-stage aggregation from small-volume experiments. | 25,216,007 | [
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Stochastic accumulation by cortical columns may explain the scalar property of multistable perception. | The timing of certain mental events is thought to reflect random walks performed by underlying neural dynamics. One class of such events--stochastic reversals of multistable perceptions--exhibits a unique scalar property: even though timing densities vary widely, higher moments stay in particular proportions to the mean. We show that stochastic accumulation of activity in a finite number of idealized cortical columns--realizing a generalized Ehrenfest urn model--may explain these observations. Modeling stochastic reversals as the first-passage time of a threshold number of active columns, we obtain higher moments of the first-passage time density. We derive analytical expressions for noninteracting columns and generalize the results to interacting columns in simulations. The scalar property of multistable perception is reproduced by a dynamic regime with a fixed, low threshold, in which the activation of a few additional columns suffices for a reversal. | 25,216,009 | [
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Targeting CD36-mediated inflammation reduces acute brain injury in transient, but not permanent, ischemic stroke. | The pathology of stroke consists of multiple pro-death processes, and CD36 has been suggested as a multimodal target to reduce oxidative stress and inflammation in ischemic stroke. Using CD36-deficient mice and SS-31, a cell permeable tetrapeptide known to down-regulate CD36 pathways, the current study investigated whether targeting CD36 is effective in transient and permanent ischemic stroke. Wild-type or CD36-deficient mice were subjected to either 30-min transient or permanent focal ischemic stroke. In parallel, a cohort of mice subjected to either transient or permanent stroke received either vehicle or 5 mg/kg of SS-31. Monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2, mRNA levels, and infarct volume and percent hemispheric swelling were measured in the postischemic brain. CD36 deficiency or SS-31 treatment significantly attenuated MCP-1 or CCR2 mRNA up-regulation and injury size in the transient ischemic stroke. However, the approaches failed to show the protective effect in permanent ischemic stroke. The study revealed that targeting CD36 has a beneficial effect on transient but not permanent focal ischemic stroke. The study thus precludes a generalized strategy targeting CD36 in ischemic stroke and suggests careful consideration of types of stroke and associated pathology in developing stroke therapies. | 25,216,018 | [
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Intercropping enhances soil carbon and nitrogen. | Intercropping, the simultaneous cultivation of multiple crop species in a single field, increases aboveground productivity due to species complementarity. We hypothesized that intercrops may have greater belowground productivity than sole crops, and sequester more soil carbon over time due to greater input of root litter. Here, we demonstrate a divergence in soil organic carbon (C) and nitrogen (N) content over 7 years in a field experiment that compared rotational strip intercrop systems and ordinary crop rotations. Soil organic C content in the top 20 cm was 4% ± 1% greater in intercrops than in sole crops, indicating a difference in C sequestration rate between intercrop and sole crop systems of 184 ± 86 kg C ha(-1) yr(-1). Soil organic N content in the top 20 cm was 11% ± 1% greater in intercrops than in sole crops, indicating a difference in N sequestration rate between intercrop and sole crop systems of 45 ± 10 kg N ha(-1) yr(-1). Total root biomass in intercrops was on average 23% greater than the average root biomass in sole crops, providing a possible mechanism for the observed divergence in soil C sequestration between sole crop and intercrop systems. A lowering of the soil δ(15) N signature suggested that increased biological N fixation and/or reduced gaseous N losses contributed to the increases in soil N in intercrop rotations with faba bean. Increases in soil N in wheat/maize intercrop pointed to contributions from a broader suite of mechanisms for N retention, e.g., complementary N uptake strategies of the intercropped plant species. Our results indicate that soil C sequestration potential of strip intercropping is similar in magnitude to that of currently recommended management practises to conserve organic matter in soil. Intercropping can contribute to multiple agroecosystem services by increased yield, better soil quality and soil C sequestration. | 25,216,023 | [
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Regression of a paraganglioma tumor of the orbit. | To describe a clinical case of an orbital paraganglioma that displayed regression after biopsy alone. Case report. A 75-year-old female was examined for a right orbital tumor suspected to be metastatic breast carcinoma. An orbital biopsy was performed with significant hemorrhage encountered requiring extensive cautery. There was apparent clinical regression of the tumor with no signs of proptosis or eye movement restriction two years after this patient's biopsy. Histology was consistent with paraganglioma (glomus tumor). Although we cannot rule out spontaneous regression of this unique tumor, we postulate that tissue necrosis caused by the use of cautery induced regression. Unless encapsulated and easily accessible, we suggest that the best management of this rare tumor is that of observation after being found negative for malignancy by biopsy given their propensity for slow progression and in rare cases, regression. | 25,216,041 | [
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Eukaryotic initiation factor 5A plays an essential role in luteinizing hormone receptor regulation. | Down-regulation of LH receptor (LHR) in the ovary by its ligand is mediated by a specific RNA-binding protein, designated LH receptor mRNA-binding protein (LRBP), through translational suppression and mRNA degradation. Using yeast 2-hybrid screens, we previously identified eukaryotic initiation factor 5A (eIF5A) as one of the proteins that interacts with LRBP during LHR mRNA down-regulation. The present study examined the role of eIF5A and its hypusination in the context of LHR mRNA down-regulation. The association of eIF5A with LRBP or LHR mRNA was determined using immunoprecipitation and RNA immunoprecipitation assays. The results showed that the association of eIF5A with the LHR mRNA-LRBP complex increased significantly during down-regulation. Furthermore, gel fractionation and the hypusination activity assay both showed increased hypusination of eIF5A during LHR mRNA down-regulation. Abolishment of hypusination by pretreatment with the chemical inhibitor GC7 prevented the association of eIF5A with LHR mRNA and LRBP. Inhibition of hypusination also reduced the extent of ligand-induced down-regulation of LHR mRNA as well as the expression of functional LHRs assessed by real-time PCR and (125)I-human chorionic gonadotropin (hCG) binding assays, respectively. The loss of human chorionic gonadotropin-mediated downstream signaling during LHR down-regulation was also restored by inhibition of hypusination of eIF5A. Thus, the present study, for the first time, reveals the crucial role of eIF5A and its hypusination in the regulation of LHR expression in the ovary. | 25,216,047 | [
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Rapoport's rule revisited: geographical distributions of human languages. | One of the most well studied ecological patterns is Rapoport's rule, which posits that the geographical extent of species ranges increases at higher latitudes. However, studies to date have been limited in their geographic scope and results have been equivocal. In turn, much debate exists over potential links between Rapoport's rule and latitudinal patterns in species richness. Humans collectively speak nearly 7000 different languages, which are spread unevenly across the globe, with loci in the tropics. Causes of this skewed distribution have received only limited study. We analyze the extent of Rapoport's rule in human languages at a global scale and within each region of the globe separately. We test the relationship between Rapoport's rule and the richness of languages spoken in different regions. We also explore the frequency distribution of language-range sizes. The language-range area distribution is strongly right-skewed, with 87% of languages having range areas less than 10,000 km(2), and only nine languages with range areas over 1,000,000 km(2). At a global scale, language-range extents and areas are positively correlated with latitude. At a global scale and in five of the six regions examined, language-range extent and language-range area are strongly correlated with language richness. Our results point to group boundary formation as a critical mediator of the relationship between Rapoport's rule and diversity patterns. Where strong group boundaries limit range overlap, as is the case with human languages, and range sizes increase with latitude, latitudinal richness gradients may result. | 25,216,049 | [
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Conjunct SEP and MEP monitoring in resection of infratentorial lesions: lessons learned in a cohort of 210 patients. | During the surgical removal of infratentorial lesions, intraoperative neuromonitoring is mostly focused on cranial nerve assessment and brainstem auditory potentials. Despite the known risk of perforating vessel injury during microdissection within the vicinity of the brainstem, there are few reports about intraoperative neuromonitoring with somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) assessing the medial lemniscus and corticospinal tract. This study analyses the occurrence of intraoperative changes in MEPs and SEPs with regard to lesion location and postoperative neurological outcome. The authors analyzed 210 cases in which patients (mean age 49 ± 13 years, 109 female) underwent surgeries involving the skull base (n = 104), cerebellum (n = 63), fourth ventricle (n = 28), brainstem (n = 12), and foramen magnum (n = 3). Of 210 surgeries, 171 (81.4%) were uneventful with respect to long-tract monitoring. Nine (23%) of the 39 SEP and/or MEP alterations were transient and were only followed by a slight permanent deficit in 1 case. Permanent deterioration only was seen in 19 (49%) of 39 cases; the deterioration was related to tumor dissection in 4 of these cases, and permanent deficit (moderate-severe) was seen in only 1 of these 4 cases. Eleven patients (28%) had losses of at least 1 modality, and in 9 of these 11 cases, the loss was related to surgical microdissection within the vicinity of the brainstem. Four of these 9 patients suffered a moderate-to-severe long-term deficit. For permanent changes, the positive predictive value for neuromonitoring of the long tracts was 0.467, the negative predictive value was 0.989, the sensitivity was 0.875, and the specificity 0.918. Twenty-eight (72%) of 39 SEP and MEP alterations occurred in 66 cases involving intrinsic brainstem tumors or tumors adjacent to the brainstem. Lesion location and alterations in intraoperative neuromonitoring significantly correlated with patients' outcome (p < 0.001, chi-square test). In summary, long-tract monitoring with SEPs and MEPs in infratentorial surgeries has a high sensitivity and negative predictive value with respect to postoperative neurological status. It is recommended especially in those surgeries in which microdissection within and in the vicinity of the brainstem might lead to injury of the brainstem parenchyma or perforating vessels and a subsequent perfusion deficit within the brainstem. | 25,216,065 | [
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Different mechanisms for role relations versus verb-action congruence effects: evidence from ERPs in picture-sentence verification. | Extant accounts of visually situated language processing do make general predictions about visual context effects on incremental sentence comprehension; these, however, are not sufficiently detailed to accommodate potentially different visual context effects (such as a scene-sentence mismatch based on actions versus thematic role relations, e.g., (Altmann & Kamide, 2007; Knoeferle & Crocker, 2007; Taylor & Zwaan, 2008; Zwaan & Radvansky, 1998)). To provide additional data for theory testing and development, we collected event-related brain potentials (ERPs) as participants read a subject-verb-object sentence (500 ms SOA in Experiment 1 and 300 ms SOA in Experiment 2), and post-sentence verification times indicating whether or not the verb and/or the thematic role relations matched a preceding picture (depicting two participants engaged in an action). Though incrementally processed, these two types of mismatch yielded different ERP effects. Role-relation mismatch effects emerged at the subject noun as anterior negativities to the mismatching noun, preceding action mismatch effects manifest as centro-parietal N400s greater to the mismatching verb, regardless of SOAs. These two types of mismatch manipulations also yielded different effects post-verbally, correlated differently with a participant's mean accuracy, verbal working memory and visual-spatial scores, and differed in their interactions with SOA. Taken together these results clearly implicate more than a single mismatch mechanism for extant accounts of picture-sentence processing to accommodate. | 25,216,075 | [
