m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation.
N6‑methyladenosine (m6A) RNA modification maintained by N6‑methyltransferases and demethylases is involved in multiple biological functions. Methyltransferase like 3 (METTL3) is a major N6‑methyltransferase. However, the role of METTL3 and its installed m6A modification in colorectal tumorigenesis remains to be fully elucidated. METTL3 is highly expressed as indicated in colorectal cancer samples in the TCGA and Oncomine databases, implying its potential role in colon tumorigenesis. SW480 cell line with stable METTL3 knockout (METTL3‑KO) was generated using CRISPR/Cas9 and were confirmed by the loss of METTL3 expression and suppression of m6A modification. The proliferation of METTL3‑KO cells was significantly inhibited compared with that of control cells. METTL3‑KO decreased the decay rate of suppressor of cytokine signaling 2 (SOCS2) RNA, resulting in elevated SOCS2 protein expression. m6A‑RNA immunoprecipitation‑qPCR (MeRIP‑qPCR) revealed that SOCS2 mRNA was targeted by METTL3 for m6A modification. Similar to METTL3‑KO SW480 cells, SW480 cells treated with 3‑deazaadenosine, an RNA methylation inhibitor, exhibited elevated SOCS2 protein expression. Increased levels of SOCS2 in METTL3‑KO SW480 cells were associated with decreased expression of leucine‑rich repeat‑containing G protein‑coupled receptor 5 (LGR5), contributing to the inhibition of cell proliferation. The underlying associations among METTL3, SOCS2, and LGR5 were further confirmed in SW480 cells transfected with si‑METTL3 and in tumor samples from patients with colorectal cancer. Taken together, our data demonstrate that an increased level of METTL3 may maintain the tumorigenicity of colon cancer cells by suppressing SOCS2.


Impact of Mycobacterium ulcerans biofilm on transmissibility to ecological niches and Buruli ulcer pathogenesis.
The role of biofilms in the pathogenesis of mycobacterial diseases remains largely unknown. Mycobacterium ulcerans, the etiological agent of Buruli ulcer, a disfiguring disease in humans, adopts a biofilm-like structure in vitro and in vivo, displaying an abundant extracellular matrix (ECM) that harbors vesicles. The composition and structure of the ECM differs from that of the classical matrix found in other bacterial biofilms. More than 80 proteins are present within this extracellular compartment and appear to be involved in stress responses, respiration, and intermediary metabolism. In addition to a large amount of carbohydrates and lipids, ECM is the reservoir of the polyketide toxin mycolactone, the sole virulence factor of M. ulcerans identified to date, and purified vesicles extracted from ECM are highly cytotoxic. ECM confers to the mycobacterium increased resistance to antimicrobial agents, and enhances colonization of insect vectors and mammalian hosts. The results of this study support a model whereby biofilm changes confer selective advantages to M. ulcerans in colonizing various ecological niches successfully, with repercussions for Buruli ulcer pathogenesis.


A stoichiometric model of early plant primary succession.
The relative importance of plant facilitation and competition during primary succession depends on the development of ecosystem nutrient pools, yet the interaction of these processes remains poorly understood. To explore how these mechanisms interact to drive successional dynamics, we devised a stoichiometric ecosystem-level model that considers the role of nitrogen and phosphorus limitation in plant primary succession. We applied this model to the primary plant community on Mount St. Helens, Washington State, to check the validity of the proposed mechanisms. Our results show that the plant community is colimited by nitrogen and phosphorus, and they confirm previous suggestions that the presence of a nitrogen-fixing legume, Lupinus lepidus, can enhance community biomass. In addition, the observed nutrient supply rates may promote alternative successional trajectories that depend on the initial plant abundances, which may explain the observed heterogeneity in community development. The model further indicates the importance of mineralization rates and other ecosystem parameters to successional rates. We conclude that a model framework based on ecological stoichiometry allows integration of key biotic processes that interact nonlinearly with biogeochemical aspects of succession. Extension of this approach will improve the understanding of the process of primary succession and its application to ecosystem rehabilitation.


Mediterranean Diet and Bladder Cancer Risk in Italy.
Previous studies have reported that Mediterranean diet is inversely related to the risk of several neoplasms; however, limited epidemiological data are available for bladder cancer. Thus, we examined the association between Mediterranean diet and this neoplasm in an Italian multicentric case-control study consisting of 690 bladder cancer cases and 665 controls. We assessed the adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which represents the major characteristics of the Mediterranean diet and ranges from 0 to 9 (from minimal to maximal adherence, respectively). We derived odds ratios (ORs) of bladder cancer according to the MDS score from multiple logistic regression models, allowing for major confounding factors. The ORs of bladder cancer were 0.72 (95% confidence interval, CI, 0.54⁻0.98) for MDS of 4⁻5 and 0.66 (95% CI, 0.47⁻0.93) for MDS of 6⁻9 (p for trend = 0.02) compared to MDS = 0⁻3. Results were similar in strata of sex, age, and education, while the risk appeared somewhat lower in never-smokers and patients with pT1⁻pT4 bladder carcinomas. Among individual components of the MDS, we observed inverse associations for greater consumption of legumes, vegetables, and fish. In our study, which was carried out on an Italian population, the higher adherence to the Mediterranean diet was related to a lower risk of bladder cancer.


Survival After Transplantation in Patients With Mutations Other Than Val30Met: Extracts From the FAP World Transplant Registry.
Liver transplantation (LTx) has been performed for hereditary transthyretin amyloidosis (ATTR) since 1990. Outcomes for a relatively large series of LTx ATTR patients with the Val30Met (mutation are available, but for non-Val30Met patients, only a few reports with a small number of patients exist. Here, we present outcomes for non-Val30Met ATTR patients after LTx, as reported to the Familial Amyloid Polyneuropathy World Transplant Registry (FAPWTR). Data regarding outcome were extracted for all non-Val30Met patients reported to the registry. Survival rates were analyzed by the Kaplan-Meier method and log-rank test. The total number of patients with a non-Val30Met mutation in the registry was 264 (174 men and 90 women), representing 57 mutations. The 10-year survival varied markedly for the 9 most common mutations, ranging from 21% for Ser50Arg to 85% for Val71Ala. Poor survival was noted for all mutations with leptomeningeal complications except for those with the Tyr114Cys mutation. Large differences in survival were observed relative to different mutations and between mutations with similar phenotypes. Excellent survival was noted for mutations, such as Leu111Met, Val71Ala, and Leu58His. Patients with mutations other than Val30Met are not a homogeneous group, and the term non-Val30Met should be used with caution or avoided. Moreover, for several mutations, data are too limited to allow evaluation of the efficacy of LTx, and continuous international collaboration is important for obtaining treatment guidance.


[Comparative study of the effect of complete prolonged neoadjuvant hormonal blockade versus standard hormonal blockade].
Radical prostatectomy is considered as a curative treatment option in clinically localised prostate cancer patients. Therapy failure is related to positive surgical margins and/or extracapsular extension. The use of neoadjuvant combined androgen blockade (CAB) withdrawal therapy, mainly in cT2 disease, has been shown to decrease positive margin rates. However, CAB therapy remains controversial since there is no proof that this approach confers any benefit in relation to biochemical and clinical disease-free survival. Increasing negatives surgical margins and lower tumour volume (TV) with prolonged CAB therapy has been recently reported. To analyse the effect of 6 months neoadjuvant CAB therapy in front of 3 months in clinically localised prostate cancer patients submitted to radical prostatectomy. The pathological stage and TV in forty-two patients treated by 6 months in front of thirty-four patients treated by 3 months were studied. The relationship of clinical stage and initial PSA concentration were analysed. TV was significantly lower in 6 months treated patients (0.97 cc vs. 0.48 cc, p = 0.05). The lowest TV was observed in cT1 patients, but significant differences only were observed in cT2 (1.5 cc vs. 0.86 cc, p = 0.04). No relationship between TV and PSA was obtained. No differences in the incidence of organ-confined disease were seen depending of the CAB length (47% vs. 43%, p = NS). However, increasing incidence of specimen-confined disease was observed in 6 months treated patients (56% vs. 74%, p = 0.05). The duration of neoadjuvant CAB can affect both TV and surgical margin status. Lower TV and increasing incidence of specimen-confined disease with 6 months CAB treatment were observed. Patients with palpable disease may be more benefited by this treatment option.


Common and contrasting themes in host cell-targeted effectors from bacterial, fungal, oomycete and nematode plant symbionts described using the Gene Ontology.
A wide diversity of plant-associated symbionts, including microbes, produce proteins that can enter host cells, or are injected into host cells in order to modify the physiology of the host to promote colonization. These molecules, termed effectors, commonly target the host defense signaling pathways in order to suppress the defense response. Others target the gene expression machinery or trigger specific modifications to host morphology or physiology that promote the nutrition and proliferation of the symbiont. When recognized by the host's surveillance machinery, which includes cognate resistance (R) gene products, defense responses are engaged to restrict pathogen proliferation. Effectors from diverse symbionts may be delivered into plant cells via varied mechanisms, including whole organism cellular entry (viruses, some bacteria and fungi), type III and IV secretion (in bacteria), physical injection (nematodes and insects) and protein translocation signal sequences (oomycetes and fungi). This mini-review will summarize both similarities and differences in effectors and effector delivery systems found in diverse plant-associated symbionts as well as how these are described with Plant-Associated Microbe Gene Ontology (PAMGO) terms.


