Interleukin-1 augments gamma-aminobutyric acidA receptor function in brain.
Interleukin-1 (IL-1), a cytokine involved in the acute phase reaction to injury and infection, has multiple effects in the central nervous system, including induction of fever and sleep and the release of several neuropeptides. We evaluated effects of IL-1 beta on inhibitory postsynaptic function at the gamma-aminobutyric acidA (GABAA) receptor. IL-1 (100 pg/ml to 10 ng/ml) augmented GABAA receptor function in cortical synaptic preparations. This effect of IL-1 was largely prevented by incubation with a specific IL-1 receptor antagonist. The related cytokines interleukin-6 and tumor necrosis factor did not augment GABA-dependent chloride transport. Similar enhancement of GABAA receptor function was observed in tissue prepared from mice previously injected intraperitoneally with IL-1 (1 microgram). Electrophysiological studies in cultured primary cortical neurons demonstrated that IL-1 enhanced the GABA-mediated increase in chloride permeability, whereas IL-1 alone produced no alterations in resting conductance. Behavioral studies indicated that IL-1 is similarly active in vivo; mice treated with IL-1 showed a decrease in open-field activity and an increase in the threshold for pentylenetetrazol-induced seizures. The interaction of IL-1 with GABAA receptors might account for the somnogenic and motor-depressant effects of this cytokine.


Absence of cooling in New Zealand and the adjacent ocean during the Younger Dryas chronozone.
As the climate warmed at the end of the last glacial period, a rapid reversal in temperature, the Younger Dryas (YD) event, briefly returned much of the North Atlantic region to near full-glacial conditions. The event was associated with climate reversals in many other areas of the Northern Hemisphere and also with warming over and near Antarctica. However, the expression of the YD in the mid- to low latitudes of the Southern Hemisphere (and the southwest Pacific region in particular) is much more controversial. Here we show that the Waiho Loop advance of the Franz Josef Glacier in New Zealand was not a YD event, as previously thought, and that the adjacent ocean warmed throughout the YD.


An algorithm for classifying tumors based on genomic aberrations and selecting representative tumor models.
Cancer is a heterogeneous disease caused by genomic aberrations and characterized by significant variability in clinical outcomes and response to therapies. Several subtypes of common cancers have been identified based on alterations of individual cancer genes, such as HER2, EGFR, and others. However, cancer is a complex disease driven by the interaction of multiple genes, so the copy number status of individual genes is not sufficient to define cancer subtypes and predict responses to treatments. A classification based on genome-wide copy number patterns would be better suited for this purpose. To develop a more comprehensive cancer taxonomy based on genome-wide patterns of copy number abnormalities, we designed an unsupervised classification algorithm that identifies genomic subgroups of tumors. This algorithm is based on a modified genomic Non-negative Matrix Factorization (gNMF) algorithm and includes several additional components, namely a pilot hierarchical clustering procedure to determine the number of clusters, a multiple random initiation scheme, a new stop criterion for the core gNMF, as well as a 10-fold cross-validation stability test for quality assessment. We applied our algorithm to identify genomic subgroups of three major cancer types: non-small cell lung carcinoma (NSCLC), colorectal cancer (CRC), and malignant melanoma. High-density SNP array datasets for patient tumors and established cell lines were used to define genomic subclasses of the diseases and identify cell lines representative of each genomic subtype. The algorithm was compared with several traditional clustering methods and showed improved performance. To validate our genomic taxonomy of NSCLC, we correlated the genomic classification with disease outcomes. Overall survival time and time to recurrence were shown to differ significantly between the genomic subtypes. We developed an algorithm for cancer classification based on genome-wide patterns of copy number aberrations and demonstrated its superiority to existing clustering methods. The algorithm was applied to define genomic subgroups of three cancer types and identify cell lines representative of these subgroups. Our data enabled the assembly of representative cell line panels for testing drug candidates.


Application of Biological Domain Knowledge Based Feature Selection on Gene Expression Data.
In the last two decades, there have been massive advancements in high throughput technologies, which resulted in the exponential growth of public repositories of gene expression datasets for various phenotypes. It is possible to unravel biomarkers by comparing the gene expression levels under different conditions, such as disease vs. control, treated vs. not treated, drug A vs. drug B, etc. This problem refers to a well-studied problem in the machine learning domain, i.e., the feature selection problem. In biological data analysis, most of the computational feature selection methodologies were taken from other fields, without considering the nature of the biological data. Thus, integrative approaches that utilize the biological knowledge while performing feature selection are necessary for this kind of data. The main idea behind the integrative gene selection process is to generate a ranked list of genes considering both the statistical metrics that are applied to the gene expression data, and the biological background information which is provided as external datasets. One of the main goals of this review is to explore the existing methods that integrate different types of information in order to improve the identification of the biomolecular signatures of diseases and the discovery of new potential targets for treatment. These integrative approaches are expected to aid the prediction, diagnosis, and treatment of diseases, as well as to enlighten us on disease state dynamics, mechanisms of their onset and progression. The integration of various types of biological information will necessitate the development of novel techniques for integration and data analysis. Another aim of this review is to boost the bioinformatics community to develop new approaches for searching and determining significant groups/clusters of features based on one or more biological grouping functions.


Scaling up in international health: what are the key issues?
The term 'scaling up' is now widely used in the international health literature, though it lacks an agreed definition. We review what is meant by scaling up in the context of changes in international health and development over the last decade. We argue that the notion of scaling up is primarily used to describe the ambition or process of expanding the coverage of health interventions, though the term has also referred to increasing the financial, human and capital resources required to expand coverage. We discuss four pertinent issues in scaling up the coverage of health interventions: the costs of scaling up coverage; constraints to scaling up; equity and quality concerns; and key service delivery issues when scaling up. We then review recent progress in scaling up the coverage of health interventions. This includes a considerable increase in the volume of aid, accompanied by numerous new health initiatives and financing mechanisms. There have also been improvements in health outcomes and some examples of successful large-scale programmes. Finally, we reflect on the importance of obtaining a better understanding of how to deliver priority health interventions at scale, the current emphasis on health system strengthening and the challenges of sustaining scaling up in the prevailing global economic environment.