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Carbon flow from volcanic CO2 into soil microbial communities of a wetland mofette. | Effects of extremely high carbon dioxide (CO2) concentrations on soil microbial communities and associated processes are largely unknown. We studied a wetland area affected by spots of subcrustal CO2 degassing (mofettes) with focus on anaerobic autotrophic methanogenesis and acetogenesis because the pore gas phase was largely hypoxic. Compared with a reference soil, the mofette was more acidic (ΔpH ∼0.8), strongly enriched in organic carbon (up to 10 times), and exhibited lower prokaryotic diversity. It was dominated by methanogens and subdivision 1 Acidobacteria, which likely thrived under stable hypoxia and acidic pH. Anoxic incubations revealed enhanced formation of acetate and methane (CH4) from hydrogen (H2) and CO2 consistent with elevated CH4 and acetate levels in the mofette soil. (13)CO2 mofette soil incubations showed high label incorporations with ∼512 ng (13)C g (dry weight (dw)) soil(-1) d(-1) into the bulk soil and up to 10.7 ng (13)C g (dw) soil(-1) d(-1) into almost all analyzed bacterial lipids. Incorporation of CO2-derived carbon into archaeal lipids was much lower and restricted to the first 10 cm of the soil. DNA-SIP analysis revealed that acidophilic methanogens affiliated with Methanoregulaceae and hitherto unknown acetogens appeared to be involved in the chemolithoautotrophic utilization of (13)CO2. Subdivision 1 Acidobacteriaceae assimilated (13)CO2 likely via anaplerotic reactions because Acidobacteriaceae are not known to harbor enzymatic pathways for autotrophic CO2 assimilation. We conclude that CO2-induced geochemical changes promoted anaerobic and acidophilic organisms and altered carbon turnover in affected soils. | 25,216,086 | [
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Di-, tri-, and tetranuclear copper(I) complexes of phenanthroline-linked dicarbene ligands. | A family of 2,9-di(3-R-1H-imidazolium-1-yl)-1,10-phenanthroline iodides and hexafluorophosphates (R = allyl, benzyl, mesityl, picolyl) were synthesized from 2,9-diiodophenanthroline and imidazole or N-substituted imidazoles. Simple reactions of these diimidazolium salts with copper powder at room temperature have afforded a series of multinuclear copper(I)-NHC complexes in good yields. The structures vary depending on the N substituents and counterions. [Cu4(L1)2(MeCN)4](PF6)4 (R = allyl) exhibits a zigzag Cu4 chain with two terminal [Cu(NHC)(MeCN)2] and two internal [Cu(phen)(NHC)] moieties. [Cu3(L2)2](PF6)3 (R = benzyl) contains a strictly linear Cu3 framework with two [Cu(NHC)2] units and a [Cu(phen)2] located at the center. Both complexes [Cu3(L4)2](PF6)3 (R = mesityl) and [Cu3(L5)2](PF6)3 (R = picolyl) consist of a triangular Cu3 core in which two copper(I) ions are surrounded by a phen and a NHC group and the third copper(I) is coordinated by two NHC groups. [Cu3(L3)2](PF6)3 derived from 2,9-di(3-benzyl-1H-benzimidazolium-1-yl)-1,10-phenanthroline hexafluorophosphate can undergo transannulation of the benzimidazolylidene ring giving [Cu2(L3')2](PF6)2. The decomposition process might involve solvent-induced rearrangement of the ligand and hydrolysis of carbene moieties. Treatment of 2,9-di(3-mesityl-1H-benzimidazolium-1-yl)-1,10-phenanthroline iodide with copper powder generated dinuclear complex [Cu2(L4)2][Cu2(μ-I)2I2] (R = mesityl) possessing a macrocyclic cation and [Cu2(μ-I)2I2](2-) anion. Tetranuclear complex [Cu4(L5)2(μ-I)2](CuI3) (R = picolyl) has been obtained from its diimidazolium iodide and copper powder. All Cu(I) complexes have been characterized by X-ray single diffraction analysis, elemental analysis, and NMR spectra. Their redox behavior and fluorescent properties have also been studied. | 25,216,090 | [
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Induction of body weight loss through RNAi-knockdown of APOBEC1 gene expression in transgenic rabbits. | In the search of new strategies to fight against obesity, we targeted a gene pathway involved in energy uptake. We have thus investigated the APOB mRNA editing protein (APOBEC1) gene pathway that is involved in fat absorption in the intestine. The APOB gene encodes two proteins, APOB100 and APOB48, via the editing of a single nucleotide in the APOB mRNA by the APOBEC1 enzyme. The APOB48 protein is mandatory for the synthesis of chylomicrons by intestinal cells to transport dietary lipids and cholesterol. We produced transgenic rabbits expressing permanently and ubiquitously a small hairpin RNA targeting the rabbit APOBEC1 mRNA. These rabbits exhibited a moderately but significantly reduced level of APOBEC1 gene expression in the intestine, a reduced level of editing of the APOB mRNA, a reduced level of synthesis of chylomicrons after a food challenge, a reduced total mass of body lipids and finally presented a sustained lean phenotype without any obvious physiological disorder. Interestingly, no compensatory mechanism opposed to the phenotype. These lean transgenic rabbits were crossed with transgenic rabbits expressing in the intestine the human APOBEC1 gene. Double transgenic animals did not present any lean phenotype, thus proving that the intestinal expression of the human APOBEC1 transgene was able to counterbalance the reduction of the rabbit APOBEC1 gene expression. Thus, a moderate reduction of the APOBEC1 dependent editing induces a lean phenotype at least in the rabbit species. This suggests that the APOBEC1 gene might be a novel target for obesity treatment. | 25,216,115 | [
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Anatomical study of the pterygomaxillary area for implant placement: cone beam computed tomographic scanning in 100 patients. | The aim of this study was to describe the average angulation and dimensions of the pterygomaxillary area in the atrophic maxilla to facilitate the orientation of pterygoid implants during their placement. A retrospective radiologic study was made. A virtual pterygoid implant, 13, 15, or 18 mm long, was placed in the pterygomaxillary area following the axis of the bone, with a distance of at least 2 mm maintained between the artery and palatine nerve and the implant. The long axis of the implant was inclined slightly toward the palatal to follow the cortical palatal bone. The angles between the long axis of the virtual implant and Frankfort horizontal were measured in both sagittal and frontal views. To calculate the average length of the pterygomaxillary area, the virtual long axis of the implant was measured from the alveolar crest to the pterygomaxillary suture. The average anteroposterior axis inclination of the pterygomaxillary area was 72.5 ± 4.9 degrees relative to Frankfort horizontal. The average angulation of the palatal vestibule was 81.3 ± 42.8 degrees relative to Frankfort horizontal. The average length of the pterygomaxillary area was 22.5 ± 4.8 mm. Pterygoid implant placement requires thorough knowledge of each patient's anatomy and individual needs. The mean position of the pterygomaxillary buttress axis was 72.5 ± 4.9 degrees to the distal and 81.3 ± 2.8 degrees to the palatal relative to Frankfort horizontal. Placement of pterygoid implants in this inclination may increase accuracy of implant placement. The average length from the tuberosity to the most apical point of the pterygoid apophysis was 22.5 ± 4.8 mm. These results suggest that an implant 15 to 18 mm in length would fit in the pterygomaxillary area to reach the cortical bone. | 25,216,128 | [
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Accuracy of positioning of implants inserted using a mucosa-supported stereolithographic surgical guide in the edentulous maxilla and mandible. | The aim of this study was to evaluate the accuracy of implants inserted using a mucosa-supported stereolithographic surgical guide and to determine the influence of surgical management of the guide (fixed or unfixed), arch (maxilla or mandible), and smoking habit (normal or hyperplastic mucosa) on accuracy. In completely edentulous subjects, preoperative computed tomography (CT) was performed, and the images were used to plan implant positions. After the implants were placed, CT was performed again, and the presurgical and postoperative images were compared. With computer software, the jaw contours from the two CT scans were matched and the deviations between the planned and actual implant positions were evaluated. Surgical technique, arch, and smoking habit were examined as independent variables, and their influence on accuracy was evaluated with a t test. Twenty-eight surgical guides (225 implants) were included in this study. Deviations between planned and actual positions were seen in the global coronal (mean±SD: 1.68±0.6 mm), global apical (2.19 ± 0.83 mm), and angular (4.67 ± 2.68 degrees) dimensions. Fixation of surgical guides (fixed: 4.09 degrees; not fixed: 5.62 degrees) and use of the guide in the maxilla (4.36 degrees; mandible: 5.46 degrees) resulted in statistically significantly less angular deviation (ie, better accuracy). Nonsmoking patients showed statistically significantly better accuracy in global coronal (nonsmokers: 1.54 mm; smokers: 1.83 mm) and global apical (nonsmokers: 2.08 mm; smokers: 2.27 mm) deviations. The greater supporting surface of the maxilla and fixation of the surgical guide improved the accuracy of the guides. The reduced mucosa thickness in nonsmokers decreased global coronal and global apical deviation. | 25,216,132 | [
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In vitro comparison of the retentive properties of ball and locator attachments for implant overdentures. | To compare the retentive properties of ball and locator attachments during 5,000 insertion-separation cycles, corresponding to approximately 4.5 years of clinical use. Four dental implants (diameter, 3.8 mm; length, 12 mm) were inserted into the prepared beds of two polyethylene blocks. Twenty acrylic prosthetic components were fabricated and connected to the ball and locator abutments. Tensile force was applied to the prosthetic components until the attachments were separated from the abutments. All samples were subjected to 5,000 insertion-separation cycles. Retention forces were measured after 10, 100, 200, 300, 400, 500, 1,000, 1,500, 2,000, 3,000, 4,000, and 5,000 insertion-separation cycles. Additionally, the wear of the attachments was measured using scanning electron microscopy. Data were analyzed to determine statistical equivalence among the two different attachments using the Student t test procedure and the Mann-Whitney U test procedure (α = .05). Ball attachments showed significant retention loss after 100, 200, 400, 500, 1,500, and 4,000 cycles, and the locator attachments showed significant retention loss after 100, 200, 300, 500, and 3,000 cycles as compared with the previous cycle (P < .05). Retention loss after 5,000 cycles was detected significantly more often for ball attachments than for locator attachments (P = .049). No significant difference was detected between the retention losses of the two attachment systems during the other cycles as compared with the initial retention values (P > .05). No significant difference was detected between the wear on the two attachment systems after 5,000 cycles (P > .05). Both attachment systems showed decreased retentive forces after 5,000 insertion-separation cycles. However, after 5,000 insertion-separation cycles, locator attachments showed better retentive properties than ball attachments. | 25,216,136 | [
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Esthetic outcome evaluation of maxillary anterior single-tooth bone-level implants with metal or ceramic abutments and ceramic crowns. | The aim of this study was to evaluate the treatment outcome of implants placed in the maxillary anterior segment. Patients were treated with bone-level implants (Straumann Bone Level Implant, Institut Straumann) that supported all-ceramic single crowns and were followed for 2 to 4 years. Titanium or ceramic abutments were used according to the quality of the soft tissue at each site. Esthetic parameters were recorded to assess treatment outcomes. Pink esthetic scores (PES) and white esthetic scores (WES) were used to evaluate the esthetic outcome of anterior single-tooth implant-supported crowns. Patient satisfaction was also evaluated by means of a questionnaire. Fifty-five implants were placed in 47 patients. At the recall examinations, all implants were confirmed to have successfully integrated and demonstrated healthy peri-implant soft tissues, as documented by generally accepted clinical parameters. Overall, the esthetic results were considered favorable, and there were no significant differences between restorations with ceramic or titanium abutments. WES values were slightly superior to PES values. None of the implants had mucosal recession. Objective and subjective evaluation of maxillary bone-level implants in the esthetic zone yielded satisfactory results. Pleasing esthetic outcomes and stable facial soft tissues were achieved. | 25,216,139 | [
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The prevalence of hearing loss in South Korea: data from a population-based study. | In the present study, we aimed to determine the prevalence of hearing loss in the South Korean population and to understand the correlation between aging, sex, and hearing loss prevalence through the analysis of data collected from the Korea National Health and Nutrition Examination Survey (KNHANES). Cross-sectional epidemiological study. The KNHANES is an ongoing population study that started in 1998. Examinations to detect diseases of the ear, nose, and throat, including audiological testing and otologic examinations, have been conducted since 2010. We included a total of 18,650 participants in the KNHANES, from 2010 to 2012, in the present study. Pure-tone audiometric testing was conducted in participants aged ≥ 12 years. The frequencies tested were 0.5, 1, 2, 3, 4, and 6 kHz. The prevalence of hearing loss in speech-relevant frequencies in the South Korean population was 9.31% for unilateral hearing loss and 13.42% for bilateral hearing loss. The overall hearing loss (unilateral or bilateral) was 22.73%. Male and older participants were more often affected by hearing loss than female and younger participants. High-frequency hearing loss appeared earlier than hearing loss at speech-relevant frequencies, and unilateral hearing loss showed a weaker correlation with aging than bilateral hearing loss. The prevalence of hearing loss in South Korea was higher in men and older participants according to the data collected from the KNHANES. The patterns of hearing loss differed between hearing loss at speech-relevant frequencies and at high frequencies. | 25,216,153 | [