The effect of honey-coated bandages compared with silver-coated bandages on treatment of malignant wounds-a randomized study.
Malignant wounds (MWs) occur in 5-10% of all cancer patients. Malodor and exudation are the most common side effects. The aim was to determine the influence of honey-coated compared with silver-coated bandages on treatment of MWs. Patients were randomly selected to enter either group A (honey-coated bandages) or group B (silver-coated bandages). Parameters were the following: wound size, cleanliness, malodor, exudation, and wound pain. Digital photographs, visual analog scales (VAS), and wound morphology registration were used for measurement at baseline and following the 4-week intervention. Sixty-nine patients with MWs and advanced cancer, aged 47-90 (median 65.6), were included. No statistically significant difference was noted between the groups with respect to wound size, degree of cleanliness, exudation, malodor, and wound pain. There was a median decrease in wound size of 15 cm² and 8 cm² in group A and B, respectively (p = 0.63). Based on post-intervention pooled data from the groups, improvement was seen in 62% of the participants with respect to wound size and in 58% (n = 69) with respect to cleanliness. The VAS score for malodor (p = 0.007) and exudation (p < 0.0001) improved significantly post-intervention. Patients with reduced wound size had a median survival time of 387 days compared with 134 days in patients with no wound reduction (p = 0.003). The use of honey-coated and silver-coated bandages improved the outcome of MWs. No differences were found between the two regimens. Both types of bandages are recommended for use by patients with MWs containing tumor debris and necrosis.


Controlling spin relaxation with a cavity.
Spontaneous emission of radiation is one of the fundamental mechanisms by which an excited quantum system returns to equilibrium. For spins, however, spontaneous emission is generally negligible compared to other non-radiative relaxation processes because of the weak coupling between the magnetic dipole and the electromagnetic field. In 1946, Purcell realized that the rate of spontaneous emission can be greatly enhanced by placing the quantum system in a resonant cavity. This effect has since been used extensively to control the lifetime of atoms and semiconducting heterostructures coupled to microwave or optical cavities, and is essential for the realization of high-efficiency single-photon sources. Here we report the application of this idea to spins in solids. By coupling donor spins in silicon to a superconducting microwave cavity with a high quality factor and a small mode volume, we reach the regime in which spontaneous emission constitutes the dominant mechanism of spin relaxation. The relaxation rate is increased by three orders of magnitude as the spins are tuned to the cavity resonance, demonstrating that energy relaxation can be controlled on demand. Our results provide a general way to initialize spin systems into their ground state and therefore have applications in magnetic resonance and quantum information processing. They also demonstrate that the coupling between the magnetic dipole of a spin and the electromagnetic field can be enhanced up to the point at which quantum fluctuations have a marked effect on the spin dynamics; as such, they represent an important step towards the coherent magnetic coupling of individual spins to microwave photons.


Gadd45β expression in chondrosarcoma: a pilot study for diagnostic and biological implications in histological grading.
Although the diagnosis of chondrosarcoma, especially the distinction between enchondroma and low-grade chondrosarcoma or low-grade chondrosarcoma and high-grade chondrosarcoma, is pathologically difficult, differential diagnosis is very important because the treatment strategies for these diseases are completely different. The grading system is crucial in predicting biologic behavior and prognosis, however, exact pathological grading is difficult using only routine examinations because the criteria of the grading system are not necessarily definitive. Growth arrest and DNA damage-inducible protein 45β (GADD45β) is an essential molecule for chondrocytes during terminal differentiation. In the present study, we investigated the immunohistochemical expression of GADD45β in enchondroma, and chondrosarcoma of histological grades I, II, and III, to clarify the diagnostic significance of GADD45β in pathological grading of chondrosarcoma. Twenty samples (enchondroma = 6, chondrosarcoma grade I = 7, grade II = 6, grade III = 1) were used for immunohistochemical analysis to investigate the expression of GADD45β. Quantitative analysis was performed to compare the number of GADD45β positive cells and pathological grading. Over 70% of the cells in enchondromas expressed GADD45β. On the other hand, the expression of GADD45β decreased significantly according to the histological grade of chondrosarcoma (grade I: 45%; grade II: 13.8%; and grade III: 3.8%). The association of GADD45β expression and pathological grading of chondrosarcoma in the present study suggests that the immunohistochemical study of GADD45β may be a specific diagnostic parameter for chondrosarcoma cell differentiation.


Decrease of plasminogen activator inhibitor-1 may contribute to the anti-invasive action of cannabidiol on human lung cancer cells.
Using human lung cancer cells, we evaluated the involvement of plasminogen activator inhibitor-1 (PAI-1) in the anti-invasive action of cannabidiol, a non-psychoactive cannabinoid. Invasion was quantified by a modified Boyden chamber assay. PAI-1 protein in cell culture media and PAI-1 mRNA were determined by immunoblotting and RT-PCR, respectively. Cannabidiol caused a profound inhibition of A549 cell invasion, accompanied by a decreased expression and secretion of PAI-1. Cannabidiol's effects on PAI-1 secretion and invasion were suppressed by antagonists to CB(1) and CB(2) receptors as well as to transient receptor potential vanilloid 1. Recombinant human PAI-1 and PAI-1 siRNA led to a concentration-dependent up- and down-regulation of invasiveness, respectively, suggesting a crucial role of PAI-1 in A549 invasiveness. Evidence for a causal link between cannabidiol's effects on PAI-1 and invasion was provided by experiments showing a reversal of its anti-invasive action by addition of recombinant PAI-1 at non-proinvasive concentrations. Key data were confirmed in two other human lung cancer cell lines (H460, H358). In vivo, a significant downregulation of PAI-1 protein by cannabidiol was demonstrated in A549 xenografts. Our data provide evidence for a hitherto unknown mechanism underlying the anti-invasive action of cannabidiol on human lung cancer cells.


Platelet Adhesion and Thrombus Formation in Whole Blood at Arterial Shear Rate at the End of Pregnancy.
Platelet reactivity has not been evaluated in integrated functional testing during normal pregnancy. Here, we analysed platelet functions under arterial shear rate in comparison with static conditions. Thirty pregnant women with uncomplicated pregnancies and 30 healthy non-pregnant women were enrolled in this study. Platelet adhesion to collagen and fibrinogen and subsequent thrombus formation were measured at arterial shear rate in whole blood using a microfluidic and imaging system. Standard light transmission aggregometry, flow cytometry of activation markers in washed platelets and impedance aggregometry in whole blood were also used to assess platelet responsiveness in static conditions. Compared to non-pregnant controls, thrombus formation on collagen fibres and firm platelet adhesion on fibrinogen under arterial shear rate were significantly reduced in pregnant women. Platelet aggregometry assays in suspension showed a slight increase in platelet reactivity in pregnant women. While platelet aggregometry and platelet activation markers in static conditions show little changes in platelet reactivity, monitoring of platelet adhesion and thrombus growth on collagen or fibrinogen under flow condition in whole blood indicates a significant decrease in pregnant women compared to controls. This decrease might contribute to counteract a hypercoagulable state and to reduce the risk of arterial thrombosis.


A catchment scale evaluation of multiple stressor effects in headwater streams.
Mitigation activities to improve water quality and quantity in streams as well as stream management and restoration efforts are conducted in the European Union aiming to improve the chemical, physical and ecological status of streams. Headwater streams are often characterised by impairment of hydromorphological, chemical, and ecological conditions due to multiple anthropogenic impacts. However, they are generally disregarded as water bodies for mitigation activities in the European Water Framework Directive despite their importance for supporting a higher ecological quality in higher order streams. We studied 11 headwater streams in the Hove catchment in the Copenhagen region. All sites had substantial physical habitat and water quality impairments due to anthropogenic influence (intensive agriculture, urban settlements, contaminated sites and low base-flow due to water abstraction activities in the catchment). We aimed to identify the dominating anthropogenic stressors at the catchment scale causing ecological impairment of benthic macroinvertebrate communities and provide a rank-order of importance that could help in prioritising mitigation activities. We identified numerous chemical and hydromorphological impacts of which several were probably causing major ecological impairments, but we were unable to provide a robust rank-ordering of importance suggesting that targeted mitigation efforts on single anthropogenic stressors in the catchment are unlikely to have substantial effects on the ecological quality in these streams. The SPEcies At Risk (SPEAR) index explained most of the variability in the macroinvertebrate community structure, and notably, SPEAR index scores were often very low (<10% SPEAR abundance). An extensive re-sampling of a subset of the streams provided evidence that especially insecticides were probably essential contributors to the overall ecological impairment of these streams. Our results suggest that headwater streams should be considered in future management and mitigation plans. Catchment-based management is necessary because several anthropogenic stressors exceeded problematic thresholds, suggesting that more holistic approaches should be preferred.


Can Health be Related to Interpersonal Violence in Middle Eastern Countries?
Preventing violence is important especially in the Middle East, where many countries are struggling with violence. Knowing the affecting factors could help public policy makers to decrease violence level. Thus, this study is aimed to analyze health and other socio-economic factors that could affect interpersonal violence in middle eastern countries. From international organization databases, we collected the panel data of Middle Eastern countries from 1990 to 2016 on prevalence of interpersonal violence as dependent variable and per capita income, life expectancy, democracy index (DI), urbanization and unemployment as explanatory factors. Several panel data diagnostic tests were performed for selecting a suitable model of estimation. The variables were entered in the model in logarithmic form. Because of heteroscedasticity, cross-sectional dependence and serial correlation of residuals, feasible generalized least squares (FGLS) was used for estimation of mentioned model using Stata 14.2. The means of interpersonal violence prevalence and life expectancy were 2462.2 (SD = 232.4) per 100000 population and 73.5 (SD = 4.5) in the Middle East, respectively. Urbanization (β = -0.0925, P < 0.01), life expectancy (β = -0.0362, P < 0.01), per capita income (β = -0.0046, P < 0.01), unemployment (β = 0.0007, P < 0.01) and democracy (β = -5.83e-06, P < 0.01) had significant relation with interpersonal violence. Life expectancy as a proxy for health is one of the main predictors of interpersonal violence, as literature supports. That is, if a society is healthier, the burden of interpersonal violence will be lower. Thus, health policy makers should consider health status as a preventive factor of violence, which is stated in health as a bridge for peace by the world health organization.