Independent and Combined Effects of Calcium and Vitamin D Supplementation on Blood Lipids in Overweight or Obese Premenopausal Women: A Triple-Blind Randomized Controlled Clinical Trial.
Dyslipidemia is often associated with obesity and contributes to the increased risk of atherosclerosis, heart disease, and stroke. This study was designed to evaluate the independent or combined effect of calcium and vitamin D (Ca + Vit D) supplementation on blood lipid profile in overweight or obese premenopausal women. This study is a triple-blind, randomized, parallel, placebo-controlled trial. About 100 overweight or obese (body mass index (BMI) of 25-40 kg/m2) premenopausal (aged 30-50 years) women, recruited from Shiraz University of Medical Sciences (SUMS) clinics, were allocated into 4 groups: (1) calcium (Ca) supplementation (2 tablets per day; each containing 500 mg calcium carbonate), (2) vitamin D (Vit D) supplementation (2 tablets per day; each containing 200 IU vitamin D3), (3) Ca + Vit D supplementation (2 tablets per day; each containing 500 mg calcium carbonate plus 200 IU vitamin D3), (4) placebo supplementation (2 tablets per day, containing micro-cellulose). All participants received a 500 kcal energy-restricted diet. Blood lipids, serum vitamin D, and anthropometric indices were measured at baseline and after 8 weeks. Physical activity and 3-day dietary records were taken at baseline and every 4 weeks during the intervention. At 8 weeks, triglyceride levels were significantly decreased in the Ca group (P = 0.002). Low-density lipoprotein (LDL) levels were decreased in the Ca + Vit D group (P = 0.04) and high-density lipoprotein (HDL) levels decreased in both the Ca and Ca + Vit D groups (P = 0.006, P = 0.004, respectively). The results of one-way ANOVA indicated that changes in the serum lipid profile levels were not significantly different among the four groups (P = 0.90, P = 0.86, P = 0.61, P = 0.27, and P = 0.19, respectively for TG, TC, LDL, HDL, and LDL/HDL). The results were not significant even after adjusting for potential covariates. Although the results were not significantly different among the four treated groups at 8 weeks, within-group changes like the reduction in triglyceride and LDL levels, respectively in the Ca group and Ca + Vit D group, and HDL levels in both the Ca and Ca + Vit D groups were significant. These changes may have potentially significant public health implications.


Phosphomolybdate assembly as a low-cost catalyst for the reduction of toxic Cr(vi) in aqueous solution.
Highly reduced phosphomolybdate hybrid compounds have been hydrothermally prepared and structurally defined. X-ray single-crystal analysis revealed that these phosphomolybdates had the following formulae: (H2bpp)6{Fe[Mo6O12(OH)3(HPO4)2(H2PO4)2]2}2·11H2O (1), (H2bpp)6{Zn[Mo6O12(OH)3(HPO4)2(H2PO4)2]2}2·11H2O (2), and (H2bpp)5.5{Mn[Mo6O12(OH)3(HPO4)2(H2PO4)2]2}2·2H2O (3) (bpp = 1,3-bi(4-pyridyl)propane). In the inorganic moiety, all Mo centers are in the +5 reduced form, representing a unique, fully reduced cluster in the polyanionic family. As a counter cation, the flexible bpp surrounds the anionic cluster to form hybrid 'core-shell' supramolecular assemblies. These hybrids are stable and insoluble in water, which can change a catalytic reaction from homogeneous to heterogeneous. Experiments showed that the three supramolecular hybrids exhibit ideally reversible multi-electron transfer behavior, and hybrid 1 is active as a heterogeneous molecular catalyst to reduce toxic Cr(vi) to nontoxic Cr(iii) at low temperature in a short period of time. Hybrid 1 serves as an electron shuttle to promote the redox reaction between Cr(vi) and HCOOH. The activation energy of the reaction is effectively decreased after the reactants are adsorbed on the solid crystal surface, and the activation energy is calculated to be 78.5 kJ·mol-1. The well-organized structures of polyoxometalates help to explain the catalytic mechanism at the molecular level.


Dhandha, dharma and disease: traditional sex work and HIV/AIDS in rural India.
This paper discusses the results of two ethnographic studies with female sex workers in rural areas of Karnataka and Rajasthan, India. In particular, we focus on women whose socio-economic status, and religious and occupational practices, are part of sex work systems that have historical precedents such that they can be termed "traditional" sex workers. The approach taken in the ethnographic work was informed by current critical approaches in medical anthropology and public health. The paper argues that in the context of an expanding HIV/AIDS epidemic in rural areas of India, understanding the historical and structural factors that operate to perpetuate female sex work as a culturally "sanctioned" occupation is critical if interventions intended to reduce the risk of HIV transmission are to succeed. We conclude that interventions designed to empower women collectively in these communities that are consistent with cultural traditions are needed to lead to healthier sexual behaviours and reduced risk of HIV/AIDS infection.


Change in power output across a high-repetition set of bench throws and jump squats in highly trained athletes.
Athletes experienced in maximal-power and power-endurance training performed 1 set of 2 common power training exercises in an effort to determine the effects of moderately high repetitions upon power output levels throughout the set. Twenty-four and 15 athletes, respectively, performed a set of 10 repetitions in both the bench throw (BT P60) and jump squat exercise (JS P60) with a resistance of 60 kg. For both exercises, power output was highest on either the second (JS P60) or the third repetition (BT P60) and was then maintained until the fifth repetition. Significant declines in power output occurred from the sixth repetition onwards until the 10th repetition (11.2% for BT P60 and 5% for JS P60 by the 10th repetition). These findings suggest that athletes attempting to increase maximal power limit their repetitions to 2 to 5 when using resistances of 35 to 45% 1RM in these exercises.


A novel method for generating and screening peptides and libraries displayed on adenovirus fiber.
Capsid-displayed adenoviral peptide libraries have been a significant, yet unfeasible goal in biotechnology. Three barriers have made this difficult: the large size of the viral genome, the low efficiency of converting plasmid-based genomes into packaged adenovirus and the fact that library amplification is hampered by the ability of two (or more) virus to co-infect one cell. Here, we present a novel vector system, pFex, which is capable of overcoming all three barriers. With pFex, modified fiber genes are recombined into the natural genetic locus of adenovirus through unidirectional Cre-lox recombination. Modified-fiber genes can be directly shuttled into replicating viral genomes in mammalian cells. The 'acceptor' vector does not contain the fiber gene, and therefore does not propagate until it has received a 'donor' fiber gene. Therefore, This methodology overcomes the low efficiency of transfecting large viral genomes and bypasses the need for transition to functional virus. Thus, with a fiber-shuttle library, one can generate and evaluate large numbers of fiber-modified adenovirus simultaneously. Finally, successful fiber genes can be rescued from virus and recombined back into shuttle plasmids, avoiding the need to propagate mixed viral pools. For proof of principal, we use this new system to screen a capsid-displayed peptide library for retargeted viral infection.