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Mapping ergonomics application to improve SMEs working condition in industrially developing countries: a critical review. | In industrially developing countries (IDC), small and medium enterprises (SMEs) account for the highest proprotion of employment. Unfortunately, the working conditions in SMEs are often very poor and expose employees to a potentially wide range of health and safety risks. This paper presents a comprehensive review of 161 articles related to ergonomics application in SMEs, using Indonesia as a case study. The aim of this paper is to investigate the extent of ergonomics application and identify areas that can be improved to promote effective ergonomics for SMEs in IDC. The most urgent issue found is the need for adopting participatory approach in contrast to the commonly implemented top-down approach. Some good practices in ergonomics application were also revealed from the review, e.g. a multidisciplinary approach, unsophisticated and low-cost solutions, and recognising the importance of productivity. The review also found that more work is still required to achieve appropriate cross-cultural adaptation of ergonomics application. | 25,216,158 | [
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Measurement of cooling detection thresholds for identification of diabetic sensorimotor polyneuropathy in type 1 diabetes. | Compared to recently-studied novel morphological measures, conventional small nerve fiber functional tests have not been systematically studied for identification of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine and compare the diagnostic performance of cooling detection thresholds (CDT) in a cross-sectional type 1 diabetes cohort. 136 subjects with type 1 diabetes and 52 healthy volunteers underwent clinical and electrophysiological examination for DSP classification concomitantly with the Toronto Clinical Neuropathy Score (TCNS) and three small fiber function tests: CDT, heart rate variability (HRV), and laser doppler imaging of axon-mediated neurogenic flare responses to cutaneous heating (LDIFLARE). Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic (ROC) curves in the type 1 diabetes cohort. Type 1 diabetes subjects were 42±17 years of age with mean HbA1c 7.9±1.7%. Fifty-nine (45%) met the case definition for DSP. CDT values were lowest in cases with DSP (18.3±8.4°C) compared to controls without DSP (28.4±3.5°C) and to healthy volunteers (29.6±1.8°C; p-value for both comparisons<0.0001). AUCCDT was 0.863 which was similar to AUCTCNS (0.858, p = 0.24) and AUCHRV (0.788, p = 0.05), but exceeded AUCLDIFLARE (0.750, p = 0.001). The threshold of <25.1°C was equivalent to the lower bound of the healthy volunteer 95% distribution [25.1, 30.8°C] and performed with 83% sensitivity and 82% specificity. Akin to novel small fiber morphological measures, CDT is a functional test that identifies DSP with very good diagnostic performance. These findings support further research that revisits the role of CDT in early DSP detection. | 25,216,179 | [
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Stochastic optimal foraging: tuning intensive and extensive dynamics in random searches. | Recent theoretical developments had laid down the proper mathematical means to understand how the structural complexity of search patterns may improve foraging efficiency. Under information-deprived scenarios and specific landscape configurations, Lévy walks and flights are known to lead to high search efficiencies. Based on a one-dimensional comparative analysis we show a mechanism by which, at random, a searcher can optimize the encounter with close and distant targets. The mechanism consists of combining an optimal diffusivity (optimally enhanced diffusion) with a minimal diffusion constant. In such a way the search dynamics adequately balances the tension between finding close and distant targets, while, at the same time, shifts the optimal balance towards relatively larger close-to-distant target encounter ratios. We find that introducing a multiscale set of reorientations ensures both a thorough local space exploration without oversampling and a fast spreading dynamics at the large scale. Lévy reorientation patterns account for these properties but other reorientation strategies providing similar statistical signatures can mimic or achieve comparable efficiencies. Hence, the present work unveils general mechanisms underlying efficient random search, beyond the Lévy model. Our results suggest that animals could tune key statistical movement properties (e.g. enhanced diffusivity, minimal diffusion constant) to cope with the very general problem of balancing out intensive and extensive random searching. We believe that theoretical developments to mechanistically understand stochastic search strategies, such as the one here proposed, are crucial to develop an empirically verifiable and comprehensive animal foraging theory. | 25,216,191 | [
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Polypyrrole-montmorillonite nanocomposite as sorbent for solid-phase microextraction of phenolic compounds in water. | A fiber-coated polypyrrole-montmorillonite nanocomposite was prepared for solid-phase microextraction. The fiber coating can be prepared easily; it is mechanically stable and exhibits relatively high thermal stability. The prepared fiber was evaluated for the extraction of some phenolic compounds from aqueous sample solutions by gas chromatography-mass spectrometry. The effects of the extraction and desorption parameters including extraction time, extraction temperature, stirring rate, ionic strength, pH and desorption temperature and time have been studied. At optimum conditions, the repeatability for one fiber (n = 5), expressed as % relative standard deviation was between 6.5 and 7.8% for the phenolic compounds. The detection limits for the studied phenolic compounds were between 0.05-1.3 ng/mL. The developed method offers the advantage of being simple to use, with shorter analysis time, lower cost, thermal stability of the fibers, and high relative recovery in comparison to conventional methods of analysis. | 25,216,242 | [
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Polymer collapse in miscible good solvents is a generic phenomenon driven by preferential adsorption. | Water and alcohol, such as methanol or ethanol, are miscible and, individually, good solvents for poly(N-isopropylacrylamide) (PNIPAm), but this polymer precipitates in water-alcohol mixtures. The intriguing behaviour of solvent mixtures that cannot dissolve a given polymer or a given protein, while the same macromolecule dissolves well in each of the cosolvents, is called cononsolvency. It is a widespread phenomenon, relevant for many formulation steps in the physicochemical and pharmaceutical industry, that is usually explained by invoking specific chemical details of the mixtures: as such, it has so far eluded any generic explanation. Here, by using a combination of simulations and theory, we present a simple and universal treatment that requires only the preferential interaction of one of the cosolvents with the polymer. The results show striking quantitative agreement with experiments and chemically specific simulations, opening a new perspective towards an operational understanding of macromolecular solubility. | 25,216,245 | [
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Repeatability of feather mite prevalence and intensity in passerine birds. | Understanding why host species differ so much in symbiont loads and how this depends on ecological host and symbiont traits is a major issue in the ecology of symbiosis. A first step in this inquiry is to know whether observed differences among host species are species-specific traits or more related with host-symbiont environmental conditions. Here we analysed the repeatability (R) of the intensity and the prevalence of feather mites to partition within- and among-host species variance components. We compiled the largest dataset so far available: 119 Paleartic passerine bird species, 75,944 individual birds, ca. 1.8 million mites, seven countries, 23 study years. Several analyses and approaches were made to estimate R and adjusted repeatability (R(adj)) after controlling for potential confounding factors (breeding period, weather, habitat, spatial autocorrelation and researcher identity). The prevalence of feather mites was moderately repeatable (R = 0.26-0.53; R(adj) = 0.32-0.57); smaller values were found for intensity (R = 0.19-0.30; R(adj )= 0.18-0.30). These moderate repeatabilities show that prevalence and intensity of feather mites differ among species, but also that the high variation within species leads to considerable overlap among bird species. Differences in the prevalence and intensity of feather mites within bird species were small among habitats, suggesting that local factors are playing a secondary role. However, effects of local climatic conditions were partially observed for intensity. | 25,216,248 | [
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Sheep lung segmental delivery strategy demonstrates adenovirus priming of local lung responses to bacterial LPS and the role of elafin as a response modulator. | Viral lung infections increase susceptibility to subsequent bacterial infection. We questioned whether local lung administration of recombinant adenoviral vectors in the sheep would alter the susceptibility of the lung to subsequent challenge with bacterial lipopolysaccharide (LPS). We further questioned whether local lung expression of elafin, a locally produced alarm anti-LPS/anti-bacterial molecule, would modulate the challenge response. We established that adenoviral vector treatment primed the lung for an enhanced response to bacterial LPS. Whereas this local effect appeared to be independent of the transgene used (Ad-o-elafin or Ad-GFP), Ad-o-elafin treated sheep demonstrated a more profound lymphopenia in response to local lung administration of LPS. The local influence of elafin in modulating the response to LPS was restricted to maintaining neutrophil myeloperoxidase activity, and levels of alveolar macrophage and neutrophil phagocytosis at higher levels post-LPS. Adenoviral vector-bacterial synergism exists in the ovine lung and elafin expression modulates such synergism both locally and systemically. | 25,216,250 | [
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EMF monitoring-concepts, activities, gaps and options. | Exposure to electromagnetic fields (EMF) is a cause of concern for many people. The topic will likely remain for the foreseeable future on the scientific and political agenda, since emissions continue to change in characteristics and levels due to new infrastructure deployments, smart environments and novel wireless devices. Until now, systematic and coordinated efforts to monitor EMF exposure are rare. Furthermore, virtually nothing is known about personal exposure levels. This lack of knowledge is detrimental for any evidence-based risk, exposure and health policy, management and communication. The main objective of the paper is to review the current state of EMF exposure monitoring activities in Europe, to comment on the scientific challenges and deficiencies, and to describe appropriate strategies and tools for EMF exposure assessment and monitoring to be used to support epidemiological health research and to help policy makers, administrators, industry and consumer representatives to base their decisions and communication activities on facts and data. | 25,216,256 | [
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Stable nonaromatic [20]dithiaporphyrin (2.1.1.1) macrocycles: synthesis, structure, spectral, electrochemical, and metal ion sensing studies. | Stable nonaromatic [20]dithiaporphyrin (2.1.1.1) macrocycles were synthesized in decent yields by condensing readily available butene-2,3-diyl-bisthiophene-2,5-diyl-bis(p-methoxyphenylmethanol) with different meso-aryl dipyrromethanes under mild acid-catalyzed conditions. The [20]dithiaporphyrin (2.1.1.1) macrocycles are the first members of the expanded porphyrin analogues of [18]dithiaporphyrin (1.1.1.1) and consist of two pyrroles and two thiophenes connected through five meso-carbon bridges. The [20]dithiaporphyrin macrocycles were confirmed by mass spectroscopy, 1D and 2D NMR spectroscopy, and X-ray crystallography. The X-ray structure revealed that the macrocycle is highly distorted and that the two thiophene rings are completely out-of-plane from the "mean-plane" defined by the dipyrromethene moiety and the two meso-carbons. In the absorption spectrum, the macrocycles showed one strong band at ∼420 nm and one weak band at ∼720 nm. The electrochemical studies revealed that the macrocycles are stable under redox conditions. The metal sensing studies indicated that these macrocycles have the potential to sense specific metal ions such as Hg(2+) ions. Two covalently linked dithiahomoporphyrin-fluorophore dyads were synthesized by coupling iodo-functionalized dithiahomoporphyrin with an ethynyl-functionalized fluorophore such as boron-dipyrromethene (BODIPY) and BF2-smaragdyrin under mild Pd(0) coupling conditions. The potential of these dyads as a fluorescent sensor for Hg(2+) was explored, and the studies indicated that both dyads can be used as fluorescent sensors. | 25,216,279 | [
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Estrogen stimulates the invasion of ovarian cancer cells via activation of the PI3K/AKT pathway and regulation of its downstream targets E‑cadherin and α‑actinin‑4. | Previous studies by our group revealed that the phosphoinositide 3‑kinase (PI3K)/AKT pathway was involved in estrogen‑induced metastasis in ovarian cancer cells. In the present study, the role and mechanism of estrogen‑induced invasion was further explored using a stable short hairpin RNA (shRNA) estrogen receptor α/β (ER α/β) SKOV3 cell line when ER α and ER β were knocked down by lentiviral infection. The effects of estrogen and LY294002, a PI3K inhibitor, on the invasion of shRNA ER α/β SKOV3 cells were evaluated in vitro and in vivo. 17‑β estradiol promoted cell invasion, activated phosphorylated AKT in a dose‑ and time‑dependent manner, decreased E‑cadherin and increased cytoplasmic α‑actinin‑4 expression. When the PI3K/AKT pathway was suppressed by LY294002, the effect of estrogen was attenuated. Estrogen stimulated the growth of shRNA ER α/β SKOV3 xenograft tumors in nude mice, whereas LY294002 inhibited the growth and antagonized the effect of estrogen. The results indicate that estrogen promotes the invasion of ovarian cancer cells via activation of the PI3K/AKT pathway, downregulation of E‑cadherin and upregulation of α‑actinin‑4 in an ER‑independent manner. Inhibiting the PI3K/AKT pathway may be a useful treatment for ovarian carcinoma. | 25,216,292 | [