Crystal structure and mechanistic implications of N2-(2-carboxyethyl)arginine synthase, the first enzyme in the clavulanic acid biosynthesis pathway.
The initial step in the biosynthesis of the clinically important beta-lactamase inhibitor clavulanic acid involves condensation of two primary metabolites, D-glyceraldehyde 3-phosphate and L-arginine, to give N2-(2-carboxyethyl)arginine, a beta-amino acid. This unusual N-C bond forming reaction is catalyzed by the thiamin diphosphate (ThP2)-dependent enzyme N2-(2-carboxyethyl)arginine synthase. Here we report the crystal structure of N2-(2-carboxyethyl)arginine synthase, complexed with ThP2 and Mg2+, to 2.35-A resolution. The structure was solved in two space groups, P2(1)2(1)2(1) and P2(1)2(1)2. In both, the enzyme is observed in a tetrameric form, composed of a dimer of two more tightly associated dimers, consistent with both mass spectrometric and gel filtration chromatography studies. Both ThP2 and Mg2+ cofactors are present at the active site, with ThP2 in a "V" conformation as in related enzymes. A sulfate anion is observed in the active site of the enzyme in a location proposed as a binding site for the phosphate group of the d-glyceraldehyde 3-phosphate substrate. The mechanistic implications of the active site arrangement are discussed, including the potential role of the aminopyrimidine ring of the ThP2. The structure will form a basis for future mechanistic and structural studies, as well as engineering aimed at production of alternative beta-amino acids.


Predicting the onset of net carbon uptake by deciduous forests with soil temperature and climate data: a synthesis of FLUXNET data.
We tested the hypothesis that the date of the onset of net carbon uptake by temperate deciduous forest canopies corresponds with the time when the mean daily soil temperature equals the mean annual air temperature. The hypothesis was tested using over 30 site-years of data from 12 field sites where CO(2) exchange is being measured continuously with the eddy covariance method. The sites spanned the geographic range of Europe, North America and Asia and spanned a climate space of 16 degrees C in mean annual temperature. The tested phenology rule was robust and worked well over a 75 day range of the initiation of carbon uptake, starting as early as day 88 near Ione, California to as late as day 147 near Takayama, Japan. Overall, we observed that 64% of variance in the timing when net carbon uptake started was explained by the date when soil temperature matched the mean annual air temperature. We also observed a strong correlation between mean annual air temperature and the day that a deciduous forest starts to be a carbon sink. Consequently we are able to provide a simple phenological rule that can be implemented in regional carbon balance models and be assessed with soil and temperature outputs produced by climate and weather models.


Topologically Protected Landau Level in the Vortex Lattice of a Weyl Superconductor.
The question whether the mixed phase of a gapless superconductor can support a Landau level is a celebrated problem in the context of d-wave superconductivity, with a negative answer: the scattering of the subgap excitations (massless Dirac fermions) by the vortex lattice obscures the Landau level quantization. Here we show that the same question has a positive answer for a Weyl superconductor: the chirality of the Weyl fermions protects the zeroth Landau level by means of a topological index theorem. As a result, the heat conductance parallel to the magnetic field has the universal value G=1/2g_{0}Φ/Φ_{0}, with Φ as the magnetic flux through the system, Φ_{0} as the superconducting flux quantum, and g_{0} as the thermal conductance quantum.


Resident Challenges With Pain and Functional Limitations in Chinese Residential Care Facilities.
Pain and functional limitations can severely impede older adults' quality of life. In Chinese residential care facilities, limited research suggests that residents potentially have significant unmet care needs with pain and related functional limitations. Therefore, we aimed to explore residents' challenges and self-management strategies in these two areas. This knowledge is essential to developing care interventions to improve quality of care and quality of life in Chinese residential care facilities. We conducted semi-structured open-ended interviews with residents (n = 21) in two facilities in eastern and central China and assessed their pain and functional status using self-report measures from Minimum Data Set 3.0. We applied descriptive statistics to the self-reported data and analyzed the interview data using thematic analysis by drawing on the Adaptive Leadership Framework. This framework proposes that individuals living with chronic conditions need to engage in work to address their complex health concerns and that they need support from the environment to facilitate problem-solving. Residents described significant unmet care needs with pain and functional limitations. To address these care needs, they adopted a substantial number of self-management strategies. While doing so, they faced significant barriers, including service gaps and inadequate direct care. The findings suggest further research to explore long-term care policy change that is needed to provide comprehensive health and medical services and adequate direct care in these facilities. The importance of establishing various types of long-term care facilities is also highlighted.


Phylogenetic and evolutionary history of influenza B viruses, which caused a large epidemic in 2011-2012, Taiwan.
The annual recurrence of the influenza epidemic is considered to be primarily associated with immune escape due to changes to the virus. In 2011-2012, the influenza B epidemic in Taiwan was unusually large, and influenza B was predominant for a long time. To investigate the genetic dynamics of influenza B viruses during the 2011-2012 epidemic, we analyzed the sequences of 4,386 influenza B viruses collected in Taiwan from 2004 to 2012. The data provided detailed insight into the flux patterns of multiple genotypes. We found that a re-emergent TW08-I virus, which was the major genotype and had co-circulated with the two others, TW08-II and TW08-III, from 2007 to 2009 in Taiwan, successively overtook TW08-II in March and then underwent a lineage switch in July 2011. This lineage switch was followed by the large epidemic in Taiwan. The whole-genome compositions and phylogenetic relationships of the representative viruses of various genotypes were compared to determine the viral evolutionary histories. We demonstrated that the large influenza B epidemic of 2011-2012 was caused by Yamagata lineage TW08-I viruses that were derived from TW04-II viruses in 2004-2005 through genetic drifts without detectable reassortments. The TW08-I viruses isolated in both 2011-2012 and 2007-2009 were antigenically similar, indicating that an influenza B virus have persisted for 5 years in antigenic stasis before causing a large epidemic. The results suggest that in addition to the emergence of new variants with mutations or reassortments, other factors, including the interference of multi-types or lineages of influenza viruses and the accumulation of susceptible hosts, can also affect the scale and time of an influenza B epidemic.


Stroke Simulation Activity: A Standardized Patient Case for Interprofessional Student Learning.
Integration of interprofessional education (IPE) activities into health professions curricula aims to promote collaborative practice with a goal of improving patient care. Through intercollegiate collaborations involving four different educational organizations and an academic health center, an interprofessional stroke simulation involving standardized patients was developed and instituted for IPE-naive student learners from medicine, nursing, physician assistant, occupational therapy, and physical therapy programs with additional involvement from pharmacy and social work learners. Herein, we describe the design of the IPE simulation and examine its impact on students' interprofessional development as assessed by students' completion of a validated IPE competency self-assessment tool and written reflective comments after the simulation. Self-assessed interprofessional interaction and values domains were evaluated before and after the activity using the shortened 16-question Interprofessional Education Collaborative Competency Self-Assessment tool; data revealed significant changes in both the values and interaction domains of the tool from pre- to postsimulation experience (p < .0001). The qualitative student reflections revealed new student realizations around the concepts of collaboration, leadership, roles of different professions, and the importance of communication after participating in the simulation. Quantitative data coupled with qualitative reflections from learners support the effectiveness of this activity for facilitating development of interprofessional competencies among health professions students.


Diagnosis and treatment of patients with thyroid cancer.
Thyroid cancer is the most common malignancy of the endocrine system, representing 3.8% of all new cancer cases in the United States and is the ninth most common cancer overall. The American Cancer Society estimates that 62,450 people in the United States will be diagnosed with thyroid cancer in 2015, and 1950 deaths will result from the disease. To review the current approach to the diagnosis and treatment of patients with thyroid cancer. Over the past 3 decades, there has been a dramatic increase in the number of people diagnosed with thyroid cancer, which may be attributable to the wide use of imaging studies, including ultrasounds, computed tomography, magnetic resonance imaging, and positron emission tomography scans that incidentally detect thyroid nodules. Thyroid cancer is divided into several main types, with papillary thyroid cancer being the most common. The treatment options for patients with thyroid cancer include the surgical removal of the entire thyroid gland (total thyroidectomy), radioactive iodine therapy, and molecular-targeted therapies with tyrosine kinase inhibitors. This article summarizes the diagnosis and treatment of thyroid cancer, with recommendations from the American Thyroid Association regarding thyroid nodules and differentiated thyroid cancer. Recently approved drugs and treatment trends are also explored. The prognosis and treatment of thyroid cancer depend on the tumor type and its stage at the time of diagnosis. Many thyroid cancers remain stable, microscopic, and indolent. The increasing treatment options for patients with thyroid cancer, including therapies that were recently approved by the US Food and Drug Administration, have kept the mortality rate from this malignancy low, despite the increase in its incidence. Early diagnosis and appropriate treatment can improve prognosis and reduce mortality.


An urticarial vasculitis case induced by glatiramer acetate.
Urticarial vasculitis (UV) is a disease characterized clinically by urticarial skin lesions and histologically by leukocytoclastic vasculitis caused by immunocomplex accumulation in post-capillary venules. Cases induced by various drugs such as cimetidine, diltiazem, potassium iodide, fluoxetine, and non-steroid inflammatory drugs have been reported in the literature. A 48-year-old female who developed pruritus and rash on her body 3 months after starting glatiramer acetate (GA) treatment for multiple sclerosis was diagnosed with UV after clinical and histopathological examination. This report presents the first case in the literature of UV induced by GA.


Long-term succession of structure and diversity of a biofilm formed in a model drinking water distribution system.
In this study, we examined the long-term development of the overall structural morphology and community composition of a biofilm formed in a model drinking water distribution system with biofilms from 1 day to 3 years old. Visualization and subsequent quantification showed how the biofilm developed from an initial attachment of single cells through the formation of independent microcolonies reaching 30 micro m in thickness to a final looser structure with an average thickness of 14.1 micro m and covering 76% of the surface. An analysis of the community composition by use of terminal restriction fragment length polymorphisms showed a correlation between the population profile and the age of the sample, separating the samples into young (1 to 94 days) and old (571 to 1,093 days) biofilms, whereas a limited spatial variation in the biofilm was observed. A more detailed analysis with cloning and sequencing of 16S rRNA fragments illustrated how a wide variety of cells recruited from the bulk water initially attached and resulted in a species richness comparable to that in the water phase. This step was followed by the growth of a bacterium which was related to Nitrospira, which constituted 78% of the community by day 256, and which resulted in a reduction in the overall richness. After 500 days, the biofilm entered a stable population state, which was characterized by a greater richness of bacteria, including Nitrospira, Planctomyces, Acidobacterium, and Pseudomonas. The combination of different techniques illustrated the successional formation of a biofilm during a 3-year period in this model drinking water distribution system.


