Ecosystem services in conservation planning: targeted benefits vs. co-benefits or costs?
There is growing support for characterizing ecosystem services in order to link conservation and human well-being. However, few studies have explicitly included ecosystem services within systematic conservation planning, and those that have follow two fundamentally different approaches: ecosystem services as intrinsically-important targeted benefits vs. substitutable co-benefits. We present a first comparison of these two approaches in a case study in the Central Interior of British Columbia. We calculated and mapped economic values for carbon storage, timber production, and recreational angling using a geographical information system (GIS). These 'marginal' values represent the difference in service-provision between conservation and managed forestry as land uses. We compared two approaches to including ecosystem services in the site-selection software Marxan: as Targeted Benefits, and as Co-Benefits/Costs (in Marxan's cost function); we also compared these approaches with a Hybrid approach (carbon and angling as targeted benefits, timber as an opportunity cost). For this analysis, the Co-Benefit/Cost approach yielded a less costly reserve network than the Hybrid approach (1.6% cheaper). Including timber harvest as an opportunity cost in the cost function resulted in a reserve network that achieved targets equivalently, but at 15% lower total cost. We found counter-intuitive results for conservation: conservation-compatible services (carbon, angling) were positively correlated with each other and biodiversity, whereas the conservation-incompatible service (timber) was negatively correlated with all other networks. Our findings suggest that including ecosystem services within a conservation plan may be most cost-effective when they are represented as substitutable co-benefits/costs, rather than as targeted benefits. By explicitly valuing the costs and benefits associated with services, we may be able to achieve meaningful biodiversity conservation at lower cost and with greater co-benefits.


Comorbidities, Exposure to Medications, and the Risk of Community-Acquired Clostridium difficile Infection: a systematic review and meta-analysis.
Clostridium difficile infection (CDI) has been extensively described in healthcare settings; however, risk factors associated with community-acquired (CA) CDI remain uncertain. This study aimed to synthesize the current evidence for an association between commonly prescribed medications and comorbidities with CA-CDI. A systematic search was conducted in 5 electronic databases for epidemiologic studies that examined the association between the presence of comorbidities and exposure to medications with the risk of CA-CDI. Pooled odds ratios were estimated using 3 meta-analytic methods. Subgroup analyses by location of studies and by life stages were conducted. Twelve publications (n=56,776 patients) met inclusion criteria. Antimicrobial (odds ratio, 6.18; 95% CI, 3.80-10.04) and corticosteroid (1.81; 1.15-2.84) exposure were associated with increased risk of CA-CDI. Among the comorbidities, inflammatory bowel disease (odds ratio, 3.72; 95% CI, 1.52-9.12), renal failure (2.64; 1.23-5.68), hematologic cancer (1.75; 1.02-5.68), and diabetes mellitus (1.15; 1.05-1.27) were associated with CA-CDI. By location, antimicrobial exposure was associated with a higher risk of CA-CDI in the United States, whereas proton-pump inhibitor exposure was associated with a higher risk in Europe. By life stages, the risk of CA-CDI associated with antimicrobial exposure greatly increased in adults older than 65 years. Antimicrobial exposure was the strongest risk factor associated with CA-CDI. Further studies are required to investigate the risk of CA-CDI associated with medications commonly prescribed in the community. Patients with diarrhea who have inflammatory bowel disease, renal failure, hematologic cancer, or diabetes are appropriate populations for interventional studies of screening.


The role of melano-macrophage aggregates in the storage of mercury and other metals: an example from yelloweye rockfish (Sebastes ruberrimus).
Melano-macrophage aggregates, collections of specialized cells of the innate immune system of fish, are considered a general biomarker for contaminant toxicity. To elucidate further the relationship between macrophage aggregates and metals exposure, yelloweye rockfish (Sebastes ruberrimus), a long-lived species, were sampled from the east and west coasts of Prince of Wales Island, Alaska. Metals concentrations in livers (inorganic Hg, methyl mercury, Se, Ni, Cd, Cu, Zn) and spleens (inorganic Hg and methyl mercury) were determined, as well as their correlations with melano-macrophage aggregate area. Sections of liver tissue were analyzed by laser ablation-inductively coupled plasma-mass spectrometry to determine how metals were spatially distributed between hepatocytes and macrophage aggregates. The concentration of inorganic Hg in whole tissue was the best predictor of macrophage area in yelloweye livers and spleens. Macrophage aggregates had higher relative concentrations than most metals compared with the surrounding hepatocytes. However, not all metals were accumulated to the same degree, as evidenced by differences in the ratios of metals in macrophages compared with hepatocytes. Laser ablation data were corroborated with the results of X-ray synchrotron fluorescence imaging of a yelloweye liver section. Hepatic macrophage aggregates in yelloweye rockfish may play an important role in the detoxification and storage of Hg and other metals.


Basal cell nevus syndrome: clinical and molecular review and case report.
Basal cell nevus syndrome (BCNS), also referred to as nevoid basal cell carcinoma syndrome or Gorlin-Goltz syndrome, was first described by Gorlin and Goltz in 1960 as an autosomal dominant disorder characterized by the early appearance of multiple basal cell carcinomas (BCCs), keratocysts of the jaw, ectopic calcifications, palmar and plantar pits, and anomalies of the ocular, skeletal, and reproductive systems. The genesis of this cancer's etiology in relation to BCNS was unclear until a few years ago when molecular analysis studies suggested a relationship between BCC and the loss-of-function mutations of the patched gene (PTCH) found on chromosome arm 9q. PTCH inhibits signaling by the membrane protein Smoothened (Smo), and this inhibition is relieved by binding sonic hedgehog (SHH) to PTCH. We describe a patient with multiple BCCs associated with x-ray anomalies of BCNS and review the basis of the SHH signaling pathway and clinical aspects of BCNS.


The metabolic syndrome and chronic liver disease.
The prevalence of the metabolic syndrome (MetS), a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder is not only associated with a higher risk of appearance of type 2 diabetes and cardiovascular events, but impacts on the liver in different ways. Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of MetS, and is characterized by triglyceride accumulation and a variable degree of hepatic injury, inflammation, and repair. In the presence of significant hepatocellular injury and inflammation, the picture is defined 'nonalcoholic steatohepatitis' (NASH), that has the potential to progress to advanced fibrosis and cirrhosis. Diagnosis of NASH is based on a liver biopsy, and active search for noninvasive tests is ongoing. Progression of steatohepatitis to advanced fibrosis or cirrhosis has been shown in at least one third of patients followed with paired biopsies. Presence of NASH is associated with lower life expectancy, both due to liver-related death and to an increase in cardiovascular events. The appearance of NAFLD is mainly dependent on increased flow of fatty acids derived from an excess of lipolysis from insulin-resistant adipose tissue. Development of NASH is based on lipotoxicity and is influenced by signals derived from outside the liver and from intrahepatic activation of inflammatory and fibrogenic pathways. The presence of the MetS is also associated with worse outcomes in patients with cirrhosis due to any causes, and has complex interactions with hepatitis C virus infection. Moreover, MetS poses a higher risk of development of hepatocellular carcinoma, not necessarily through the development of NASH-related cirrhosis. In conclusion, the presence of metabolic alterations has a severe and multifaceted impact on the liver, and is responsible for a higher risk of liver-dependent and -independent mortality.


Comparison of in vivo and in vitro models to evaluate pulp temperature rise during exposure to a Polywave® LED light curing unit.
To measure and compare in vivo and in vitro pulp temperature (PT) increase (ΔTEMP) over baseline, physiologic temperature using the same intact upper premolars exposed to the same Polywave® LED curing light. After local Ethics Committee approval (#255,945), local anesthesia, rubber dam isolation, small occlusal preparations/minute pulp exposure (n=15) were performed in teeth requiring extraction for orthodontic reasons. A sterile probe of a temperature measurement system (Temperature Data Acquisition, Physitemp) was placed within the pulp chamber and the buccal surface was sequentially exposed to a LED LCU (Bluephase 20i, Ivoclar Vivadent) using the following exposure modes: 10-s low or high, 5-s Turbo, and 60-s high. Afterwards, the teeth were extracted and K-type thermocouples were placed within the pulp chamber through the original access. The teeth were attached to an assembly simulating the in vivo environment, being similarly exposed while real-time temperature (°C) was recorded. ΔTEMP values and time for temperature to reach maximum (ΔTIME) were subjected to two-way ANOVA and Bonferroni's post-hoc tests (pre-set alpha 0.05). Higher ΔTEMP was observed in vitro than in vivo. No significant difference in ΔTIME was observed between test conditions. A significant, positive relationship was observed between radiant exposure and ΔTEMP for both conditions (in vivo: r2=0.917; p<0.001; in vitro: r2=0.919; p<0.001). Although the in vitro model overestimated in vivo PT increase, in vitro PT rise was close to in vivo values for clinically relevant exposure modes.


Age-dependent alterations in the efficacy of phenylephrine-induced contractions in vascular smooth muscle isolated from the corpus cavernosum of impotent men.
Steady-state contractile responses elicited by phenylephrine activation of the alpha 1-adrenergic receptor subtype were studied in vascular smooth muscle strips isolated from the corpus cavernosum of impotent men. The dissociation constant of phenylephrine was determined by the method of partial irreversible receptor inactivation over a wide range of alpha 1-adrenergic receptor alkylation levels. Statistical analysis of mean population values revealed a significantly greater mean efficacy for phenylephrine-induced contractions in older patients (60-73 years old) than in younger patients (40-59 years old), in the absence of similar alterations in the mean phenylephrine dissociation constant (affinity). In addition, there was no significant effect of the diabetic state on the mean phenylephrine affinity or efficacy estimates. However, despite the absence of age- or pathology-dependent variations in agonist affinity, as assessed by group mean calculations, a detailed examination of all isolated tissues on an individual basis revealed that the phenylephrine affinity estimates varied over a range of almost two orders of magnitude. Furthermore, a linear regression analysis revealed a highly significant positive correlation between agonist affinity and the location of the phenylephrine concentration-response curve, which was characterized by a slope significantly less than unity. In conclusion, an increased efficacy of phenylephrine-induced contractions in vitro is consistent with the hypothesis that augmented corporal vascular smooth muscle contractility in vivo may contribute to the pathophysiology of impotence in older patients.