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Forest stand growth dynamics in Central Europe have accelerated since 1870. | Forest ecosystems have been exposed to climate change for more than 100 years, whereas the consequences on forest growth remain elusive. Based on the oldest existing experimental forest plots in Central Europe, we show that, currently, the dominant tree species Norway spruce and European beech exhibit significantly faster tree growth (+32 to 77%), stand volume growth (+10 to 30%) and standing stock accumulation (+6 to 7%) than in 1960. Stands still follow similar general allometric rules, but proceed more rapidly through usual trajectories. As forest stands develop faster, tree numbers are currently 17-20% lower than in past same-aged stands. Self-thinning lines remain constant, while growth rates increase indicating the stock of resources have not changed, while growth velocity and turnover have altered. Statistical analyses of the experimental plots, and application of an ecophysiological model, suggest that mainly the rise in temperature and extended growing seasons contribute to increased growth acceleration, particularly on fertile sites. | 25,216,297 | [
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Odour enrichment increases adult-born dopaminergic neurons in the mouse olfactory bulb. | The olfactory bulb (OB) is the first brain region involved in the processing of olfactory information. In adult mice, the OB is highly plastic, undergoing cellular/molecular dynamic changes that are modulated by sensory experience. Odour deprivation induces down-regulation of tyrosine hydroxylase (TH) expression in OB dopaminergic interneurons located in the glomerular layer (GL), resulting in decreased dopamine in the OB. Although the effect of sensory deprivation is well established, little is known about the influence of odour enrichment on dopaminergic cells. Here we report that prolonged odour enrichment on C57BL/6J strain mice selectively increases TH-immunopositive cells in the GL by nearly 20%. Following odour enrichment on TH-green fluorescent protein (GFP) transgenic mice, in which GFP identified both mature TH-positive cells and putative immature dopaminergic cells expressing TH mRNA but not TH protein, we found a similar 20% increase in GFP-expressing cells, with no changes in the ratio between TH-positive and TH-negative cells. These data suggest that enriched conditions induce an expansion in the whole dopaminergic lineage. Accordingly, by using 5-bromo-2-deoxyuridine injections to label adult-generated cells in the GL of TH-GFP mice, we found an increase in the percentage of 5-bromo-2-deoxyuridine-positive dopaminergic cells in enriched compared with control conditions, whereas no differences were found for calretinin- and calbindin-positive subtypes. Strikingly, the fraction of newborn cells among the dopaminergic population doubled in enriched conditions. On the whole, our results demonstrate that odour enrichment drives increased integration of adult-generated dopaminergic cells that could be critical to adapt the OB circuits to the environmental incoming information. | 25,216,299 | [
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Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. | Dipeptidyl peptidase-4 (DPP4) is a widely expressed enzyme transducing actions through an anchored transmembrane molecule and a soluble circulating protein. Both membrane-associated and soluble DPP4 exert catalytic activity, cleaving proteins containing a position 2 alanine or proline. DPP4-mediated enzymatic cleavage alternatively inactivates peptides or generates new bioactive moieties that may exert competing or novel activities. The widespread use of selective DPP4 inhibitors for the treatment of type 2 diabetes has heightened interest in the molecular mechanisms through which DPP4 inhibitors exert their pleiotropic actions. Here we review the biology of DPP4 with a focus on: 1) identification of pharmacological vs physiological DPP4 substrates; and 2) elucidation of mechanisms of actions of DPP4 in studies employing genetic elimination or chemical reduction of DPP4 activity. We review data identifying the roles of key DPP4 substrates in transducing the glucoregulatory, anti-inflammatory, and cardiometabolic actions of DPP4 inhibitors in both preclinical and clinical studies. Finally, we highlight experimental pitfalls and technical challenges encountered in studies designed to understand the mechanisms of action and downstream targets activated by inhibition of DPP4. | 25,216,328 | [
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Agenesia of the left atrial appendage: possible but very rare. | : Agenesia of the left atrial appendage in a patient with atrial fibrillation is shown. Although of interest, the prevalence of this abnormality is very low. | 25,216,332 | [
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Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age. | The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven by the spatial nature of the studies so far. Alternatively, relational binding may simply require more attentional resources. We assessed relational and conjunctive binding in three age groups and we included an interfering task (i.e., an articulatory suppression task). Binding was examined in a working memory (WM) task using non-spatial features: shape and colour. Thirty-one young adults (mean age = 22.35), 30 middle-aged adults (mean age = 54.80) and 30 older adults (mean age = 70.27) performed the task. Results show an effect of type of binding and an effect of age but no interaction between type of binding and age. The interaction between type of binding and interference was significant. These results indicate that aging affects relational binding and conjunctive binding similarly. However, relational binding is more susceptible to interference than conjunctive binding, which suggests that relational binding may require more attentional resources. We suggest that a general decline in WM resources associated with frontal dysfunction underlies age-related deficits in WM binding. | 25,216,357 | [
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Determinants of functional disability in Huntington's disease: role of cognitive and motor dysfunction. | The clinical syndrome of Huntington's disease (HD) is notable for a triad of motor, cognitive, and emotional features. All HD patients eventually become occupationally disabled; however, the factors that render HD patients unable to maintain employment have not been extensively studied. This review begins by discussing the clinical triad of HD, highlighting the distinction in the motor disorder between involuntary movements, such as chorea, and voluntary movement impairment, with the latter contributing more to functional disability. Cognitive disorder clearly contributes to disability, though the relative contribution compared to motor is difficult to unravel, especially because many of the tests used to asses "cognition" have a strong motor component. The role of emotional changes in disability needs more study. The literature on contributions to functional disability, driving impairment, and nursing home placement is reviewed. Relevant experience is presented from the long-standing JHU HD observational study on motor versus cognitive onset, as well as on cognitive and motor features at the time when individuals discontinued working. Finally, we briefly review government policies in several countries on disability determination. We interpret the data from our own studies and from the literature to indicate that there is usually a close relationship between cognitive and motor dysfunction, and that it is critical to take both into consideration in determining disability. © 2014 International Parkinson and Movement Disorder Society. | 25,216,368 | [
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Animal models of Huntington's disease for translation to the clinic: best practices. | Mouse models of Huntington's disease (HD) recapitulate many aspects of the human disease. These genetically modified mice are powerful tools that are used not only to examine the pathogenesis of the disease, but also to assess the efficacy of potential new treatments. Disappointingly, in the past few years we have seen the success of potential therapies in animal studies, subsequently followed by failure in clinical trials. We discuss here a number of factors that influence the translatability of findings from the preclinical to the clinical realm. In particular, we discuss issues related to sample size, reporting of information regarding experimental protocols and mouse models, assignment to experimental groups, incorporation of cognitive measures for early phases of the disease, environmental enrichment, surrogate measures for survival, and the use of more than one HD mouse model. Although it is reasonable to question the appropriateness of the animal models used, we argue that it is more parsimonious to assume that improvements in experimental design and publication of negative results will lead to improved translatability to the clinic and insights about HD pathophysiology. | 25,216,369 | [
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Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches. | Since the identification of the Huntington's disease (HD) gene, knowledge has accumulated about mechanisms directly or indirectly affected by the mutated Huntingtin protein. Transgenic and knock-in animal models of HD facilitate the preclinical evaluation of these targets. Several treatment approaches with varying, but growing, preclinical evidence have been translated into clinical trials. We review major landmarks in clinical development and report on the main clinical trials that are ongoing or have been recently completed. We also review clinical trial settings and designs that influence drug-development decisions, particularly given that HD is an orphan disease. In addition, we provide a critical analysis of the evolution of the methodology of HD clinical trials to identify trends toward new processes and endpoints. Biomarker studies, such as TRACK-HD and PREDICT-HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q-Motor) measures, and novel cognitive endpoints. All of these endpoints are currently applied in ongoing clinical trials, which will provide insight into their reliability, sensitivity, and validity, and their use may expedite proof-of-concept studies. We also outline the specific opportunities that could provide a framework for a successful avenue toward identifying and efficiently testing and translating novel mechanisms of action in the HD field. | 25,216,371 | [
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Competitive coordination control of the AIE and micro states of supramolecular gel: an efficient approach for reversible dual-channel stimuli-response materials. | An organogelator (G2) based on multi self-assembly driving forces, fluorescent signal groups and coordination binding sites was designed and synthesized. G2 could form a stable Cd(2+)-coordinated supramolecular metallogel (CdG) accompanied by strong brilliant blue aggregation-induced fluorescence emission (AIE). By the competitive coordination of Cd(2+) with gelator and I(−), the AIE of CdG could be reversibly switched "on-off-on" under gel–gel states via alternative adding I(−) and Cd(2+) into CdG. Interestingly, because of the competitive coordination of Cd(2+) with I(−), the micro structure of the CdG xerogel carried out dramatic changes and formed lots of micro cavities. These micro cavities could absorb iodine vapour and caused the color of CdG xerogel change from white to brown. The CdG could not only act as a convenient high selective and sensitive I(-) detection test kit (detection limit for I(-) is 1.0 × 10(-7) M) but also as rewritable dual-channel security display materials. | 25,216,393 | [
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Changes in the frequencies of abdominal wall hernias and the preferences for their repair: a multicenter national study from Turkey. | Abdominal wall hernias are a common problem in the general population. A Western estimate reveals that the lifetime risk of developing a hernia is about 2%. As a result, hernia repairs likely comprise the most frequent general surgery operations. More than 20 million hernias are estimated to be repaired every year around the world. Numerous repair techniques have been described to date however tension-free mesh repairs are widely used today because of their low hernia recurrence rates. Nevertheless, there are some ongoing debates regarding the ideal approach (open or laparoscopic), the ideal anesthesia (general, local, or regional), and the ideal mesh (standard polypropylene or newer meshes). | 25,216,417 | [
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Giant inguinoscrotal hernia--report of a rare case with literature review. | Massive inguinoscrotal hernias extending below the midpoint of the inner thigh, in the standing position constitute giant inguinoscrotal hernias. We report a patient who presented with giant right inguinal hernia with bilateral hydrocele for 25 years. He had no cardiorespiratory illnesses. He was taken up for surgery under general anesthesia after preoperative respiratory exercises. Sliding hernia with entire greater omentum, small bowel, and appendix as contents was identified. Meshplasty after omentectomy with bilateral subtotal excision of sac, right orchidectomy, and scrotoplasty were done. Giant inguinoscrotal hernias pose significant problems while replacing bowel contents because of the increase in intraabdominal and intrathoracic pressures. Recurrence is another complication seen after successful surgical management. Various techniques such as preoperative pneumoperitoneum, debulking abdominal contents with extensive bowel resections, or omentectomy and phrenectomy have been tried. Postoperative elective ventilation is also needed in many cases. We describe simple reduction with omentectomy as a viable technique in this patient. He did not need elective ventilation due to preoperative respiratory exercises and preparation and review of the literature. | 25,216,421 | [