Tuberculous meningitis.
Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is hampered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. Antibiotic regimens for TBM are based on those used to treat pulmonary tuberculosis, which probably results in suboptimal drug levels in the cerebrospinal fluid, owing to poor blood-brain barrier penetrance. The role of adjunctive anti-inflammatory, host-directed therapies - including corticosteroids, aspirin and thalidomide - has not been extensively explored. To address this deficit, two expert meetings were held in 2009 and 2015 to share findings and define research priorities. This Review summarizes historical and current research into TBM and identifies important gaps in our knowledge. We will discuss advances in the understanding of inflammation in TBM and its potential modulation; vascular and hypoxia-mediated tissue injury; the role of intensified antibiotic treatment; and the importance of rapid and accurate diagnostics and supportive care in TBM.


Prostate-specific antigen doubling time as a progression criterion in an active surveillance programme for patients with localized prostate cancer.
To elucidate the role of prostate-specific antigen (PSA) doubling time (PSAdt) as a progression criterion in patients with low-risk prostate cancer managed by active surveillance (AS). To assess the correlation between PSAdt during AS and final histopathology after radical prostatectomy (RP) in patients meeting predefined progression criteria. A total of 258 consecutive patients on an AS programme were included in the study. The PSAdt was calculated in patients with two or more PSA values, and 95% confidence intervals (CIs) were calculated in patients with four or more PSA values. Progression risk groups were defined as follows: high-risk: PSAdt <3 years, rebiopsy Gleason score (GS) ≥4 + 3, more than three positive biopsy cores, and/or bilateral tumour or cT ≥2c disease; intermediate-risk: PSAdt 3-5 years, GS = 3 + 4 or cT2b disease; and low-risk: PSAdt >5 years, without histopathological or clinical progression. Definitive treatment was recommended for patients in the high-risk group and treatment options were discussed with those in the intermediate-risk group. A total of 2291 PSA values obtained during AS were available, of which 2071 were considered valid in the 258 patients. PSAdt values with 95% CIs were calculated in 221 patients based on a median of 8 PSA values. The 95% CIs for PSAdt overlapped considerably and in up to 91% of the patients, the 95% CIs overlapped among the risk group definitions. A total of 26% (68/258 patients) underwent RP after meeting the progression criteria. There was no association between preoperative PSAdt and final histopathology (P = 0.87). The uncertainty of calculated PSAdt during AS leads to a significant risk of patients being misclassified in terms of risk of progression, which limits the use of PSAdt in the management of patients on AS.


Clinical Outcomes of an Optimized Prolate Ablation Procedure for Correcting Residual Refractive Errors Following Laser Surgery.
The purpose of this study was to investigate the clinical efficacy of an optimized prolate ablation procedure for correcting residual refractive errors following laser surgery. We analyzed 24 eyes of 15 patients who underwent an optimized prolate ablation procedure for the correction of residual refractive errors following laser in situ keratomileusis, laser-assisted subepithelial keratectomy, or photorefractive keratectomy surgeries. Preoperative ophthalmic examinations were performed, and uncorrected distance visual acuity, corrected distance visual acuity, manifest refraction values (sphere, cylinder, and spherical equivalent), point spread function, modulation transfer function, corneal asphericity (Q value), ocular aberrations, and corneal haze measurements were obtained postoperatively at 1, 3, and 6 months. Uncorrected distance visual acuity improved and refractive errors decreased significantly at 1, 3, and 6 months postoperatively. Total coma aberration increased at 3 and 6 months postoperatively, while changes in all other aberrations were not statistically significant. Similarly, no significant changes in point spread function were detected, but modulation transfer function increased significantly at the postoperative time points measured. The optimized prolate ablation procedure was effective in terms of improving visual acuity and objective visual performance for the correction of persistent refractive errors following laser surgery.


Vagal nerve stimulation: clinical and electrophysiological effects on vocal fold function.
More than 16,000 vagal nerve stimulators (VNSs) have been implanted for refractory epileptic seizures. The most commonly reported side effect is hoarseness. This study examines the effects of VNS placement on vocal fold function. Eleven patients who had undergone VNS placement at our institution were recruited. Subjective evaluation by a panel of speech and language pathologists of both connected speech and videolaryngoscopy recordings were used both at rest and during VNS activation. Additional subjective evaluation included use of the Voice Handicap Index for the study group. These results were compared to data from age- and sex-matched controls. Objective data included maximum phonation time in the study and control groups, as well as laryngeal electromyography performed on the VNS-implanted patients only. Motor unit potential morphology and recruitment, as well as spontaneous activity, were analyzed bilaterally for the cricothyroid and thyroarytenoid muscles. Significant differences were found between the study and control groups subjectively for vocal quality and videolaryngoscopy parameters. Vocal fold tension, supraglottic muscular hyperfunction, and reduced vocal fold mobility were the most common findings during VNS activation. Two of 10 patients had immobile left vocal folds in the absence of active stimulation. The maximum phonation time was generally reduced in the subject group, but this reduction did not reach statistical significance. Finally, 6 of 10 patients had abnormal electromyographic results, including large-amplitude polyphasic motor unit potentials and decreased recruitment. We conclude that implantation of a VNS can affect vocal fold function. The effects are magnified during periods of active stimulation. There is the potential for nerve degeneration after prolonged repetitive stimulation, and there may be a trend toward greater vocal fold dysfunction with higher stimulation parameters.


The difficulty in handling poisonings associated with Chinese traditional medicine: a poison control center experience for 1991-1993.
The purpose of this prospective case series was to outline the characteristics of Chinese traditional medicine poisonings and develop essential information for poison prevention and management. All phone inquiries made to the Poison Center related to Chinese traditional medicines from January 1, 1991 to December 31, 1993 were included. Standardized questionnaires were used to capture relevant information. Among the 318 phone inquiries about Chinese traditional medicines, 273 cases were classified as poisonings; and 22 mortalities occurred (6.9%). All of the poisonings occurred because of suicide attempts, accidents, or erroneous or improper use or processing. In our study, 47% of the potential toxic effects of Chinese traditional medicines were either unknown or could not be found in the literature. There existed undefinable uncertainty in attributing the clinical effects to the exposures to Chinese traditional medicines. We recommend that the strategy in handling Chinese traditional medicine poisonings to decrease mortality should be comprised of confirmation of the generic name of the substances and the specific part of the plant used, awareness of improper processing methods, maintenance of records on a broad review of systems and laboratory data, identification of active principles and potential interactions among the individual active agents; verification of histopathologic effects of the toxins; development of information on toxicodynamics and toxicokinetics; intensive supportive care for poisoned patients, and investigation of potential antidotes. There are several regulatory options available to health authorities to control the unrestricted use of these potentially toxic medicines and to help safeguard the public.


Induction of parkinsonian resting tremor by stimulation of the caudal zona incerta nucleus: a clinical study.
We hypothesise that parkinsonian tremor arises when the caudal zona incerta (cZI) and subthalamic nucleus (STN) are deprived of dopamine and become increasingly responsive to motor cortical alpha and beta frequency oscillations. These oscillations are synchronised and amplified through the basal ganglia thalamocortical loop and entrained into the cerebello-thalamocortical loop via the cZI. On receiving potent gamma-aminobutyric acid (GABA)-ergic alpha and beta frequency oscillations in cZI afferents, ventrolateral (VL) thalamocortical neurons become hyperpolarised and rebound burst fire, generating 4-6 Hz tremor oscillations. We test this hypothesis by stimulating the cZI at alpha and beta frequencies using deep brain stimulation (DBS) in non-tremulous parkinsonian patients to see whether a 4-6 Hz tremor can be induced. This study included 11 patients with non-tremulous Parkinson's disease (PD), who had DBS leads implanted in a range of targets, including the cZI, STN, VL nucleus, globus pallidus internus (GPi), centromedian and parafascicular nucleus (CM/Pf), and the pedunculopontine nucleus (PPN). All patients underwent stimulation of active contacts within their respective targets at a standard pulse width, with frequencies ranging from 5 to 80 Hz up to a maximum tolerated voltage. The frequency of the tremor induced in the hands was recorded by accelerometry. Resting tremor in the 4-6 Hz range could be readily induced following stimulation of the cZI and the VL nucleus between 5 and 40 Hz. Tremor was also seen following STN stimulation; however, this was only at high stimulation voltages (>5 volts). No tremor could be induced following CM/Pf, PPN or GPi stimulation. We discuss the implications of these findings and argue that resting tremor in PD is generated in the cortico-ZI-VL-thalamocortical loop rather than in the cortico-basal-ganglia-thalamocortical loop.


The disposition of cocaine and opiate analytes in hair and fingernails of humans following cocaine and codeine administration.
This study investigated the disposition patterns of cocaine and opiates into hair and fingernail specimens collected from 8 volunteers enrolled in a 10-week inpatient clinical study. All subjects were African-American males with a confirmed drug use history. Scalp hair and fingernail scrapings were collected weekly throughout the course of the study. Head hair was collected from the posterior vertex region, and fingernail scrapings were collected along the entire ventral surface of the nail plate. The specimens were introduced to successive decontamination washes including an isopropanol wash and three phosphate buffer washes. All decontamination washes were collected and analyzed. All specimens were enzymatically digested prior to being subjected to solid-phase extraction and derivatization. Analyses were performed using electron impact gas chromatography-mass spectrometry. Analytes investigated included eight cocaine analytes and five codeine analytes. The limit of quantitation for all analytes ranged from 0.1 to 0.5 ng/mg for both matrices. Cocaine was present at the highest concentrations of any analyte in both hair and nail. Benzoylecgonine and ecgonine methyl ester were the primary metabolites in both matrices and were typically less than 15% of cocaine concentrations. Codeine was the only opiate analyte identified in either hair or nail. Observed drug disposition profiles were different for hair and nails. A significant dose-response relationship was observed for hair specimens. The mean peak concentrations in hair after low dosing were half the concentration observed after high-dose administration. Generally, no clear relationship was evident between nail drug concentrations and dose. Decontamination washes removed less than 20% of the total drug present in hair, but removed most of the drug concentrations (60-100%) in nail. This investigation demonstrated that higher concentrations of drug were found in the subjects' hair than in their fingernails and that cocaine was found in both matrices at a greater concentration than codeine. Although both hair and nail have similar physical and chemical properties and may share common mechanisms of drug incorporation, this clinical study suggests that there are distinct differences in their disposition profiles.