Automated Classification and Cluster Visualization of Genotypes Derived from High Resolution Melt Curves.
High Resolution Melting (HRM) following PCR has been used to identify DNA genotypes. Fluorescent dyes bounded to double strand DNA lose their fluorescence with increasing temperature, yielding different signatures for different genotypes. Recent software tools have been made available to aid in the distinction of different genotypes, but they are not fully automated, used only for research purposes, or require some level of interaction or confirmation from an analyst. We describe a fully automated machine learning software algorithm that classifies unknown genotypes. Dynamic melt curves are transformed to multidimensional clusters of points whereby a training set is used to establish the distribution of genotype clusters. Subsequently, probabilistic and statistical methods were used to classify the genotypes of unknown DNA samples on 4 different assays (40 VKORC1, CYP2C9*2, CYP2C9*3 samples in triplicate, and 49 MTHFR c.665C>T samples in triplicate) run on the Roche LC480. Melt curves of each of the triplicates were genotyped separately. Automated genotyping called 100% of VKORC1, CYP2C9*3 and MTHFR c.665C>T samples correctly. 97.5% of CYP2C9*2 melt curves were genotyped correctly with the remaining 2.5% given a no call due to the inability to decipher 3 melt curves in close proximity as either homozygous mutant or wild-type with greater than 99.5% posterior probability. We demonstrate the ability to fully automate DNA genotyping from HRM curves systematically and accurately without requiring any user interpretation or interaction with the data. Visualization of genotype clusters and quantification of the expected misclassification rate is also available to provide feedback to assay scientists and engineers as changes are made to the assay or instrument.


H/D exchange at sp(3) carbons in the coordination sphere of platinum(II).
The [PtCl(η(1)-CH2CH2OR)(Me2phen)], Me2phen = 2,9-dimethyl-1,10-phenanthroline, complex is indefinitely stable in the solid state; however, when dissolved in protic deuterated solvents at basic pH, it undergoes H-D exchange at the Me2phen Me's. An analogous H-D exchange process takes place in the related [PtCl2(Me2phen)] complex which is sterically strained and very easily can detach one nitrogen of Me2phen yielding a T-shaped species. In contrast, the H-D exchange is considerably slower in the [Pt(OR)2(Me2phen)] complex characterized by smaller size and lower trans-labilizing effect of the oxygen donor ligands. It is suggested that the formation of a T-shaped intermediate could foster the C-H activation via oxidative addition to the metal centre. In accord with this hypothesis, the H/D exchange was found to be considerably slower in analogous complexes with 6,6'-dimethyl-2,2'-bipyridyl (Me2bpy), where the greater flexibility of Me2bpy, as compared to Me2phen, reduces the strain in the four coordinate substrate and hence the propensity to dissociate one end of the bidentate ligand.


Modification of Immunological Parameters, Oxidative Stress Markers, Mood Symptoms, and Well-Being Status in CFS Patients after Probiotic Intake: Observations from a Pilot Study.
The present study discusses about the effects of a combination of probiotics able to stimulate the immune system of patients affected by Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). To this purpose, patients diagnosed according to Fukuda's criteria and treated with probiotics were analyzed by means of clinical and laboratory evaluations, before and after probiotic administrations. Probiotics were selected considering the possible pathogenic mechanisms of ME/CFS syndrome, which has been associated with an impaired immune response, dysregulation of Th1/Th2 ratio, and high oxidative stress with exhaustion of antioxidant reserve due to severe mitochondrial dysfunction. Immune and oxidative dysfunction could be related with the gastrointestinal (GI) chronic low-grade inflammation in the lamina propria and intestinal mucosal surface associated with dysbiosis, leaky gut, bacterial translocation, and immune and oxidative dysfunction. Literature data demonstrate that bacterial species are able to modulate the functions of the immune and oxidative systems and that the administration of some probiotics can improve mucosal barrier function, modulating the release of proinflammatory cytokines, in CFS/ME patients. This study represents a preliminary investigation to verifying the safety and efficacy of a certain combination of probiotics in CFS/ME patients. The results suggest that probiotics can modify the well-being status as well as inflammatory and oxidative indexes in CFS/ME patients. No adverse effects were observed except for one patient, which displayed a flare-up of symptoms, although all inflammatory parameters (i.e., cytokines, fecal calprotectin, ESR, and immunoglobulins) were reduced after probiotic intake. The reactivation of fatigue symptoms in this patient, whose clinical history reported the onset of CFS/ME following mononucleosis, could be related to an abnormal stimulation of the immune system as suggested by a recent study describing an exaggerated immune activation associated with chronic fatigue.


Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc.
The ligand specificity of fibroblast growth factor receptor 2 (FGFR2) is determined by the alternative splicing of exons 8 (IIIb) or 9 (IIIc). Exon IIIb is included in epithelial cells, whereas exon IIIc is included in mesenchymal cells. Although a number of cis elements and trans factors have been identified that play a role in exon IIIb inclusion in epithelium, little is known about the activation of exon IIIc in mesenchyme. We report here the identification of a splicing enhancer required for IIIc inclusion. This 24-nucleotide (nt) downstream intronic splicing enhancer (DISE) is located within intron 9 immediately downstream of exon IIIc. DISE was able to activate the inclusion of heterologous exons rat FGFR2 IIIb and human beta-globin exon 2 in cell lines from different tissues and species and also in HeLa cell nuclear extracts in vitro. DISE was capable of replacing the intronic activator sequence 1 (IAS1), a known IIIb splicing enhancer and vice versa. This fact, together with the requirement for DISE to be close to the 5'-splice site and the ability of DISE to promote binding of U1 snRNP, suggested that IAS1 and DISE belong to the same class of cis-acting elements.


The impact of the level of the intestinal short chain Fatty acids in inflammatory bowel disease patients versus healthy subjects.
The aim of this study was to determine the changes of short chain fatty acids (SCFAs) in faeces of inflammatory bowel disease (IBD) patients compared to healthy subjects. SCFAs such as pyruvic, lactic, formic, acetic, propionic, isobutyric and butyric acids were analyzed by using high performance liquid chromatography (HPLC). This study showed that the level of acetic, 162.0 micromol/g wet faeces, butyric, 86.9 micromol/g wet faeces, and propionic acids, 65.6 micromol/g wet faeces, decreased remarkably in IBD faecal samples when compared with that of healthy individuals, 209.7, 176.0, and 93.3 micromol/g wet faeces respectively. On the contrary, lactic and pyruvic acids showed higher levels in faecal samples of IBD than in healthy subjects. In the context of butyric acid level, this study also found that the molar ratio of butyric acid was higher than propionic acid in both faecal samples. This might be due to the high intake of starch from rice among Malaysian population. It was concluded that the level of SCFAs differ remarkably between faecal samples in healthy subjects and that in IBD patients providing evidence that SCFAs more likely play an important role in the pathogenesis of IBD.


For-profit colleges.
For-profit, or proprietary, colleges are the fastest-growing postsecondary schools in the nation, enrolling a disproportionately high share of disadvantaged and minority students and those ill-prepared for college. Because these schools, many of them big national chains, derive most of their revenue from taxpayer-funded student financial aid, they are of interest to policy makers not only for the role they play in the higher education spectrum but also for the value they provide their students. In this article, David Deming, Claudia Goldin, and Lawrence Katz look at the students who attend for-profits, the reasons they choose these schools, and student outcomes on a number of broad measures and draw several conclusions. First, the authors write, the evidence shows that public community colleges may provide an equal or better education at lower cost than for-profits. But budget pressures mean that community colleges and other nonselective public institutions may not be able to meet the demand for higher education. Some students unable to get into desired courses and programs at public institutions may face only two alternatives: attendance at a for-profit or no postsecondary education at all. Second, for-profits appear to be at their best with well-defined programs of short duration that prepare students for a specific occupation. But for-profit completion rates, default rates, and labor market outcomes for students seeking associate's or higher degrees compare unfavorably with those of public postsecondary institutions. In principle, taxpayer investment in student aid should be accompanied by scrutiny concerning whether students complete their course of study and subsequently earn enough to justify the investment and pay back their student loans. Designing appropriate regulations to help students navigate the market for higher education has proven to be a challenge because of the great variation in student goals and types of programs. Ensuring that potential students have complete and objective information about the costs and expected benefits of for-profit programs could improve postsecondary education opportunities for disadvantaged students and counter aggressive and potentially misleading recruitment practices at for-profit colleges, the authors write.


Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers.
Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) and their matched controls. Comparison of whole genome sequence (WGS) and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3), and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome.


Cognitive mapping: using local knowledge for planning health research.
Cognitive mapping is a participatory research methodology that documents, in visual form, a construct of the local environment in which people live and work. We adapted this method to provide detailed data about study locales to inform recruitment and retention strategies for HIV prevention community based clinical trials. Four cognitive mapping studies were undertaken between 2005 and 2010, in and around Johannesburg in Orange Farm, and Hillbrow. Participants included members of clinical trial Community Advisory Boards (CAB), young people recruited from schools in Hillbrow and an organization for out of school youth, and men recruited from a database of men in the community interested in taking part in research. These groups participated in reconnaissance walks and in depth interviews, and drew detailed sketch maps. The cognitive maps defined the physical boundaries of the research locales, provided insights into their social histories, and identified important characteristics of the population such as movement, social and sexual networks, ethnic and other divisions. Important differences between the official cartographic maps and the cognitive maps were raised. The mapping data was applied by identifying key areas for recruitment that recruitment staff members were less familiar with and that may otherwise have been overlooked. Cognitive mapping is an effective, rapid and low cost method that can be used to inform recruitment and retention strategies for community-based clinical trial research. The method also provides a means for clinical trial researchers to involve the local community in research and to familiarise them with the social setting.


