Analysis of virus textures in transmission electron microscopy images.
In this paper we propose an ensemble of texture descriptors for analyzing virus textures in transmission electron microscopy images. Specifically, we present several novel multi-quinary (MQ) codings of local binary pattern (LBP) variants: the MQ version of the dense LBP, the MQ version of the rotation invariant co-occurrence among adjacent LBPs, and the MQ version of the LBP histogram Fourier. To reduce computation time as well as to improve performance, a feature selection approach is utilized to select the thresholds used in the MQ approaches. In addition, we propose new variants of descriptors where two histograms, instead of the standard one histogram, are produced for each descriptor. The two histograms (one for edge pixels and the other for non-edge pixels) are calculated for training two different SVMs, whose results are then combined by sum rule. We show that a bag of features approach works well with this problem. Our experiments, using a publicly available dataset of 1500 images with 15 classes and same protocol as in previous works, demonstrate the superiority of our new proposed ensemble of texture descriptors. The MATLAB code of our approach is available at https://www.dei.unipd.it/node/2357.


The Cholesterol-Lowering Effect of Oats and Oat Beta Glucan: Modes of Action and Potential Role of Bile Acids and the Microbiome.
Consumption of sufficient quantities of oat products has been shown to reduce host cholesterol and thereby modulate cardiovascular disease risk. The effects are proposed to be mediated by the gel-forming properties of oat β-glucan which modulates host bile acid and cholesterol metabolism and potentially removes intestinal cholesterol for excretion. However, the gut microbiota has emerged as a major factor regulating cholesterol metabolism in the host. Oat β-glucan has been shown to modulate the gut microbiota, particularly those bacterial species that influence host bile acid metabolism and production of short chain fatty acids, factors which are regulators of host cholesterol homeostasis. Given a significant role for the gut microbiota in cholesterol metabolism it is likely that the effects of oat β-glucan on the host are multifaceted and involve regulation of microbe-host interactions at the gut interface. Here we consider the potential for oat β-glucan to influence microbial populations in the gut with potential consequences for bile acid metabolism, reverse cholesterol transport (RCT), short-chain fatty acid (SCFA) production, bacterial metabolism of cholesterol and microbe-host signaling.


Efficient Calculation of Molecular Integrals over London Atomic Orbitals.
The use of London atomic orbitals (LAOs) in a nonperturbative manner enables the determination of gauge-origin invariant energies and properties for molecular species in arbitrarily strong magnetic fields. Central to the efficient implementation of such calculations for molecular systems is the evaluation of molecular integrals, particularly the electron repulsion integrals (ERIs). We present an implementation of several different algorithms for the evaluation of ERIs over Gaussian-type LAOs at arbitrary magnetic field strengths. The efficiencies of generalized McMurchie-Davidson (MD), Head-Gordon-Pople (HGP), and Rys quadrature schemes are compared. For the Rys quadrature implementation, we avoid the use of high precision arithmetic and interpolation schemes in the computation of the quadrature roots and weights, enabling the application of this algorithm seamlessly to a wide range of magnetic fields. The efficiency of each generalized algorithm is compared by numerical application, classifying the ERIs according to their total angular momenta and evaluating their performance for primitive and contracted basis sets. In common with zero-field integral evaluation, no single algorithm is optimal for all angular momenta; thus, a simple mixed scheme is put forward that selects the most efficient approach to calculate the ERIs for each shell quartet. The mixed approach is significantly more efficient than the exclusive use of any individual algorithm.


Evidence for separate neural mechanisms for the timing of discrete and sustained responses.
Methamphetamine (MAP), an indirect dopamine agonist, has been shown to produce a leftward shift in the time of responding under operant response protocols that encourage repetitive responding (e.g., lever pressing). Given the involvement of striatal dopamine activity in the control of discrete motor behavior, as well as in the timing of these responses, an important question arises as to whether a dissociation is possible between changes in the timing of discrete responding and timing of other behaviors. Rats were trained on a modified peak-interval (PI) procedure such that reward was contingent upon the presence of the animal's snout in a nosepoke apparatus at the target time, as an alternative to the typical requirement of a discrete head entry response. Thus spatial selection, but not necessarily motor behavior, at the appropriate time was required to receive a reward. Rats were given MAP in one of 3 doses (0.5, 1.0, or 1.5 mg/kg), or a saline control injection before PI sessions to determine whether the drug elicits a dose-dependent effect on timing of spatial position, as it has been shown to do for discrete behaviors. Following administration of MAP, the peak time of the proportion of time spent in the nosepoke did not change, while the peak time of the rate of response shifted to the left. Single-trial analysis revealed a similar pattern: Position of response step functions defined by being in the nosepoke did not shift, but step functions based on response rate changed with increasing doses of MAP. These data support a model of multiple timing processes controlling different behaviors, at least one of which is specific to discrete motor behavior and is modifiable by dopamine.


Microscopic haematuria at time of diagnosis is associated with lower disease stage in patients with newly diagnosed bladder cancer.
To determine whether the severity of haematuria (microscopic or gross) at diagnosis influences the disease stage at presentation in patients diagnosed with bladder cancer. We conducted a multi-institutional observational cohort study of patients who were newly diagnosed with bladder cancer between August 1999 and May 2012. We reviewed the degree of haematuria, demographic information, clinical and social history, imaging, and pathology. The association of haematuria severity with incident tumour stage and grade was evaluated using logistic regression. Patients diagnosed with bladder cancer presented with gross haematuria (GH; 1 083, 78.3%), microscopic haematuria (MH; 189, 13.7%) or without haematuria (112, 8.1%). High-grade disease was found in 64% and 57.1% of patients presenting with GH and MH, respectively, and severity of haematuria was not associated with higher grade disease. Stage of disease at diagnosis for patients presenting with MH was Ta/carcinoma in situ (CIS) in 68.8%, T1 in 19.6%, and ≥T2 in 11.6%. Stage of disease at diagnosis for patients presenting with GH was Ta/CIS in 55.9%, T1 in 19.6%, and ≥T2 in 17.9%. On multivariate analyses, GH was independently associated with ≥T2 disease at diagnosis (odds ratio 1.69, 95% confidence interval 1.05-2.71, P = 0.03). Among patients with newly diagnosed bladder cancer, presentation with GH is associated with a more advanced pathological stage. Earlier detection of disease, before development of GH, could influence survival in patients with bladder cancer. Type of haematuria at presentation does not impact grade of disease.


A systematic review of triage-related interventions to improve patient flow in emergency departments.
Overcrowding in emergency departments is a worldwide problem. A systematic literature review was undertaken to scientifically explore which interventions improve patient flow in emergency departments. A systematic literature search for flow processes in emergency departments was followed by assessment of relevance and methodological quality of each individual study fulfilling the inclusion criteria. Studies were excluded if they did not present data on waiting time, length of stay, patients leaving the emergency department without being seen or other flow parameters based on a nonselected material of patients. Only studies with a control group, either in a randomized controlled trial or in an observational study with historical controls, were included. For each intervention, the level of scientific evidence was rated according to the GRADE system, launched by a WHO-supported working group. The interventions were grouped into streaming, fast track, team triage, point-of-care testing (performing laboratory analysis in the emergency department), and nurse-requested x-ray. Thirty-three studies, including over 800,000 patients in total, were included. Scientific evidence on the effect of fast track on waiting time, length of stay, and left without being seen was moderately strong. The effect of team triage on left without being seen was relatively strong, but the evidence for all other interventions was limited or insufficient. Introducing fast track for patients with less severe symptoms results in shorter waiting time, shorter length of stay, and fewer patients leaving without being seen. Team triage, with a physician in the team, will probably result in shorter waiting time and shorter length of stay and most likely in fewer patients leaving without being seen. There is only limited scientific evidence that streaming of patients into different tracks, performing laboratory analysis in the emergency department or having nurses to request certain x-rays results in shorter waiting time and length of stay.


The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children.
Multisystem inflammatory syndrome in children (MIS-C) manifests as a severe and uncontrolled inflammatory response with multiorgan involvement, occurring weeks after SARS-CoV-2 infection. Here, we utilized proteomics, RNA sequencing, autoantibody arrays, and B cell receptor (BCR) repertoire analysis to characterize MIS-C immunopathogenesis and identify factors contributing to severe manifestations and intensive care unit admission. Inflammation markers, humoral immune responses, neutrophil activation, and complement and coagulation pathways were highly enriched in MIS-C patient serum, with a more hyperinflammatory profile in severe than in mild MIS-C cases. We identified a strong autoimmune signature in MIS-C, with autoantibodies targeted to both ubiquitously expressed and tissue-specific antigens, suggesting autoantigen release and excessive antigenic drive may result from systemic tissue damage. We further identified a cluster of patients with enhanced neutrophil responses as well as high anti-Spike IgG and autoantibody titers. BCR sequencing of these patients identified a strong imprint of antigenic drive with substantial BCR sequence connectivity and usage of autoimmunity-associated immunoglobulin heavy chain variable region (IGHV) genes. This cluster was linked to a TRBV11-2 expanded T cell receptor (TCR) repertoire, consistent with previous studies indicating a superantigen-driven pathogenic process. Overall, we identify a combination of pathogenic pathways that culminate in MIS-C and may inform treatment.


The importance of exercising in space.
As a direct consequence of exposure to microgravity, astronauts experience a set of physiological changes which can have serious medical implications when they return to earth. Most immediate and significant are the headward shift of body fluids and the removal of gravitational loading from bone and muscles, which lead to progressive changes in the cardiovascular and musculoskeletal systems. Cardiovascular adaptations result in an increased incidence of orthostatic intolerance (fainting) following flight, decreased cardiac output, and reduced capacity for exercise. Changes in the musculoskeletal system contribute significantly to impaired function experienced in the post-flight period. The underlying factor producing these changes is the absence of gravity, and countermeasures are therefore designed primarily to simulate earthlike movements, stresses, and system interactions. Exercise is one approach that has had wide operational use and acceptance in both the US and Russian space programmes, and it has enabled humans to stay relatively healthy in space for well over a year. Although it remains the most effective countermeasure currently available, significant physiological degradation still occurs. The development of other countermeasures will be necessary for missions of longer duration, for example for human exploration of Mars.