Preparation and physicochemical properties of surfactant-free emulsions using electrolytic-reduction ion water containing lithium magnesium sodium silicate.
Surfactant-free emulsions by adding jojoba oil, squalane, olive oil, or glyceryl trioctanoate (medium chain fatty acid triglycerides, MCT) to electrolytic-reduction ion water containing lithium magnesium sodium silicate (GE-100) were prepared, and their physiochemical properties (thixotropy, zeta potential, and mean particle diameter) were evaluated. At an oil concentration of 10%, the zeta potential was ‒22.3 ‒ ‒26.8 mV, showing no marked differences among the emulsions of various types of oil, but the mean particle diameters in the olive oil emulsion (327 nm) and MCT emulsion (295 nm) were smaller than those in the other oil emulsions (452-471 nm). In addition, measurement of the hysteresis loop area of each type of emulsion revealed extremely high thixotropy of the emulsion containing MCT at a low concentration and the olive emulsion. Based on these results, since surfactants and antiseptic agents markedly damage sensitive skin tissue such as that with atopic dermatitis, surfactant- and antiseptic-free emulsions are expected to be new bases for drugs for external use.


Biphasic Cell-Size and Growth-Rate Homeostasis by Single Bacillus subtilis Cells.
The growth rate of single bacterial cells is continuously disturbed by random fluctuations in biosynthesis rates and by deterministic cell-cycle events, such as division, genome duplication, and septum formation. It is not understood whether, and how, bacteria reject these growth-rate disturbances. Here, we quantified growth and constitutive protein expression dynamics of single Bacillus subtilis cells as a function of cell-cycle progression. We found that, even though growth at the population level is exponential, close inspection of the cell cycle of thousands of single Bacillus subtilis cells reveals systematic deviations from exponential growth. Newborn cells display varying growth rates that depend on their size. When they divide, growth-rate variation has decreased, and growth rates have become birth size independent. Thus, cells indeed compensate for growth-rate disturbances and achieve growth-rate homeostasis. Protein synthesis and growth of single cells displayed correlated, biphasic dynamics from cell birth to division. During a first phase of variable duration, the absolute rates were approximately constant and cells behaved as sizers. In the second phase, rates increased, and growth behavior exhibited characteristics of a timer strategy. These findings demonstrate that, just like size homeostasis, growth-rate homeostasis is an inherent property of single cells that is achieved by cell-cycle-dependent rate adjustments of biosynthesis and growth.


Silver Nanowire/MnO2 Nanowire Hybrid Polymer Nanocomposites: Materials with High Dielectric Permittivity and Low Dielectric Loss.
This study reports the fabrication of hybrid nanocomposites based on silver nanowire/manganese dioxide nanowire/poly(methyl methacrylate) (AgNW/MnO2NW/PMMA), using a solution casting technique, with outstanding dielectric permittivity and low dielectric loss. AgNW was synthesized using the hard-template technique, and MnO2NW was synthesized employing a hydrothermal method. The prepared AgNW:MnO2NW (2.0:1.0 vol %) hybrid nanocomposite showed a high dielectric permittivity (64 at 8.2 GHz) and low dielectric loss (0.31 at 8.2 GHz), which are among the best reported values in the literature in the X-band frequency range (8.2-12.4 GHz). The superior dielectric properties of the hybrid nanocomposites were attributed to (i) dimensionality match between the nanofillers, which increased their synergy, (ii) better dispersion state of AgNW in the presence of MnO2NW, (iii) positioning of ferroelectric MnO2NW in between AgNWs, which increased the dielectric permittivity of nanodielectrics, thereby increasing dielectric permittivity of the hybrid nanocomposites, (iv) barrier role of MnO2NW, i.e., cutting off the contact spots of AgNWs and leading to lower dielectric loss, and (v) AgNW aligned structure, which increased the effective surface area of AgNWs, as nanoelectrodes. Comparison of the dielectric properties of the developed hybrid nanocomposites with the literature highlights their great potential for flexible capacitors.


Internal fat mediates the impact of age on diabetes onset in chinese people between 30 and 44 years old.
We sought to measure the effect of controlling body fat indexes on decreasing the incidence of type 2 diabetes mellitus (T2DM) mathematically. Study samples were selected from a well-established cohort in Suzhou, China between 2004 and 2008, comprising 6364 males and 9678 females. The questionnaire contained socio-demographic characteristics, smoking, alcohol consumption, diet, physical activity, personal and family medical history and current medication. Multiple linear regression, Cox regression and mediation analyses were performed to determine the relationship among age, body fat indexes and T2DM onset. All the three body fat indexes [the body mass index (BMI), waist-to-hip ratio (WHR) and body fat percentage] showed a significant positive association (P<0.05) with age and T2DM. Significant indirect effects (IE) were detected for age, which were mediated respectively through WHR [IE=1.10, 95%CI: 1.07-1.13; P<0.001], the BMI (IE=1.15, 95%CI: 1.11-1.18; P<0.001), and body fat percentage (IE=1.09, 95%CI: 1.07-1.12; P<0.001). The combined body fat index score demonstrated a significant association with age (P<0.001) and a stronger relationship with the onset of diabetes (P<0.001) along with a significant mediating effect (IE=1.17; 95%CI: 1.13-1.22; P<0.001). The total effect of age on T2DM was 1.60 (95%CI: 1.21-2.10; P=0.0008). As a result, the three body fat indexes jointly mediated 33.97% of the age impact on diabetes onset. This pilot study revealed important roles for body fat indexes in mediating the age pathway to the onset of diabetes. Controling body fat in the appropriate range could reduce 33.97% of the risk of T2DM onset with increasing age.


Detailed reconstruction of the musculature in Limnognathia maerski (Micrognathozoa) and comparison with other Gnathifera.
Limnognathia maerski is the single species of the recently described taxon, Micrognathozoa. The most conspicuous character of this animal is the complex set of jaws, which resembles an even more intricate version of the trophi of Rotifera and the jaws of Gnathostomulida. Whereas the jaws of Limnognathia maerski previously have been subject to close examinations, the related musculature and other organ systems are far less studied. Here we provide a detailed study of the body and jaw musculature of Limnognathia maerski, employing confocal laser scanning microscopy of phalloidin stained musculature as well as transmission electron microscopy (TEM). This study reveals a complex body wall musculature, comprising six pairs of main longitudinal muscles and 13 pairs of trunk dorso-ventral muscles. Most longitudinal muscles span the length of the body and some fibers even branch off and continue anteriorly into the head and posteriorly into the abdomen, forming a complex musculature. The musculature of the jaw apparatus shows several pairs of striated muscles largely related to the fibularium and the main jaws. The jaw articulation and function of major and minor muscle pairs are discussed. No circular muscles or intestinal musculature have been found, but some newly discovered muscles may supply the anal opening. The organization in Limnognathia maerski of the longitudinal and dorso-ventral muscle bundles in a loose grid is more similar to the organization found in rotifers rather than gnathostomulids. Although the dorso-ventral musculature is probably not homologous to the circular muscles of rotifers, a similar function in body extension is suggested. Additionally, a functional comparison between the jaw musculature of Limnognathia maerski, Rotifera and Gnathostomulida, emphasizes the important role of the fibularium in Limnognathia maerski, and suggests a closer functional resemblance to the jaw organization in Rotifera.


Specialization of the right hemisphere for visuomotor control.
The accuracy of saccades directed towards the remembered positions of targets in left (LVF) or right (RVF) visual hemifield was measured. The majority of right-handed subjects were found to be more accurate at directing their gaze to locations in the LVF than in the RVF, suggesting that the right hemisphere is superior to the left in oculomotor control. Even after completion of a corrective saccade following the primary saccade, subjects systematically undershot target direction and overshot target depth, suggesting that visual feedback normally plays an important role in the fine guidance of gaze after the completion of a primary saccade.


Southern Phosphorus Indices, Water Quality Data, and Modeling (APEX, APLE, and TBET) Results: A Comparison.
Phosphorus (P) Indices in the southern United States frequently produce different recommendations for similar conditions. We compared risk ratings from 12 southern states (Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, and Texas) using data collected from benchmark sites in the South (Arkansas, Georgia, Mississippi, North Carolina, Oklahoma, and Texas). Phosphorus Index ratings were developed using both measured erosion losses from each benchmark site and Revised Universal Soil Loss Equation 2 predictions; mostly, there was no difference in P Index outcome. The derived loss ratings were then compared with measured P loads at the benchmark sites by using equivalent USDA-NRCS P Index ratings and three water quality models (Annual P Loss Estimator [APLE], Agricultural Policy Environmental eXtender [APEX], and Texas Best Management Practice Evaluation Tool [TBET]). Phosphorus indices were finally compared against each other using USDA-NRCS loss ratings model estimate correspondence with USDA-NRCS loss ratings. Correspondence was 61% for APEX, 48% for APLE, and 52% for TBET, with overall P index correspondence at 55%. Additive P Indices (Alabama and Texas) had the lowest USDA-NRCS loss rating correspondence (31%), while the multiplicative (Arkansas, Florida, Louisiana, Mississippi, South Carolina, and Tennessee) and component (Georgia, Kentucky, and North Carolina) indices had similar USDA-NRCS loss rating correspondence-60 and 64%, respectively. Analysis using Kendall's modified Tau suggested that correlations between measured and calculated P-loss ratings were similar or better for most P Indices than the models.


A multiligand based Pd catalyst for C-N cross-coupling reactions.
An alternative approach to catalyst development, which led to a Pd catalyst based on two biarylphosphine ligands for C-N cross-coupling reactions, is reported. By effectively being able to take the form of multiple catalysts this system manifests the best properties that catalysts based on either of the two ligands exhibit separately and displays the highest reactivity and substrate scope of any system that has been reported to date for these reactions.