Diffuse alveolar hemorrhage after leflunomide therapy in a patient with rheumatoid arthritis.
We report the case of a young man, affected by rheumatoid arthritis who developed a rapid-onset short-of-breath, hemoptysis, and severe weakness, about 2 weeks after the administration of leflunomide. Chest radiography showed central bilateral opacities and pleural effusion as confirmed by the high-resolution computed tomography that demonstrated diffuse ground-glass and interlobular septal thickening as well. On admission at the Emergency Department, a microhematuria and a severe anemia were also documented. On the basis of the clinico-radiologic presentation, a pulmonary hemorrhage was likely to occur; so to clarify the origin of this process, a complete serologic examination was performed but all the antibodies were negative. Finally a renal biopsy was performed and it showed a pauci-immunologic glomerulonephritis and the bronchioloalveolar lavage confirmed the diffuse alveolar hemorrhage. In conclusion, the diagnosis of leflunomide-pulmonary-renal syndrome was rendered. The treatment with leflunomide was suspended; the conditions of the patient gradually improved and he became completely asymptomatic 1 week later.


Bacterial complement escape.
Complement activation is a crucial step in our innate immune defense against invading bacteria. Complement proteins can quickly recognize invading bacteria and subsequently label them for phagocytosis or kill them by direct lysis. In order to survive in the human host, bacterial pathogens have evolved a number of excreted and membrane-bound proteins that interfere with several steps of the complement cascade. In this chapter we summarize the most successful complement-modulating strategies by human bacterial pathogens.


Advances in pancreatic cancer biomarkers.
Biomarkers play an essential role in the management of patients with invasive cancers. Pancreatic ductal adenocarcinoma (PDC) associated with poor prognosis due to advanced presentation and limited therapeutic options. This is further complicated by absence of validated screening and predictive biomarkers for early diagnosis and precision treatments respectively. There is emerging data on biomarkers in pancreatic cancer in past two decades. So far, the CA 19-9 remains the only approved biomarker for diagnosis and response assessment but limited by low sensitivity and specificity. In this article, we aim to review current and future biomarkers that has potential serve as critical tools for early diagnostic, predictive and prognostic indications in pancreatic cancer.


Genome-Wide Polygenic Score and the Risk of Ischemic Stroke in a Prospective Cohort: The Hisayama Study.
Background and Purpose- Environmental and genetic factors contribute to the development of ischemic stroke (IS). We recently developed a genome-wide polygenic risk score (PRS) for IS using case-control datasets from 4 large-scale observational studies conducted in Japan. Our objective in the present study was to confirm the association between the PRS and the risk of IS with data from an independent prospective cohort recruited from the general Japanese population. Methods- A total of 3038 subjects aged ≥40 years were followed up for 10 years (2002-2012). The genome-wide PRS was calculated using genotype data from >350 000 single-nucleotide polymorphisms. The PRS levels were divided into quintiles. High and low genetic risk groups were defined as top 60% and bottom 40% of PRS, respectively. The hazard ratio (HR) for the development of IS was estimated using a Cox proportional hazards model. Results- During the follow-up period, 91 cases developed first-ever IS. The age- and sex-adjusted HR for IS increased with higher PRS levels (P for trend, 0.03). Subjects with the highest quintile level of PRS had a 2.44-fold (95% CI, 1.16-5.12) greater risk for IS than those with the lowest quintile level after adjusting for age and sex. A similar association was observed after adjusting for environmental risk factors (P for trend, 0.03). As compared with low genetic risk group, the age- and sex-adjusted HR in high genetic risk group was 1.63 (95% CI, 1.04-2.55), which was comparable to the HR of hypertension (HR, 1.41), diabetes mellitus (HR, 1.72), and smoking (HR, 1.54). The age- and sex-adjusted HR increased with the number of environmental risk factors in both high and low genetic risk groups without significant interaction. Conclusions- A high genome-wide PRS was a significant risk factor for IS independent of environmental risk factors in a general Japanese population. This finding suggests that PRS may be useful to identify individuals at a high risk of IS.


pH-Induced Transformation of Biodegradable Multilamellar Nanovectors for Enhanced Tumor Penetration.
Herein we describe biodegradable nanovectors comprised of block copolymers of poly(ethylene glycol) and poly(trimethylene carbonate) (PEG-PTMC) that change their morphology and surface charge when exposed to tumor environment conditions. Well-defined, drug-loaded nanovectors were prepared via direct hydration using liquid oligo(ethylene glycol) as a dispersant. Systematic introduction of basic imidazole-functional TMC derivatives, through modular polymerization, resulted in polymers that self-assembled in multilamellar nanoparticles (at neutral pH) and that were loaded with hydrophobic drugs. The resultant multilamellar nanovectors demonstrated a significant size reduction and charge reversal at pH ≈ 6.5, which yielded cationic nanovectors that were tailored for tumor penetration. In vitro studies using 3D heterospheroids demonstrate that this platform has excellent potential to promote enhanced tumor penetration under physiological conditions.


Analysis of dynamic susceptibility contrast MRI time series based on unsupervised clustering methods.
We compare five different unsupervised clustering techniques as tools for the analysis of dynamic susceptibility contrast MRI time series. The study included four subjects: two subjects with stroke and two subjects without focal neurological deficit. The goal was to determine the robustness and reliability of clustering methods in providing a self-organized segmentation of perfusion MRI data sharing common properties of signal dynamics. For this purpose, the relative signal reduction time series was computed for each pixel. Clustering of the resulting high-dimensional feature vectors was performed by minimal free-energy deterministic annealing, self-organizing maps, two variants of fuzzy c-means clustering (FVQ and FSM), and the neural gas algorithm. Clustering results were evaluated by visual assessment of cluster assignment maps and corresponding signal time curves as well as by quantitative comparison of cluster assignment maps with conventional pixel-specific perfusion parameter maps based on quantitative receiver operating characteristic (ROC) curve analysis. Clustering methods provided a functional segmentation with respect to vessel size, detected side asymmetries of contrast-agent first pass, and identified regions of perfusion deficits in subjects with stroke. As confirmed by quantitative ROC analysis, the clustering approach can detect regions of reduced brain perfusion with high accuracy when compared to conventional analysis by pixel-specific cerebral blood volume and mean transit time maps. We conclude that by unveiling differences of signal dynamics and amplitude, clustering is a useful tool to analyze and visualize regional properties of brain perfusion. Thus, it may contribute to the computer-aided diagnosis of cerebral circulation deficits by noninvasive neuroimaging.


Multi-wavelength immunoassays using surface plasmon-coupled emission.
We describe a new method for multi-wavelength immunoassays using surface plasmon-coupled emission (SPCE). This phenomenon is coupling of excited fluorophores with a nearby thin metal film, in our case silver, resulting in strongly directional emission into the underlying glass substrate. The angle at which the radiation propagate through the prism depends on the surface plasmon angle for the relevant wavelength. These angles depend on emission wavelength, allowing measurement of multiple analytes using multiple emission wavelengths. We demonstrated this possibility using antibodies labeled with either Rhodamine Red-X or AlexaFluor 647. These antibodies were directed against an antigen protein bound to the silver surface. The emission from each labeled antibody occurred at a different angle on the glass prism, allowing independent measurement of surface binding of each antibody. This method of SPCE immunoassays can be readily extended to 4 or more wavelengths.


Movement decoding using neural synchronization and inter-hemispheric connectivity from deep brain local field potentials.
Correlating electrical activity within the human brain to movement is essential for developing and refining interventions (e.g. deep brain stimulation (DBS)) to treat central nervous system disorders. It also serves as a basis for next generation brain-machine interfaces (BMIs). This study highlights a new decoding strategy for capturing movement and its corresponding laterality from deep brain local field potentials (LFPs). LFPs were recorded with surgically implanted electrodes from the subthalamic nucleus or globus pallidus interna in twelve patients with Parkinson's disease or dystonia during a visually cued finger-clicking task. We introduce a method to extract frequency dependent neural synchronization and inter-hemispheric connectivity features based upon wavelet packet transform (WPT) and Granger causality approaches. A novel weighted sequential feature selection algorithm has been developed to select optimal feature subsets through a feature contribution measure. This is particularly useful when faced with limited trials of high dimensionality data as it enables estimation of feature importance during the decoding process. This novel approach was able to accurately and informatively decode movement related behaviours from the recorded LFP activity. An average accuracy of 99.8% was achieved for movement identification, whilst subsequent laterality classification was 81.5%. Feature contribution analysis highlighted stronger contralateral causal driving between the basal ganglia hemispheres compared to ipsilateral driving, with causality measures considerably improving laterality discrimination. These findings demonstrate optimally selected neural synchronization alongside causality measures related to inter-hemispheric connectivity can provide an effective control signal for augmenting adaptive BMIs. In the case of DBS patients, acquiring such signals requires no additional surgery whilst providing a relatively stable and computationally inexpensive control signal. This has the potential to extend invasive BMI, based on recordings within the motor cortex, by providing additional information from subcortical regions.