Epidemiological pattern of meningococcal disease in Valencia, Spain. Impact of a mass immunization campaign with meningococcal C polysaccharide vaccine.
The objective of this study was to define the epidemiological pattern of meningococcal disease in the autonomous region of Valencia, Spain, and the impact of a mass immunization campaign against serogroup C meningococcus. Data were obtained from a prospective surveillance program for invasive bacterial diseases in children < 15 y of age that began in the Valencia region on 1 December, 1995. During the period 1996-98, 213 cases of meningococcal disease were detected, representing an annual incidence of 11.3/100,000 children < 15 y. Serogroup C accounted for 31% and 38.5% of cases in 1996 and 1997, respectively (annual incidences of 2.9 and 5.4 cases/100,000 children < 15 y). An immunization campaign with the meningococcal C polysaccharide vaccine, which included all persons between 18 months and 19 y of age, began in late 1997 (vaccination coverage of 86%). In 1998, the annual incidence of meningococcal C disease fell to 1.4 cases per 100,000 children < 15 y of age. These results mirror the increase in the reported incidence of serogroup C meningococcal disease in Spain in the 1990s, a trend that was reversed after the introduction of the mass vaccination campaign. Meningococcal polysaccharide vaccine seems to be an effective public health tool for the management of this serious communicable disease.


Short-time dynamics in dispersions with competing short-range attraction and long-range repulsion.
Dynamic clustering of globular Brownian particles in dispersions exhibiting competing short-range attraction and long-range repulsion (SALR) such as low-salinity protein solutions has gained a lot of interest over the past few years. While the structure of the various cluster phases has been intensely explored, little is known about the dynamics of SALR systems. We present the first systematic theoretical study of short-time diffusion and rheological transport properties of two-Yukawa potential SALR systems in the single-particle dominated dispersed-fluid phase, using semi-analytic methods where the salient hydrodynamic interactions are accounted for. We show that the dynamics has unusual features compared to reference systems with pure repulsion or attraction. Results are discussed for the hydrodynamic function characterizing short-time diffusion that reveals an intermediate-range-order (cluster) peak, self-diffusion and sedimentation coefficients, and high-frequency viscosity. As important applications, we discuss the applicability of two generalized Stokes-Einstein relations, and assess the wavenumber range required for the determination of self-diffusion in a dynamic scattering experiment.


Incidence of cancer in the mineral-wool producing industry in Norway.
This study concerned the Norwegian phase of a European collaborative investigation on workers in man-made mineral fiber production. A study population of 2,361 men from four Norwegian plants was examined for mortality and cancer incidence, especially lung cancer, based on a comparison of observed and expected figures, the latter determined according to the five-year age-specific mortality and incidence rates for the entire country. Violent deaths among workers with less than one year of employment represented the only significant mortality excess. A borderline, statistically significant excess risk was found for cancer of the buccal cavity and pharynx, but the fact that the excess occurred in one factory only led to the assumption that the risk was associated with factors other than mineral wool. An excess risk for lung cancer was also found among those with 20 years or more since first exposure (9 observed and 4.36 expected). The risk that emerged was presumably initiated before 1960, when the environmental conditions were more hazardous than later.


Late vaccination reinforcement during a measles epidemic in Niamey, Niger (2003-2004).
Low measles vaccination coverage (VC) leads to recurrent epidemics in many African countries. We describe VC before and after late reinforcement of vaccination activities during a measles epidemic in Niamey, Niger (2003-2004) assessed by Lot Quality Assurance Sampling (LQAS). Neighborhoods of Niamey were grouped into 46 lots based on geographic proximity and population homogeneity. Before reinforcement activities, 96% of lots had a VC below 70%. After reinforcement, this proportion fell to 78%. During the intervention 50% of children who had no previous record of measles vaccination received their first dose (vaccination card or parental recall). Our results highlight the benefits and limitations of vaccine reinforcement activities performed late in the epidemic.


The Effect of Edge Bundling and Seriation on Sensemaking of Biclusters in Bipartite Graphs.
Exploring coordinated relationships (e.g., shared relationships between two sets of entities) is an important analytics task in a variety of real-world applications, such as discovering similarly behaved genes in bioinformatics, detecting malware collusions in cyber security, and identifying products bundles in marketing analysis. Coordinated relationships can be formalized as biclusters. In order to support visual exploration of biclusters, bipartite graphs based visualizations have been proposed, and edge bundling is used to show biclusters. However, it suffers from edge crossings due to possible overlaps of biclusters, and lacks in-depth understanding of its impact on user exploring biclusters in bipartite graphs. To address these, we propose a novel bicluster-based seriation technique that can reduce edge crossings in bipartite graphs drawing and conducted a user experiment to study the effect of edge bundling and this proposed technique on visualizing biclusters in bipartite graphs. We found that they both had impact on reducing entity visits for users exploring biclusters, and edge bundles helped them find more justified answers. Moreover, we identified four key trade-offs that inform the design of future bicluster visualizations. The study results suggest that edge bundling is critical for exploring biclusters in bipartite graphs, which helps to reduce low-level perceptual problems and support high-level inferences.


Respiratory oscillations in alveolar oxygen tension measured in arterial blood.
Arterial oxygen partial pressure can increase during inspiration and decrease during expiration in the presence of a variable shunt fraction, such as with cyclical atelectasis, but it is generally presumed to remain constant within a respiratory cycle in the healthy lung. We measured arterial oxygen partial pressure continuously with a fast intra-vascular sensor in the carotid artery of anaesthetized, mechanically ventilated pigs, without lung injury. Here we demonstrate that arterial oxygen partial pressure shows respiratory oscillations in the uninjured pig lung, in the absence of cyclical atelectasis (as determined with dynamic computed tomography), with oscillation amplitudes that exceeded 50 mmHg, depending on the conditions of mechanical ventilation. These arterial oxygen partial pressure respiratory oscillations can be modelled from a single alveolar compartment and a constant oxygen uptake, without the requirement for an increased shunt fraction during expiration. Our results are likely to contribute to the interpretation of arterial oxygen respiratory oscillations observed during mechanical ventilation in the acute respiratory distress syndrome.


Emdogain stimulates matrix degradation by osteoblasts.
Emdogain has been used clinically for periodontal regeneration, although the underlying molecular mechanisms are not clear at present. In this study, we hypothesized that Emdogain stimulated degradation of type I collagen via osteoblasts. We showed that Emdogain enhanced cell-mediated degradation of type I collagen in an MMP-dependent manner. Although MG-63 cells spontaneously produced a zymogen form of MMP-1, treatment with Emdogain significantly induced the generation of the active form of this enzyme. We demonstrated that MMP-3 was produced from MG63 cells in response to Emdogain in a MEK1/2-dependent manner. Concomitantly, blocking of MEK1/2 activation by U0126 significantly inhibited the generation of the active form of MMP-1 without affecting the total production of this collagenase. These results suggest that Emdogain facilitates tissue regeneration through the activation of the collagenase, MMP-1, that degrades matrix proteins in bone tissue microenvironments.


Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial.
To assess the efficacy of an abbreviated Stanford V regimen in patients with early-stage Hodgkin lymphoma (HL). PATIENTS AND METHODS PATIENTS: with untreated nonbulky stage I-IIA supradiaphragmatic HL were eligible for the G4 study. Stanford V chemotherapy was administered for 8 weeks followed by radiation therapy (RT) 30 Gy to involved fields (IF). Freedom from progression (FFP), disease-specific survival (DSS) and overall survival (OS) were estimated. All 87 enrolled patients completed the abbreviated regimen. At a median follow-up of 10 years, FFP, DSS and OS are 94%, 99% and 94%, respectively. Therapy was well tolerated with no treatment-related deaths. Mature results of the abbreviated Stanford V regimen in nonbulky early-stage HL are excellent and comparable to the results from other contemporary therapies.


miR-205 is a critical regulator of lacrimal gland development.
The tear film protects the terrestrial animal's ocular surface and the lacrimal gland provides important aqueous secretions necessary for its maintenance. Despite the importance of the lacrimal gland in ocular health, molecular aspects of its development remain poorly understood. We have identified a noncoding RNA (miR-205) as an important gene for lacrimal gland development. Mice lacking miR-205 fail to properly develop lacrimal glands, establishing this noncoding RNA as a key regulator of lacrimal gland development. Specifically, more than half of knockout lacrimal glands never initiated, suggesting a critical role of miR-205 at the earliest stages of lacrimal gland development. RNA-seq analysis uncovered several up-regulated miR-205 targets that may interfere with signaling to impair lacrimal gland initiation. Supporting this data, combinatorial epistatic deletion of Fgf10, the driver of lacrimal gland initiation, and miR-205 in mice exacerbates the lacrimal gland phenotype. We develop a molecular rheostat model where miR-205 modulates signaling pathways related to Fgf10 in order to regulate glandular development. These data show that a single microRNA is a key regulator for early lacrimal gland development in mice and highlights the important role of microRNAs during organogenesis.


Correlates of anal intercourse vary by partner type among substance-using women: baseline data from the UNITY study.
Data are limited about anal intercourse among women at risk of HIV infection. HIV-negative non-injection drug using women at sexual risk (N = 404) were recruited. At baseline, 41.7% reported anal intercourse in the prior 3 months; of these, 88.2% reported unprotected anal intercourse (UAI). Factors associated with UAI varied by partner type: UAI with a steady partner was associated with younger age, depressive symptoms, and experience of battering; UAI with casual partners was associated with younger age, cocaine use and negative outcome expectancies for condom use; UAI with exchange partners was associated with cocaine use, negative outcome expectancies for condom use and depressive symptoms. Younger women were more likely to report unprotected anal intercourse if they did not use birth control. Specific counseling messages are needed to identify and address this risk and associated factors, including partner relationships, substance use, birth control, mental health issues and domestic violence.