Post-needling soreness after myofascial trigger point dry needling: Current status and future research.
Post-dry needling soreness is a common complication of myofascial trigger point (MTrP) dry needling treatment. The prevention, management and relevance of this complication remain uncertain. This paper examines the current state of knowledge and suggests directions for further studies in this area. MTrPs are hypersensitive nodules in skeletal muscles' taut bands, present in several pain conditions. Dry needling has been recommended for relieving MTrP pain. MTrP dry needling procedures have shown to be associated with post-needling soreness, which is thought to be a consequence of the neuromuscular damage, and hemorrhagic and inflammatory reaction generated by the needle. Postneedling soreness is a very frequent effect after deep dry needling, usually lasting less than 72 h. It may not be especially distressing for most patients. However, patients presenting with higher levels of post-needling soreness, not perceiving dry needling effectiveness in the first session, or not having high myofascial pain intensity before treatment, could be the most likely to find post-needling soreness more distressing, functionally limiting and to abandon treatment. Future research should assess the clinical relevance of post-needling soreness. Post-needling soreness should be considered when investigating dry needling effectiveness since it could overlie the original myofascial pain and influence the patients' pain ratings.


The influence of occupation and age on maximal and rapid lower extremity strength.
The aims of this study were to 1) examine the influence of age and occupation on maximal and rapid strength of the lower-extremity muscles and 2) examine the relationship between maximal and rapid strength and physical workload (work index (WI)) in the blue-collar (BC) cohort. Peak torque (PT) and peak rate of torque development (peakRTD) of the leg extensors (LE), leg flexors (LF), and plantar flexors (PF) were assessed in 47 young (age = 24.1 ± 2.4 years) and 41 middle-aged (52.4 ± 5.2 years) white-collar (WC) and BC men. Middle-aged workers exhibited lower PT for all muscles, and peakRTD for the LF and PF muscles. A positive relationship (r = 0.59; P < 0.01) was observed between WI and peakRTD for the PF in the young BC workers, however, this relationship was negative (r = -0.45; P = 0.053) for the LF of the middle-aged BC workers. Lowering physical work demands and/or incorporating effective health-related practices for employees may be appealing strategies to enhance aging workers' productivity and longevity in the workforce.


EXPERIMENTAL PLEURISY-RESOLUTION OF A FIBRINOUS EXUDATE.
Fibrinous pleurisy produced by a sterile inflammatory irritant offers opportunity for study of the part taken by enzymes of leucocytes in the resolution of a fibrinous exudate. When turpentine is injected into the subcutaneous tissue of the dog, an abscess results, but when an equal quantity of turpentine is injected into the pleural cavity, there is abundant exudation of coagulable fluid and the serous surfaces are covered by a layer of fibrin. Accumulation of fluid which can be followed during life by percussion of the animal's chest reaches a maximum at the end of three days, and then gradually subsides, so that at the end of six days, in most instances, the cavity contains no fluid. Fibrin, though diminished in amount at the time when fluid has been absorbed, is still present, and gradually disappears; at the end of two or three weeks the cavity has returned to the normal, save for a few organized adhesions. Turpentine injected into the right pleural cavity may cause serofibrinous pleurisy on the left side; this inflammation may reach a maximum intensity at a time when pleurisy on the right side is subsiding. During the early stage of inflammation fibrinous exudate, freed from the serum by washing in salt solution, undergoes digestion when suspended in an alkaline (0.2 per cent. sodium carbonate) or in an acid medium (0.2 per cent. acetic acid). At the end of five days, at a time when fluid is disappearing from the pleural cavity, digestion fails to occur in an alkaline medium, but occurs with much activity in the presence of acid. During the first stage of the inflammatory reaction, when fluid is abundant and the fibrin which is present digests in alkali, thus indicating the presence of leucoprotease, polynuclear leucocytes are very numerous in the meshes of the fibrin. In the second stage, the exuded fibrin contains only one enzyme digesting in the presence of acid. At this time polynuclear leucocytes have disappeared and only mononuclear cells are embedded in the fibrin. Products of proteolytic digestion, namely, peptone and albumose, absent in the exuded fluid during the first day or two days of inflammation, are present after three days and are found in less quantity at a later period. The exuded fluid does not at any stage of the inflammatory reaction lose it spower to inhibit both enzymes contained in the leucocytes. The exudate remains alkaline throughout the period of inflammation, but its alkalinity is less than that of the blood and diminishes slightly with the progress of inflammation. Since the acids, which in vitro favor the action of the enzyme, present alone during the second stage of the inflammatory reaction, do not occur in the body, the possibility has suggested itself that carbon-dioxide brings this enzyme into action. If carbon-dioxide is passed through normal salt solution in which strips of such fibrin are suspended, digestion is greatly hastened. The normal inhibition exerted by blood serum upon the enzyme is overcome by carbon-dioxide and in the presence of a small quantity of blood serum, carbon-dioxide causes greater enzymotic activity than in the presence of salt solution alone.


Early additional food and fluids for healthy breastfed full-term infants.
Widespread recommendations from health organisations encourage exclusive breastfeeding for six months. However, the addition of other fluids or foods before six months is common in many countries and communities. This practice suggests perceived benefits of early supplementation or lack of awareness of the possible risks. To assess the benefits and harms of supplementation for full-term healthy breastfed infants and to examine the timing and type of supplementation. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 March 2014) and reference lists of all relevant retrieved papers. Randomised or quasi-randomised controlled trials in infants under six months of age comparing exclusive breastfeeding versus breastfeeding with any additional food or fluids. Two review authors independently selected the trials, extracted data and assessed risk of bias. We included eight trials (984 randomised infants/mothers). Six trials (n = 613 analysed) provided data on outcomes of interest to this review. The variation in outcome measures and time points made it difficult to pool results from trials. Data could only be combined in a meta-analysis for one secondary outcome (weight change). The trials that provided outcome data compared exclusively breastfed infants with breastfed infants who were allowed additional nutrients in the form of artificial milk, glucose, water or solid foods.In relation to the majority of the older trials, the description of study methods was inadequate to assess the risk of bias. The two more recent trials, were found to be at low risk of bias for selection and detection bias. The overall quality of the evidence for the main comparison was low.In one trial (170 infants) comparing exclusively breastfeeding infants with infants who were allowed additional glucose water, there was a significant difference favouring exclusive breastfeeding up to and including week 20 (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.05 to 1.99), with more infants in the exclusive breastfed group still exclusively breastfeeding. Conversely in one small trial (39 infants) comparing exclusive breastfed infants with non-exclusive breastfed infants who were provided with artificial milk, fewer infants in the exclusive breastfed group were exclusively breastfeeding at one week (RR 0.58, 95% CI 0.37 to 0.92) and at three months (RR 0.44, 95% CI 0.26 to 0.76) and there was no significant difference in the proportion of infants continuing any breastfeeding at three months between groups (RR 0.76, 95% CI 0.56 to 1.03).For infant morbidity (six trials), one newborn trial (170 infants) found a statistically, but not clinically, significant difference in temperature at 72 hours (mean difference (MD) 0.10 degrees, 95% CI 0.01 to 0.19), and that serum glucose levels were higher in glucose supplemented infants in the first 24 hours, though not at 48 hours (MD -0.24 mmol/L, 95% CI -0.51 to 0.03). Weight loss was also higher (grams) in infants at six, 12, 24 and 48 hours of life in the exclusively breastfed infants compared to those who received additional glucose water (MD 7.00 g, 95% CI 0.76 to 13.24; MD 11.50 g, 95% CI 1.71 to 21.29; MD 13.40 g, 95% CI 0.43 to 26.37; MD 32.50 g, 95% CI 12.91 to 52.09), but no difference between groups was observed at 72 hours of life. In another trial (47 infants analysed), we found no significant difference in weight loss between the exclusively breastfeeding group and the group allowed either water or glucose water on either day three or day five (MD 1.03%, 95% CI -0.18 to 2.24) and (MD 0.20%, 95% CI -1.18 to 1.58).Three trials with four- to six-month-old infants provided no evidence to support any benefit from the addition of complementary foods at four months versus exclusive breastfeeding to six months nor any risks related either morbidity or weight change (or both).None of the trials reported on the remaining primary outcomes, infant mortality or physiological jaundice. We were unable to fully assess the benefits or harms of supplementation or to determine the impact from timing and type of supplementation. We found no evidence of benefit to newborn infants and possible negative effects on the duration of breastfeeding from the brief use of additional water or glucose water, and the quality of the evidence from a small pilot study on formula supplementation was insufficient to suggest a change in practice away from exclusive breastfeeding. For infants at four to six months, we found no evidence of benefit from additional foods nor any risks related to morbidity or weight change. Future studies should examine the longer-term effects on infants and mothers, though randomising infants to receive supplements without medical need may be problematic.We found no evidence for disagreement with the recommendation of international health associations that exclusive breastfeeding should be recommended for healthy infants for the first six months.


MicroRNA let-7b regulates genomic balance by targeting Aurora B kinase.
The let-7 microRNA (miRNA) family has been implicated in the regulation of diverse cellular processes and disease pathogenesis. In cancer, loss-of-function of let-7 miRNAs has been linked to tumorigenesis via increased expression of target oncogenes. Excessive proliferation rate of tumor cells is often associated with deregulation of mitotic proteins. Here, we show that let-7b contributes to the maintenance of genomic balance via targeting Aurora B kinase, a key regulator of the spindle assembly checkpoint (SAC). Our results indicate that let-7b binds to Aurora B kinase 3'UTR reducing mRNA and protein expression of the kinase. In cells, excess let-7b induced mitotic defects characteristic to Aurora B perturbation including increased rate of polyploidy and multipolarity, and premature SAC inactivation that leads to forced exit from chemically induced mitotic arrest. Moreover, the frequency of aneuploid HCT-116 cells was significantly increased upon let-7b overexpression compared to controls. Interestingly, together with a chemical Aurora B inhibitor, let-7b had an additive effect on polyploidy induction in HeLa cells. In breast cancer patients, reduced let-7b expression was found to be associated with increased Aurora B expression in grade 3 tumors. Furthermore, let-7b was found downregulated in the most aggressive forms of breast cancer determined by clinicopathological parameters. Together, our findings suggest that let-7b contributes to the fidelity of cell division via regulation of Aurora B. Moreover, the loss of let-7b in aggressive tumors may drive tumorigenesis by up-regulation of Aurora B and other targets of the miRNA, which further supports the role of let-7b in tumor suppression.