Enrichment of elevated plasma F2t-isoprostane levels in individuals with autism who are stratified by presence of gastrointestinal dysfunction.
Etiology is unknown in the majority of individuals with autism spectrum disorder (ASD). One strategy to investigate pathogenesis is to stratify this heterogeneous disorder based on a prominent phenotypic feature that enriches for homogeneity within population strata. Co-occurring gastrointestinal dysfunction (GID) characterizes a subset of children with ASD. Our current objective was to investigate a potential pathophysiological measure to test the hypothesis that children with both ASD and GID have a more severe metabolic dysfunction than children with ASD-only, given that the highly metabolically active brain and gastrointestinal system may additively contribute measurable impairment. Plasma levels of F2t-Isoprostanes (F2-IsoPs), a gold standard biomarker of oxidative stress, were measured in 87 children in four groups: ASD-GID, ASD-only, GID-only and Unaffected. F2-IsoP levels were elevated in all 3 clinical groups compared to the Unaffected group, with the ASD-GID group significantly elevated above the ASD-only group (mean, SD in pg/mg: ASD-GID 53.6, 24.4; ASD-only 36.5, 13.3; p = 0.007). Adjusting for age, sex, and triglyceride levels, F2-IsoP levels remained significantly different between study groups, with a moderate effect size of η(p)(2) = 0.187 (p = 0.001). Elevation in peripheral oxidative stress is consistent with, and may contribute to, the more severe functional impairments in the ASD-GID group. With unique medical, metabolic, and behavioral features in children with ASD-GID, the present findings serve as a compelling rationale for both individualized approaches to clinical care and integrated studies of biomarker enrichment in ASD subgroups that may better address the complex etiology of ASD.


The attachment of V79 and human periodontal ligament fibroblasts on periodontally involved root surfaces following treatment with EDTA, citric acid, or tetracycline HCL: an SEM in vitro study.
The present in vitro study has been designed to establish and compare the effects of citric acid, EDTA, and tetracycline HCl on human periodontally diseased roots on the structure, attachment, and orientation of V79 (primary Chinese hamster lung fibroblasts) cells and human periodontal ligament fibroblasts (HPDL). Commercially available V79 cells and HPDL derived from healthy human third molars were used in this study. These fibroblasts were left in solution for seven days in order to attain confluence. Forty single-rooted teeth were obtained from patients diagnosed with periodontitis. The crown part was removed under constant irrigation and the root was split vertically into two equal halves, thus, yielding 80 specimens. Following scaling and root planing, the specimens were washed with phosphate buffered saline (PBS) and kept in 50 microg/ml gentamycin sulphate solution for 24 hours. The root pieces were then treated as follows: citric acid at pH 1, 24% EDTA, or with a 10% solution of tetracycline HCl and were then placed in V79 fibroblast cultures and HPDL cultures. The specimens were harvested after four weeks and were fixed in 2.5% glutaraldehyde in PBS before preparation for scanning electron microscopy (SEM). The behavior of V79 cells was similar to that of human periodontal ligament cells on root conditioned surfaces. V79 and HPDL showed a healthy morphology on root surfaces treated with citric acid and EDTA and a relatively unhealthy appearance on root surfaces treated with tetracycline HCl and distilled water (control group). The results suggest the use of citric acid and EDTA as root conditioning agents favorably affects the migration, attachment, and morphology of fibroblasts on human root surfaces, which may play a significant role in periodontal healing and regeneration.


First Report of Leaf Spot Caused by Corynespora cassiicola on Baphicacanthus cusia in China.
Baphicacanthus cusia is a perennial herbaceous plant in the family Acanthaceae that is native to China, where it grows in warm temperate mountainous or hilly regions. It is commonly used as a Chinese herbal medicine. In March 2012, symptoms of leaf spot were observed on leaves of B. cusia in Long'an County, Guangxi, China, where this plant is extensively cultivated. Symptoms were initially small brown dots which developed into irregular to circular leaf spots. These spots enlarged and overlapped, extending until the 7- to 9-cm-long and 3- to 4-cm-wide leaves withered entirely, mostly within 2 months. On potato dextrose agar (PDA), the same fungus was cultured from 92% of 75 symptomatic leaf samples that had been surface sterilized in a 45-second dip in 0.1% mercuric chloride. Fungal structures were observed on diseased leaves: conidiophores (85 to 460 × 4 to 8 μm) were erect, brown, single or in clusters, and conidia (36 to 90 × 5 to 16 μm) were single or in chains of two to four, brown, cylindrical or obclavate, straight or slightly curved, with 3 to 18 pseudosepta and a conspicuous hilum. Three single-spore isolates were identified as Corynespora cassiicola (Berk & Curt.) Wei based on morphological and cultural characteristics (1). The rDNA internal transcribed spacer (ITS) region of one isolate, ZY-1, was sequenced (GenBank Accession No. JX908713), and it showed 100% identity to C. cassiicola, GenBank FJ852716, an isolate from Micronesia cultured from Ipomoea batatas (2). Pathogenicity tests were performed with each of the three isolates by spraying conidial suspensions (5 × 104 conidia/ml) containing 0.1% Tween 20 onto the surfaces of leaves of 60-day-old, 20-cm tall plants. For each isolate, 30 leaves from five replicate plants were treated. Control plants were treated with sterilized water containing 0.1% Tween 20. All plants were incubated for 36 h at 25°C and 90% relative humidity in an artificial climate chamber, and then moved into a greenhouse. Seven days after inoculation, dark brown spots typical of field symptoms were observed on all inoculated leaves, but no symptoms were seen on water-treated control plants. Koch's postulates were fulfilled by reisolation of C. cassiicola from diseased leaves. To our knowledge, this is the first report of C. cassiicola infecting B. cusia worldwide. References: (1) M. B. Ellis. Dematiaceous Hyphomycetes. Commonwealth Mycological Institute: Kew, Surrey, England, 1971. (2) L. J. Dixon et al. Phytopathology 99:1015, 2009.


High Prevalence of Staphylococcus aureus Enterotoxin Gene Cluster Superantigens in Cystic Fibrosis Clinical Isolates.
Staphylococcus aureus is a highly prevalent respiratory pathogen in cystic fibrosis (CF). It is unclear how this organism establishes chronic infections in CF airways. We hypothesized that S. aureus isolates from patients with CF would share common virulence properties that enable chronic infection. 77 S. aureus isolates were obtained from 45 de-identified patients with CF at the University of Iowa. We assessed isolates phenotypically and used genotyping assays to determine the presence or absence of 18 superantigens (SAgs). We observed phenotypic diversity among S. aureus isolates from patients with CF. Genotypic analysis for SAgs revealed 79.8% of CF clinical isolates carried all six members of the enterotoxin gene cluster (EGC). MRSA and MSSA isolates had similar prevalence of SAgs. We additionally observed that EGC SAgs were prevalent in S. aureus isolated from two geographically distinct CF centers. S. aureus SAgs belonging to the EGC are highly prevalent in CF clinical isolates. The greater prevalence in these SAgs in CF airway specimens compared to skin isolates suggests that these toxins confer selective advantage in the CF airway.


Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults.
There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting.