"Leaky" Rationality: How Research on Behavioral Decision Making Challenges Normative Standards of Rationality.
For more than 30 years, decision-making research has documented that people often violate various principles of rationality, some of which are so fundamental that theorists of rationality rarely bother to state them. We take these characteristics of decision making as a given but argue that it is problematic to conclude that they typically represent departures from rationality. The very psychological processes that lead to "irrational" decisions (e.g., framing, mental accounting) continue to exert their influence when one experiences the results of the decisions. That is, psychological processes that affect decisions may be said also to "leak" into one's experience. The implication is that formal principles of rationality do not provide a good enough normative standard against which to assess decision making. Instead, what is needed is a substantive theory of rationality-one that takes subjective experience seriously, considers both direct and indirect consequences of particular decisions, considers how particular decisions fit into life as a whole, and considers the effects of decisions on others. Formal principles may play a role as approximations of the substantive theory that can be used by theorists and decision makers in cases in which the formal principles can capture most of the relevant considerations and leakage into experience is negligible.


Analysis of the cat eye syndrome critical region in humans and the region of conserved synteny in mice: a search for candidate genes at or near the human chromosome 22 pericentromere.
We have sequenced a 1.1-Mb region of human chromosome 22q containing the dosage-sensitive gene(s) responsible for cat eye syndrome (CES) as well as the 450-kb homologous region on mouse chromosome 6. Fourteen putative genes were identified within or adjacent to the human CES critical region (CESCR), including three known genes (IL-17R, ATP6E, and BID) and nine novel genes, based on EST identity. Two putative genes (CECR3 and CECR9) were identified, in the absence of EST hits, by comparing segments of human and mouse genomic sequence around two solitary amplified exons, thus showing the utility of comparative genomic sequence analysis in identifying transcripts. Of the 14 genes, 10 were confirmed to be present in the mouse genomic sequence in the same order and orientation as in human. Absent from the mouse region of conserved synteny are CECR1, a promising CES candidate gene from the center of the contig, neighboring CECR4, and CECR7 and CECR8, which are located in the gene-poor proximal 400 kb of the contig. This latter proximal region, located approximately 1 Mb from the centromere, shows abundant duplicated gene fragments typical of pericentromeric DNA. The margin of this region also delineates the boundary of conserved synteny between the CESCR and mouse chromosome 6. Because the proximal CESCR appears abundant in duplicated segments and, therefore, is likely to be gene poor, we consider the putative genes identified in the distal CESCR to represent the majority of candidate genes for involvement in CES.


A population-based study of KCNH7 p.Arg394His and bipolar spectrum disorder.
We conducted blinded psychiatric assessments of 26 Amish subjects (52 ± 11 years) from four families with prevalent bipolar spectrum disorder, identified 10 potentially pathogenic alleles by exome sequencing, tested association of these alleles with clinical diagnoses in the larger Amish Study of Major Affective Disorder (ASMAD) cohort, and studied mutant potassium channels in neurons. Fourteen of 26 Amish had bipolar spectrum disorder. The only candidate allele shared among them was rs78247304, a non-synonymous variant of KCNH7 (c.1181G>A, p.Arg394His). KCNH7 c.1181G>A and nine other potentially pathogenic variants were subsequently tested within the ASMAD cohort, which consisted of 340 subjects grouped into controls subjects and affected subjects from overlapping clinical categories (bipolar 1 disorder, bipolar spectrum disorder and any major affective disorder). KCNH7 c.1181G>A had the highest enrichment among individuals with bipolar spectrum disorder (χ(2) = 7.3) and the strongest family-based association with bipolar 1 (P = 0.021), bipolar spectrum (P = 0.031) and any major affective disorder (P = 0.016). In vitro, the p.Arg394His substitution allowed normal expression, trafficking, assembly and localization of HERG3/Kv11.3 channels, but altered the steady-state voltage dependence and kinetics of activation in neuronal cells. Although our genome-wide statistical results do not alone prove association, cumulative evidence from multiple independent sources (parallel genome-wide study cohorts, pharmacological studies of HERG-type potassium channels, electrophysiological data) implicates neuronal HERG3/Kv11.3 potassium channels in the pathophysiology of bipolar spectrum disorder. Such a finding, if corroborated by future studies, has implications for mental health services among the Amish, as well as development of drugs that specifically target HERG3/Kv11.3.


Two-point discrimination assessment of the upper extremities of healthy young Turkish individuals.
This study aims to measure the two-point discrimination (TPD) values of the upper extremities of healthy young Turkish individuals. Between March 2016 and June 2016, a total of 60 healthy students (31 males, 29 females; mean age: 22.0±1.7 years; range, 19 to 27 years) were included. Eleven grand upper limb parts which take innervation from the brachial plexus were measured with an esthesiometer. The values at the dominant sides were statistically significantly greater than the non-dominant sides at those areas: upper lateral arm (p=0.001), lower lateral arm (p=0.001), mid-posterior arm (p=0.001), mid-lateral forearm (p=0.001), mid-posterior forearm (p=0.012), skin over the first dorsal interossei muscle (p=0.031), and palmar surface of distal phalanx of the thumb (p=0.045). Both dominant and non-dominant lower lateral arm TPD measurement results increased in males compared to females, indicating a statistically significant difference (p=0.005 and p=0.011, respectively). Also, dominant and non-dominant mid-posterior arm measurement scores were found to statistically significantly increase in males compared to females (p=0.019 and p=0.040, respectively). Our study results show that laterality, with lower values on the non-dominant side, but not the sex, has an effect on TPD. The findings of this study may be useful in establishing the normative data for TPD in the upper extremity parts of healthy young Turkish individuals.


Cognitive Functioning as a Moderator in the Relationship Between the Perceived Neighborhood Physical Environment and Physical Activity in Belgian Older Adults.
Objective: To investigate whether the relationship of neighborhood environmental factors with physical activity (PA) is moderated by cognitive functioning in Belgian older adults. Methods: Seventy-one older adults completed validated questionnaires on PA and environmental perceptions, wore an accelerometer, and completed a computerized assessment of cognitive functioning. Moderated linear regression analyses were conducted in SPSS 24.0. Results: Overall cognitive functioning significantly moderated the associations of traffic safety and street connectivity with PA. Detailed analyses showed that these factors were only positively associated with PA in older adults with lower cognitive functioning. In addition, particularly, performance on tests assessing visuospatial and episodic memory moderated these associations. Discussion: Living in traffic-safe neighborhoods with short and many alternative routes might motivate older adults with lower cognitive functioning to be active. As such, the increase in PA might improve their cognitive abilities. This knowledge is crucial for health practitioners to develop effective PA promotion initiatives.


Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: A Systematic Review of Reviews.
This review was commissioned by the World Health Organization and presents a summary of the latest research evidence on the impact of coronavirus disease 2019 (COVID-19) on people with diabetes (PWD). To review the evidence regarding the extent to which PWD are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or of suffering its complications, including associated mortality. We searched the Cochrane COVID-19 Study Register, Embase, MEDLINE, and LitCOVID on 3 December 2020. Systematic reviews synthesizing data on PWD exposed to SARS-CoV-2 infection, reporting data on confirmed SARS-CoV-2 infection, admission to hospital and/or to intensive care unit (ICU) with COVID-19, and death with COVID-19 were used. One reviewer appraised and extracted data; data were checked by a second. Data from 112 systematic reviews were narratively synthesized and displayed using effect direction plots. Reviews provided consistent evidence that diabetes is a risk factor for severe disease and death from COVID-19. Fewer data were available on ICU admission, but where available, these data also signaled increased risk. Within PWD, higher blood glucose levels both prior to and during COVID-19 illness were associated with worse COVID-19 outcomes. Type 1 diabetes was associated with worse outcomes than type 2 diabetes. There were no appropriate data for discerning whether diabetes was a risk factor for acquiring SARS-CoV-2 infection. Due to the nature of the review questions, the majority of data contributing to included reviews come from retrospective observational studies. Reviews varied in the extent to which they assessed risk of bias. There are no data on whether diabetes predisposes to infection with SARS-CoV-2. Data consistently show that diabetes increases risk of severe COVID-19. As both diabetes and worse COVID-19 outcomes are associated with socioeconomic disadvantage, their intersection warrants particular attention.


UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST).
Soft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues. Gastrointestinal stromal tumour (GIST) is the commonest STS and arises within the wall of the gastrointestinal (GI) tract. While most GISTs occur in the stomach they do occur in all parts of the GI tract. As with other STS, it is important that GISTs are managed by expert teams, to ensure consistent and optimal treatment, as well as recruitment to clinical trials, and the ongoing accumulation of further knowledge of the disease. The development of appropriate guidance, by an experienced panel referring to the evidence available, is therefore a useful foundation on which to build progress in the field. British Sarcoma Group guidelines for the management of GIST were initially developed by a panel of physicians experienced in the management of GIST. This current version has been updated and amended with reference to other European and US guidance. We have received input from representatives of all diagnostic and treatment disciplines as well as patient representatives. Levels of evidence and strength of recommendation gradings are those used by ESMO adapted from those published by the Infectious Disease Society of America. The guidelines cover aetiology, genetics and underlying molecular mechanisms, diagnosis and initial investigations, staging and risk stratification, surgery, neoadjuvant and adjuvant therapy, the management of advanced disease and follow-up. The importance of mutational analysis in guiding treatment is highlighted, since this can indicate the most effective treatment and avoid administration of ineffective drugs, emphasising the need for management in specialist centres.