Identifying and Tracking Defects in Dynamic Supramolecular Polymers.
A central paradigm of self-assembly is to create ordered structures starting from molecular monomers that spontaneously recognize and interact with each other via noncovalent interactions. In recent years, great efforts have been directed toward perfecting the design of a variety of supramolecular polymers and materials with different architectures. The resulting structures are often thought of as ideally perfect, defect-free supramolecular fibers, micelles, vesicles, etc., having an intrinsic dynamic character, which are typically studied at the level of statistical ensembles to assess their average properties. However, molecular simulations recently demonstrated that local defects that may be present or may form in these assemblies, and which are poorly captured by conventional approaches, are key to controlling their dynamic behavior and properties. The study of these defects poses considerable challenges, as the flexible/dynamic nature of these soft systems makes it difficult to identify what effectively constitutes a defect and to characterize its stability and evolution. Here, we demonstrate the power of unsupervised machine-learning techniques to systematically identify and compare defects in supramolecular polymer variants in different conditions, using as a benchmark 5 Å resolution coarse-grained molecular simulations of a family of supramolecular polymers. We show that this approach allows a complete data-driven characterization of the internal structure and dynamics of these complex assemblies and of the dynamic pathways for defects formation and resorption. This provides a useful, generally applicable approach to unambiguously identify defects in these dynamic self-assembled materials and to classify them based on their structure, stability, and dynamics.


High temperature dilute acid pretreatment of coastal Bermuda grass for enzymatic hydrolysis.
Dilute sulfuric acid was used to pretreat coastal Bermuda grass at high temperature prior to enzymatic hydrolysis. After both pretreatment and enzymatic hydrolysis processes, the highest yield of total sugars (combined xylose and glucose) was 97% of the theoretical value. The prehydrolyzate liquor was analyzed for inhibitory compounds (furfural, hydroxymethylfurfural (HMF)) in order to assess potential risk for inhibition during the following fermentation. Accounting for the formation of the inhibitory compounds, a pretreatment with 1.2% acid at 140 °C for 30 min with a total sugar yield of 94% of the theoretical value may be more favorable for fermentation. From this study, it can be concluded that dilute sulfuric acid pretreatment can be successfully applied to coastal Bermuda grass to achieve high yields of monomeric glucose and xylose with acceptable levels of inhibitory compound formation.


T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3.
Cell lineage specification depends on both gene activation and gene silencing, and in the differentiation of T helper progenitors to Th1 or Th2 effector cells, this requires the action of two opposing transcription factors, T-bet and GATA-3. T-bet is essential for the development of Th1 cells, and GATA-3 performs an equivalent role in Th2 development. We report that T-bet represses Th2 lineage commitment through tyrosine kinase-mediated interaction between the two transcription factors that interferes with the binding of GATA-3 to its target DNA. These results provide a novel function for tyrosine phosphorylation of a transcription factor in specifying alternate fates of a common progenitor cell.


Does Postural Awareness Contribute to Exercise-Induced Improvements in Neck Pain Intensity? A Secondary Analysis of a Randomized Controlled Trial Evaluating Tai Chi and Neck Exercises.
Secondary analysis of a randomized controlled trial. This secondary analysis aims to examine associations of improvement of chronic neck pain with patients' and intervention-related characteristics. Previous research has found that Tai Chi and neck exercises significantly improved chronic nonspecific neck pain; however, the factors for treatment success remain unclear. Subjects with chronic nonspecific neck pain were randomly assigned to 12 weeks of group Tai Chi or conventional neck exercises, and they attended 12 weekly sessions of 60 to 90 minutes. The interventions included exercises to improve body awareness, that is, interoceptive and postural awareness. A linear forward stepwise regression analysis was conducted to examine associations with improvements in neck pain intensity. Potential predictor variables included baseline pain, age, sex, the type of intervention, attendance rate and home practice duration, and changes in psychological well-being, perceived stress, and postural and interoceptive awareness during the study. Overall 75 patients were randomized into Tai Chi or conventional exercises, with the majority being women (78.7%). Participants reported an average pain intensity of 50.7 ± 20.4 mm visual analog scale at baseline, and the average reduction of pain intensity in both groups was 21.4 ± 21.3 mm visual analog scale. Regression analysis revealed that reductions in pain intensity from baseline to 12 weeks were predicted by higher pain intensity at baseline (r = 0.226, P < 0.001), a decrease in anxiety (r = 0.102, P = 0.001), and an increase in postural awareness (r = 0.078, P = 0.0033), explaining a total of 40.6% of variance. Neck pain improvement was significantly associated with changes in postural awareness in subject with chronic nonspecific neck pain independent of treatment characteristics. Training of postural awareness might be an important mechanism of action of different exercise-based interventions for chronic neck pain. N /A.


Preoperative androgen-deprivation therapy for clinical stage T3 prostate cancer.
The widespread availability of luteinizing hormone-releasing hormone analogues has renewed interest in androgen-deprivation therapy (ADT) before radical prostatectomy. Neoadjuvant ADT in patients with clinically localized tumors has resulted in decreased margin-positive rates and increased rates of organ-confined disease. Unfortunately, the pathological effects of ADT in patients with locally advanced (cT3) prostate cancer have been less marked. This article reviews our experience with neoadjuvant hormonal therapy in patients with clinical stage T3 prostate cancer. In a case-control study of cT3 patients undergoing radical retropubic prostatectomy between 1985 and 1992, 72 patients receiving preoperative ADT were compared with a matched group of 144 untreated patients in terms of pathological outcome and long-term disease-free survival. A local downstaging effect in hormonally treated patients was suggested by lower rates of extracapsular extension, but only 31% had organ-confined disease. Hormonally treated patients showed no benefit in survival or disease progression compared with patients who did not receive this therapy. Although preoperative ADT may decrease the incidence of extracapsular extension in clinical stage T3 prostate cancer, our data suggest that it has no significant effect on survival or disease progression in patients with locally advanced disease.


Swift transformation and locomotion of polymorphonuclear leukocytes and microglia as observed by VEC-DIC microscopy (video microscopy).
The detailed assembly used by us for video-enhanced contrast-differential interference contrast (VEC-DIC) microscopy (video microscopy is first described. Employing such video microscopy, we then examined the morphological changes occurring during locomotion and activation processes of polymorphonuclear leukocytes (PMNL) and microglia at an almost electron microscopic magnification. Upon contacting the substratum, PMNL transformed into a polarized ameboid shape and crawled extending pseudopodia, as has been well documented previously. The PMNL sometimes displayed a peculiar locomotion as if they were stepping on "tiny legs", or sliding on a treadmill of cell membrane. Cultured microglia were observed to exist in 4 forms; ramified, reactive, villous, and ameboid. Microglia in the reactive form pivoted, circled and crawled on the astroglial cell layer using their transparent lamellipodia with no morphological changes in their cell body. Unlike PMNL, reactive microglia exhibited no agitated movements of their intracellular organelles, including granules and cytosol, during locomotion. Lamellipodia on the undersurface of the cell body touching the cell layer adhesively, appeared to serve as the locomotive apparatus. When activated, both floating PMNL and microglia of villous form assumed an ameboid shape within a few seconds. Microglia occasionally swam in the medium waving their lamellipodia towards a target object (e.g. zymosan A particles), remodelling to an amorphous ameboid form and covering up the target. We attempt to discuss such swift morphological changes from the standpoint of thermodynamic potential of Gibbs free energy which is stored within the cells.


Delphinidin suppresses ultraviolet B-induced cyclooxygenases-2 expression through inhibition of MAPKK4 and PI-3 kinase.
Cyclooxygenase-2 (COX-2), a key mediator of inflammation, and its product, prostaglandin E(2) (PGE(2)), enhance carcinogenesis, particularly in skin. Ultraviolet (UV) B is the most carcinogenic component of solar irradiation, and a crucial role of COX-2 in UVB-mediated skin carcinogenesis has been reported. Here, we investigated the effects of delphinidin, an abundant dietary anthocyanin, on UVB-induced COX-2 upregulation and the underlying molecular mechanism. We found that delphinidin suppressed UVB-induced COX-2 expression in JB6 P+ mouse epidermal cells. COX-2 promoter activity and PGE(2) production were also suppressed by delphinidin treatment within non-cytotoxic concentrations. Activator protein-1 and nuclear factor-kappaB, crucial transcription factors involved in COX-2 expression, were activated by UVB and delphinidin abolished this activation. UVB-induced phosphorylation of c-Jun N-terminal kinase, p38 kinase and Akt was inhibited by delphinidin. The activities of mitogen-activated protein kinase kinase (MAPKK) 4 and phosphatidylinositol-3 kinase (PI-3K) were inhibited markedly by delphinidin. A pull-down assay using delphinidin-Sepharose beads revealed that delphinidin binds directly with MAPKK4 or PI-3K in a manner that was competitive with adenosine triphosphate. Moreover, in vivo investigations using mouse skin revealed that the upregulation of COX-2 expression, MAPKK4 activity and PI-3K activity induced by UVB was abolished with delphinidin treatment. Collectively, our results demonstrated that delphinidin targets MAPKK4 and PI-3K directly to suppress COX-2 overexpression, suggesting a potential protective role for delphinidin against UVB-mediated skin carcinogenesis.