Italian populations during the Copper Age: assessment of biological affinities through morphological dental traits.
The Copper Age (3rd millennium BC) was characterized by considerable socioeconomic transformations and coincided with the discovery of metallurgy. In this study we reconstruct the peopling of Italy during this period on the basis of dental morphology traits. Dental remains from 41 sites throughout Italy were analyzed; only three of the sites (Laterza and two from Sicily) span from the late Copper Age to the early Bronze Age. To work with adequate samples, we pooled the collections into nine geographically and culturally homogeneous groups. Dental morphological traits were scored on 8,891 teeth from 1,302 individuals using the ASUDAS scale. The correlation between the mean measure of divergence and geographic distances (calculated as air distances) was computed. Multidimensional scaling with the minimum spanning tree and maximum-likelihood methods was applied to assess the relationships between groups. The results revealed a substantial genetic homogeneity among the populations throughout the Italian peninsula during the Copper Age with the exception of Sardinia, which tends to diverge from the continental samples. Phenetic and geographic distances correlate highly significantly only when the southern samples from Sicily and Laterza are removed from the analysis, which indicates that these groups may have experienced genetic admixture with external populations.


Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats.
High blood pressure, or "hypertension," is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension.


Development and evaluation of a questionnaire to measure the perceived implementation of the mission statement of a competency based curriculum.
A mission statement (MS) sets out the long-term goals of an institution and is supposed to be suited for studying learning environments. Yet, hardly any study has tested this issue so far. The aim of the present study was the development and psychometric evaluation of an MS-Questionnaire (MSQ) focusing on explicit competencies. We investigated to what extent the MSQ captures the construct of learning environment and how well a faculty is following--in its perception--a competency orientation in a competency-based curriculum. A questionnaire was derived from the MS "teaching" (Medical Faculty, Heinrich-Heine University Düsseldorf) which was based on (inter-) nationally accepted goals and recommendations for a competency based medical education. The MSQ was administered together with the Dundee Ready Education Environment Measure (DREEM) to 1119 students and 258 teachers. Cronbach's alpha was used to analyze the internal consistency of the items. Explorative factor analyses were performed to analyze homogeneity of the items within subscales and factorial validity of the MSQ. Item discrimination was assessed by means of part-whole corrected discrimination indices, and convergent validity was analyzed with respect to DREEM. Demographic variations of the respondents were used to analyze the inter-group variations in their responses. Students and teachers perceived the MS implementation as "moderate" and on average, students differed significantly in their perception of the MS. They thought implementation of the MS was less successful than faculty did. Women had a more positive perception of educational climate than their male colleagues and clinical students perceived the implementation of the MS on all dimensions significantly worse than preclinical students. The psychometric properties of the MSQ were very satisfactory: Item discrimination was high. Similarly to DREEM, the MSQ was highly reliable among students (α = 0.92) and teachers (α = 0.93). In both groups, the MSQ correlated highly positively with DREEM (r = 0.79 and 0.80, p < 0.001 each). Factor analyses did not reproduce the three areas of the MS perfectly. The subscales, however, could be identified as such both among teachers and students. The perceived implementation of faculty-specific goals can be measured in an institution to some considerable extent by means of a questionnaire developed on the basis of the institution's MS. Our MSQ provides a reliable instrument to measure the learning climate with a strong focus on competencies which are increasingly considered crucial in medical education. The questionnaire thus offers additional information beyond the DREEM. Our site-specific results imply that our own faculty is not yet fully living up to its competency-based MS. In general, the MSQ might prove useful for faculty development to the increasing number of faculties seeking to measure their perceived competency orientation in a competency-based curriculum.


Olive (Olea europaea) leaf methanolic extract prevents HCl/ethanol-induced gastritis in rats by attenuating inflammation and augmenting antioxidant enzyme activities.
Gastritis is preponderantly characterized by inflammation of the lining epithelial layer and the chronic gastritis is considered as a pre-cancer lesion. For many centuries olive (Olea europaea) leaf has been used for its putative health potential, nonetheless, to date, the gastroprotective effects of olive leaves have not been studied yet. Hence, in this study we investigated whether olive leaf extract (OLE) could protect gastric mucosa against HCl/ethanol-induced gastric mucosal damage in rats. Hcl/ethanol administration caused significant damage to the gastric mucosa, as confirmed by gastric ulcer index and histological evaluation. However, this damage was largely prevented by pre-administering 20mg/kg omeprazole or 100mg/kg OLE. Interestingly, the damage was completely prevented by pre-administering 200 and 300mg/kg OLE. Moreover, OLE attenuated the inflammatory response by decreasing nuclear factor-κB (NF-κB), cycloxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expressions, and down-regulating inducible nitric oxide synthase (iNOS) and interleukin-1β (IL-1β) in gastric mucosa. The gastroprotective mechanism of OLE involved the promotion of enzymatic and nonenzymatic molecules (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione reduced form), promoting nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression, halting lipid peroxidation and preventing the overproduction of nitric oxide. Together, our findings clearly demonstrated that OLE could prevent HCl/ethanol-induced gastritis by attenuating inflammation and oxidant/antioxidant imbalance. Indeed, OLE could potentially be useful as a natural therapy for gastritis.


[Regeneration of the retina using pigment epithelial cell transplantation].
At has been reported that transplantation of appropriate cells, growth factors, and/or extracellular matrix may help the regeneration of damaged tissues or organs. Some growth factors, such as basic fibroblast growth factor(bFGF), have been successfully transferred to patients with ischemic heart disease. Embryonic dopamine neurons were also transplanted into the brains of patients with Parkinson's disease successfully. We have also performed cultured auto iris pigment epithelial cell (IPE) transplantation into the subretinal space after removal of choroidal neovascularization in patients with age-related macular degeneration (AMD). Here, we report the results of auto IPE transplantation in 35 patients, who could be followed for more than 6 months. We also tried to apply cell transplantation to other retinal diseases by managing the transplanted cells as introduced growth factor genes. Auto IPE transplantation was performed after removal of choroidal neovascular membranes (CNV). Visual acuity wes improved by more than 0.2 log MAR in 18 of 35 patients (51.5%), it was unchanged in 11 patients (31.5%), and it was worsened in 6 patients (17%). No significant difference was observed in comparison to patients who underwent CNV removal only. However, unlike the previous reports, we found no patients showing rejection. We also found that the cultured transplanted cells never showed proliferation under the retina or in the vitreous cavity and concluded that cultured auto IPE transplantation can be performed safely without complications. Next, we examined whether cell transplantation can be expanded to other degenerative retinal diseases. One of our results showed that host RPE may play an important role against the transplanted cells in the subretinal regions. When we introduced bFGF gene into the cells, we found synexpression cluster of the genes in the cells. One of the most prominent movements among the genes was lysyl oxidase like-1 gene, which plays an important role in the maturation of the extracellular collagen and in cell attachment. However, when we examined the cell attachment on the culture plates after 12 hours of culture, no significant difference was observed between the cells with or without bFGF. Further, when we examined the area of the cells transplanted into the subretinal space of rats during successive follow-up using fluorescein marker (EGFP), no statistical significance was observed. The gene expression pattern may be different when we introduce different growth factor gene. No antibody production was generated against the growth factor gene introduced cells after cell transplantation. Further, when we made transgenic mice expressing bFGF or Axokine cDNA in the RPE of rd mice, no photoreceptor degeneration was observed. One of the reasons was suspected to be that bFGF was expressed systemically by the promoter of tyrosinase related-protein 1 gene and may lead to lethality. Another reason was suspected to be suppression of the function of Axokine by the down-regulation of the ciliary neurotrophic factor or its receptor gene. Conversely, when we produced photoreceptor degeneration by constant light damage in the rats, we found partial photoreceptor rescue by transplantation of the growth factor gene introduced RPE. We show here the possibility that growth factor gene introduced cell transplantation may be applied to retinal diseases, if we select appropriate cells and genes.


Knowledge, attitude and practices regarding HIV/AIDS among adult fishermen in coastal areas of Karachi.
Migrant populations are at high risk of Human Immuno Deficiency Virus infection (HIV) and Acquired Immunodeficiency Syndrome (AIDS). Studies of HIV/AIDS knowledge, attitudes and practices among fishermen in developing countries have shown gaps in knowledge and fear of contagion with ambivalent attitudes towards HIV/AIDS and inconsistent universal precautions adherence. The aim of this study was to determine the knowledge, attitude and practices regarding HIV/AIDS among adult fishermen in a coastal area of Karachi, Pakistan. Community based cross sectional study was conducted among fishermen in coastal area of Karachi from June to September 2012. A total of 297 adult fishermen were selected by using simple random sampling technique from different sectors of coastal village. Data were collected using a structured validated questionnaire. The frequency distribution of both dependent and independent variables were worked out. Comparisons of knowledge, attitude and practices regarding HIV/AIDS by socio-demographic characteristics were made using logistic regression. Out of 297 fishermen, majority had in-appropriate knowledge (93.6%), negative attitude (75.8%) and less adherent sexual practices (91.6%). In univariate analysis, lower education and higher income were significantly associated (OR 2.25, 95% CI, 1.11, 4.55), (OR = 3.04 CI 1.03-9.02, p value 0.04) with negative attitude and un-safe practices towards HIV/AIDS respectively, whereas no significant association of socio-economic characteristics with knowledge, attitude and practices were observed in multivariate analysis. This study suggests that fishermen had very poor knowledge, negative attitudes towards HIV and AIDS and had unsafe sexual practices which suggest that they lack the basic understanding of HIV/AIDS infection. Extensive health education campaign should be provided to the vulnerable sections of the society for the control of HIV/AIDS.