Is There a Difference in Infection Risk Between Single and Multiple Doses of Prophylactic Antibiotics? A Meta-analysis.
The prevention of surgical site infection guidelines issued by the Centers for Disease Control and Prevention (CDC) recently recommended that only a single dose of preoperative antibiotics be administered to patients undergoing clean-contaminated procedures based on data from a variety of surgical disciplines. For orthopaedic procedures, where postoperative infections can have significant consequences, the existing evidence for this recommendation is widely debated. Is there a difference in postoperative infection risk when utilizing a single dose of preoperative antibiotics compared with multiple doses of perioperative antibiotics for orthopaedic procedures where implants are placed? MEDLINE, EMBASE, Google Scholar, and Cochrane were systematically reviewed for randomized controlled trials (RCTs) of a single dose of preoperative antibiotics compared with pre- and postoperative prophylaxis from 1980 to 2017 for all orthopaedic procedures where implants were being placed. Infection (both superficial and deep) as a primary outcome through all available followup was required for inclusion. Fourteen RCTs detailing 9691 orthopaedic procedures were included for analysis, including seven arthroplasty, one spine, and six general orthopaedic trials (two specific to hip fracture fixation). Pooled infection outcomes were analyzed with random-effects modeling in light of study heterogeneity. Bias was evaluated using the Cochrane risk of bias tool as well as a funnel plot for publication bias, and quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Bias was largely uncertain; however, a high risk of bias was noted in four studies. No significant overall publication bias was noted. The quality of evidence was determined to be very low based on the GRADE tool, downgraded based on risk of bias, inconsistency, and imprecision. Despite the quality of evidence, the data were pooled in light of the current recommendations from the CDC to critically evaluate the recommendation that a single dose of antibiotics be utilized. There were no differences in infection risk between single- versus multiple-dose groups (single: 83 of 4263 [2%], multiple: 101 of 5428 [2%]; odds ratio, 0.92 [95% confidence interval, 0.56-1.51]; p = 0.740, I = 36% for statistical heterogeneity). There is no difference in infection risk between a single dose and multiple doses of perioperative antibiotics for orthopaedic procedures where implants are utilized, consistent with recent recommendations. However, the quality of evidence for orthopaedic procedures is low, and a randomized study with a sufficient sample size is needed to examine the issue before universal adoption of a single antibiotic dose. Level I, therapeutic study.


Serum CEA and CA 19-9: potential future diagnostic or screening tests for gallbladder cancer?
The poor prognosis of gallbladder cancer and the presence of high-risk populations make the identification of a screening test for this disease very desirable. As part of an ongoing case-control study of gallbladder cancer being conducted in Mexico City, Mexico, and in La Paz, Bolivia, blood specimens were sought from all patients with cancer of the gallbladder and on controls of similar age and sex undergoing upper abdominal surgery. Each sample was analyzed for carcino-embryonic antigen (CEA) and CA 19-9. Using the specimens from Bolivia, a serum CEA cutoff of 4.0 ng/ml yielded a sensitivity of 50.0% and a specificity of 92.7%, while a serum CA 19-9 cutoff of 20.0 units/ml yielded a sensitivity of 79.4% and a specificity of 79.2%. Using ROC curve analysis, the latter was a much better test than the former (p less than 0.05). Using the tests in series or in parallel did not substantively improve the results. The specimens from Mexico were used for validation purposes, and yielded very similar results. In conclusion, serum CA 19-9 and CEA are fairly good tests for discriminating patients with gallbladder cancer from patients with gallstones and no cancer, the former being a better test than the latter. These tests may be useful in identifying disease recurrences. In addition, if a sufficiently high-risk population could be identified, this could potentially become a useful screening test for this serious disease, allowing early intervention. However, additional data are needed prior to recommending this clinically.


Benefits, risks, and safety of external beam radiation therapy for breast cancer.
Breast cancer is a common and complex disease often necessitating multimodality care. Breast cancer may be treated with surgical resection, radiotherapy (RT), and systemic therapy, including chemotherapy, hormonal therapy, and targeted therapies, or a combination thereof. In the past 50 years, RT has played an increasingly significant role in the treatment of breast cancer, resulting in improvements in locoregional control and survival for women undergoing mastectomy who are at high risk of recurrence, and allowing for breast conservation in certain settings. Although radiation provides significant benefit to many women with breast cancer, it is also associated with risks of toxicity, including cardiac and pulmonary toxicity, lymphedema, and secondary malignancy. RT techniques have advanced and continue to evolve dramatically, offering increased precision and reproducibility of treatment delivery and flexibility of treatment schedule. This increased sophistication of RT offers promise of improved outcomes by maintaining or improving efficacy, reducing toxicity, and increasing patient access and convenience. A review of the role of radiation therapy in breast cancer, its associated toxicities and efforts in toxicity reduction is presented.


Associations between physical facilities and organizational participation and levels of physical activity of adults in Tainan, Taiwan.
During the past decade many studies have endeavored to evaluate the relationships between environmental attributes and physical activity, but there is limited data on this subject in Taiwan. This is the first study to investigate both objective and subjective environments in relation to different levels of physical activity in adults in Tainan, Taiwan. A 2-stage survey examining relationships between physical and social environments and physical activity was designed. It was administered to a sample including 231 community directors and 804 randomly selected residents. Community audits and telephone interviews were used as the objective and subjective measures in the study, respectively. No correlation was found between the objective and the subjective measures of physical environments. Only the subjective measures were significantly related to city residents' physical activities. Perceived physical facility was found to be correlated with engagement in physical activity, whereas organizational participation was associated with the regularity of physical activity. Of the 4 types of leisure activity examined in this study, dancing and aerobic activities are more likely to be engaged in regularly. Factors associated with the regularity of physical activity are not the same as factors associated with engagement in physical activity.


Marek's Disease Virus-Encoded MicroRNA 155 Ortholog Critical for the Induction of Lymphomas Is Not Essential for the Proliferation of Transformed Cell Lines.
MicroRNAs (miRNAs) are small noncoding RNAs with profound regulatory roles in many areas of biology, including cancer. MicroRNA 155 (miR-155), one of the extensively studied multifunctional miRNAs, is important in several human malignancies such as diffuse large B cell lymphoma and chronic lymphocytic leukemia. Moreover, miR-155 orthologs KSHV-miR-K12-11 and MDV-miR-M4, encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) and Marek's disease virus (MDV), respectively, are also involved in oncogenesis. In MDV-induced T-cell lymphomas and in lymphoblastoid cell lines derived from them, MDV-miR-M4 is highly expressed. Using excellent disease models of infection in natural avian hosts, we showed previously that MDV-miR-M4 is critical for the induction of T-cell lymphomas as mutant viruses with precise deletions were significantly compromised in their oncogenicity. However, those studies did not elucidate whether continued expression of MDV-miR-M4 is essential for maintaining the transformed phenotype of tumor cells. Here using an in situ CRISPR/Cas9 editing approach, we deleted MDV-miR-M4 from the MDV-induced lymphoma-derived lymphoblastoid cell line MDCC-HP8. Precise deletion of MDV-miR-M4 was confirmed by PCR, sequencing, quantitative reverse transcription-PCR (qRT-PCR), and functional analysis. Continued proliferation of the MDV-miR-M4-deleted cell lines demonstrated that MDV-miR-M4 expression is not essential for maintaining the transformed phenotype, despite its initial critical role in the induction of lymphomas. Ability to examine the direct role of oncogenic miRNAs in situ in tumor cell lines is valuable in delineating distinct determinants and pathways associated with the induction or maintenance of transformation in cancer cells and will also contribute significantly to gaining further insights into the biology of oncogenic herpesviruses.IMPORTANCE Marek's disease virus (MDV) is an alphaherpesvirus associated with Marek's disease (MD), a highly contagious neoplastic disease of chickens. MD serves as an excellent model for studying virus-induced T-cell lymphomas in the natural chicken hosts. Among the limited set of genes associated with MD oncogenicity, MDV-miR-M4, a highly expressed viral ortholog of the oncogenic miR-155, has received extensive attention due to its direct role in the induction of lymphomas. Using a targeted CRISPR-Cas9-based gene editing approach in MDV-transformed lymphoblastoid cell lines, we show that MDV-miR-M4, despite its critical role in the induction of tumors, is not essential for maintaining the transformed phenotype and continuous proliferation. As far as we know, this was the first study in which precise editing of an oncogenic miRNA was carried out in situ in MD lymphoma-derived cell lines to demonstrate that it is not essential in maintaining the transformed phenotype.


Production of proteins and commodity chemicals using engineered Bacillus subtilis platform strain.
Currently, increasing demand of biochemicals produced from renewable resources has motivated researchers to seek microbial production strategies instead of traditional chemical methods. As a microbial platform, Bacillus subtilis possesses many advantages including the generally recognized safe status, clear metabolic networks, short growth cycle, mature genetic editing methods and efficient protein secretion systems. Engineered B. subtilis strains are being increasingly used in laboratory research and in industry for the production of valuable proteins and other chemicals. In this review, we first describe the recent advances of bioinformatics strategies during the research and applications of B. subtilis. Secondly, the applications of B. subtilis in enzymes and recombinant proteins production are summarized. Further, the recent progress in employing metabolic engineering and synthetic biology strategies in B. subtilis platform strain to produce commodity chemicals is systematically introduced and compared. Finally, the major limitations for the further development of B. subtilis platform strain and possible future directions for its research are also discussed.


The Plant-Associated Microbe Gene Ontology (PAMGO) Consortium: community development of new Gene Ontology terms describing biological processes involved in microbe-host interactions.
All microbes that form beneficial, neutral, or pathogenic associations with hosts face similar challenges. They must physically adhere to and/or gain entry to host tissues; they must avoid, suppress, or tolerate host defenses; they must acquire nutrients from the host and successfully multiply. Microbes that associate with hosts come from many kingdoms of life and include bacteria, fungi, oomycetes, and nematodes. The increasing numbers of full genome sequences from these diverse microbes provide the opportunity to discover common mechanisms by which the microbes forge and maintain intimate associations with host organisms. However, cross-genome analyses have been hindered by lack of a universal vocabulary for describing biological processes involved in the interplay between microbes and their hosts. The Plant-Associated Microbe Gene Ontology (PAMGO) Consortium has been working for three years as an official interest group of the Gene Ontology (GO) Consortium to develop well-defined GO terms that describe many of the biological processes common to diverse plant- and animal-associated microbes. Creating these terms, over 700 at this time, has required a synthesis of diverse points of view from many research communities. The use of these terms in genome annotation will allow cross-genome searches for genes with common function (without demand for sequence similarity) and also improve the interpretation of data from high-throughput microarray and proteomic analyses. This article, and the more focused mini-reviews that make up this supplement to BMC Microbiology, describe the development and use of these terms.