Critique: Research strategies for decoding the neurochemical basis of resistance to stress.
Because stress is implicated in serious psychiatric and physical illnesses, it is important to investigate the central neurochemical mechanisms which determine resistance to stress. Two features of much existing animal work limit its relevance to man. First, it has disregarded differences between individuals, focussing instead on group means. Secondly, it has concentrated on noxious forms of stress. Preliminary studies suggest that inferences from this work may not apply to individual differences, or to non-noxious stress. Therefore, a strategy is proposed for addressing the neurochemical basis of individual differences in resistance to non-noxious stress.


The context of learning anatomy: does it make a difference?
This study set out to ascertain whether the context in which anatomy is learnt made a difference to students' perceptions of learning. An Approach to Learning Inventory (ASSIST) and a 31-item Anatomy Learning Experience Questionnaire (ALE) were administered to 224 students (77 dental, 132 medical and 19 speech and language) as a multi-site study. Results revealed that 45% adopted a strategic, 39% a deep and 14% a surface approach. Trends between professions are similar for a deep or strategic approach (both ~ 40%). However, a surface approach differed between professions (7% dentistry, 16% medicine, 26% speech and language science). Dental students responded more to being able to use their knowledge than did other groups (P = 0.0001). Medical students found the dissecting environment an intimidating one and subsequently reported finding online resources helpful (P = 0.015 and P = 0.003, respectively). Speech and language science students reported that they experienced greater difficulties with learning anatomy; they reported finding the amount to learn daunting (P = 0.007), struggled to remember what they did last semester (P = 0.032) and were not confident in their knowledge base (P = 0.0001). All students responded strongly to the statement 'I feel that working with cadaveric material is an important part of becoming a doctor/dentist/health care professional'. A strong response to this statement was associated with students adopting a deep approach (P = 0.0001). This study has elucidated that local curriculum factors are important in creating an enabling learning environment. There are also a number of generic issues that can be identified as being inherent in the learning of anatomy as a discipline and are experienced across courses, different student groups and institutions.


Telehealth and Remote Interventions for Children With Cerebral Palsy: Scoping Review.
Remote treatment, or telehealth, has shown promise for children with cerebral palsy (CP) prior to 2020; however, the beginning of the global COVID-19 pandemic limiting access to hospitals for face-to-face treatments has driven the need for telehealth and led to a surge in its development. Due to the recent developments, there has been limited synthesis of the available evidence of telehealth for children with CP. This study aimed to analyze and summarize the existing evidence for telehealth interventions for the treatment of children with CP and identify any areas requiring further research. A scoping review was performed. A systematic search of available literature in MEDLINE and PubMed was performed during July 2021. Inclusion criteria for articles were primary research and systematic reviews that investigated telehealth, included children with CP, were published between 2010-2021, and were written in English. Exclusion criteria were secondary research other than systematic reviews; interventions that did not meet the World Health Organization definition of telehealth; or studies where all participants were aged >18 years, children's results were not reported separately, or there were no results reported for children with CP. A scoping review was chosen due to the expected heterogeneity of the participants, as well as the expected small sample sizes and inconsistency of measured outcomes; therefore, a narrative reporting of the results was considered appropriate. In all, 5 papers were identified, which included the results of 11 studies-2 of the included articles were systematic reviews, which included the results of 3 studies each. These 6 studies, together with 5 primary research articles, were included in this scoping review. The existing evidence is of low methodological quality, primarily consisting of case series. There is some evidence that the requirements of telehealth differ depending on the children's developmental stage and functional level. Telehealth is reported to reduce caregiver burden. There is mixed evidence on children's compliance with telehealth. Overall, the results of telehealth interventions for the treatment of children with CP were positive, indicating either comparable or improved results compared with children receiving usual face-to-face care. The evidence base is lacking in breadth and methodological quality to provide robust clinical recommendations. Most studies investigated hand function only, indicating the limited scope of existing research. However, this review shows that telehealth has demonstrated potential to improve function for children with CP while making health care services more accessible and reducing caregiver burden. Areas requiring further research include telehealth interventions for the lower limb, postural management, and pain control and the barriers to implementing telehealth.


Long-term effects of a 12 weeks high-intensity functional exercise program on physical function and mental health in nursing home residents with dementia: a single blinded randomized controlled trial.
Research indicates that exercise can have a positive effect on both physical and mental health in nursing home patients with dementia, however the lasting effect is rarely studied. In a previously published article we investigated the immediate effect of a 12 weeks functional exercise program on physical function and mental health in nursing home residents with dementia. In this paper we studied the long-term effect of this exercise program. We explored the differences between the exercise and control group from baseline to 6 months follow-up and during the detraining period from month 3 to 6. A single blind, randomized controlled trial was conducted and a total of 170 nursing home residents with dementia were included. The participants were randomly allocated to an intervention (n = 87) or a control group (n = 83). The intervention consisted of intensive strengthening and balance exercises in small groups twice a week for 12 weeks. The control condition was leisure activities. Thirty participants were lost between baseline and six-month follow-up. Linear mixed model analyses for repeated measurements were used to investigate the effect of exercise after detraining period. The exercise group improved their scores on Berg Balance Scale from baseline to 6 months follow-up by 2.7 points in average. The control group deteriorated in the same period and the difference between groups was statistically significant (p = 0.031). The exercise group also scored better on NPI agitation sub-score after 6 months (p = 0.045). The results demonstrate long-time positive effects of a high intensity functional exercise program on balance and indicate a positive effect on agitation, after an intervention period of 12 weeks followed by a detraining period of 12 weeks. Identifier at ClinicalTrials.gov: NCT02262104.


A fast wavelet-based reconstruction method for magnetic resonance imaging.
In this work, we exploit the fact that wavelets can represent magnetic resonance images well, with relatively few coefficients. We use this property to improve magnetic resonance imaging (MRI) reconstructions from undersampled data with arbitrary k-space trajectories. Reconstruction is posed as an optimization problem that could be solved with the iterative shrinkage/thresholding algorithm (ISTA) which, unfortunately, converges slowly. To make the approach more practical, we propose a variant that combines recent improvements in convex optimization and that can be tuned to a given specific k-space trajectory. We present a mathematical analysis that explains the performance of the algorithms. Using simulated and in vivo data, we show that our nonlinear method is fast, as it accelerates ISTA by almost two orders of magnitude. We also show that it remains competitive with TV regularization in terms of image quality.