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Resorbable synthetic mesh supported with omentum flap in the treatment of giant hiatal hernia. | Covering a large hiatal hernia with a mesh has become a basic procedure in the last few years. However, mesh implants are associated with high complication rates (esophageal erosion, perforation, fistula, etc.). We propose using a synthetic resorbable mesh supported with an omental flap as a possible solution to this problem. A 54-year-old female patient with a large hiatal defect (9 cm) was laparoscopically implanted with a synthetic resorbable mesh supported with an omental flap. The surgical procedure was successful and the patient was discharged on postoperative day 2. On a follow-up examination 6 months after surgery, she remained free of relapse or complication signs. Supporting an implanted resorbable mesh with an omental flap may be a solution to the problems posed by large esophageal hiatus defects. However, more studies based on larger patient samples and longer follow-up periods are necessary. | 25,216,419 | [
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Use of stapling devices for safe cholecystectomy in acute cholecystitis. | Many techniques are described for the ligation of a difficult cystic duct (CD). The aim of this study is to assess the effectiveness and safety of stapling of a difficult CD in acute cholecystitis using Endo-GIA. From January 2008 to June 2012, 1441 patients with cholelithiasis underwent laparoscopic cholecystectomy (LC) at the Department of General Surgery, Haydarpasa Numune Education and Research Hospital. Of these, 19 (0.62%) were identified as having a difficult CD and were ligated using an Endo-GIA stapler. All patients were successfully treated with a laparoscopic approach. The length of hospital stay was 3.4 days. There were umbilical wound infections in 4 patients (21%). The length of follow-up ranged from 1.0 to 50.4 months. In conclusion, Endo-GIA is a safe and easy treatment method for patients with a dilated and difficult CD. The cystic artery should be isolated and ligated if possible before firing the Endo-GIA stapler. If isolation and stapling are not possible, fibrin sealant can be applied to avoid bleeding. The vascular Endo-GIA can be applied in a large CD, but for acute cholecystitis with an edematous CD, the Endo-GIA roticulator 4.8 or 3.5 stapler is preferred. | 25,216,423 | [
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Tissue management with tri-staple technology in major and minor laparoscopic liver resections. | One of the most relevant technologic advancements in laparoscopic liver resection (LLR) is owing to the improved ability to safely secure and divide vascular and biliary structures and the liver parenchyma by the use of endostaplers. We compared, retrospectively, 35 LLRs with the Tri-Staple technology versus 57 LLRs without, during a 14-month period. Colorectal liver metastases were overall the main indication for LLR. Neither major hepatectomy nor left lateral sectionectomy was done in the nonstapled group. Mean surgical time and blood loss were similar, whereas the tumor number and size were significantly larger in the stapled group (P ≤ 0.01). The conversion rate was 0% and 3.5% (n = 2); and the morbidity rate was 9% (n = 3) and 12% (n = 7), respectively, in the stapled and nonstapled group (P = 0.8). No overall 3-month mortality was recorded. Endo GIA Reloads with Tri-Staple technology allow a proper division of the intrahepatic vessels and biliary structure. These devices in LLRs are safe and feasible, allowing major hepatectomy and complex cases as 2-staged procedures and laparoscopic living donor liver resections. | 25,216,429 | [
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The combination application of space filling and closed irrigation suction in reconstruction of sacral decubitus ulcer. | Dead space and poor drainage are the main reasons for intractable sacral decubitus ulcers. The objective of this study was to investigate the effects of treatment for sacral decubitus ulcer using space filling through muscle flap and closed irrigation. A total of 22 patients with serious sacral decubitus ulcer were treated with space filling through muscle flap and closed irrigation. After debridement of the decubitus ulcer, the infected areas over the bony prominence and osseous prominences were debrided. We elevated biceps femoris long head or semitendinosus and semimembranosus muscle. Pedicled by proximal part of muscle, the muscle flap was elevated to cover the ischial tuberosity. Transfusion systems of inflow and outflow drainage were placed between the muscle flap and ischial tuberosity. Wound healing and complications were observed. One wound dehiscence healed after secondary suturing. One wound gradually healed by dressing change after 3 weeks. The other cases had good results. Space filling and closed irrigation were complementary. The use of these two methods simultaneously is useful for the management of sacral decubitus ulcers. | 25,216,432 | [
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Disability-adjusted life years (DALYs) in general population with pelvic organ prolapse: a study based on the prolapse quality-of-life questionnaire (P-QOL). | To evaluate the impact of pelvic organ prolapse (POP) on quality of life in symptomatic and asymptomatic women. This is a cross-sectional study in a general population of adult women. Symptomatic and asymptomatic women with POP were studied. Symptomatic women were defined as those who reported the presence/feeling of lump/bulge/pressure in the vagina and on vaginal examination had the sign of POP defined as the leading edge of the vagina wall/cervix presenting at or beyond the hymeneal remnants. All women were asked to self-complete the Prolapse Quality of life questionnaire (P-QOL) to estimate the disability-adjusted life-years (DALYs) lost due to symptomatic POP. DALYs for a symptomatic POP were calculated as the sum of the years of life lost due to premature mortality (YLL) in the population and the years lost due to disability (YLD). To determinate the optimal threshold of each P-QOL domain in relationship to the symptomatic POP population a receiver operating curve (ROC) and area under curve (AUC) analysis were used. A total of 785 were recruited. Only 539 (68.7%) consented to participate in the study. The mean age was 47 years (range 18-82 years). The total scores for each of the P-QOL domains were found to be significantly higher in symptomatic prolapse subjects compared to asymptomatic subjects (p<0.05). Estimated DALY lost per year per 1000 women obtained were 217.0 vs 324.8, lost years of 14.5 vs 10.3 in 50 vs 60-year old women. In this group of women with POP the quality of life is severely affected. The DALYs revealed lost years due to symptomatic POP. | 25,216,448 | [
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Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint. | The spindle assembly checkpoint arrests mitotic progression until each kinetochore secures a stable attachment to the spindle. Despite fluctuating noise, this checkpoint remains robust and remarkably sensitive to even a single unattached kinetochore among many attached kinetochores; moreover, the checkpoint is silenced only after the final kinetochore-spindle attachment. Experimental observations have shown that checkpoint components stream from attached kinetochores along microtubules towards spindle poles. Here we incorporate this streaming behaviour into a theoretical model that accounts for the robustness of checkpoint silencing. Poleward streams are integrated at spindle poles, but are diverted by any unattached kinetochore; consequently, accumulation of checkpoint components at spindle poles increases markedly only when every kinetochore is properly attached. This step change robustly triggers checkpoint silencing after, and only after, the final kinetochore-spindle attachment. Our model offers a conceptual framework that highlights the role of spatiotemporal regulation in mitotic spindle checkpoint signalling and fidelity of chromosome segregation. | 25,216,458 | [
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Highly selective and sensitive optical sensor for determination of Pb2+ and Hg2+ ions based on the covalent immobilization of dithizone on agarose membrane. | A highly sensitive and selective optical membrane for determination of Hg(2+) and Pb(2+) was prepared by covalent immobilization of dithizone on agarose membrane. In addition to its high stability, reproducibility and relatively long lifetime, the proposed optical sensor revealed good selectivity for target ions over a large number of alkali, alkaline earth, transition, and heavy metal ions. The proposed optical membrane displays linear responses from 1.1×10(-8) to 2.0×10(-6) mol L(-1) and 1.2×10(-8) to 2.4×10(-6) mol L(-1) for Hg(2+) and Pb(2+), respectively. The limits of detection (LOD) were 2.0×10(-9) mol L(-1) and 4.0×10(-9) mol L(-1) for Hg(2+) and Pb(2), respectively. The prepared optical membrane was successfully applied to the determination of Hg(2+) and Pb(2+) in industrial wastes, spiked tap water and natural waters without any preconcentration step. | 25,216,460 | [
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Immediate and mid-term effects of pyrimethanil toxicity on microalgae by simulating an episodic contamination. | Since pesticides can represent a threat for non-target aquatic communities, including microalgae, we looked at the effects of the fungicide pyrimethanil on the growth of the freshwater green microalgae Selenastrum capricornutum. Additionally, attenuation of the toxicity of pyrimethanil due to its dissipation in the water was assessed. Pyrimethanil-contaminated samples were taken from outdoor mesocosms one (1.4 mg L(-1) of pyrimethanil) and ten (0.78 mg L(-1) of pyrimethanil) days after pyrimethanil application. Different dilutions were prepared using both nutrient-rich culture medium (LC Oligo) and non-contaminated mesocosm samples, and cell growth inhibition was assessed. Reference mesocosm samples were also diluted with LC Oligo in order to verify how the nutrient concentration in the LC Oligo could improve cell growth. Comparing cell growth of population exposed to pyrimethanil-treated sample taken at day 1 with cells growing in reference sample and LC Oligo, the growth inhibition was 80% (± 6.5) and 95% (± 2.0), respectively. The toxicity of samples taken from contaminated mesocosms at day 10 was attenuated to 34% (± 15) (when compared with reference sample) and 88% (± 3.0) (when compared with LC Oligo), as pyrimethanil concentrations in the mesocosms decreased. In conclusion, (i) pyrimethanil can be an environmental disturber for the microalgae; (ii) the toxicity of pyrimethanil in water was reduced almost 2.4 times (when compared with the reference sample) at as short a period as 10d if assuming that pesticide entrance is not continuous; (iii) toxicity of an environmental sample could be underestimated if the sample/medium used in dilution presents different nutrient levels. | 25,216,469 | [
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Multilayer surface albedo for face recognition with reference images in bad lighting conditions. | In this paper, we propose a multilayer surface albedo (MLSA) model to tackle face recognition in bad lighting conditions, especially with reference images in bad lighting conditions. Some previous researches conclude that illumination variations mainly lie in the large-scale features of an image and extract small-scale features in the surface albedo (or surface texture). However, this surface albedo is not robust enough, which still contains some detrimental sharp features. To improve robustness of the surface albedo, MLSA further decomposes it as a linear sum of several detailed layers, to separate and represent features of different scales in a more specific way. Then, the layers are adjusted by separate weights, which are global parameters and selected for only once. A criterion function is developed to select these layer weights with an independent training set. Despite controlled illumination variations, MLSA is also effective to uncontrolled illumination variations, even mixed with other complicated variations (expression, pose, occlusion, and so on). Extensive experiments on four benchmark data sets show that MLSA has good receiver operating characteristic curve and statistical discriminating capability. The refined albedo improves recognition performance, especially with reference images in bad lighting conditions. | 25,216,483 | [
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Multispectral photometric stereo for acquiring high-fidelity surface normals. | Multispectral imaging and photometric stereo are common in 3D imaging but rarely have been combined. Reconstructing a 3D object's shape using photometric stereo is challenging owing to indirect illumination, specular reflection, and self-shadows, and removing interreflection in photometric stereo is problematic. A new multispectral photometric-stereo method removes interreflection on diffuse materials using multispectral-reflectance information and reconstructs 3D shapes with high accuracy. You can integrate this method into photometric-stereo systems by simply substituting the original camera with a multispectral camera. | 25,216,479 | [
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Distributed Cooperative Optimal Control for Multiagent Systems on Directed Graphs: An Inverse Optimal Approach. | In this paper, the inverse optimal approach is employed to design distributed consensus protocols that guarantee consensus and global optimality with respect to some quadratic performance indexes for identical linear systems on a directed graph. The inverse optimal theory is developed by introducing the notion of partial stability. As a result, the necessary and sufficient conditions for inverse optimality are proposed. By means of the developed inverse optimal theory, the necessary and sufficient conditions are established for globally optimal cooperative control problems on directed graphs. Basic optimal cooperative design procedures are given based on asymptotic properties of the resulting optimal distributed consensus protocols, and the multiagent systems can reach desired consensus performance (convergence rate and damping rate) asymptotically. Finally, two examples are given to illustrate the effectiveness of the proposed methods. | 25,216,491 | [