Oral anticoagulants in atrial fibrillation with valvular heart disease and bioprosthetic heart valves.
Current guidelines endorse the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). However, little is known about their safety and efficacy in valvular heart disease (VHD). Similarly, there is a paucity of data regarding NOACs use in patients with a bioprosthetic heart valve (BPHV). We, therefore, performed a network meta-analysis in the subgroups of VHD and meta-analysis in patients with a BPHV. PubMed, Cochrane and Embase were searched for randomised controlled trials. Summary effects were estimated by the random-effects model. The outcomes of interest were a stroke or systemic embolisation (SSE), myocardial infarction (MI), all-cause mortality, major adverse cardiac events, major bleeding and intracranial haemorrhage (ICH). In patients with VHD, rivaroxaban was associated with more ICH and major bleeding than other NOACs, while edoxaban 30 mg was associated with least major bleeding. Data combining all NOACs showed a significant reduction in SSE, MI and ICH (0.70, [0.57 to 0.85; p<0.001]; 0.70 [0.50 to 0.99; p<0.002]; and 0.46 [0.24 to 0.86; p<0.01], respectively). Analysis of 280 patients with AF and a BPHV showed similar outcomes with NOACs and warfarin. NOACs performed better than warfarin for a reduction in SSE, MI and ICH in patients with VHD. Individually NOACs performed similarly to each other except for an increased risk of ICH and major bleeding with rivaroxaban and a reduced risk of major bleeding with edoxaban 30 mg. In patients with a BPHV, results with NOACs seem similar to those with warfarin and this needs to be further explored in larger studies.


Comparison of outcomes and usefulness of carvedilol across a spectrum of left ventricular ejection fractions in patients with heart failure in clinical practice.
Heart failure (HF) in the community differs meaningfully from that in clinical trials, particularly the higher prevalence of patients with preserved left ventricular (LV) ejection fraction (EF) typically excluded from clinical trials, thus limiting knowledge of their responsiveness to beta-blocker therapy. From a community-based registry of 4,280 patients with HF starting treatment with the beta blocker carvedilol, we compared characteristics, carvedilol titration, and outcomes of patients according to LVEF >40% or <40% (as in clinical trials) and across the spectrum of LVEF <21%, 21% to 30%, 31% to 40%, and >40%. Patients with preserved EF (LVEF >40%) were older and more often women and hypertensive. Lower LVEF was associated with worse functional class and more HF hospitalizations in the previous year. Carvedilol dose decreased with increasing LVEF. Hospitalization rates for HF related inversely to LVEF before starting carvedilol therapy and decreased from the previous year in all LVEF groups during follow-up. Although 1-year mortality rate decreased from 8% with LVEF < or =20% to 6% with LVEF >40%, adjusted hazard ratios were not significantly different across LVEF groups. Thus, characteristics of community patients with HF vary across the spectrum of LVEF. Patients with HF and preserved EF treated with carvedilol in the community improve symptomatically and experience fewer HF hospitalizations after initiating carvedilol. In conclusion, without a control group, the effect of carvedilol on outcomes is not conclusive and trials of carvedilol in patients with HF and preserved EF should be undertaken.


Guidance for peptide vaccines for the treatment of cancer.
Recent progress in fundamental understanding of tumor immunology has opened a new avenue of cancer vaccines. Currently, the development of new cancer vaccines is a global topic and has attracted attention as one of the most important issues in Japan. There is an urgent need for the development of guidance for cancer vaccine clinical studies in order to lead to drug development. Peptide vaccines characteristically have the effect of indirectly acting against cancer through the immune system - a mechanism of action that clearly differs from anticancer drugs that exert a direct effect. Thus, the clinical development of cancer peptide vaccines should be planned and implemented based on the mechanism of action, which differs significantly from conventional anticancer drug research. The Japanese Society for Biological Therapy has created and published Guidance for peptide vaccines for the treatment of cancer as part of its mission and responsibilities towards cancer peptide vaccine development, which is now pursued globally. We welcome comments from regulators and business people as well as researchers in this area.


Exfoliation of graphite with triazine derivatives under ball-milling conditions: preparation of few-layer graphene via selective noncovalent interactions.
A ball-milling treatment can be employed to exfoliate graphite through interactions with commercially available melamine under solid conditions. This procedure allows the fast production of relatively large quantities of material with a low presence of defects. The milling treatment can be modulated in order to achieve graphene flakes with different sizes. Once prepared, the graphene samples can be redispersed in organic solvents, water, or culture media, forming stable dispersions that can be used for multiple purposes. In the present work, we have screened electron-rich benzene derivatives along with triazine derivatives in their respective ability to exfoliate graphite. The results suggest that the formation of a hydrogen-bonding network is important for the formation of multipoint interactions with the surfaces of graphene, which can be used for the exfoliation of graphite and the stabilization of graphene in different solvents. Aminotriazine systems were found to be the best partners in the preparation and stabilization of graphene layers in different solvents, while the equivalent benzene derivatives did not show comparable exfoliation ability. Computational studies have also been performed to rationalize the experimental results. The results provide also the basis for further work in the preparation of noncovalently modified graphene, where derivatives of aminotriazines can be designed to form extensive hydrogen-bond 2D networks on the graphene surface with the aim of manipulating their electronic and chemical properties.


Inpatient Versus Outpatient Management of Negative Pressure Wound Therapy in Pediatric Patients.
Negative pressure wound therapy (NPWT) is commonly used to manage complex wounds in the pediatric population. With recently developed portable NPWT devices, providers have the opportunity to transition NPWT to the outpatient setting. However, there are no studies describing outpatient NPWT in pediatric patients. Therefore, the purpose of our study was to leverage a population-level analysis to advance our current knowledge about outpatient NPWT use in pediatric patients. We analyzed the Truven Health Analytics MarketScan Commercial Claims Database from 2006 to 2014 to identify children treated with NPWT. We compared patient characteristics, indications, complications before and after NPWT, health care utilization within 30 d of NPWT initiation, and health care cost profile of patients treated with NPWT primarily as outpatients versus inpatients. Outpatient NPWT was defined as patients with ≤50% of NPWT coded during an inpatient hospitalization, whereas inpatient NPWT was defined as patients with >50% of NPWT. We identified 3184 patients (1621 inpatients and 1563 outpatients) aged 0-17 y, who were treated with NPWT from 2006 to 2014. Outpatient NPWT was implemented across multiple ages, comorbidities, and indications, with a low complication rate (2.4%). After controlling for hematologic comorbidity and indications, outpatient NPWT was associated with lower risk of complications (odds ratio: 0.57, 95% confidence interval 0.38-0.86) and lower median total costs ($5602.03) compared with inpatient ($15,233.21) therapy. Outpatient NPWT management in pediatric patients was associated with low complication rates. Additional studies are necessary to determine the most overall cost-effective treatment setting for NPWT in the pediatric population.


Genome Sequences of Shewanella baltica and Shewanella morhuae Strains Isolated from the Gastrointestinal Tract of Freshwater Fish.
We present here the genome sequences of Shewanella baltica strain CW2 and Shewanella morhuae strain CW7, isolated from the gastrointestinal tract of Salvelinus namaycush (lean lake trout) and Coregonus clupeaformis (whitefish), respectively. These genome sequences provide insights into the niche adaptation of these specific species in freshwater systems.


Gene duplication and divergence produce divergent MHC genotypes without disassortative mating.
Genes of the major histocompatibility complex (MHC) exhibit heterozygote advantage in immune defence, which in turn can select for MHC-disassortative mate choice. However, many species lack this expected pattern of MHC-disassortative mating. A possible explanation lies in evolutionary processes following gene duplication: if two duplicated MHC genes become functionally diverged from each other, offspring will inherit diverse multilocus genotypes even under random mating. We used locus-specific primers for high-throughput sequencing of two expressed MHC Class II B genes in Leach's storm-petrels, Oceanodroma leucorhoa, and found that exon 2 alleles fall into two gene-specific monophyletic clades. We tested for disassortative vs. random mating at these two functionally diverged Class II B genes, using multiple metrics and different subsets of exon 2 sequence data. With good statistical power, we consistently found random assortment of mates at MHC. Despite random mating, birds had MHC genotypes with functionally diverged alleles, averaging 13 amino acid differences in pairwise comparisons of exon 2 alleles within individuals. To test whether this high MHC diversity in individuals is driven by evolutionary divergence of the two duplicated genes, we built a phylogenetic permutation model. The model showed that genotypic diversity was strongly impacted by sequence divergence between the most common allele of each gene, with a smaller additional impact of monophyly of the two genes. Divergence of allele sequences between genes may have reduced the benefits of actively seeking MHC-dissimilar mates, in which case the evolutionary history of duplicated genes is shaping the adaptive landscape of sexual selection.


Alcohol consumption, alcohol dehydrogenase 3 polymorphism, and colorectal adenomas.
Alcohol is a probable risk factor with regard to colorectal neoplasm and is metabolized to the carcinogen acetaldehyde by the genetically polymorphic alcohol dehydrogenase 3 (ADH3) enzyme. We evaluated whether the association between alcohol and colorectal adenomas is modified by ADH3 polymorphism. We recruited 433 cases with adenomatous polyps and 436 polyp-free controls among Caucasians undergoing endoscopy between 1995 and 2000. Frequency and amount of habitual alcohol consumption were assessed by beverage type, using a validated self-administered food frequency questionnaire. All participants provided blood for genotyping of ADH3. Multivariate analyses adjusting for gender, age, and indication for endoscopy showed that alcohol increased the risk of colorectal adenomas among women [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.0-3.2, >/=10 versus <1 drink/week]. Among men, the risk of adenomas was increased only for those consuming > 21 drinks/week (OR, 1.8; 95% CI, 0.9-3.8, compared with men drinking < 1 drink/week). Among subjects in the highest tertile of alcohol consumption, those with the ADH3*1/*1 genotype were at higher risk (OR, 1.8; 95% CI, 1.0-3.1) than those with other ADH3 genotypes (OR, 1.2; 95% CI, 0.7-1.9) when compared with those in the lowest tertile with ADH3*1/*2 or ADH3*2/*2 genotypes. In conclusion, our findings are consistent with results of other studies, suggesting that alcohol consumption elevates the risk of adenomatous colorectal polyps. ADH3 polymorphism may modify the association between alcohol consumption and colorectal adenomas.