Connecting and separating mind-sets: culture as situated cognition.
People perceive meaningful wholes and later separate out constituent parts (D. Navon, 1977). Yet there are cross-national differences in whether a focal target or integrated whole is first perceived. Rather than construe these differences as fixed, the proposed culture-as-situated-cognition model explains these differences as due to whether a collective or individual mind-set is cued at the moment of observation. Eight studies demonstrated that when cultural mind-set and task demands are congruent, easier tasks are accomplished more quickly and more difficult or time-constrained tasks are accomplished more accurately ( Koreans, Korean Americans; STUDY 2: Hong Kong Chinese; STUDY 3: European- and Asian-heritage Americans; STUDY 4: Americans; 5 Hong Kong Chinese; STUDY 6: Americans; STUDY 7: Norwegians; STUDY 8: African-, European-, and Asian-heritage Americans). Meta-analyses (d = .34) demonstrated homogeneous effects across geographic place (East-West), racial-ethnic group, task, and sensory mode-differences are cued in the moment. Contrast and separation are salient individual mind-set procedures, resulting in focus on a single target or main point. Assimilation and connection are salient collective mind-set procedures, resulting in focus on multiplicity and integration.


Quantitative PCR of bone marrow BCL2/IgH+ cells at diagnosis predicts treatment response and long-term outcome in follicular non-Hodgkin lymphoma.
By real-time quantitative polymerase chain reaction (RQ-PCR), we evaluated BCL2/IgH(+) cells in the bone marrow (BM) and peripheral blood (PB) from 86 patients with follicular lymphoma treated with the sequential administration of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and rituximab. At diagnosis, the amount of BCL2/IgH(+) cells in the BM was low (1 BCL2/IgH(+) cell in 1000-100 000 normal cells) in 43% of patients, intermediate (1 in 100-1000) in 34%, and high (> 1 in 100) in 23%. A 2 log decrease of BCL2/IgH(+) cells was achieved after CHOP and an additional 2 log reduction following rituximab. By multivariate analysis, a low level of BCL2/IgH(+) cells in the BM at diagnosis was the best predictor for the achievement of a complete clinical and molecular response. At 5 years, the event-free survival rates of patients with a low/intermediate or high tumor infiltration in the BM were 59% and 32%, respectively. The freedom from recurrence of patients who achieved a molecular response in the BM, no matter whether after CHOP alone or CHOP and rituximab, was 64% as compared to 32% for patients who did not (P < .006). RQ-PCR performed at presentation on BM samples predicts treatment response and long-term clinical outcome in patients with follicular lymphoma.


Donor and tissue profile of a community eye bank in Eastern India.
The purpose of this study is to analyze the donor and tissue profile of a community eye bank in Eastern India. Eye bank records were analyzed for the period July 2007-June 2011. Variables analyzed included donor demographics (age, gender, and ethnicity), donor cause of death, consent for recovery, death-to-preservation interval, preservation-to-utilization interval, endothelial cell density (ECD), corneal suitability for transplantation, and corneal tissue utilization. During this study period, 743 corneal tissues were retrieved from 373 donors (male:female = 263:110). The mean age of donors was 52 ± 21 years (range: 3-95 years). The most common donor age group was 41-50 and 71-80 years. Most of the donors belonged to one religious faith (99%). The most common causes of death were cardiorespiratory failure (34%) followed by road traffic accident (30%). Majority donors were motivated (n = 320; 86%), and remaining (n = 53; 14%) were voluntary. Most of the consents were given by sons or daughters of the deceased (45%) followed by siblings (18%). Mean death-to-preservation interval was 3.9 ± 1.9 h. Mean preservation-to-utilization interval was 56.0 ± 24.4 h. The mean ECD of donor corneal tissue was 2857 ± 551 cells/mm 2 and the median value was 2898 cells/mm 2 . Of harvested corneas 556 (75%) corneal tissues were utilized. The most common causes of nonutilization were septicemia in donor (n = 56; 30%) and poor quality of tissue (n = 55; 30%). Although, there is significant corneal tissue utilization, there is a need for increased awareness among people in order to augment voluntary donations.


Quantitative proteomic analysis by iTRAQ(R) for the identification of candidate biomarkers in ovarian cancer serum.
Ovarian cancer is the most lethal gynecologic malignancy, with the majority of cases diagnosed at an advanced stage when treatments are less successful. Novel serum protein markers are needed to detect ovarian cancer in its earliest stage; when detected early, survival rates are over 90%. The identification of new serum biomarkers is hindered by the presence of a small number of highly abundant proteins that comprise approximately 95% of serum total protein. In this study, we used pooled serum depleted of the most highly abundant proteins to reduce the dynamic range of proteins, and thereby enhance the identification of serum biomarkers using the quantitative proteomic method iTRAQ(R). Medium and low abundance proteins from 6 serum pools of 10 patients each from women with serous ovarian carcinoma, and 6 non-cancer control pools were labeled with isobaric tags using iTRAQ(R) to determine the relative abundance of serum proteins identified by MS. A total of 220 unique proteins were identified and fourteen proteins were elevated in ovarian cancer compared to control serum pools, including several novel candidate ovarian cancer biomarkers: extracellular matrix protein-1, leucine-rich alpha-2 glycoprotein-1, lipopolysaccharide binding protein-1, and proteoglycan-4. Western immunoblotting validated the relative increases in serum protein levels for several of the proteins identified. This study provides the first analysis of immunodepleted serum in combination with iTRAQ(R) to measure relative protein expression in ovarian cancer patients for the pursuit of serum biomarkers. Several candidate biomarkers were identified which warrant further development.


Electronic individual identification of zebrafish using radio frequency identification (RFID) microtags.
Although individual electronic tagging using passive integrated acoustic (PIT) tags is established, it is mainly for fish >60 mm in length and is unsuitable for fish of <30 mm, like zebrafish. We used radio frequency identification (RFID) microtags (1 mm in diameter and 6 mm in length, with a mass of ~10 mg) to individually identify juvenile zebrafish (length 16-42 mm, mass 138-776 mg) for the first time, and studied the effects of intracoelomic implantation on fish survival and microtag loss, growth, spawning and exploratory behaviour. After 5.5 months, both high survival (82%) and low microtag loss (11%) were achieved. The smallest surviving fish weighed 178 mg, and success in microtag reading was 73% for the size class 350-450 mg (26 mm). Greater success was achieved when fish were larger at the time of tagging but no negative effects on growth were observed for any size class and some tagged fish spawned. No significant differences in behavioural responses could be detected between tagged fish and untagged controls after 2 months. Overall, the results suggest that the tagging method is highly suitable for fish as small as zebrafish juveniles. We think this method will provide significant advances for researchers of the ever-growing fish model community and more generally for all small-fish users. Tagging is essential when one needs to identify fish (e.g. particular genotypes with no external cue), to run longitudinal monitoring of individual biological traits (e.g. growth) or to repeat assays with the same individual at discrete points in time (e.g. behaviour studies). Such a method will find applications in physiology, genetics, behaviour and (eco)toxicology fields.


Rapid serodiagnosis of leptospirosis using the IgM-specific Dot-ELISA: comparison with the microscopic agglutination test.
The dot enzyme-linked immunosorbent assay (Dot-ELISA) was compared to the microscopic agglutination test (MA test) for the diagnosis of human leptospirosis. Of 177 sera from 68 soldiers who trained in the Republic of Panama, 102 sera were positive in the MA test and 93 of these sera were positive in the IgM-specific Dot-ELISA. Incidence of infection was 50 of 68 patients with the MA test and 48 of 68 in the IgM Dot-ELISA. Five MA test-positive sera were reactive only in the IgG-specific Dot-ELISA, suggesting previous exposure. All 21 infecting serovars of Leptospira interrogans, as determined by positive reactions in the MA test or culture of blood and urine specimens, were reactive in the Dot-ELISA. Of 75 sera negative in the MA test, 61 were nonreactive in the Dot-ELISA. However, 9 of these 14 Dot-ELISA-positive/MA test-negative sera were acute samples from patients whose later sera were MA test-positive. Positive reactions in the IgM Dot-ELISA occurred in 2 of 30 control, 4 of 10 Lyme disease, 1 of 11 relapsing fever, and 1 of 8 yaws sera; 10 syphilis patient sera were nonreactive. The IgM-specific Dot-ELISA appears to be sensitive and specific for the serodiagnosis of acute leptospirosis. In addition, this rapid test is inexpensive, simple to perform, utilizes minute volumes of killed leptospiral antigen and is easily adaptable to field use.


Analysis of the Microbiome in the Adenoids of Korean Children with Otitis Media with Effusion.
The adenoid pad, which is located between the orifice of the Eustachian tube (ET) and posterior nasal cavity, can affect the development of otitis media with effusion (OME) because of its anatomical location. The aim of the present study was to evaluate adenoid microbial colonization through 16S ribosomal RNA (rRNA) pyrosequencing, an advanced molecular technique, and to document the relationship with OME. Adenoid samples were collected using sterile cotton from 32 children during ventilation tube insertion. Sixteen children with OME who underwent tonsillectomy and adenoidectomy due to obstructive symptoms were assigned to the OME group and sixteen children without OME were assigned to the control group. We performed a 16S rRNA-based culture-independent survey of bacterial communities using the MiSeq platform. The diversity index, mean operational taxonomic units, and Shannon index were lower in the OME group than those in the control group. A taxonomic analysis showed differences in microbiota distribution between the OME and control groups at the phylum, genus, and species levels. The analysis, which was based on weighted UniFrac distances, revealed differences in microbial composition between the two groups. Bacterial community analysis using 16S rRNA pyrosequencing allows us to understand the relationship between the microbial communities of adenoids and the development of OME better.