Transforming emergency care for older adults.
Already crowded and stressful, US emergency departments (EDs) are facing the challenge of serving an aging population that requires complex and lengthy evaluations. Creative solutions are necessary to improve the value and ensure the quality of emergency care delivered to older adults while more fully addressing their complex underlying physical, social, cognitive, and situational needs. Developing models of geriatric emergency care, including some that are already in use at dedicated geriatric EDs, incorporate a variety of physical, procedural, and staffing changes. Among the options for "geriatricizing" emergency care are approaches that may eliminate the need for an ED visit, such as telemedicine; for initial hospitalization, such as patient observation units; and for rehospitalization, such as comprehensive discharge planning. By transforming their current safety-net role to becoming a partner in care coordination, EDs have the opportunity to become better integrated into the broader health care system, improve patient health outcomes, contribute to optimizing the health care system, and reduce overall costs of care-keys to improving emergency care for patients of all ages.


Long-term evolution and transmission dynamics of swine influenza A virus.
Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12 years of systematic surveillance in this region, supplemented with data stretching back 34 years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.


Clinical signs of trachoma are prevalent among Solomon Islanders who have no persistent markers of prior infection with Chlamydia trachomatis.
Background: The low population-prevalence of trachomatous trichiasis and high prevalence of trachomatous inflammation-follicular (TF) provide contradictory estimates of the magnitude of the public health threat from trachoma in the Solomon Islands. Improved characterisation of the biology of trachoma in the region may support policy makers as they decide what interventions are required. Here, age-specific profiles of anti-Pgp3 antibodies and conjunctival scarring were examined to determine whether there is evidence of ongoing transmission and pathology from ocular Chlamydia trachomatis (Ct) infection. Methods: A total of 1511 individuals aged ≥1 year were enrolled from randomly selected households in 13 villages in which >10% of children aged 1-9 years had TF prior to a single round of azithromycin mass drug administration undertaken six months previously. Blood was collected to be screened for antibodies to the Ct antigen Pgp3. Tarsal conjunctival photographs were collected for analysis of scarring severity. Results: Anti-Pgp3 seropositivity was 18% in 1-9 year olds, sharply increasing around the age of sexual debut to reach 69% in those over 25 years. Anti-Pgp3 seropositivity did not increase significantly between the ages of 1-9 years and was not associated with TF (p=0.581) or scarring in children (p=0.472). Conjunctival scars were visible in 13.1% of photographs. Mild (p<0.0001) but not severe (p=0.149) scars increased in prevalence with age. Conclusions: Neither conjunctival scars nor lymphoid follicles were associated with antibodies to Ct, suggesting that they are unlikely to be a direct result of ocular Ct infection . Clinical signs of trachoma were prevalent in this population but were not indicative of the underlying rates of Ct infection. The current World Health Organization guidelines for trachoma elimination indicated that this population should receive intervention with mass distribution of antibiotics, but the data presented here suggest that this may not have been appropriate.


Stimulatory action of internal protons on Slo1 BK channels.
We investigated the internal pH-sensitivity of heterologously expressed hSlo1 BK channels. In the virtual absence of Ca(2+) and Mg(2+) to isolate the voltage-dependent gating transitions, low internal pH enhanced macroscopic hSlo1 currents by shifting the voltage-dependence of activation to more negative voltages. The activation time course was faster and the deactivation time course was slower with low pH. The estimated K(d) value of the stimulatory effect was approximately pH = 6.5 or 0.35 micro M. The stimulatory effect was maintained when the auxiliary subunit mouse beta1 was coexpressed. Treatment of the hSlo1 channel with the histidine modifying agent diethyl pyrocarbonate also enhanced the hSlo1 currents and greatly diminished the internal pH sensitivity, suggesting that diethyl pyrocarbonate and low pH may work on the same effector mechanism. High concentrations of Ca(2+) or Mg(2+) also masked the stimulatory effect of low internal pH. These results indicate that the acid-sensitivity of the Slo BK channel may involve the channel domain implicated in the divalent-dependent activation.


A comprehensive survey of retracted articles from the scholarly literature.
The number of retracted scholarly articles has risen precipitously in recent years. Past surveys of the retracted literature each limited their scope to articles in PubMed, though many retracted articles are not indexed in PubMed. To understand the scope and characteristics of retracted articles across the full spectrum of scholarly disciplines, we surveyed 42 of the largest bibliographic databases for major scholarly fields and publisher websites to identify retracted articles. This study examines various trends among them. We found, 4,449 scholarly publications retracted from 1928-2011. Unlike Math, Physics, Engineering and Social Sciences, the percentages of retractions in Medicine, Life Science and Chemistry exceeded their percentages among Web of Science (WoS) records. Retractions due to alleged publishing misconduct (47%) outnumbered those due to alleged research misconduct (20%) or questionable data/interpretations (42%). This total exceeds 100% since multiple justifications were listed in some retraction notices. Retraction/WoS record ratios vary among author affiliation countries. Though widespread, only miniscule percentages of publications for individual years, countries, journals, or disciplines have been retracted. Fifteen prolific individuals accounted for more than half of all retractions due to alleged research misconduct, and strongly influenced all retraction characteristics. The number of articles retracted per year increased by a factor of 19.06 from 2001 to 2010, though excluding repeat offenders and adjusting for growth of the published literature decreases it to a factor of 11.36. Retracted articles occur across the full spectrum of scholarly disciplines. Most retracted articles do not contain flawed data; and the authors of most retracted articles have not been accused of research misconduct. Despite recent increases, the proportion of published scholarly literature affected by retraction remains very small. Articles and editorials discussing retractions, or their relation to research integrity, should always consider individual cases in these broad contexts. However, better mechanisms are still needed for raising researchers' awareness of the retracted literature in their field.


Maspin and MCM2 immunoprofiling in salivary gland carcinomas.
The pathogenesis of salivary gland carcinomas is very complex and prognostic markers are difficult to find in these carcinomas of which the different subtypes have varying malignant potential. The study was conducted to examine the cellular distribution of maspin and MCM2 in salivary gland carcinomas and their value to predict lymph node metastasis. Fifty three paraffin blocks of different lesions (15 muco-epidermoid carcinoma, 14 adenoid cystic carcinoma, 3 epi-myoepithelial carcinoma, 5 salivary duct carcinoma, 5 malignant pleomorphic adenoma, 6 polymorphous low grade adenocarcinoma and 5 acinic cell carcinoma) were prepared for immunohistochemical staining with maspin and MCM2 antibodies. ANOVA and Pearson correlation tests were used for the statistical analysis of the results. All salivary gland carcinomas express maspin and MCM2 with variable cellular localization. There was a significant difference in the expression of each antibody between mucoepidermoid carcinoma, adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. No association was found between examined markers and lymph node metastasis. Salivary gland carcinomas express maspin and MCM2 with variable levels and cellular localization, consisting important markers of biological behavior in these tumors. The level of MCM2 expression can be used in the differential diagnosis of adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. Further study with large sample size is recommended to assess their value in prediction of lymph node metastasis.


Effects of human serum on Balamuthia mandrillaris interactions with human brain microvascular endothelial cells.
Balamuthia mandrillaris is a free-living amoeba and a causative agent of fatal granulomatous encephalitis. In the transmission of B. mandrillaris into the central nervous system (CNS), haematogenous spread is thought to be the primary step, followed by blood-brain barrier penetration. The objectives of the present study were (i) to determine the effects of serum from healthy individuals on the viability of B. mandrillaris, and (ii) to determine the effects of serum on B. mandrillaris-mediated blood-brain barrier perturbations. It was determined that normal human serum exhibited limited amoebicidal effects, i.e. approximately 40 % of trophozoites were killed. The residual subpopulation, although viable, remained static over longer incubations. Using human brain microvascular endothelial cells (HBMEC), which form the blood-brain barrier, it was observed that B. mandrillaris exhibited binding (>80 %) and cytotoxicity (>70 %) to HBMEC. However, normal human serum exhibited more than 60 % inhibition of B. mandrillaris binding and cytotoxicity to HBMEC. ELISAs showed that both serum and saliva samples exhibit the presence of anti-B. mandrillaris antibodies. Western blots revealed that normal human serum reacted with several B. mandrillaris antigens with approximate molecular masses of 148, 115, 82, 67, 60, 56, 44, 42, 40 and 37 kDa. Overall, the results demonstrated that normal human serum has inhibitory effects on B. mandrillaris growth and viability, as well as on their binding and subsequent cytotoxicity to HBMEC. A complete understanding of B. mandrillaris pathogenesis is crucial to develop therapeutic interventions and/or to design preventative measures.


Serodetection of Ehrlichia canis amongst dogs in central Namibia.
Ehrlichia canis is a major pathogen in dogs throughout Africa, yet it has not been reported in Namibia. The aim of this study was to determine the seroprevalence of canine ehrlichiosis in central Namibia using the ImmunoComb assay (Biogal, Galed Laboratories). The study included 76 dogs that presented to the Rhino Park Veterinary Clinic in the north-western suburb of Khomasdal, Windhoek, Namibia, as well as 30 stray dogs from the Windhoek branch of the Society for the Prevention of Cruelty to Animals. Of the 106 dogs tested, 53.8% were seropositive at titres > 1:80. Dogs that presented with symptoms of E. canis infection had a significantly higher seroprevalence (86.6%) compared with apparently healthy dogs (41.6%) (P = 0.00). Location of habitation was significant (P < 0.017), with a high percentage of dogs exposed to E. canis living in the northern or north-western part of Windhoek. As the first study to serologically establish E. canis as a major pathogen in dogs in central Namibia, it is notable that the highest proportion of seropositive dogs came from low-income areas. Further investigation is necessary to describe the ecology of this important tick-borne pathogen of companion animals in Namibia.


Quantumlike statistics of deterministic wave-particle interactions in a circular cavity.
A deterministic low-dimensional iterated map is proposed here to describe the interaction between a bouncing droplet and Faraday waves confined to a circular cavity. Its solutions are investigated theoretically and numerically. The horizontal trajectory of the droplet can be chaotic: it then corresponds to a random walk of average step size equal to half the Faraday wavelength. An analogy is made between the diffusion coefficient of this random walk and the action per unit mass ℏ/m of a quantum particle. The statistics of droplet position and speed are shaped by the cavity eigenmodes, in remarkable agreement with the solution of Schrödinger equation for a quantum particle in a similar potential well.