A study of the transport of lithium across the erythrocyte membrane in vivo and of the effects of the ion transport inhibitors digoxin and dipyridamole.
1. We have given an oral load of lithium carbonate to healthy volunteers in order to investigate the transport of lithium across the erythrocyte membrane in vivo and the effects of known inhibitors of that transport. 2. Using this technique we have shown that pretreatment with either digoxin, an inhibitor of the sodium/potassium pump, or dipyridamole, an inhibitor of the anion transporter, does not alter the plasma or erythrocyte lithium concentration profiles, nor any of the pharmacokinetic variables derived from these data, and we conclude that these two transport pathways do not contribute significantly to the in vivo handling of lithium by erythrocytes. 3. We have also shown that erythrocyte lithium concentrations measured directly differ significantly from the predicted concentrations calculated using the two-compartment pharmacokinetic model which has been used in some earlier comparisons of in vitro and in vivo lithium handling. 4. We suggest that the in vivo administration of lithium carbonate may permit a specific measure of the in vivo activity of the sodium/sodium countertransport pathway.


Neuronal target identification requires AHA-1-mediated fine-tuning of Wnt signaling in C. elegans.
Electrical synaptic transmission through gap junctions is a vital mode of intercellular communication in the nervous system. The mechanism by which reciprocal target cells find each other during the formation of gap junctions, however, is poorly understood. Here we show that gap junctions are formed between BDU interneurons and PLM mechanoreceptors in C. elegans and the connectivity of BDU with PLM is influenced by Wnt signaling. We further identified two PAS-bHLH family transcription factors, AHA-1 and AHR-1, which function cell-autonomously within BDU and PLM to facilitate the target identification process. aha-1 and ahr-1 act genetically upstream of cam-1. CAM-1, a membrane-bound receptor tyrosine kinase, is present on both BDU and PLM cells and likely serves as a Wnt antagonist. By binding to a cis-regulatory element in the cam-1 promoter, AHA-1 enhances cam-1 transcription. Our study reveals a Wnt-dependent fine-tuning mechanism that is crucial for mutual target cell identification during the formation of gap junction connections.


Military Standard Testing of Commercially Available Supraglottic Airway Devices for Use in a Military Combat Setting.
Airway obstruction is the second leading cause of death on the battlefield. The harsh conditions of the military combat setting require that devices be able to withstand extreme circumstances. Military standards (MIL-STD) testing is necessary before devices are fielded. We sought to determine the ability of supraglottic airway (SGA) devices to withstand MIL-STD testing. We tested 10 SGA models according to nine MIL-STD-810H test methods. We selected these tests by polling five military and civilian emergency-medicine subject matter experts (SMEs), who weighed the relevance of each test. We performed tests on three devices for each model, with operational and visual examinations, to assign a score (1 to 10) for each device after each test. We calculated the final score of each SGA model by averaging the score of each device and multiplying that by the weight for each test, for a possible final score of 2.6 to 26.3. The scores for the SGA models were LMA Classic Airway, 25.9; AuraGain Disposable Laryngeal Mask, 25.5; i-gel Supraglottic Airway, 25.2; Solus Laryngeal Mask Airway, 24.4; LMA Fastrach Airway, 24.4; AuraStraight Disposable Laryngeal Mask, 24.1; King LTS-D Disposable Laryngeal Tube, 22.1; LMA Supreme Airway, 21.0; air-Q Disposable Intubating Laryngeal Airway, 20.1; and Baska Mask Supraglottic Airway, 18.1. The limited (one to three) samples available for testing provide adequate preliminary information but restrict the range of failures that could be discovered. Lower scoring SGA models may not be optimal for military field use. Models scoring sufficiently close to the top performers (LMA Classic, AuraGain, i-gel, Solus, LMA Fastrach, AuraStraight) may be viable for use in the military setting. The findings of our testing should help guide device procurement appropriate for different battlefield conditions.


Stage of exercise and health-related quality of life among overweight and obese adults.
This paper reports a study whose main aim was to understand the correlation between stages of exercise and health-related qualities of life among overweight and obese adults in Taiwan. Regular exercise has been shown to improve health-related quality of life in the general population and among patients with chronic diseases. Nevertheless, systematic investigations of the correlation between exercise stages and the health-related quality of life among overweight and obese adults are lacking in Taiwan. A cross-section of people from the weight loss clinics of a medical centre in Taipei was recruited to the study. The Chinese version of the Stages of Exercise and the Taiwanese version of Short Form 36 questionnaires were used to collect data from those whose body mass indexes were equal to or >24 kg/m2. The data were collected in 2003. In total, 212 overweight and obese adults participated in the study. The majority were in the preparation (38.2%) or contemplation (31.6%) stages of exercise; relatively few were in the action (14.2%) or maintenance (11.3%) stages, and the smallest number (4.7%) were in the precontemplation stage. Although over 70% of respondents were not in the habit of taking regular exercise, their motivations were very high. For the Short Form 36 scales, the highest scores were for physical functioning (84.5 +/- 17.3), while the lowest were for general health (55.5 +/- 20.9), vitality (59.8 +/- 18.1), and mental health (MH) (66.0 +/- 17.9). Different stages of exercise showed statistically significant differences within the eight domains of Short Form 36 (Wilks = 0.733, P = 0.001); a statistically significant difference was also found for physical functioning (P < or = 0.001), general health (P = 0.003), and vitality (P = 0.005). Since stages of exercise are correlated with health-related quality of life among overweight and obese adults, healthcare providers need to understand what stages people are at in order to educate them to achieve a better quality of life and to motivate those who are inactive to do more exercise on a regular basis.


Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation.
Pdx1 (IPF-1 in humans, which is altered in MODY-4) is essential for pancreas development and mature beta-cell function. Pdx1 is expressed dynamically within the developing foregut, but how its expression characteristics are linked to the various steps of organ specification, differentiation, and function is unknown. Deletion of a conserved enhancer region (Area I-II-III) from Pdx1 produced a hypomorphic allele (Pdx1(DeltaI-II-III)) with altered timing and level of expression, which was studied in combination with wild-type and protein-null alleles. Lineage labeling in homozygous Area I-II-III deletion mutants (Pdx1(DeltaI-II-III/DeltaI-II-III)) revealed lack of ventral pancreatic bud specification and early-onset hypoplasia in the dorsal bud. Acinar tissue formed in the hypoplastic dorsal bud, but endocrine maturation was greatly impaired. While Pdx1(-/-) (protein-null) mice have nonpancreatic abnormalities (e.g., distorted pylorus, absent Brunner's glands), these structures formed normally in Pdx1(DeltaI-II-III/DeltaI-II-III) and Pdx1(DeltaI-II-III/-) mice. Surprisingly, heterozygous (Pdx1(+/DeltaI-II-III)) mice had abnormal islets and a more severe prediabetic condition than Pdx1(+/-) mice. These findings provide in vivo evidence of the differential requirements for the level of Pdx1 gene activity in the specification and differentiation of the various organs of the posterior foregut, as well as in pancreas and gut endocrine cell differentiation.