Interhuman transmission as a potential key parameter for geographical variation in the prevalence of Pneumocystis jirovecii dihydropteroate synthase mutations.
Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations are associated with failure of prophylaxis with sulfa drugs. This retrospective study sought to better understand the geographical variation in the prevalence of these mutations. DHPS polymorphisms in 394 clinical specimens from immunosuppressed patients who received a diagnosis of P. jirovecii pneumonia and who were hospitalized in 3 European cities were examined using polymerase chain reaction (PCR) single-strand conformation polymorphism. Demographic and clinical characteristics were obtained from patients' medical charts. Of the 394 patients, 79 (20%) were infected with a P. jirovecii strain harboring one or both of the previously reported DHPS mutations. The prevalence of DHPS mutations was significantly higher in Lyon than in Switzerland (33.0% vs 7.5%; P < .001). The proportion of patients with no evidence of sulfa exposure who harbored a mutant P. jirovecii DHPS genotype was significantly higher in Lyon than in Switzerland (29.7% vs 3.0%; P < .001). During the study period in Lyon, in contrast to the Swiss hospitals, measures to prevent dissemination of P. jirovecii from patients with P. jirovecii pneumonia were generally not implemented, and most patients received suboptimal prophylaxis, the failure of which was strictly associated with mutated P. jirovecii. Thus, nosocomial interhuman transmission of mutated strains directly or indirectly from other individuals in whom selection of mutants occurred may explain the high proportion of mutations without sulfa exposure in Lyon. Interhuman transmission of P. jirovecii, rather than selection pressure by sulfa prophylaxis, may play a predominant role in the geographical variation in the prevalence in the P. jirovecii DHPS mutations.


Lumbar spine surgery reduces postoperative opioid use in the veteran population.
The United States has been facing a worsening opioid epidemic over the past two decades. The veteran population represents a large and vulnerable group with a higher burden of mental health comorbidities. The purpose of this study was to analyze the impact of lumbar spine surgery on postoperative opioid usage in the United States veteran population. A retrospective cohort study was conducted using the Veterans Affairs Informatics and Computing Infrastructure database. Patients who underwent lumbar spine surgery were stratified into three groups by their preoperative opioid claims within 365 days of surgery. Postoperative cumulative morphine milligram equivalents (MME) were tracked for each group and the paired Wilcoxon signed rank test was used to compare cumulative preoperative MME (days -365-0) to cumulative postoperative MME (days 91-455). At one year, 30.6% of patients in the high preoperative opioid group and 73.1% of patients in the low preoperative opioid group were no longer using opioids. In the opioid naive cohort, 10.0% of patients were still using opioids at one year. Among all patients, median cumulative postoperative MME was significantly less than median cumulative preoperative MME (P<0.001). High preoperative opioid usage of more than 3 claims was most significantly associated with continued postoperative opioid usage (odds ratio 12.55, P<0.001). From 2010 to 2020 the proportion of patients with preoperative opioid claims decreased (58.8% to 34.8%). In the veteran population, lumbar spine surgery was effective in getting 50% of patients who were on opioids preoperatively to discontinue opioids postoperatively. Even minimal exposure to opioids preoperatively resulted in a 2.69-time increase in risk of being on opioids at one year versus opioid naive patients. This study affirms that despite being a high-risk population, the veteran population has a similar response to lumbar spine surgery as the general population in regards to opioid dependence.


Organic cation transporters modulate the uptake and cytotoxicity of picoplatin, a third-generation platinum analogue.
Picoplatin, a third-generation platinum agent, is efficacious against lung cancers that are otherwise resistant or become refractory during platinum treatment. This effort was aimed at the determination of the influence of organic cation transporters 1, 2, and 3 (OCT1, OCT2, and OCT3) and their genetic variants on cellular uptake of picoplatin and on the individual components of the ensuing cytotoxicity such as DNA adduct formation. The effect of OCT1 on picoplatin pharmacokinetics and antitumor efficacy was determined using OCT knockout mice and HEK293 xenografts stably expressing OCT1. The uptake and DNA adduct formation of picoplatin were found to be significantly enhanced by the expression of the OCTs. Expression of OCT1 and OCT2, but not OCT3, significantly enhanced picoplatin cytotoxicity, which was reduced in the presence of an OCT inhibitor. Common reduced functional variants of OCT1 and OCT2 led to reduction in uptake and DNA adduct formation of picoplatin in comparison with the reference OCT1 and OCT2. Pharmacokinetic parameters of picoplatin in Oct1(-/-) and Oct1(+/+) mice were not significantly different, suggesting that the transporters do not influence the disposition of the drug. In contrast, the volume of OCT1-expressing xenografts in mice was significantly reduced by picoplatin treatment, suggesting that OCT1 may enhance the antitumor efficacy of picoplatin. These studies provide a basis for follow-up clinical studies that would seek to examine the relationship between the anticancer efficacy of picoplatin and expression levels of OCTs and their genetic variants in tumors. Mol Cancer Ther; 9(4); 1058-69. (c)2010 AACR.


T Cell Immunity To Enterovirus 71 Infection In Humans And Implications For Vaccine Development.
Enterovirus 71 (EV-A71) is one of the major pathogens causing hand, foot and mouth disease (HFMD). Some strains can lead to neurological disease and fatality in children. Up to date, there is no FDA-approved vaccine to prevent severe HFMD and mortality. Although the inactivated vaccine has advanced to production in China, lack of long-term protection and the requirement of multiple boosters have necessitated the development of other types of vaccines. Recent studies indicate that cellular and not humoral immunity determines the clinical outcome of EV-A71 infections. High levels of cytokines such as IL-1β, IL-6, IL-10 and IFN-γ tend to correlate with clinical severity in patients with pulmonary edema and encephalitis. The live attenuated vaccine may serve as the preferred choice as it can induce excellent humoral and cellular immunity as well as live-long immunity. Expression of certain HLA alleles such as TNF-α promoter type II (-308 allele), HLA-A33 and HLA-DR17 responses have been linked to severe HFMD. However, the high variability of MHC genes could restrict T cell recognition and be a major obstacle in the design of peptide vaccines. Hence, the development of a T cell universal vaccine (incorporating both CD4+ and CD8+ T cell epitopes) that induces broad, multifunctional and cross-reactive CD8+ T cell responses maybe desirable.


Physical principles demonstrate that the biceps femoris muscle relative to the other hamstring muscles exerts the most force: implications for hamstring muscle strain injuries.
Of the hamstring muscle group the biceps femoris muscle is the most commonly injured muscle in sports requiring interval sprinting. The reason for this observation is unknown. The objective of this study was to calculate the forces of all three hamstring muscles, relative to each other, during a lengthening contraction to assess for any differences that may help explain the biceps femoris predilection for injury during interval sprinting. To calculate the displacement of each individual hamstring muscle previously performed studies on cadaveric anatomical data and hamstring kinematics during sprinting were used. From these displacement calculations for each individual hamstring muscle physical principles were then used to deduce the proportion of force exerted by each individual hamstring muscle during a lengthening muscle contraction. These deductions demonstrate that the biceps femoris muscle is required to exert proportionally more force in a lengthening muscle contraction relative to the semimembranosus and semitendinosus muscles primarily as a consequence of having to lengthen over a greater distance within the same time frame. It is hypothesized that this property maybe a factor in the known observation of the increased susceptibility of the biceps femoris muscle to injury during repeated sprints where recurrent higher force is required.


An updated Asia Pacific Consensus Recommendations on colorectal cancer screening.
Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.


Determination of reference intervals for common chemistry and immunoassay tests for Kenyan adults based on an internationally harmonized protocol and up-to-date statistical methods.
Due to a lack of reliable reference intervals (RIs) for Kenya, we set out to determine RIs for 40 common chemistry and immunoassay tests as part of the IFCC global RI project. Apparently healthy adults aged 18-65 years were recruited according to a harmonized protocol and samples analyzed using Beckman-Coulter analyzers. Value assigned serum panels were measured to standardize chemistry results. The need for partitioning reference values by sex and age was based on between-subgroup differences expressed as standard deviation ratio (SDR) or bias in lower or upper limits (LLs and ULs) of the RI. RIs were derived using a parametric method with/without latent abnormal value exclusion (LAVE). Sex-specific RIs were required for uric acid, creatinine, total bilirubin (TBil), total cholesterol (TC), ALT, AST, CK, GGT, transferrin, transferrin saturation (TfSat) and immunoglobulin-M. Age-specific RIs were required for glucose and triglyceride for both sexes, and for urea, magnesium, TC, HDL-cholesterol ratio, ALP, and ferritin for females. LAVE was effective in optimizing RIs for AST, ALT, GGT iron-markers and CRP by reducing influence of latent anemia and metabolic diseases. Thyroid profile RIs were derived after excluding volunteers with anti-thyroid antibodies. Kenyan RIs were comparable to those of other countries participating in the global study with a few exceptions such as higher ULs for TBil and CRP. Kenyan RIs for major analytes were established using harmonized protocol from well-defined reference individuals. Standardized RIs for chemistry analytes can be shared across sub-Saharan African laboratories with similar ethnic and life-style profile.


Neuroplasticity, limbic neuroblastosis and neuro-regenerative disorders.
The brain is a dynamic organ of the biological renaissance due to the existence of neuroplasticity. Adult neurogenesis abides by every aspect of neuroplasticity in the intact brain and contributes to neural regeneration in response to brain diseases and injury. The occurrence of adult neurogenesis has unequivocally been witnessed in human subjects, experimental and wildlife research including rodents, bats and cetaceans. Adult neurogenesis is a complex cellular process, in which generation of neuroblasts namely, neuroblastosis appears to be an integral process that occur in the limbic system and basal ganglia in addition to the canonical neurogenic niches. Neuroblastosis can be regulated by various factors and contributes to different functions of the brain. The characteristics and fate of neuroblasts have been found to be different among mammals regardless of their cognitive functions. Recently, regulation of neuroblastosis has been proposed for the sensorimotor interface and regenerative neuroplasticity of the adult brain. Hence, the understanding of adult neurogenesis at the functional level of neuroblasts requires a great scientific attention. Therefore, this mini-review provides a glimpse into the conceptual development of neuroplasticity, discusses the possible role of different types of neuroblasts and signifies neuroregenerative failure as a potential cause of dementia.