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Approximation-Based Discrete-Time Adaptive Position Tracking Control for Interior Permanent Magnet Synchronous Motors. | This paper considers the problem of discrete-time adaptive position tracking control for a interior permanent magnet synchronous motor (IPMSM) based on fuzzy-approximation. Fuzzy logic systems are used to approximate the nonlinearities of the discrete-time IPMSM drive system which is derived by direct discretization using Euler method, and a discrete-time fuzzy position tracking controller is designed via backstepping approach. In contrast to existing results, the advantage of the scheme is that the number of the adjustable parameters is reduced to two only and the problem of coupling nonlinearity can be overcome. It is shown that the proposed discrete-time fuzzy controller can guarantee the tracking error converges to a small neighborhood of the origin and all the signals are bounded. Simulation results illustrate the effectiveness and the potentials of the theoretic results obtained. | 25,216,493 | [
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Aminoglycoside-induced damage in the statocyst of the longfin inshore squid, Doryteuthis pealeii. | Squid are a significant component of the marine biomass and are a long-established model organism in experimental neurophysiology. The squid statocyst senses linear and angular acceleration and is the best candidate for mediating squid auditory responses, but its physiology and morphology are rarely studied. The statocyst contains mechano-sensitive hair cells that resemble hair cells in the vestibular and auditory systems of other animals. We examined whether squid statocyst hair cells are sensitive to aminoglycosides, a group of antibiotics that are ototoxic in fish, birds, and mammals. To assess aminoglycoside-induced damage, we used immunofluorescent methods to image the major cell types in the statocyst of longfin squid (Doryteuthis pealeii). Statocysts of live, anesthetized squid were injected with either a buffered saline solution or neomycin at concentrations ranging from 0.05 to 3.0 mmol l(-1). The statocyst hair cells of the macula statica princeps were examined 5 h post-treatment. Anti-acetylated tubulin staining showed no morphological differences between the hair cells of saline-injected and non-injected statocysts. The hair cell bundles of the macula statica princeps in aminoglycoside-injected statocysts were either missing or damaged, with the amount of damage being dose-dependent. The proportion of missing hair cells did not increase at the same rate as damaged cells, suggesting that neomycin treatment affects hair cells in a nonlethal manner. These experiments provide a reliable method for imaging squid hair cells. Further, aminoglycosides can be used to induce hair cell damage in a primary sensory area of the statocyst of squid. Such results support further studies on loss of hearing and balance in squid. | 25,216,502 | [
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Enteric pathogens and cellular transformation: bridging the gaps. | Cancer patients in general, either due to the nature of their underlying illness or because of being on chemotherapeutic regimens, are at increased risk of infection. Indeed, microbes can exploit the innate plasticity of the epithelial cells to promote their trans-differentiation into a mesenchymal phenotype in a process called epithelial-to-mesenchymal transition (EMT). This process as well as the reverse, mesenchymal-epithelial transition, occurs repeatedly during normal embryonic development and is recapitulated during pathologies such as tissue fibrosis or tumor metastasis. Multiple signaling pathways including TGFβ, Wnt and Notch working together with transcription factors such as Slug, Snail, Twist, Zeb1 and 2 suppress E-cadherin, induce EMT and result in loss of cell-cell adhesion, increased tumor progression and migration. In addition, in approximately 20% of all cases, microbial organisms including pathobionts of the commensal microbiota, have been implicated in inflammatory processes that promote tumor growth. Thus, the dynamic process of EMT serves to enhance tumor progression and is also involved in the generation of cancer stem cells (CSCs) across multiple organ systems including colon cancer. Suffice to say, EMT and CSC molecular pathways activated by pathogens, may represent a unique therapeutic alternative to conventional anti-neoplastic strategy to mitigate early stage metastasis and/or frank malignancy. | 25,216,513 | [
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RASAL2 down-regulation in ovarian cancer promotes epithelial-mesenchymal transition and metastasis. | Ovarian cancer is the most lethal gynecologic malignancy, and transcoelomic metastasis is responsible for the greatest disease mortality. Although intensive efforts have been made, the mechanism behind this process remains unclear. RASAL2 is a GTPase activating proteins (GAPs) which was recently reported as a tumor suppressor in breast cancer. In this study, we identified RASAL2 as a regulator of epithelial-mesenchymal transition (EMT) and metastasis in ovarian cancer. RASAL2 was down-regulated in ovarian cancer samples compared with normal tissue samples, especially in advanced stages and grades. RASAL2 knockdown in ovarian cancer cell lines promoted in vitro anchorage-independent growth, cell migration and invasion and in vivo tumor formation. Moreover, we observed EMT in RASAL2-depleted cells. E-cadherin-mediated cell-cell adhesion was attenuated, and mesenchymal markers were up-regulated. Further investigation revealed that the oncogenic role of RASAL2 down-regulation was mediated by the Ras-ERK pathway. RASAL2 knockdown activated the Ras-ERK pathway, and inhibition of the pathway reversed the functional effects of RASAL2 depletion. Together, our results implicate RASAL2 as an EMT regulator and tumor suppressor in ovarian cancer, and down-regulation of RASAL2 promotes ovarian cancer progression. | 25,216,515 | [
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Pharmacokinetics of imipenem in critically ill patients during empirical treatment of nosocomial pneumonia: a comparison of 0.5-h and 3-h infusions. | In critically ill patients, pathophysiological changes alter the pharmacokinetics of antibiotics. Imipenem exhibits primarily time-dependent killing. Its administration by prolonged infusion may increase the time for which its plasma concentration exceeds the minimum inhibitory concentrations (MICs) of suspected pathogens. The objectives of this study were to compare the pharmacokinetic parameters of imipenem administered by standard short infusion (1g imipenem/1g cilastatin over 30min three times daily) and by extended infusion with a reduced total dose (0.5g imipenem/0.5g cilastatin over 3h four times daily) and to compare the target pharmacokinetic/pharmacodynamic indices, namely percentage of the dosing interval for which the free plasma concentration of imipenem exceeds the MIC and 4× MIC (%fT>MIC and %fT>4×MIC) of 0.5, 1, 2 and 4mg/L, for these two regimens in critically ill adult patients with nosocomial pneumonia on Day 2 of empirical antibiotic therapy. The study included 22 patients. Whilst no significant differences were found between both groups for %fT>MIC, %fT>4×MIC was 87.4±12.19%, 68.6±15.08%, 47.31±6.64% and 27.81±9.52% of the 8-h interval in the short infusion group for MICs of 0.5, 1, 2 and 4mg/L, respectively, and 85.15±17.57%, 53.14±27.27%, 13.55±24.47% and 0±0% of the 6-h interval for the extended infusion group. In conclusion, administration of 0.5g of imipenem by a 3-h infusion every 6h does not provide sufficient drug concentrations to treat infections caused by pathogens with a MIC of ≥2mg/L. | 25,216,543 | [
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Complexity measures for the evolutionary categorization of organisms. | Complexity measures are used to compare the genomic characteristics of five organisms belonging to distinct classes spanning the evolutionary tree: higher eukaryotes, amoebae, unicellular eukaryotes and bacteria. The comparisons are undertaken using the full four-letter alphabet and the coarse grained two-letter alphabets AG-CT and AT-CG. We show that the conditional probability matrix for the four-letter and AT-CG alphabet is markedly asymmetric in eukaryotes while it is nearly symmetric in bacterial genomes. Spatial asymmetry is revealed in the four-letter alphabet, signifying that the probability fluxes are nonvanishing and thus the reading sense of a sequence is irreversible for all organisms. Calculations of the block entropy and excess entropy demonstrate that the human genome accommodates better all possible block configurations, especially for long blocks. With respect to point-to-point details and to spatial arrangement of blocks the exit distance distributions from a particular letter demonstrate long distance characteristics in the eukaryotic sequences for all three alphabets, while the bacterial (prokaryotic) genomes deviate indicating short range characteristics. Overall, the conditional probability, the fluxes, the block entropy content and the exit distance distributions can be used as markers, discriminating between eukaryotic and prokaryotic DNA, allowing in many cases to discern details related to finer classes. In all cases the reduction from four letters to two masks some important statistical and spatial properties, with the AT-CG alphabet having higher ability of discrimination than the AG-CT one. In particular, the AT-CG alphabet reduction accentuates the CpG related properties (conditional probabilities w32, long ranged exit distance distribution for A and T nucleotides), but masks sequence asymmetry and irreversibility in all examined organisms. | 25,216,557 | [
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COMT met allele differentially predicts risk versus severity of aberrant eating in a large community sample. | Prefrontal dopamine (DA) transmission participates in the reinforcement of reward-driven behaviors like eating. Because catechol-O-methyltransferase (COMT) degrades DA and is expressed in the prefrontal cortex, variation in the COMT gene may modulate eating behavior. Previous studies have shown that the met allele of the COMT val158met single nucleotide polymorphism (SNP) is associated with Bulimia Nervosa (BN). The specific aim of this study was to test whether the met allele increased risk for, and severity of, eating disorder symptomatology in community volunteers. Caucasian adults (N=1003; 51.2% female) from the University of Pittsburgh Adult Health and Behavior Project (AHAB) were genotyped and completed the Eating Disorders Inventory (EDI). Logistic and Poisson regression analyses assessed genotype-dependent presence and severity of eating disorder symptomatology. The met allele was significantly associated with the presence of symptoms on the Bulimia subscale and the severity of Body Dissatisfaction scores. All EDI subscales significantly predicted BMI. To our knowledge, these are the first data indicating that the COMT met allele increases risk for some symptoms of disordered eating, while increasing severity of others, in a community sample. These novel findings may have important implications for understanding the etiology of heterogeneous disordered eating phenotypes. | 25,216,558 | [
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Attentional biases to body shape images in adolescents with anorexia nervosa: an exploratory eye-tracking study. | Body image distortion (BID) plays an important role in the etiology and maintenance of anorexia nervosa (AN). Previous studies of BID in AN showed small biases in visual scanning behavior (VSB) towards images of body shapes. The aim of this study is to investigate biases in VSB when body shape images compete with images with a different theme (social interactions) for subjects׳ attention. When images of thin body shapes (TBS) were presented alongside images of social interactions, AN patients (n=13) spent significantly more time looking at TBSs rather than at social interactions, but controls (n=20) did not. When images of fat body shapes (FBS) were presented alongside images of social interactions, AN patients spent significantly more time looking at FBSs rather than at social interactions, but controls did not. When images of TBSs, FBSs and social interactions were presented alongside each other, AN patients demonstrated a hierarchy in their attention allocation, choosing to spend the most viewing time on TBS images, followed by FBS images and then images with social interactions. Under the three experimental conditions, AN patients demonstrated large biases in their visual scanning behavior (VSB). Biases in VSB may provide physiologically objective measures that characterize patients with AN. | 25,216,561 | [
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Human papillomavirus type 16 E7 oncoprotein causes a delay in repair of DNA damage. | Patients with human papillomavirus related (HPV+) head and neck cancers (HNCs) demonstrate improved clinical outcomes compared to traditional HPV negative (HPV-) HNC patients. We have recently shown that HPV+ HNC cells are more sensitive to radiation than HPV- HNC cells. However, roles of HPV oncogenes in regulating the response of DNA damage repair remain unknown. Using immortalized normal oral epithelial cell lines, HPV+ HNC derived cell lines, and HPV16 E7-transgenic mice we assessed the repair of DNA damage using γ-H2AX foci, single and split dose clonogenic survival assays, and immunoblot. The ability of E7 to modulate expression of proteins associated with DNA repair pathways was assessed by immunoblot. HPV16 E7 increased retention of γ-H2AX nuclear foci and significantly decreased sublethal DNA damage repair. While phospho-ATM, phospho-ATR, Ku70, and Ku80 expressions were not altered by E7, Rad51 was induced by E7. Correspondingly, HPV+ HNC cell lines showed retention of Rad51 after γ-radiation. Our findings provide further understanding as to how HPV16 E7 manipulates cellular DNA damage responses that may underlie its oncogenic potential and influence the altered sensitivity to radiation seen in HPV+ HNC as compared to HPV- HNC. | 25,216,575 | [