Evolutionary Processes Driving the Rise and Fall of Staphylococcus aureus ST239, a Dominant Hybrid Pathogen.
Selection plays a key role in the spread of antibiotic resistance, but the evolutionary drivers of clinically important resistant strains remain poorly understood. Here, we use genomic analyses and competition experiments to study Staphylococcus aureus ST239, a prominent MRSA strain that is thought to have been formed by large-scale recombination between ST8 and ST30. Genomic analyses allowed us to refine the hybrid model for the origin of ST239 and to date the origin of ST239 to 1920 to 1945, which predates the clinical introduction of methicillin in 1959. Although purifying selection has dominated the evolution of ST239, parallel evolution has occurred in genes involved in antibiotic resistance and virulence, suggesting that ST239 has evolved toward an increasingly pathogenic lifestyle. Crucially, ST239 isolates have low competitive fitness relative to both ST8 and ST30 isolates, supporting the idea that fitness costs have driven the demise of this once-dominant pathogen strain. IMPORTANCE The rise of antibiotic resistance in most pathogenic bacteria has been driven by the spread of a small number of epidemically successful resistant strains. However, the processes that drive the rise and fall of these "superbugs" remain poorly understood. In our study, we investigated Staphylococcus aureus ST239, an important MRSA strain that has been a leading cause of serious hospital-acquired infections. We show here that ST239 was formed by the exchange of a very large fragment of DNA carrying resistance genes between strains of S. aureus sometime before 1945. The introduction of the antibiotic methicillin in 1959 provided a key advantage for Methicillin-Resistant Staphylococcus aureus (MRSA) strains. Interestingly, we found that ST239 has low competitive ability compared to other strains of S. aureus, and this evolutionary hindrance may explain why the prevalence of ST239 has declined precipitously at a global scale.


Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children.
Owing to insufficient evidence in children, target plasma concentrations of efavirenz are based on studies in adults. Our analysis aimed to evaluate the pediatric therapeutic thresholds and characterize the determinants of virological suppression in African children. We analyzed data from 128 African children (aged 1.7-13.5 years) treated with efavirenz, lamivudine, and one among abacavir, stavudine, or zidovudine, and followed up to 36 months. Individual pharmacokinetic (PK) measures [plasma concentration 12 hours after dose (C12h), plasma concentration 24 hours after dose (C24h), and area under the curve (AUC0-24)] were estimated using population PK modeling. Cox multiple failure regression and multivariable fractional polynomials were used to investigate the risks of unsuppressed viral load associated with efavirenz exposure and other factors among 106 initially treatment-naive children, and likelihood profiling was used to identify the most predictive PK thresholds. The risk of viral load >100 copies per milliliter decreased by 42% for every 2-fold increase in efavirenz mid-dose concentration [95% confidence interval (CI): 23% to 57%; P < 0.001]. The most predictive PK thresholds for increased risk of unsuppressed viral load were C12h 1.12 mg/L [hazard ratio (HR): 6.14; 95% CI: 2.64 to 14.27], C24h 0.65 mg/L (HR: 6.57; 95% CI: 2.86 to 15.10), and AUC0-24 28 mg·h/L (HR: 5.77; 95% CI: 2.28 to 14.58). Children older than 8 years had a more than 10-fold increased risk of virological nonsuppression (P = 0.005); among children younger than 8 years, boys had a 5.31 times higher risk than girls (P = 0.007). Central nervous system adverse events were infrequently reported. Our analysis suggests that the minimum target C24h and AUC0-24 could be lowered in children. Our findings should be confirmed in a prospective pediatric trial.


Vegetable Diversity, Injurious Falls, and Fracture Risk in Older Women: A Prospective Cohort Study.
The importance of vegetable diversity for the risk of falling and fractures is unclear. Our objective was to examine the relationship between vegetable diversity with injurious falling and fractures leading to hospitalization in a prospective cohort of older Australian women (n = 1429, ≥70 years). Vegetable diversity was quantified by assessing the number of different vegetables consumed daily. Vegetable intake (75 g servings/day) was estimated using a validated food frequency questionnaire at baseline (1998). Over 14.5 years, injurious falls (events = 568, 39.7%), and fractures (events = 404, 28.3%) were captured using linked health records. In multivariable-adjusted Cox regression models, women with greater vegetable diversity (per increase in one different vegetable/day) had lower relative hazards for falls (8%; p = 0.02) and fractures (9%; p = 0.03). A significant interaction between daily vegetable diversity (number/day) and total vegetable intake (75 g servings/day) was observed for falls (pinteraction = 0.03) and fractures (pinteraction < 0.001). The largest benefit of higher vegetable diversity were observed in the one third of women with the lowest vegetable intake (<2.2 servings/day; falls HR 0.83 95% CI (0.71⁻0.98); fractures HR 0.74 95% CI (0.62⁻0.89)). Increasing vegetable diversity especially in older women with low vegetable intake may be an effective way to reduce injurious fall and fracture risk.


A Neptune-sized transiting planet closely orbiting a 5–10-million-year-old star.
Theories of the formation and early evolution of planetary systems postulate that planets are born in circumstellar disks, and undergo radial migration during and after dissipation of the dust and gas disk from which they formed. The precise ages of meteorites indicate that planetesimals—the building blocks of planets—are produced within the first million years of a star's life. Fully formed planets are frequently detected on short orbital periods around mature stars. Some theories suggest that the in situ formation of planets close to their host stars is unlikely and that the existence of such planets is therefore evidence of large-scale migration. Other theories posit that planet assembly at small orbital separations may be common. Here we report a newly born, transiting planet orbiting its star with a period of 5.4 days. The planet is 50 per cent larger than Neptune, and its mass is less than 3.6 times that of Jupiter (at 99.7 per cent confidence), with a true mass likely to be similar to that of Neptune. The star is 5–10 million years old and has a tenuous dust disk extending outward from about twice the Earth–Sun separation, in addition to the fully formed planet located at less than one-twentieth of the Earth–Sun separation.


DINeR: Database for Insect Neuropeptide Research.
Neuropeptides are responsible for regulating a variety of functions, including development, metabolism, water and ion homeostasis, and as neuromodulators in circuits of the central nervous system. Numerous neuropeptides have been identified and characterized. However, both discovery and functional characterization of neuropeptides across the massive Class Insecta has been sporadic. To leverage advances in post-genomic technologies for this rapidly growing field, insect neuroendocrinology requires a consolidated, comprehensive and standardised resource for managing neuropeptide information. The Database for Insect Neuropeptide Research (DINeR) is a web-based database-application used for search and retrieval of neuropeptide information of various insect species detailing their isoform sequences, physiological functionality and images of their receptor-binding sites, in an intuitive, accessible and user-friendly format. The curated data includes representatives of 50 well described neuropeptide families from over 400 different insect species. Approximately 4700 FASTA formatted, neuropeptide isoform amino acid sequences and over 200 records of physiological functionality have been recorded based on published literature. Also available are images of neuropeptide receptor locations. In addition, the data include comprehensive summaries for each neuropeptide family, including their function, location, known functionality, as well as cladograms, sequence alignments and logos covering most insect orders. Moreover, we have adopted a standardised nomenclature to address inconsistent classification of neuropeptides. As part of the H2020 nEUROSTRESSPEP project, the data will be actively maintained and curated, ensuring a comprehensive and standardised resource for the scientific community. DINeR is publicly available at the project website: http://www.neurostresspep.eu/diner/.


Depolarization of nuclear spin polarized 129Xe gas by dark rubidium during spin-exchange optical pumping.
Continuous-flow spin-exchange optical pumping (SEOP) continues to serve as the most widespread method of polarizing 129Xe for magnetic resonance experiments. Unfortunately, continuous-flow SEOP still suffers from as-yet unidentified inefficiencies that prevent the production of large volumes of xenon with a nuclear spin polarization close to theoretically calculated values. In this work we use a combination of ultra-low field nuclear magnetic resonance spectroscopy and atomic absorption spectroscopy (AAS) measurements to study the effects of dark Rb vapor on hyperpolarized 129Xe in situ during continuous-flow SEOP. We find that dark Rb vapor in the optical cell outlet has negligible impact on the final 129Xe polarization at typical experimental conditions, but can become significant at higher oven temperatures and lower flow rates. Additionally, in the AAS spectra we also look for a signature of paramagnetic Rb clusters, previously identified as a source of xenon depolarization and a cause for SEOP inefficiency, for which we are able to set an upper limit of 8.3×1015 Rb dimers per cm3.


On benchmark problems, challenges, and competitions in electrokinetics-A review.
In this critical review, we comment on the absence of widely shared benchmark problems and relevant challenges or even attractive competitions in the field of electrokinetics. We argue that in some other scientific domains that are, similarly as electrokinetics, strongly multidisciplinary, the existence of these tools is very beneficial because it stimulates the discussion about what constitutes the bottleneck of further progress, allows easier exploitation of results provided by other scientific and engineering disciplines, and, last but not least, makes the research domain attractive and visible to a broader public, including students. The goal of this review is to provoke some discussion that might perhaps lead to compensating for these shortcomings.


Fringe-orientation maps and fringe skeleton extraction by the two-dimensional derivative-sign binary-fringe method.
The fringe-orientation information of an interferometric fringe pattern is provided in the form of a fringe-orientation map by spin filtering. The fringe-orientation information is an important feature of fringe patterns and is helpful in many fringe-pattern processing algorithms. With the help of a fringe-orientation map the two-dimensional derivative-sign binary-fringe method is developed to extract fringe skeletons from a fringe pattern with an arbitrary fringe distribution. This fringe skeleton extraction method does not require thresholds and a thinning process. It is relatively robust and highly accurate.