Target-distractor similarity has a larger impact on visual search in school-age children than spacing.
In typically developing children, crowding decreases with increasing age. The influence of target-distractor similarity with respect to orientation and element spacing on visual search performance was investigated in 29 school-age children with normal vision (4- to 6-year-olds [N = 16], 7- to 8-year-olds [N = 13]). Children were instructed to search for a target E among distractor Es (feature search: all flanking Es pointing right; conjunction search: flankers in three orientations). Orientation of the target was manipulated in four directions: right (target absent), left (inversed), up, and down (vertical). Spacing was varied in four steps: 0.04°, 0.5°, 1°, and 2°. During feature search, high target-distractor similarity had a stronger impact on performance than spacing: Orientation affected accuracy until spacing was 1°, and spacing only influenced accuracy for identifying inversed targets. Spatial analyses showed that orientation affected oculomotor strategy: Children made more fixations in the "inversed" target area (4.6) than the vertical target areas (1.8 and 1.9). Furthermore, age groups differed in fixation duration: 4- to 6-year-old children showed longer fixation durations than 7- to 8-year-olds at the two largest element spacings (p = 0.039 and p = 0.027). Conjunction search performance was unaffected by spacing. Four conclusions can be drawn from this study: (a) Target-distractor similarity governs visual search performance in school-age children, (b) children make more fixations in target areas when target-distractor similarity is high, (c) 4- to 6-year-olds show longer fixation durations than 7- to 8-year-olds at 1° and 2° element spacing, and (d) spacing affects feature but not conjunction search-a finding that might indicate top-down control ameliorates crowding in children.


Pulsed glucocorticoids enhance dystrophic muscle performance through epigenetic-metabolic reprogramming.
In humans, chronic glucocorticoid use is associated with side effects like muscle wasting, obesity, and metabolic syndrome. Intermittent steroid dosing has been proposed in Duchenne Muscular Dystrophy patients to mitigate the side effects seen with daily steroid intake. We evaluated biomarkers from Duchenne Muscular Dystrophy patients, finding that, compared with chronic daily steroid use, weekend steroid use was associated with reduced serum insulin, free fatty acids, and branched chain amino acids, as well as reduction in fat mass despite having similar BMIs. We reasoned that intermittent prednisone administration in dystrophic mice would alter muscle epigenomic signatures, and we identified the coordinated action of the glucocorticoid receptor, KLF15 and MEF2C as mediators of a gene expression program driving metabolic reprogramming and enhanced nutrient utilization. Muscle lacking Klf15 failed to respond to intermittent steroids. Furthermore, coadministration of the histone acetyltransferase inhibitor anacardic acid with steroids in mdx mice eliminated steroid-specific epigenetic marks and abrogated the steroid response. Together, these findings indicate that intermittent, repeated exposure to glucocorticoids promotes performance in dystrophic muscle through an epigenetic program that enhances nutrient utilization.


Efficacy of the Theory of Planned Behaviour: a meta-analytic review.
The Theory of Planned Behaviour (TPB) has received considerable attention in the literature. The present study is a quantitative integration and review of that research. From a database of 185 independent studies published up to the end of 1997, the TPB accounted for 27% and 39% of the variance in behaviour and intention, respectively. The perceived behavioural control (PBC) construct accounted for significant amounts of variance in intention and behaviour, independent of theory of reasoned action variables. When behaviour measures were self-reports, the TPB accounted for 11% more of the variance in behaviour than when behaviour measures were objective or observed (R2s = .31 and .21, respectively). Attitude, subjective norm and PBC account for significantly more of the variance in individuals' desires than intentions or self-predictions, but intentions and self-predictions were better predictors of behaviour. The subjective norm construct is generally found to be a weak predictor of intentions. This is partly attributable to a combination of poor measurement and the need for expansion of the normative component. The discussion focuses on ways in which current TPB research can be taken forward in the light of the present review.


AlzPharm: integration of neurodegeneration data using RDF.
Neuroscientists often need to access a wide range of data sets distributed over the Internet. These data sets, however, are typically neither integrated nor interoperable, resulting in a barrier to answering complex neuroscience research questions. Domain ontologies can enable the querying heterogeneous data sets, but they are not sufficient for neuroscience since the data of interest commonly span multiple research domains. To this end, e-Neuroscience seeks to provide an integrated platform for neuroscientists to discover new knowledge through seamless integration of the very diverse types of neuroscience data. Here we present a Semantic Web approach to building this e-Neuroscience framework by using the Resource Description Framework (RDF) and its vocabulary description language, RDF Schema (RDFS), as a standard data model to facilitate both representation and integration of the data. We have constructed a pilot ontology for BrainPharm (a subset of SenseLab) using RDFS and then converted a subset of the BrainPharm data into RDF according to the ontological structure. We have also integrated the converted BrainPharm data with existing RDF hypothesis and publication data from a pilot version of SWAN (Semantic Web Applications in Neuromedicine). Our implementation uses the RDF Data Model in Oracle Database 10g release 2 for data integration, query, and inference, while our Web interface allows users to query the data and retrieve the results in a convenient fashion. Accessing and integrating biomedical data which cuts across multiple disciplines will be increasingly indispensable and beneficial to neuroscience researchers. The Semantic Web approach we undertook has demonstrated a promising way to semantically integrate data sets created independently. It also shows how advanced queries and inferences can be performed over the integrated data, which are hard to achieve using traditional data integration approaches. Our pilot results suggest that our Semantic Web approach is suitable for realizing e-Neuroscience and generic enough to be applied in other biomedical fields.


Adolescents' health behaviors and obesity: Does race affect this epidemic?
This study explores the influence of health behaviors and individual attributes on adolescent overweight and obesity using data from Wave II (Add Health). Structural equation model/path analysis using maximum likelihood estimation was utilized to analyze the relationships of health behaviors and attributes with obesity. Results of the model reveal that the causal paths (adolescents' attributes and health behaviors) for overweight and obesity were different for African American and Caucasian adolescents. Generally, African Americans were more susceptible to overweight and obesity than Caucasians. Although increasing levels of vigorous physical activities lowers the risk for obesity among African American and Caucasian adolescents alike, low family SES and being sedentary were associated with overweight and obesity among Caucasians. No significant associations were found among African Americans. Increased hours of sleep at night relate positively with obesity among African Americans. These findings suggest important elements in the consideration of race in developing effective intervention and prevention approaches for curbing the obesity epidemic among U.S. adolescents.


Towards a more efficient Hydrothermal Carbonization: Processing water recirculation under different conditions.
The use of Processing Water (PW) on the Hydrothermal Carbonization (HTC) of tunisian pine cones was investigated under different temperature (200 and 240 °C) and residence time conditions (3 and 20 h). Recirculating PW improved the HC (hydrochar) solid yield, without being detrimental to the carbon content of the HC. The heating value of the HCs, that with a single reaction already involved a rise of this parameter in the range 22.1-55.8% as compared to the raw material, was further increased up to 24.9-58.6% for cyclic runs. This was attributed to enhanced secondary char formation by reusing liquid, although this effect depended on the severity of previous HTC and was affected by both temperature and time. The HCs showed an increment on C and especially on N for cyclic runs. Also, thermal degradation peaks during HC TGA/DTA analyses showed a broader temperature range decomposition upon pyrolysis when PW was recirculated. The modifications of HC surface morphologies and functional groups was also investigated and associated to related reaction mechanisms.