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Autophagy regulates amyotrophic lateral sclerosis-linked fused in sarcoma-positive stress granules in neurons. | Mutations in fused in sarcoma (FUS), a DNA/RNA binding protein, have been associated with familial amyotrophic lateral sclerosis (fALS), which is a fatal neurodegenerative disease that causes progressive muscular weakness and has overlapping clinical and pathologic characteristics with frontotemporal lobar degeneration. However, the role of autophagy in regulation of FUS-positive stress granules (SGs) and aggregates remains unclear. We found that the ALS-linked FUS(R521C) mutation causes accumulation of FUS-positive SGs under oxidative stress, leading to a disruption in the release of FUS from SGs in cultured neurons. Autophagy controls the quality of proteins or organelles; therefore, we checked whether autophagy regulates FUS(R521C)-positive SGs. Interestingly, FUS(R521C)-positive SGs were colocalized to RFP-LC3-positive autophagosomes. Furthermore, FUS-positive SGs accumulated in atg5(-/-) mouse embryonic fibroblasts (MEFs) and in autophagy-deficient neurons. However, FUS(R521C) expression did not significantly impair autophagic degradation. Moreover, autophagy activation with rapamycin reduced the accumulation of FUS-positive SGs in an autophagy-dependent manner. Rapamycin further reduced neurite fragmentation and cell death in neurons expressing mutant FUS under oxidative stress. Overall, we provide a novel pathogenic mechanism of ALS associated with a FUS mutation under oxidative stress, as well as therapeutic insight regarding FUS pathology associated with excessive SGs. | 25,216,585 | [
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Hemodynamic and metabolic effects of estrogen plus progestin therapy in hypertensive postmenopausal women treated with an ACE-inhibitor or a diuretic. | The aim of the study was to assess the hemodynamic and metabolic actions of estrogen plus progestin therapy (EPT) in hypertensive, postmenopausal women treated with perindopril (ACEI) or hydrochlorothiazide (HCTZ). A group of normotensive postmenopausal women was also studied. 100 hypertensive and 40 normotensive postmenopausal women were recruited for the study. The hypertensive females were randomly assigned to receive ACEI or HCTZ for 12 months. The patients of the ACEI group and the patients of the HCTZ group, as well as normotensives, were further subdivided into two subgroups each. One subgroup received estrogen plus progestin therapy (EPT+), the other subgroup received no hormone replacement (EPT-). Combined hormone replacement with transdermal patches releasing 17β-estradiol and norethisterone was used. Office and 24-hour ambulatory blood pressure was measured at baseline and during follow-up. Renal plasma flow (RPF) was measured using the clearance of [125I]-iodohippuran. Pulse wave velocity (PWV) was determined with an automatic device. In normotensive postmenopausal women, transdermal estrogen plus progestin therapy increases RPF and insulin sensitivity, decreases PWV, decreases total and LDL cholesterol, and decreases uric acid serum levels. Perindopril (4 mg/day) and hydrochlorothiazide (25 mg/day) were equally effective in reducing blood pressure in postmenopausal, hypertensive subjects. In these females, perindopril increased RPF and decreased PWV and plasma insulin levels. These effects of the ACEI were not altered by estrogen plus progestin therapy. Hydrochlorothiazide decreased RPF and increased plasma insulin and uric acid concentrations in hypertensive subjects whom were not receiving estrogen plus progestin therapy. The unfavorable metabolic and hemodynamic actions of the diuretic were counteracted by estrogen plus progestin therapy. Concomitant estrogen plus progestin therapy may be a method to avoid unfavorable hemodynamic and metabolic effects of thiazide diuretics in hypertensive, postmenopausal women. | 25,216,597 | [
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Advances in percutaneous coronary interventions for elderly patients. | Coronary heart disease (CHD) is one of the leading causes of morbidity and the most common cause of death in older adults. Paradoxically, elderly patients tend to be systematically excluded from randomized-controlled cardiovascular trials, which complicates decision-making in this population. Management of CHD in the elderly is frequently more difficult in virtue of chronic comorbid conditions and aging-intrinsic dynamics. Despite these challenges, the number of elderly and very elderly patients undergoing percutaneous coronary interventions (PCI) is increasing. Elderly patients in many registries and large clinical series exhibit even a greater benefit from interventional procedures than younger patients, but they have a higher rate of overall complications. We present an overview of the current available evidence of PCI in older adults with stable and unstable CHD, including comparisons between drug-eluting and bare-metal stents, transfemoral and transradial access, and methods of revascularization. Adjuvant antiplatelet and antithrombotic therapies are also discussed. | 25,216,617 | [
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Postoperative nomogram to predict the probability of metastasis in Enneking stage IIB extremity osteosarcoma. | Metastasis is the most crucial prognostic factor in osteosarcoma. The goal of this study was to develop a new nomogram to predict the probability of metastasis in Enneking stage IIB extremity osteosarcoma after neoadjuvant chemotherapy and limb salvage surgery. We examined medical records of 91 patients who had undergone surgery between March 1994 and March 2007. A nomogram was developed using multivariate logistic regression. The nomogram was validated internally by bootstrapping-method (200 repetitions) and externally in independent validation set (n = 34). A Youden-derived cutoff value was assigned to the nomogram to predict dichotomous outcomes for metastasis. The nomogram was built from four predictors of tumor site, serum alkaline phosphatase, intracapsular extension, and Huvos grade, and an additional clause that the cutoff value should be added to the total points in the cases of incomplete surgical resection. P-value of Hosmer and Lemshow Goodness-of-fit test of this model was 0.649. Area under receiver operating curve values of 0.83 (95% confidence interval [CI], 0.75 to 0.92) in the training set and 0.80 (95% CI, 0.63 to 0.96) in the validation set were obtained. The accuracy of dichotomous outcomes was 79.1% (95% CI, 0.69 to 0.86) and 82.4% (95% CI, 0.63 to 0.92) in the training and validation sets. We have developed a new high-performance nomogram to predict the probability of metastasis in Enneking stage IIB extremity osteosarcoma after limb salvage surgery. | 25,216,622 | [
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Risk stratification in very old adults: how to best gauge risk as the basis of management choices for patients aged over 80. | Cardiovascular disease (CVD) is the leading cause of mortality in older adults, however, in the elderly accurate stratification of CVD risk to guide management decisions is challenging due to the heterogeneity of the population. Conventional assessment of CVD and therapeutic risk is based on extrapolation of guidelines developed from evidence demonstrated in younger individuals and fails to weight the increased burden of complications and multimorbidity. Using a comprehensive geriatric based assessment of older adults with CVD that includes an estimation of complexity of multimorbidity as well as traditional risk assessment provides a patient centered approach that allows for management decisions congruent with patient preferences. This review examines the complexity of risk stratification in adults over 80, assessment methods to augment current tools and the basis of management decisions to optimize patient and family centered goals. | 25,216,619 | [
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Effect of manganese supplementation on the membrane integrity and the mitochondrial potential of the sperm of grazing Nelore bulls. | The effect of dietary manganese (Mn(2+)) supplementation on the reproductive performance of Nelore bulls was evaluated by assessment of sperm membrane integrity. Sixty Nelore bulls (Bos taurus indicus) aged 18-20 mo were randomly divided into four groups (n=15) receiving dietary Mn(2+) supplementation at 540, 1300, 3800 and 6300mg/kg (treatments TC, T1300, T3800 and T6300, respectively). The diets were changed for the groups every 70d. Semen samples were obtained 15 and 56d after the diet change, which corresponded to the period of adjustment to the new diet and the time required for a complete spermatogenesis cycle, respectively. Sperm integrity was assessed by detection of: intact (IMe) or damaged (DMe) membranes, intact (IA) or damaged (DA) acrosomes, and high (HM) or low (LM) mitochondrial membrane potentials. Only bulls from the TC treatment showed a significant increase in the production of intact sperm [IMe/IA/LM] and decrease in the production of sperm with damaged acrosome [IMe/DA/LM] or completely damaged sperm [DMe/DA/LM] (P<0.05). The Mn(2+) concentrations in the semen were positively correlated with the incidence of sperm with IMe, DA, and LM and negatively correlated with number of sperm with DMe, IA, and LM. Therefore, dietary Mn(2+) supplementation for Nelore bulls must be limited to 540mg of Mn(2+)/kg given that higher doses are detrimental to the integrity of the plasma and acrosomal sperm membranes. | 25,216,627 | [
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Trigonal versus extratrigonal botulinum toxin-A: a systematic review and meta-analysis of efficacy and adverse events. | Botulinum toxin-A (BoNT-A) is a potent neurotoxin that is an effective treatment for patients with pharmacologically refractory detrusor overactivity (DO). Data assessing the effectiveness of trigonal BoNT-A are limited. This study evaluates adverse events (AEs) and short-term efficacy associated with trigonal and extratrigonal BoNT-A. Electronic databases (PubMed, EMBASE, and the Cochrane database) were searched for studies comparing trigonal and extratrigonal BoNT-A for DO. Meta-analyses were performed using the random effects model. Outcome measures included incidence of AEs and short-term efficacy. Six studies describing 258 patients met the inclusion criteria. The meta-analysis did not show significant differences between trigonal and extratrigonal BoNT-A for acute urinary retention (AUR; 4.2 vs 3.7 %; odds ratio [OR]: 1.068, 95 % confidence interval [CI]: 0.239-4.773; P = 0.931) or high post-void residual (PVR; 25.8 vs 22.2 %; OR: 0.979; 95 % CI: 0.459-2.088; P = 0.956). The incidence of urinary tract infection (UTI; 7.5 vs 21.0 %; OR: 0.670; 95 % CI: 0.312-1.439; P = 0.305), haematuria (15.8 vs 25.9 %; OR: 0.547; 95 % CI: 0.264-1.134; P = 0.105) and post-operative muscle weakness (9.2 vs 11.3 %; OR: 0.587; 95 % CI: 0.205-1.680, P = 0.320) was similar in both groups. Finally, differences in short-term cure rates between two study arms were not statistically significant (52.9 vs 56.9 %; OR: 1.438; 95 % CI: 0.448-4.610; P = 0.542). Although data are limited, no significant differences between trigonal and extratrigonal BoNT-A in terms of AEs and short-term efficacy were observed. Additional randomised controlled trials are required to define optimal injection techniques and sites for administering intra-vesical BoNT-A. | 25,216,630 | [
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One-step integration of multiple genes into the oleaginous yeast Yarrowia lipolytica. | Yarrowia lipolytica is an unconventional yeast, and is generally recognized as safe (GRAS). It provides a versatile fermentation platform that is used commercially to produce many added-value products. Here we report a multiple fragment assembly method that allows one-step integration of an entire β-carotene biosynthesis pathway (~11 kb, consisting of four genes) via in vivo homologous recombination into the rDNA locus of the Y. lipolytica chromosome. The highest efficiency was 21%, and the highest production of β-carotene was 2.2 ± 0.3 mg per g dry cell weight. The total procedure was completed in less than one week, as compared to a previously reported sequential gene integration method that required n weeks for n genes. This time-saving method will facilitate synthetic biology, metabolic engineering and functional genomics studies of Y. lipolytica. | 25,216,641 | [
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Atrial and ventricular specification of ADSCs is stimulated by different doses of BMP4. | To investigate the effect of BMP4 on cardiomyocyte differentiation of adipose tissue-derived stem cells (ADSCs), mouse ADSCs were treated with different concentrations of BMP4 in media containing fetal bovine serum (FBS) or Knockout™ Serum Replacement (KoSR). 3 weeks after cardiac induction, differentiated ADSCs expressed some cardiac-specific genes and proteins. BMP4 treatment upregulated the expression of cardiac transcription factors. In both FBS and KoSR-supplemented media, lower concentrations of BMP4 had a positive effect on the expression of MLC2A gene, while MLC2V was more expressed with higher concentrations of BMP4. BMP4 treatment in KoSR supplemented medium was more efficient for cardiac induction. Supplementation of culture media with insulin-transferrin-selenium improved the expression of MLC2A gene. The results of this study indicated that BMP4 is important for cardiac differentiation of the ADSCs. However, BMP4 was not enough for structural and functional maturation of the ADSC-derived cardiomyocytes. | 25,216,643 | [
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Cloning, homology modeling, and reaction mechanism analysis of a novel cis-epoxysuccinate hydrolase from Klebsiella sp. | The gene encoding a novel cis-epoxysuccinate hydrolase, which hydrolyzes cis-epoxysuccinate to L (+)-tartaric acid, was cloned from Klebsiella sp. BK-58 and expressed in Escherichia coli. The ORF was 825 bp encoding a mature protein of 274 amino acids with a molecular mass of 30.1 kDa. Multiple sequence alignment showed that the enzyme belonged to the haloacid dehalogenase-like super family. Homology modeling and site-directed mutagenesis were performed to investigate the structural characteristics of the enzyme. Its overall structure consisted of a core domain formed by six-stranded parallel β-sheets flanked by seven α-helices and a subdomain that had a four helix bundle structure. Residues D48, T52, R85, N165, K195, Y201, A219, H221, and D224 were catalytically important forming the active pocket between the two domains. An (18)O-labeling study suggested that the catalytic reaction of the enzyme proceeded through a two-step mechanism. | 25,216,644 | [