A meta-analytic review of relationship-based interventions for low-income families with infants and toddlers: facilitating supportive parent-child interactions.
Relationship-based intervention programs are increasingly being implemented as a way to enhance parent-child interaction quality. In this meta-analytic review, we examined the effectiveness of 19 recent relationship-based interventions serving socioeconomically disadvantaged families with infants and toddlers (N = 6,807). This review specifically focused on intervention effectiveness in terms of improving supportive parenting behaviors, as measured by observational assessments of dyadic parent-child interactions. Meta-analytic results indicated significant, yet modest, effectiveness across all interventions (d = .23). Intervention characteristics such as participant randomization, breadth of intervention services offered, duration, child age at the start of the intervention, professional qualifications of the intervenor, and type of play task used during assessment were tested as possible moderators of effectiveness. Significant differences in effectiveness were found between randomized and nonrandomized interventions. Within the subsample of randomized interventions, programs that were shorter in duration, that provided direct services to the parent-child dyad, used intervenors with professional qualifications, and assessed parent-child interactions with free-play tasks were the most effective, highlighting important considerations for designing effective intervention protocol tailored to the needs of this high-risk population.


Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial.
The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of non- invasive ventilation, treatment in the intensive care unit and death. This is a multi-centre, randomised, Placebo-controlled, 2-arm ratio 1:1, parallel group double-blind study. 226 participants are recruited at the trial sites/hospitals, where the study will take place in Denmark: Aalborg, Bispebjerg, Gentofte, Herlev, Hillerød, Hvidovre, Odense and Slagelse hospitals. • Patient admitted to Danish emergency departments, respiratory medicine departments or internal medicine departments • Age≥ 18 years • Hospitalized ≤48 hours • Positive COVID-19 test / diagnosis during the hospitalization (confirmed). • Men or non-fertile women. Fertile women* must not be pregnant, i.e. negative pregnancy test must be available at inclusion • Informed consent signed by the patient *Defined as after menarche and until postmenopausal (no menstruation for 12 months) Exclusion criteria: • At the time of recruitment, the patient uses >5 LO2/min (equivalent to 40% FiO2 if measured) • Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinoline derivatives • Neurogenic hearing loss • Psoriasis • Retinopathy • Maculopathy • Visual field changes • Breastfeeding • Severe liver diseases other than amoebiasis (INR> 1.5 spontaneously) • Severe gastrointestinal, neurological and hematological disorders (investigator-assessed) • eGFR <45 ml/min/1.73 m2 • Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) of> 480/470 ms). • Myasthenia gravis • Treatment with digoxin* • Glucose-6-phosphate dehydrogenase deficiency • Porphyria • Hypoglycaemia (Blood glucose at any time since hospitalization of <3.0 mmol/L) • Severe mental illness which significantly impedes cooperation • Severe linguistic problems that significantly hinder cooperation • Treatment with ergot alkaloids *The patient must not be treated with digoxin for the duration of the intervention. For atrial fibrillation/flutter, select according to the Cardiovascular National Treatment Guide (NBV): Calcium antagonist, Beta blocker, direct current (DC) conversion or amiodarone. In case of urgent need for digoxin treatment (contraindication for the aforementioned equal alternatives), the test drug should be paused, and ECG should be taken daily. Control group: The control group will receive the standard treatment + placebo for both types of intervention medication at all times. If part or all the intervention therapy being investigated becomes standard treatment during the study, this may also be offered to the control group. Intervention group: The patients in the intervention group will also receive standard care. Immediately after randomisation to the intervention group, the patient will begin treatment with: Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 If the patient is unable to take the medication orally by themselves, the medication will, if possible, be administered by either stomach-feeding tube, or alternatively, temporary be changed to clarithromycin 500 mg x 2 (this only in agreement with either study coordinator Pradeesh Sivapalan or principal investigator Jens-Ulrik Stæhr Jensen). This will also be done in the control group if necessary. The patient will switch back to azithromycin when possible. Hydroxychloroquine: Furthermore, the patient will be treated with hydroxychloroquine as follows: Day 1-15: 200 mg x 2 MAIN OUTCOMES: • Number of days alive and discharged from hospital within 14 days (summarises both whether the patient is alive and discharged from hospital) ("Days alive and out of hospital") RANDOMISATION: The sponsor (Chronic Obstructive Pulmonary Disease Trial Network, COP:TRIN) generates a randomisation sequence. Randomisation will be in blocks of unknown size and the final allocation will be via an encrypted website (REDCap). There will be stratification for age (>70 years vs. <=70 years), site of recruitment and whether the patient has any of the following chronic lung diseases: COPD, asthma, bronchiectasis, interstitial lung disease (Yes vs. No). Participants and study personnel will both be blinded, i.e. neither will know which group the participant is allocated to. This study requires 226 patients randomised 1:1 with 113 in each group. Protocol version 1.8, from April 16, 2020. Recruitment is ongoing (first patient recruited April 6, 2020; final patient expected to be recruited October 31, 2020). ClinicalTrials.gov Identifier: NCT04322396 (registered March 26, 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Anticoccidial activity of the methanolic extract of Musa paradisiaca root in chickens.
The study was designed to evaluate the anticoccidial activity of the methanolic extract of Musa paradisiaca root in chickens. The chickens were divided into six groups of 12 chickens each. Each chicken in five groups was infected with 8,000 infective coccidia (Eimeria tenella) oocysts at day 28 of age while one group served as uninfected control. At day 7 post-infection, two chickens remaining in each group were sacrificed for postmortem examination to confirm coccidiosis. Also at day 7 post-infection, each chicken in four infected groups was given graded doses (250, 500 and 1,000 mg/kg b.w.) of the extract or amprolium (conventional drug). Two groups (an infected and uninfected group) did not receive treatment. Parameters used to assess progress of infection and response to treatment included clinical signs typical of coccidiosis, oocyst count per gramme of faeces (OPG) and packed cell volume (PCV). Treatment of previously infected chickens with M. paradisiaca root extract resulted in a progressive decrease in severity of observed clinical signs, marked reductions in OPG and a gradual increase in PCV. In each case, the changes were dose dependent. There was no significant difference in mean OPG and mean PCV of the extract (at 1,000 mg/kg b.w.) and amprolium-treated groups at termination of the study (at day 50 of age). In the acute toxicity study, the extract was found to be non-toxic to the chickens even at the highest dose of 4,000 mg/kg b.w. The results of this study demonstrated that the extract has anticoccidial activity in a dose-dependent manner and at a dosage of 1,000 mg/kg b.w. had similar efficacy with amprolium in the treatment of chicken coccidiosis.


Domestication reduces alternative splicing expression variations in sorghum.
Domestication is known to strongly reduce genomic diversity through population bottlenecks. The resulting loss of polymorphism has been thoroughly documented in numerous cultivated species. Here we investigate the impact of domestication on the diversity of alternative transcript expressions using RNAseq data obtained on cultivated and wild sorghum accessions (ten accessions for each pool). In that aim, we focus on genes expressing two isoforms in sorghum and estimate the ratio between expression levels of those isoforms in each accession. Noticeably, for a given gene, one isoform can either be overexpressed or underexpressed in some wild accessions, whereas in the cultivated accessions, the balance between the two isoforms of the same gene appears to be much more homogenous. Indeed, we observe in sorghum significantly more variation in isoform expression balance among wild accessions than among domesticated accessions. The possibility exists that the loss of nucleotide diversity due to domestication could affect regulatory elements, controlling transcription or degradation of these isoforms. Impact on the isoform expression balance is discussed. As far as we know, this is the first time that the impact of domestication on transcript isoform balance has been studied at the genomic scale. This could pave the way towards the identification of key domestication genes with finely tuned isoform expressions in domesticated accessions while being highly variable in their wild relatives.


Change in serum proteome during allogeneic hematopoietic stem cell transplantation and clinical significance of serum C-reactive protein and haptoglobin.
Successful hematopoietic stem cell transplantation (HSCT) involves the restoration of hematopoietic function after engraftment, arising from the differentiation and proliferation of hematopoietic stem cells. Several factors could influence the course of allogeneic-HSCT (allo-HSCT). Therefore, knowledge of serum proteome changes during the allo-HSCT period might increase the efficacy of diagnosis and disease prevention efforts. This study conducted proteomic analyses to find proteins that were significantly altered in response to allo-HSCT. Sera from five representative patients who underwent allo-HSCT were analyzed by 2-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry, and were measured on a weekly basis before and after allo-HSCT in additional 78 patients. Fourteen protein spots showing changes in expression were further examined, and most proteins were identified as acute phase proteins (APPs). Studies of 78 additional patients confirmed that C-reactive protein (CRP) and haptoglobin undergo expression changes during allo-HSCT and thus may have the potential to serve as representative markers of clinical events after allo-HSCT. Maximal CRP level affected the development of major transplant-related complications (MTCs) and other problems such as fever of unknown origin. Particularly, an increase in CRP level 21 days after allo-HSCT was found to be an independent risk factor for MTC. Maximal haptoglobin and haptoglobin level 14 days after allo-HSCT were predictive of relapses in underlying hematologic disease. Our results indicated that CRP and haptoglobin were significantly expressed during allo-HSCT, and suggest that their level can be monitored after allo-HSCT to assess the risks of early transplant-related complications and relapse.


Training laypersons and hospital personnel in basic resuscitation techniques: an approach to impact the global trauma burden in Mozambique.
Over half of prehospital deaths in low-income countries are the result of airway compromise, respiratory failure, or uncontrolled hemorrhage; all three conditions can be addressed using simple first-aid measures. For both hospital personnel and laypersons, a basic trauma resuscitation training in modified ABCD (airway, breathing, circulation, disability) techniques can be easily learned and applied to increase the number of first responders in Mozambique, a resource-challenged country. A trauma training session was administered to 100 people in Mozambique: half were hospital personnel from 7 district medical centers and the other half were selected laypersons. This session included a pre-test, intervention, and post-test to evaluate and demonstrate first response skills. Eighty-eight people completed both the pre- and post-tests. Following the education intervention, both groups demonstrated an improvement in test scores. Hospital personnel had a mean post-test score of 60% (SD = 17, N = 43) and community laypeople had a mean score of 51% (SD = 16, N = 45). A t test for equal variances demonstrated significant difference between the post-intervention scores for the two groups (p = 0.01). All 100 participants were able to open an airway, externally control hemorrhage, and transport a patient with appropriate precautions. The trauma training session served as new information that improved knowledge as well as skills for both groups, and increased the number of capable responders in Mozambique. This study supports WHO recommendations to utilize the strengths of a developing nation-population-as the first step in establishing an organized trauma triage system.