The impact of epidermal growth factor receptor gene status on gefitinib-treated Japanese patients with non-small-cell lung cancer.
We investigated the relationships between genetic factors and clinical outcome in Japanese non-small-cell lung cancer (NSCLC) patients treated with gefitinib. Ninety-eight NSCLC patients who had been treated with gefitinib, were screened for mutations in epidermal growth factor receptor (EGFR) exons 18-21, KRAS exon2, and polymorphisms including the CA simple sequence repeat in intron1 (CA-SSR1) and single nucleotide polymorphisms in the promoter region (-216G/T and -191C/A), using a PCR-based assay and direct sequencing. The EGFR copy number status was also evaluated using a fluorescence in situ hybridization assay. EGFR and KRAS mutations were found in 38 (38.8%) and 8 (8.2%) of the 98 patients, respectively. A high EGFR copy number status was identified in 31 (41.3%) of the 75 assessable patients. Drug-sensitive EGFR mutations limited to exon19 deletions and L858R were independent predictive factors of a stronger sensitivity to gefitinib (p = 0.0002), the overall survival (OS) (p = 0.0036), and prolonged progression-free survival (PFS) (p < 0.0001). The EGFR copy number status was not related to a sensitivity to gefitinib and prolonged OS and PFS. Regarding polymorphisms, patients with a short CA-SSR1 showed a prolonged OS as compared with those with a long length in patients with a drug-sensitive EGFR mutation, although this difference was not significant (p = 0.13). Thus, drug-sensitive EGFR mutations predict a favorable clinical outcome and a high EGFR copy number may not be related to clinical benefits in gefitinib-treated Japanese patients with NSCLC. Our findings also suggest that the CA-SSR1 length may influence the clinical outcome in patients with a drug-sensitive EGFR mutation.


Educational and Exercise Intervention to Prevent Falls and Improve Participation in Subjects With Neurological Conditions: The NEUROFALL Randomized Controlled Trial.
Background: Falls, mobility impairments and lack of social support lead to participation restrictions in people with neurological conditions. The aim of this multicenter, single blinded randomized controlled trial was to test whether an educational program focusing on fall prevention and safe mobility reduces falls and increases social participation among people with neurological conditions. Methods: Ninety people with Stroke (n = 25), multiple sclerosis (n = 33) and Parkinson disease (n = 32), median age 63 (31-89), were randomized. A permuted block algorithm stratified by field center was used to allocate participants to an education group (EG, n = 42) consisting of an educational program focused on fall prevention and tailored balance exercises and a control group (CG, n = 48) receiving usual treatments. After baseline assessment, each participants was followed for 6 months with telephone contacts by blinded interviewers. Being fallers (>1 fall) and time to become a faller were used as primary outcomes. Community Integration Questionnaire (CIQ) and Instrumental Activities of Daily Living (IADL) scales assessed treatment effects on social integration and daily living activities. Results: Over a median (Interquartile Range) follow-up of 189 (182-205) days, [EG = 188 (182-202), CG = 189 (182-209)] fallers were 10 in the CG and 11 in the EG (hazard ratio 0.95, 95% confidence interval (CI) 0.45 to 2.5; P = 0.94). At follow-up the EG scored significantly better than CG on the CIQ (+1.7 points, CI: 0.1 to 3.3) and IADL (+2.2 points, CI: 0.4 to 4.0). Conclusions: This educational program did not reduce the risk of falls but it improved the ability to carry out activities of daily living and decreased participation restrictions in people with neurological conditions.


Effect of sulfonylureas on triglyceride metabolism in the rat liver: possible role of the lysosomes in hepatic lipolysis.
It has been suggested previously that chlorpropamide and other hypoglycemic sulfonylureas interfere with hepatic triglyceride breakdown. Since ketogenesis from endogenous hepatic lipid stores is a measure of hepatic triglyceride hydrolysis, ketogenesis derived from endogenous lipids as well as ketogenesis derived from exogenously added isotopic oleate was determined in isolated hepatocytes from fasted rats in an attempt to identify the nature of the direct effects of sulfonylureas on hepatic lipid metabolism. Ketogenesis from endogenous lipids was inhibited by 1 mM chlorpropamide, while ketone production from exogenous oleate did not change. The effect of chlorpropamide on hepatic triglyceride metabolism was further studied in the isolated perfused liver of normal rats in the presence of a continuous [3H]oleate infusion and in isolated liver cells incubated in the presence of [3H]oleate. In liver perfusion experiments, 1 mM chlorpropamide enhanced the incorporation of tritium into triglycerides (but not other lipid classes) and increased both liver triglyceride content and triglyceride secretion. Using isolated cells similar effects could be demonstrated at 0.5 mM chlorpropamide. Chlorpropamide, tolbutamide, and carbutamide, all of which inhibited endogenous ketogenesis in isolated liver cells, also inhibited lysosomal triglyceride lipase activity in rat liver homogenates. The drugs were not inhibitory towards alkaline lipase activity. Demethylglycodiazin (2-benzolsulfonamid--5-(beta-hydroxyethoxy)-pyrimidin), which did not inhibit endogenous ketogenesis in isolated liver cells, did not affect lysosomal lipase activity. The lysosomotropic drug chloroquine was markedly antiketogenic when tested in liver cells. The reduction in endogenous ketogenesis, the enhanced accumulation of liver triglycerides, and the stimulation of hepatic triglyceride output by chlorpropamide are ascribed to an interference of the drug with hepatic triglyceride breakdown. The present results also suggest that the lysosomes play a significant role in hepatic lipolysis.


Towards optimising the production of and expression from polycistronic vectors in embryonic stem cells.
Polycistronic vectors linked by self-processing 2A peptides have been successfully used in cellular reprogramming. The expression of these vectors has yet to be well documented in embryonic stem cells. In the present study, we generated expression cassettes containing combinatorial arrangements of 3 pancreatic transcriptions factors (Pdx1, Nkx2.2 and Ngn3) together with an eGFP reporter, all linked by self-processing 2A peptides. The study tested the utility of constructing complex expression cassettes by ligating multiple components, each flanked by unique restriction sites. This approach allowed flexible and efficient design and construction of a combinatorial array of polycistronic constructs, which were expressed after transient transfection into embryonic stem cells. The inclusion of EGFP provided for a convenient proxy measure of expression and showed that expression was similar regardless of EGFP's position within a 2A polycistronic construct. Expression of terminal EGFP was 51% and 24% more efficient when linked by T2A compared to F2A or E2A peptides, respectively. The highest level of expression was achieved when all genes in a construct were linked exclusively by T2A peptides. This effect of T2A was independent of the type of promoter used, as a similar increase in terminal EGFP expression was observed when the polycistronic constructs were under the control of a CAG promoter compared to the CMV promoter, even though the GAG promoter was more efficient in this model than the CMV promoter. The study provides guidance on design strategies and methods for the efficient generation and expression of 2A polycistronic constructs in embryonic stem cells.