Epidemiological and clinical aspects of incidental carcinoma of the prostate in Africans: experience at the Lagos University Teaching Hospital, Lagos and the Kenyatta National Hospital, Nairobi.
Twenty patients in Lagos and 24 patients in Nairobi with incidental carcinoma of the prostate in resected glands for benign hyperplasia were studied at the Lagos University Teaching Hospital (1978-1982) and at Kenyatta National Hospital (1988-1992), respectively. The age range for the Lagos group was 45-78 years with a mean age of 61 years and a peak incidence in the seventh decade (60-69 year age group) compared to the Nairobi group with age range of 50-89 years with a mean age of 66 years and a peak incidence in the eighth decade (70-79 year age group). Both groups had predominantly well differentiated low grade stage TIA (AI) incidental carcinoma of the prostate, being 80% in the Lagos group and 79.2% in the Nairobi group. High grade undifferentiated stage TIB (A2) incidental carcinoma of the prostate was present in 20% of the Lagos group and 20.8% of the Nairobi group. In both groups, the majority of patients (80%) in the Lagos group and (79.2%) in the Nairobi group presented late with similar symptoms of prostatic obstruction.


Application of marrow mesenchymal stem cell-derived extracellular matrix in peripheral nerve tissue engineering.
To advance molecular and cellular therapy into the clinic for peripheral nerve injury, modification of neural scaffolds with the extracellular matrix (ECM) of peripheral nerves has been established as a promising alternative to direct inclusion of support cells and/or growth factors within a neural scaffold, while cell-derived ECM proves to be superior to tissue-derived ECM in the modification of neural scaffolds. Based on the fact that bone marrow mesenchymal stem cells (BMSCs), just like Schwann cells, are adopted as support cells within a neural scaffold, in this study we used BMSCs as parent cells to generate ECM for application in peripheral nerve tissue engineering. A chitosan nerve guidance conduit (NGC) and silk fibroin filamentous fillers were respectively prepared for co-culture with purified BMSCs, followed by decellularization to stimulate ECM deposition. The ECM-modified NGC and lumen fillers were then assembled into a chitosan-silk fibroin-based, BMSC-derived, ECM-modified neural scaffold, which was implanted into rats to bridge a 10 mm-long sciatic nerve gap. Histological and functional assessments after implantation showed that regenerative outcomes achieved by our engineered neural scaffold were better than those achieved by a plain chitosan-silk fibroin scaffold, and suggested the benefits of BMSC-derived ECM for peripheral nerve repair. Copyright © 2016 John Wiley & Sons, Ltd.


Single payer: good metaphor, bad politics.
Health insurance reform requires political solutions, not technocratic fixes. Single payer frames the problem as a grossly inefficient bursar's office. Great political leadership means reframing the problem as a faulty social compact, rewriting the compact, and making everybody play by the new rules. Most of all, great leadership means explaining in powerful language why participating in the new social compact would fulfill both enlightened self-interest and social responsibility.


Evaluation of automated speed enforcement on Loop 101 freeway in Scottsdale, Arizona.
Speed cameras can reduce speeding and injury crashes, but in many communities they are confined to low-speed settings such as residential streets and school zones. In 2006 the city of Scottsdale, Arizona, implemented a 9-month pilot program to evaluate the feasibility and effects of highly visible speed camera enforcement on a busy urban freeway. This was the first use of fixed speed cameras on a major US highway. Deployment of six cameras along an 8-mile corridor was associated with large declines in mean speeds and an 88% decrease in the odds of vehicles traveling 11 mph or more above the 65 mph limit. Traffic speeds increased soon after the pilot program was suspended. In addition to reducing speeding along the enforcement corridor, speed cameras were associated with large reductions in speeding on the same highway but 25 miles away from the camera installations. However, traffic speeds were fairly stable on urban freeways in Scottsdale that were not part of the study road. Public opinion surveys found widespread concerns about speeding on the Loop 101 freeway and high levels of support for speed camera enforcement on this road.


Efficient extra- and intracellular alkalinization improves cardiovascular functions in severe lactic acidosis induced by hemorrhagic shock.
Lactic acidosis is associated with cardiovascular failure. Buffering with sodium bicarbonate is proposed in severe lactic acidosis. Bicarbonate induces carbon dioxide generation and hypocalcemia, both cardiovascular depressant factors. The authors thus investigated the cardiovascular and metabolic effects of an adapted sodium bicarbonate therapy, including prevention of carbon dioxide increase with hyperventilation and ionized calcium decrease with calcium administration. Lactic acidosis was induced by hemorrhagic shock. Twenty animals were randomized into five groups: (1) standard resuscitation with blood retransfusion and norepinephrine (2) adapted sodium bicarbonate therapy (3) nonadapted sodium bicarbonate therapy (4) standard resuscitation plus calcium administration (5) hyperventilation. Evaluation was focused in vivo on extracellular pH, on intracellular pH estimated by P nuclear magnetic resonance and on myocardial contractility by conductance catheter. Aortic rings and mesenteric arteries were isolated and mounted in a myograph, after which arterial contractility was measured. All animals in the hyperventilation group died prematurely and were not included in the statistical analysis. When compared with sham rats, shock induced extracellular (median, 7.13; interquartile range, [0.10] vs. 7.30 [0.01]; P = 0.0007) and intracellular acidosis (7.26 [0.18] vs. 7.05 [0.13]; P = 0.0001), hyperlactatemia (7.30 [0.01] vs. 7.13 [0.10]; P = 0.0008), depressed myocardial elastance (2.87 [1.31] vs. 0.5 [0.53] mmHg/μl; P = 0.0001), and vascular hyporesponsiveness to vasoconstrictors. Compared with nonadapted therapy, adapted bicarbonate therapy normalized extracellular pH (7.03 [0.12] vs. 7.36 [0.04]; P < 0.05), increased intracellular pH to supraphysiological values, improved myocardial elastance (1.68 [0.41] vs. 0.72 [0.44] mmHg/μl; P < 0.05), and improved aortic and mesenteric vasoreactivity. A therapeutic strategy based on alkalinization with sodium bicarbonate along with hyperventilation and calcium administration increases pH and improves cardiovascular function.


Distribution of Short-Term and Lifetime Predicted Risks of Cardiovascular Diseases in Peruvian Adults.
Short-term risk assessment tools for prediction of cardiovascular disease events are widely recommended in clinical practice and are used largely for single time-point estimations; however, persons with low predicted short-term risk may have higher risks across longer time horizons. We estimated short-term and lifetime cardiovascular disease risk in a pooled population from 2 studies of Peruvian populations. Short-term risk was estimated using the atherosclerotic cardiovascular disease Pooled Cohort Risk Equations. Lifetime risk was evaluated using the algorithm derived from the Framingham Heart Study cohort. Using previously published thresholds, participants were classified into 3 categories: low short-term and low lifetime risk, low short-term and high lifetime risk, and high short-term predicted risk. We also compared the distribution of these risk profiles across educational level, wealth index, and place of residence. We included 2844 participants (50% men, mean age 55.9 years [SD 10.2 years]) in the analysis. Approximately 1 of every 3 participants (34% [95% CI 33 to 36]) had a high short-term estimated cardiovascular disease risk. Among those with a low short-term predicted risk, more than half (54% [95% CI 52 to 56]) had a high lifetime predicted risk. Short-term and lifetime predicted risks were higher for participants with lower versus higher wealth indexes and educational levels and for those living in urban versus rural areas (P<0.01). These results were consistent by sex. These findings highlight potential shortcomings of using short-term risk tools for primary prevention strategies because a substantial proportion of Peruvian adults were classified as low short-term risk but high lifetime risk. Vulnerable adults, such as those from low socioeconomic status and those living in urban areas, may need greater attention regarding cardiovascular preventive strategies.


Varying degrees of ventricular unloading in the heterotopic rat heart transplant model demonstrated by magnetic resonance imaging.
Left ventricular assist device placement is an increasingly common treatment for cardiac failure, resulting in cardiac unloading and potentially reversing the remodelling changes seen in heart failure. A popular animal model for human ventricular unloading is the rodent heterotopic non-working heart transplant; the volume loading status of this preparation is important to interpreting the resulting reverse remodelling yet has not been previously investigated. This study was designed to assess the variability of left ventricular volume loading in the rodent transplant model. Heterotopic abdominal heart transplant was performed on syngeneic rats; high resolution cine magnetic resonance imaging was subsequently performed on the heterotopic transplanted hearts in anesthetised rats, after variable post-transplant recovery times, in order to assess ventricular loading status. Highly variable left ventricular volume loading status was demonstrated, with some hearts exhibiting considerable ventricular filling and ejection. These observations call into question the assumption that studies using this model are consistently examining fully unloaded ventricles, and indicate the desirability of in vivo imaging of such hearts to quantify the degree of ventricular loading.