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The posterior parietal cortex (PPC) mediates anticipatory motor control. | Flexible and precisely timed motor control is based on functional interaction within a cortico-subcortical network. The left posterior parietal cortex (PPC) is supposed to be crucial for anticipatory motor control by sensorimotor feedback matching. Intention of the present study was to disentangle the specific relevance of the left PPC for anticipatory motor control using transcranial direct current stimulation (tDCS) since a causal link remains to be established. Anodal vs. cathodal tDCS was applied for 10 min over the left PPC in 16 right-handed subjects in separate sessions. Left primary motor cortex (M1) tDCS served as control condition and was applied in additional 15 subjects. Prior to and immediately after tDCS, subjects performed three tasks demanding temporal motor precision with respect to an auditory stimulus: sensorimotor synchronization as measure of anticipatory motor control, interval reproduction and simple reaction. Left PPC tDCS affected right hand synchronization but not simple reaction times. Motor anticipation was deteriorated by anodal tDCS, while cathodal tDCS yielded the reverse effect. The variability of interval reproduction was increased by anodal left M1 tDCS, whereas it was reduced by cathodal tDCS. No significant effects on simple reaction times were found. The present data support the hypothesis that left PPC is causally involved in right hand anticipatory motor control exceeding pure motor implementation as processed by M1 and possibly indicating subjective timing. Since M1 tDCS particularly affects motor implementation, the observed PPC effects are not likely to be explained by alterations of motor-cortical excitability. | 25,216,648 | [
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Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus. | The objective of this paper is to examine if there is an association between low levels of 25-hydroxyvitamin D (25(OH)D) and insulin resistance (IR) in nondiabetic women with systemic lupus erythematosus (SLE) and to evaluate its impact on arterial stiffness. In this cross-sectional study 25(OH)D, insulin, insulin resistance measured by the homeostatic model assessment (HOMA-IR), homocysteine, fibrinogen, characteristics of SLE, medications and pulse-wave velocity (PWV) were measured in 106 nondiabetic women with SLE and 101 matched controls. Women with SLE tended to have lower 25(OH)D levels (p = 0.078) and a higher frequency of 25(OH)D deficiency (defined as < 10 ng/ml) than controls (p = 0.058). Patients from the lowest quartile of the 25(OH)D range had higher PWV (p = 0.043), fasting glucose (p = 0.035), insulinemia (p ≤ 0.001), HOMA-IR (p = 0.006), C4 (p = 0.012), as well as more frequent IR (p = 0.002) and metabolic syndrome (p = 0.052) than those in the upper quartile, and no differences were found in age, body mass index (BMI), blood pressure, lipid levels and renal function. In women with SLE, 25(OH)D inversely correlated with insulin (p = 0.006), HOMA-IR (p = 0.008) and C4 (p = 0.048) and tended to correlate with fibrinogen (p = 0.060) after adjustment for BMI, age, SLEDAI, prednisone dose, renal function, inflammation markers and seasonal variation, but not with PWV. In controls, 25(OH)D correlated only with homocysteine after the same adjustment, and the correlation with PWV tended to be significant after adjustment for BMI and age (r = -0.190, p = 0.10). Low 25(OH)D levels were found to be associated with increased IR in nondiabetic women with SLE independently of BMI. Low 25(OH)D levels, but not IR, could be associated with increased arterial stiffness in these patients. | 25,216,653 | [
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Organizational aspects of primary care related to avoidable hospitalization: a systematic review. | Often used indicators for the quality of primary care are hospital admissions rates for conditions which are potentially avoidable by well-functioning primary care. Such hospitalizations are frequently termed as ambulatory care sensitive conditions (ACSCs). We aim to investigate which characteristics of primary care organization influence avoidable hospitalization for chronic ACSCs. MEDLINE, Embase and SciSearch were searched for publications on avoidable hospitalization and primary care. Studies were included if peer reviewed, written in English, published between January 1997 and November 2013, conducted in high income countries, identified hospitalization for ACSC as outcome measures and researched organization characteristics of primary care. A risk of bias assessment was performed to assess the quality of the articles. A total of 1778 publications were reviewed, of which 49 met inclusion criteria. Twenty-two primary care factors were found. Factors were clustered into four primary care clusters: system-level characteristics, accessibility, structural and organizational characteristics and organization of the care process. Adequate physician supply and better longitudinal continuity of care reduced avoidable hospitalizations. Furthermore, inconsistent results were found on the effectiveness of various disease management programs in reducing hospitalization rates. Available evidence suggests that strong primary care in terms of adequate primary care physician supply and long-term relationships between primary care physicians and patients reduces hospitalizations for chronic ACSCs. There is a lack of evidence for the positive effects of many other organizational primary care aspects, such as specific disease management programs. | 25,216,664 | [
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Alternative diagnoses in patients in whom the GP considered the diagnosis of pulmonary embolism. | Pulmonary embolism (PE) often presents with nonspecific symptoms and may be an easily missed diagnosis. When the differential diagnosis includes PE, an empirical list of frequently occurring alternative diagnoses could support the GP in diagnostic decision making. To identify common alternative diagnoses in patients in whom the GP suspected PE but in whom PE could be ruled out. To investigate how the Wells clinical decision rule for PE combined with a point-of-care d-dimer test is associated with these alternative diagnoses. Secondary analysis of the Amsterdam Maastricht Utrecht Study on thrombo-Embolism (Amuse-2) study, which validated the Wells PE rule combined with point-of-care d-dimer testing in primary care. All 598 patients had been referred to and diagnosed in secondary care. All diagnostic information was retrieved from the GPs' medical records. In 516 patients without PE, the most frequent alternative diagnoses were nonspecific thoracic pain/dyspnoea (42.6%), pneumonia (13.0%), myalgia (11.8%), asthma/chronic obstructive pulmonary disease (4.8%), panic disorder/hyperventilation (4.1%) and respiratory tract infection (2.3%). Pneumonia occurred almost as frequent as PE. Patients without PE with either a positive Wells rule (>4) or a positive d-dimer test, were more often (odds ratio = 2.1) diagnosed with a clinically relevant disease than patients with a negative Wells rule and negative d-dimer test. In primary care patients suspected of PE, the most common clinically relevant diagnosis other than PE was pneumonia. A positive Wells rule or a positive d-dimer test are not only positively associated with PE, but also with a high probability of other clinically relevant disease. | 25,216,665 | [
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... |
Non-fatal work-related traumatic brain injuries treated in US hospital emergency departments, 1998-2007. | Little is known about work-related traumatic brain injuries (WRTBI). This study describes non-fatal WRTBIs treated in US emergency departments (ED) from 1998 through 2007. Non-fatal WRTBIs were identified from the National Electronic Injury Surveillance System occupational supplement (NEISS-Work) using the diagnoses of concussion, internal organ injury to the head and skull fracture. WRTBI rates and rate ratios were calculated, and the trend in rates was assessed. An estimated 586,600 (95% CI=±150,000) WRTBIs were reported during the 10-year period at a rate of 4.3 (CI=±1.1) per 10,000 full-time equivalent (FTE) workers (1 FTE=2000 h per year). From 1998 through 2007, the rate of WRTBIs increased at an average of 0.21 per 10,000 FTE per year (p<0.0001) and the rate of fall-related WRTBIs increased at an average of 0.10 per 10,000 FTE (p<0.0001). During the same period, the annual rate of WRTBIs resulting in hospitalisation increased 0.04 per 10,000 FTE (p<0.0001). Ten percent of WRTBIs were hospitalised, compared with hospitalisation of 2% all NEISS-Work injuries. Also, workers with highest fall-related TBI rates per 10,000 FTE were the youngest (2.4; CI=±1.4) and oldest (55 and older) workers (1.9; CI=±0.8). Non-fatal WRTBIs are one of the most serious workplace injuries among ED-treated work-related injuries. Non-fatal WRTBIs are much more likely to result in hospitalisation compared with other types of injuries. The upward trend of WRTBI rates from 1998 through 2007 underscore the need for more directed effective prevention methods to reduce WRTBI injuries. | 25,216,672 | [
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... |
tRNAs: new tricks from old dogs. | tRNA biology has lately seen a revival with the discovery of tRNA cleavage products as mediators of stress responses. In this issue of The EMBO Journal, Blanco et al now report that tRNA methylation, by protecting from cleavage, is relevant for normal brain development. The versatility of tRNA is further emphasized by a recent study in Cell that uncovered differential expression of tRNAs as a means to accustom codon usage bias to the needs in proliferating versus differentiating cells. | 25,216,676 | [
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0.04439005,
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Newly antibacterial and antiadhesive lipopeptide biosurfactant secreted by a probiotic strain, Propionibacterium freudenreichii. | A lipopeptide biosurfactant production from a probiotic type strain of Propionibacterium freudenreichii subsp. freudenreichii is being reported here for the first time. This biosurfactant is able to reduce the surface tension of water from 72 to 38 mN/m with an increase of the biosurfactant concentration up to critical micelle concentration value of 1.59 mg/ml. The production of the biosurfactant was found to be much higher in medium containing sunflower oil compared to the glucose-containing medium. The maximum emulsifying activity (E24 = 72 %) was attained with used frying sunflower oil, while kerosene and starch had the lowest emulsifying activity. Biosurfactant production seems to be parallel to cell growth. The produced biosurfactant was relatively thermo-stable and no appreciable changes in biosurfactant activity occurred at temperature ranges of 25-85 °C. The analysis of the extracted biosurfactant by thin layer chromatography, infrared spectroscopy, and (1)H and (13)CNMR spectroscopy revealed the chemical nature of the biosurfactant as lipopeptide. Produced lipopeptide was evaluated for its antimicrobial and antiadhesive activity and showed significant antimicrobial and antiadhesive action against a wide range of pathogenic bacteria and fungi. A total growth inhibition was observed over Rhodococcus erythropolis, while the best result of antiadhesion was obtained against Pseudomonas aeruginosa. | 25,216,696 | [
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Replication fork recovery and regulation of common fragile sites stability. | The acquisition of genomic instability is a triggering factor in cancer development, and common fragile sites (CFS) are the preferential target of chromosomal instability under conditions of replicative stress in the human genome. Although the mechanisms leading to CFS expression and the cellular factors required to suppress CFS instability remain largely undefined, it is clear that DNA becomes more susceptible to breakage when replication is impaired. The models proposed so far to explain how CFS instability arises imply that replication fork progression along these regions is perturbed due to intrinsic features of fragile sites and events that directly affect DNA replication. The observation that proteins implicated in the safe recovery of stalled forks or in engaging recombination at collapsed forks increase CFS expression when downregulated or mutated suggests that the stabilization and recovery of perturbed replication forks are crucial to guarantee CFS integrity. | 25,216,703 | [
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... |
Current status of viroid taxonomy. | Viroids are the smallest autonomous infectious nucleic acids known so far. With a small circular RNA genome of about 250-400 nt, which apparently does not code for any protein, viroids replicate and move systemically in host plants. Since the discovery of the first viroid almost forty-five years ago, many different viroids have been isolated, characterized and, frequently, identified as the causal agents of plant diseases. The first viroid classification scheme was proposed in the early 1990s and adopted by the International Committee on Taxonomy of Viruses (ICTV) a few years later. Here, the current viroid taxonomy scheme and the criteria for viroid species demarcation are discussed, highlighting the main taxonomic questions currently under consideration by the ICTV Viroid Study Group. The impact of correct taxonomic annotation of viroid sequence variants is also addressed, taking into consideration the increasing application of next-generation sequencing and bioinformatics for known and previously unrecognized viroids. | 25,216,773 | [
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... |
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