Parental separation in childhood as a risk factor for depression in adulthood: a community-based study of adolescents screened for depression and followed up after 15 years.
Earlier research has investigated the association between parental separation and long-term health outcomes among offspring, but few studies have assessed the potentially moderating role of mental health status in adolescence. The aim of this study was to analyze whether parental separation in childhood predicts depression in adulthood and whether the pattern differs between individuals with and without earlier depression. A community-based sample of individuals with adolescent depression in 1991-93 and matched non-depressed peers were followed up using a structured diagnostic interview after 15 years. The participation rate was 65% (depressed n = 227; non-depressed controls n = 155). Information on parental separation and conditions in childhood and adolescence was collected at baseline. The outcome was depression between the ages 19-31 years; information on depression was collected at the follow-up diagnostic interview. The statistical method used was binary logistic regression. Our analyses showed that depressed adolescents with separated parents had an excess risk of recurrence of depression in adulthood, compared with depressed adolescents with non-separated parents. In addition, among adolescents with depression, parental separation was associated with an increased risk of a switch to bipolar disorder in adulthood. Among the matched non-depressed peers, no associations between parental separation and adult depression or bipolar disorder were found. Parental separation may have long-lasting health consequences for vulnerable individuals who suffer from mental illness already in adolescence.


Can serum NGAL levels be used as an inflammation marker on hemodialysis patients with permanent catheter?
Neutrophil gelatinase-associated lipocalin (NGAL) is a member of lipocalin family and released from many tissues and cells. We aimed to investigate the relationship among serum NGAL levels, the inflammation markers (IL-6, hs-CRP, TNF-α) and different vascular access types used in dialysis patients. The study population included 90 patients and 30 healthy age-matched controls. The patients were divided into three groups (I, II, III) and group IV included the controls. In group I and II, the patients were with central venous permanent catheter and arterio-venous fistula, respectively. Group III included 30 patients with chronic renal failure. Hemogram, biochemical assays, ferritin, IL-6, hs-CRP, TNF-α, and NGAL were evaluated in all groups. Serum NGAL levels were markedly higher in group I than in group II (7645.80 ± 924.61 vs. 4131.20 ± 609.87 pg/mL; p < 0.05). Positive correlation was detected between NGAL levels and duration of catheter (r: 0.903, p: 0.000), hs-CRP (r: 0.796, p: 0.000), IL-6 (r: 0.687, p: 0.000), TNF-α (r: 0.568, p: 0.000) levels and ferritin (r: 0.318, p: 0.001), whereas NGAL levels were negatively correlated with serum albumin levels (r: -0.494, p: 0.000). In multiple regression analysis, duration of catheter hs-CRP and TNF-α were predictors of NGAL in hemodialysis patients. Inflammation was observed in hemodialysis patients and increases with catheter. Our findings show that a strong relationship among serum NGAL levels, duration of catheter, hs-CRP and TNF-α. NGAL may be used as a new inflammation marker in hemodialysis patients.


Quantitative assessment of angiogenesis and osteogenesis after transplantation of bone: comparison of isograft and allograft bone in mice.
We performed a vital microscopic study in mice bearing dorsal skinfold chambers to characterize microvascular perfusion and leukocyte/endothelium interaction and their effects on elongation and mineralization of neonatal isograft and allograft bone. Isograft (C57/BL to C57/BL) and allograft bone (C57/ BL to BALB/C) revascularized simultaneously. However, vascular perfusion and density were lower in allograft bone than in isograft bone. Leukocyte/endothelium interaction was the same in isograft and allograft bones. Revascularization was not detected in allograft bone transplanted to presensitized recipients. Moreover, in preexisting vessels at the transplantation site, leukocyte/endothelium interaction was altered in allograft bone of presensitized recipients, despite a normal systemic leukocyte count. Femoral growth resulting from thickening of both epiphyses did not differ between experimental groups, however, mineralization occurred in isograft bone only. Isograft bone was histologically intact, allograft bone hypovital and allograft bone in presensitized recipients necrotic 12 days after implantation. Our findings suggest that graft incorporation or rejection is mediated by the microvasculature and that presensitizing of recipients accelerates rejection of allograft bone.


A Strain-Based Method to Estimate Tire Parameters for Intelligent Tires under Complex Maneuvering Operations.
The possibility of using tires as active sensors opens the door to a huge number of different ways to accomplish this goal. In this case, based on a tire equipped with strain sensors, also known as an Intelligent Tire, relevant vehicle dynamics information can be provided. The purpose of this research is to improve the strain-based methodology for Intelligent Tires to estimate all tire forces, based only on deformations measured in the contact patch. Firstly, through an indoor test rig data, an algorithm has been developed to pick out the relevant features of strain data and correlate them with tire parameters. This information of the tire contact patch is then transmitted to a fuzzy logic system to estimate the tire parameters. To evaluate the reliability of the proposed estimator, the well-known simulation software CarSim has been used to back up the estimation results. The software CarSim has been used to provide the vehicle parameters in complex maneuvers. Finally, the estimations have been checked with the simulation results. This approach has enabled the behaviour of the intelligent tire to be tested for different maneuvers and velocities, providing key information about the tire parameters directly from the only contact that exists between the vehicle and the road.


Lessons learned from 12 years of teaching second-degree BSN students.
Second-degree BSN-accelerated nursing programs are no longer considered new or rare, with many schools of nursing having programs that have been in place for over a decade. Auburn University is one such school. The focus and motivation of these students make teaching them challenging and rewarding. The authors describe lessons learned including how to promote socialization of accelerated nursing-degree students and use faculty resources efficiently.


Phylogenetic diversity and genotypical complexity of H9N2 influenza A viruses revealed by genomic sequence analysis.
H9N2 influenza A viruses have become established worldwide in terrestrial poultry and wild birds, and are occasionally transmitted to mammals including humans and pigs. To comprehensively elucidate the genetic and evolutionary characteristics of H9N2 influenza viruses, we performed a large-scale sequence analysis of 571 viral genomes from the NCBI Influenza Virus Resource Database, representing the spectrum of H9N2 influenza viruses isolated from 1966 to 2009. Our study provides a panoramic framework for better understanding the genesis and evolution of H9N2 influenza viruses, and for describing the history of H9N2 viruses circulating in diverse hosts. Panorama phylogenetic analysis of the eight viral gene segments revealed the complexity and diversity of H9N2 influenza viruses. The 571 H9N2 viral genomes were classified into 74 separate lineages, which had marked host and geographical differences in phylogeny. Panorama genotypical analysis also revealed that H9N2 viruses include at least 98 genotypes, which were further divided according to their HA lineages into seven series (A-G). Phylogenetic analysis of the internal genes showed that H9N2 viruses are closely related to H3, H4, H5, H7, H10, and H14 subtype influenza viruses. Our results indicate that H9N2 viruses have undergone extensive reassortments to generate multiple reassortants and genotypes, suggesting that the continued circulation of multiple genotypical H9N2 viruses throughout the world in diverse hosts has the potential to cause future influenza outbreaks in poultry and epidemics in humans. We propose a nomenclature system for identifying and unifying all lineages and genotypes of H9N2 influenza viruses in order to facilitate international communication on the evolution, ecology and epidemiology of H9N2 influenza viruses.


360 degrees prophylactic cryoretinopexy. A clinical and experimental study.
Complications occurred after 360 degrees prophylactic cryoretinopexy in three of six eyes in which fellow eyes had previously developed aphakic retinal detachment. Two of the six prophylactically treated eyes developed retinal detachment in advance of anticipated cataract surgery, and a third developed vitreitis and progressive preretinal membrane formation after uncomplicated cataract extraction. In an experiment study with rhesus monkeys, preretinal membrane formation was produced by administering heavy freezes with 360 degrees cryoretinopexy. Although the quantities of cold were considered excessive for clinical use, the cryoretinopexy used clinically in this series must also be considered excessive. The use of 360 degrees cryoretinopexy in the management of eyes at high risk for retinal detachment must be considered judiciously. Particular caution must be exercised in administering cryoretinopexy to nondetached retinas so as to avoid heavy freezes, which destroy the linear retinal layers.


The application of CE-MS in the trace analysis of environmental pollutants and food contaminants.
In this review, selected applications of CE-MS in recent years have been highlighted for the separation, detection and determination of environmental pollutants and food contaminants in selected samples. Trace analysis by CE-MS of analytes such as low molecular mass amines, nitroaromatics, alkylphosphonic acids, azo dyes, antidepressants, and antibiotic drugs, among others, in air, sediment and water samples have been reviewed. The CE-MS analysis of pesticides such as triazolopyrimidine sulphoanilides, different types of antibiotics (sulphonamides, beta-lactones, quinolones and tetracyclines) and other exogenous compounds such as acrylamide and toxic oligopeptides in food samples has also been reviewed. The review gives details on the fragmentations, where available, that the ionic species exhibit in-source and in ion trap, triple quadrupole and ToF MS analysers. A critical evaluation is also given of these recent CE-MS analytical methods for the separation, detection and determination of trace levels of such pollutants and contaminants with analytical information on the treatment of the samples, CE separation conditions, linearity ranges, LODs and recoveries from the different matrices presented.