Trichosanthes kirilowii: A New Host of Cucurbit mild mosaic virus in China.
Chinese cucumber (Trichosanthes kirilowii Maxim.) is a type of perennial liana plant of the Cucurbitaceae family that is mainly distributed in East Asia and northern Australia. It is an important medicinal plant and commonly used in Chinese herbalism, where it is considered to be one of the 50 fundamental herbs (2). During the summer and autumn of 2012, T. kirilowii plants showing symptoms of mild mosaic on the upper leaves and bright yellow color on the lower leaves were observed in the Haidian district of Beijing, China. Recently similar symptoms induced by Cucurbit mild mosaic virus (CuMMV) on squash have been reported. CuMMV is a new member of the genus Fabavirus in the Comovirinae subfamily, discovered in China in 2006 (1). Total RNA was extracted from five leaf samples of independent plants and used for reverse transcription with an oligo (dT)18 primer, followed by PCR with a pair of CuMMV virus-specific primers FaR13012F (5'-CGAGTGCGAGTTAGAAATTGGGATG-3') and FaR15783R (5'-TCACTTTGAGGTGATAAAACAATCC-3') to amplify a 2,772-bp fragment including RNA-dependent RNA polymerase (RdRp) coding region. The expected target fragment was obtained in all symptomatic plant samples but not from an asymptomatic plant. Nucleotide sequence comparison analysis showed that the virus isolated from T. kirilowii (GenBank Accession No. KC959843) had 95.33% nucleotide identity and 99.15% amino acid identity in the RdRp sequence with a CuMMV isolate from squash (GenBank Accession No. FJ194941) (1). In addition, symptomatic samples tested positive for CuMMV by Western blot using CuMMV small coat protein (SCP) specific polyclonal antibody (1). To our knowledge, this is the first report of T. kirilowii as natural host of CuMMV in China. The impact of CuMMV on T. kirilowii production remains to be determined; however, the extended host range for this virus suggests a potential threat of CuMMV to cucurbit crops in China. References: (1) S. W. Dong et al. Arch. Virol.157:597, 2012. (2) J. H. Hong et al. China Pharmacist 7:561, 2004.


Young driver crash rates by licensing age, driving experience, and license phase.
Few studies have concurrently assessed the influence of age and experience on young driver crashes, in particular in the post-Graduated Driver Licensing (GDL) era. Further, little attention is given to the transition from intermediate to full licensure. We examined the independent and joint contributions of licensing age, driving experience, and GDL license phase on crash rates among the population of young New Jersey (NJ) drivers. From a unique linked database containing licensing and crash data, we selected all drivers who obtained their NJ intermediate license at 17-20 years old from 2006-2009 (n=410,230). We determined the exact age at which each driver obtained an intermediate and full license and created distinct, fixed cohorts of drivers based on their age at intermediate licensure. For each cohort, we calculated and graphed observed monthly crash rates over the first 24 months of licensure. Further, we examined crash rates by age at licensure, driving experience (i.e., time since licensure), and license phase. First-month crash rates were higher among the youngest drivers (licensed at 17y0m). Drivers who were licensed later experienced a reduced "steepness" in the slope of their crash rates in the critical initial months of driving, but there did not appear to be any incremental benefit of later licensure once drivers had six months of driving experience. Further, at each age, those with more driving experience had lower crash rates; however, the benefit of increased experience was greatest for the substantial proportion of teens licensed immediately after becoming eligible (at 17y0m). Finally, independent of age and experience, teen drivers' crash risk increased substantially at the point of transition to a full license, while drivers of a similar age who remained in the intermediate phase continued to experience a decline in crash rates. Age and driving experience interact to influence crash rates. Further, independent of these two factors, there is an abrupt increase in crash risk at the point of transition from intermediate to full licensure. Future studies should investigate whether this increase is accounted for by a change in driving exposure, driving behaviors, and/or other factors.


A simple and sensitive detection of small molecule-protein interactions based on terminal protection-mediated exponential strand displacement amplification.
We herein describe a simple and sensitive strategy to detect a small molecule-protein interaction based on terminal protection-mediated exponential strand displacement amplification (eSDA). In principle, the small molecule linked to a DNA probe protects the DNA probe against the exonuclease I-catalyzed degradation after its binding to the corresponding target protein. The protected DNA probe then serves as a template to promote eSDA. Consequently, a large number of duplexes are produced, which leads to a high fluorescence from a double-stranded DNA specific fluorescent dye, SYBR Green I. As a model system to prove this sensing strategy, the interaction between biotin and streptavidin (SA), which is known to be the strongest among the non-covalent biological interactions, was selected and its analytical performance was thoroughly investigated. As a result, SA was sensitively detected with the limit of detection of 16 pM. In addition, the practical applicability of this method was successfully demonstrated by reliably determining the SA in human serum.


Infection in Southern Chinese Patients with Systemic Lupus Erythematosus: Spectrum, Drug Resistance, Outcomes, and Risk Factors.
To investigate the spectrum, antibiotic-resistant pattern, risk factors, and outcomes of infection in patients hospitalized with systemic lupus erythematosus (SLE). We collected the clinical and microbiological data from hospitalized patients with SLE with infection between June 2005 and June 2015, and then conducted retrospective analyses. Among our sample of 3815 hospitalized patients, 1321 (34.6%) were diagnosed with infection. The majority (78.3%) of infection occurred within 5 years of SLE onset. Bacterial infection was predominant (50.6%), followed by viral infection (36.4%) and fungal infection (12.5%). The lungs (33.7%) and upper respiratory tracts (26.3%) were most commonly affected. Gram-negative bacteria (GNB) were predominant over gram-positive bacteria (178 isolates vs 90 isolates). The most frequently isolated bacteria were Escherichia coli (24.6%), followed by Acinetobacter baumannii (13.4%) and coagulase-negative Staphylococcus (13.4%). Multidrug-resistant (MDR) strains were detected in 26.9% of bacterial isolates. The most common fungus was Candida spp. (99 episodes), followed by Aspergillus (24 episodes) and Cryptococcus neoformans (13 episodes). The overall mortality rate for this cohort was 2.2%; 48 patients died of infection. Factors associated with bacterial and viral infection were higher Systemic Lupus Erythematosus Disease Activity Index, renal involvement, thrombocytopenia, accumulated dose of glucocorticoids (GC), and treatment with cyclophosphamide (CYC). Renal involvement, accumulated dose of GC, and treatment with CYC were associated with fungal infection. Infection was the leading cause of mortality in patients hospitalized with SLE. There were some notable features of infection in Chinese patients including early onset, higher proportion of respiratory tract involvement, predominance of GNB with emergence of MDR isolates, and a variety of pathogens.


Surface plasmons in nanowires with toroidal magnetic structure.
We consider the problem of the influence of a toroidal magnetization on a cylindrical surface plasmon polariton (SPP) propagating along a nanowire of a circular cross section. It follows from the dispersion equations that the SPP wavenumber linearly depends on the toroidal moment and the effect of magneto-optical nonreciprocity appears. The numerical solution of the dispersion equations demonstrates that the corresponding splitting of the SPP dispersion curves for two opposite directions of the toroidal moment is increased by an order of magnitude with respect to the planar case. The largest values of this splitting are observed for systems with relatively low optical losses, as is demonstrated by calculations for SPPs in a gold cylinder surrounded by rare-earth bismuth iron garnet.


Retrospective study on the impact of ulnar nerve dislocation on the pathophysiology of ulnar neuropathy at the elbow.
High resolution ultrasonography (US) has been used for diagnosis and evaluation of entrapment peripheral neuropathy. Ulnar neuropathy at the elbow (UNE) is the second most common focal entrapment neuropathy. The ulnar nerve tends to move to the anteromedial side and sometimes subluxates or dislocates over the medial epicondyle as the elbow is flexed. Dislocation of the ulnar nerve during elbow flexion may contribute to friction injury. We aimed to investigate the effects which the dislocation of ulnar nerve at the elbow could have on the electrophysiologic pathology of UNE. We retrospectively reviewed 71 arms of UNE. The demographic data, electrodiagnosis findings and US findings of ulnar nerve were analyzed. We classified the electrodiagnosis findings of UNE into three pathologic types; demyelinating, sensory axonal loss, and mixed sensorimotor axonal loss. The arms were grouped into non-dislocation, partial dislocation, and complete dislocation groups according to the findings of nerve dislocation in US examination. We compared the electrodiagnosis findings, ulnar nerve cross sectional areas in US and electrodiagnosis pathology types among the groups. A total of 18 (25.3%) arms showed partial dislocation, and 15 (21.1%) arms showed complete dislocation of ulnar nerve in US. In the comparison of electrodiagnosis findings, the partial and complete dislocation groups showed significantly slower conduction velocities and lower amplitudes than non-dislocation group in motor conduction study. In the sensory conduction study, the conduction velocity was significantly slower in partial dislocation group and the amplitude was significantly lower in complete dislocation group than non-dislocation group. In the comparison of US findings, patients in partial and complete dislocation groups showed significantly larger cross sectional areas of the ulnar nerve. The comparison of electrodiagnosis pathologic types among the groups revealed that there were significantly larger proportions of the axonal loss (sensory axonal loss or mixed sensorimotor axonal loss) in partial and complete dislocation groups than non-dislocation group. The ulnar nerve dislocation could influence on the more severe damage of the ulnar nerve in patients with UNE. It might be important to evaluate the dislocation of the ulnar nerve using US in diagnosing ulnar neuropathy for predicting the prognosis and determining the treatment direction of UNE.


Iatrogenic vitamin K deficiency and life threatening coagulopathy.
A man was admitted with abdominal pain. Treatment for acute diverticulitis was instituted with intravenous antibiotics and oral limitation. Imaging demonstrated a complex inflammatory mass. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen were within normal limits. However, repeat preoperative clotting studies demonstrated a severe unexpected coagulopathy to have developed since admission that could have caused fatal intraoperative exsanguination. Direct assays showed severe, isolated deficiency of vitamin K dependent clotting factors, and mixing studies normalised both the PT and APTT, ruling out a coagulation inhibitor. The coagulopathy responded to intravenous vitamin K administration. Dietary insufficiency underlies vitamin K deficiency in the presence of normal biliary and enteral function. A significant coagulopathy can result with additional eradication of intestinal microflora. Hypoprothombinaemia is recognised as a consequence of protracted treatment with broad spectrum antibiotics, and vigilance is required for those at risk. The development of such a rapid and unexpected coagulopathy posed a complex preoperative management issue delaying operative intervention; although avoided by fortuitous preoperative screening, it could have caused significant intraoperative bleeding. The remarkably specific lack of vitamin K dependent clotting factors strongly suggested a vitamin K deficiency and administration of coumarins was ruled out.