Prospective evaluation of blue-light flexible cystoscopy with hexaminolevulinate in non-muscle-invasive bladder cancer.
To evaluate the utility of blue-light flexible cystoscopy (BLFC) for surveillance of non-muscle-invasive bladder cancer (NMIBC). Prospective cohort of consecutive patients who underwent office-based BLFC for NMIBC. Clinical information was collected including cystoscopic findings and pathological data. A total of 322 cases were performed on 190 patients. The mean age was 71 years and 83% were men. The highest stage prior to BLFC was Ta, carcinoma in situ (CIS), T1, and T2 in 45.3%, 18.4%, 30% and 2%, respectively. Prior to BLFC, 16.8%, 60.5%, and 16.8% were low grade (LG), high grade (HG), and CIS, respectively. Intravesical bacille Calmette-Guérin and intravesical chemotherapy were used in 54.2% and 18.4%, respectively. White-light cystoscopy (WLC) and BLFC were both normal in 173 (53.7%) of cases. WLC was normal and BLFC was abnormal in 26 (8%) cases. Of these, 15 had office-based biopsy and cancer was detected in 13 (87%; six CIS, four HG Ta, three LG Ta). Both WLC and BLFC were positive in 83 (25.8%) cases and 33% had additional tumours found. Cancer was found in 27 (75%) of WLC+/BLFC+ who underwent office-based biopsy including 19 LG Ta, six HG Ta, and two CIS. Incorporation of BLFC in clinical practice has potential advantages of finding cancer in cases with normal WLC. BLFC detected additional cancers in 33% of patients with positive WLC and BLFC, which can improve surveillance and performance of office-based biopsy. Further research is needed to determine cost-effectiveness and impact on recurrence rates.


Natural disturbance reduces disease risk in endangered rainforest frog populations.
Natural disturbances can drive disease dynamics in animal populations by altering the microclimates experienced by hosts and their pathogens. Many pathogens are highly sensitive to temperature and moisture, and therefore small changes in habitat structure can alter the microclimate in ways that increase or decrease infection prevalence and intensity in host populations. Here we show that a reduction of rainforest canopy cover caused by a severe tropical cyclone decreased the risk of endangered rainforest frogs (Litoria rheocola) becoming infected by a fungal pathogen (Batrachochytrium dendrobatidis). Reductions in canopy cover increased the temperatures and rates of evaporative water loss in frog microhabitats, which reduced B. dendrobatidis infection risk in frogs by an average of 11-28% in cyclone-damaged areas, relative to unaffected areas. Natural disturbances to the rainforest canopy can therefore provide an immediate benefit to frogs by altering the microclimate in ways that reduce infection risk. This could increase host survival and reduce the probability of epidemic disease outbreaks. For amphibian populations under immediate threat from this pathogen, targeted manipulation of canopy cover could increase the availability of warmer, drier microclimates and therefore tip the balance from host extinction to coexistence.


The joint effects of apolipoprotein B, apolipoprotein A1, LDL cholesterol, and HDL cholesterol on risk: 3510 cases of acute myocardial infarction and 9805 controls.
Plasma levels of apolipoprotein B (apoB), the main surface protein on LDL particles, and LDL-C, the amount of cholesterol in those particles, are closely correlated and, considered separately, are positive risk factors. Plasma levels of apolipoprotein A(1), the main surface protein on HDL particles, and HDL-C, the amount of cholesterol in those particles, are also closely correlated with each other and, considered separately, are negative risk factors. The interdependence of these four risk factors is unclear. Case-control study among 3510 acute myocardial infarction patients (without prior vascular disease, diabetes, or statin use) in UK hospitals and 9805 controls. Relative risks (age, sex, smoking, and obesity-adjusted) were more strongly related to apoB than to LDL-C and, given apoB, more strongly negatively related to apoA(1) than to HDL-C. The ratio apoB/apoA(1) was uncorrelated with time since symptom onset in cases, was reproducible in samples collected a few years apart in controls (correlation 0.81), and encapsulated almost all the predictive power of these four measurements. Its effect was continuous, substantial throughout the UK normal range [relative risk, top vs. bottom decile of this ratio, 7.3 (95% CI 5.8-9.2)] and varied little with age. The ratio apoB/apoA(1) was substantially more informative about risk (chi(1)(2) = 550) than were commonly used measures such as LDL-C/HDL-C, total/HDL cholesterol, non-HDL cholesterol, and total cholesterol (chi(1)(2) = 407, 334, 204, and 105, respectively). Given apoB and apoA(1), the relationship with risk of LDL-C was reversed, and this reversal was strengthened by appropriate allowance for random measurement errors in two correlated variables. Given usual apoB, lower LDL-C (consistent with smaller LDL particles) was associated with higher risk (P < 0.0001). During the first 8 h after symptom onset HDL-C increased by about 10%, precluding reliable assessment of the joint relationship of apoA(1) and pre-onset HDL-C with risk in such retrospective case-control studies. Apolipoprotein ratios are more informative about risk than lipid fractions are. This suggests that, among lipoprotein particles of a particular type (LDL or HDL), some smaller and larger subtypes differ in their effects on risk. Direct measurements of even more specific subtypes of lipoprotein particles may be even more informative about risk.


Higher risk of renal disease in chronic hepatitis C patients: Antiviral therapy survival benefit in patients on hemodialysis.
Several studies have shown that chronic hepatitis C (CHC) infection has a negative impact on kidney function, as well as survival, in patients with chronic kidney disease (CKD) or on hemodialysis. The aim of this nationwide registry study was to describe renal disease in Swedish patients with CHC. In the present study, patients were identified for CHC (B18.2) and CKD (N18) according to the International Classification of Diseases (ICD)-10 in the nationwide Swedish inpatient care day surgery (1997-2013) and non-primary outpatient care (2001-2013) patient registries. Hemodialysis was defined using the procedure code in the non-primary outpatient care. For each patient, up to five non-CHC diagnosed age/sex/place of residency-matched comparators were drawn from the general population at the time of diagnosis. Follow-up started at the date of CHC diagnosis and patients accrued person-time until, whichever came first, death, emigration or December 31st, 2013. Between 2001 and 2013, 42,522 patients received a CHC diagnosis. Of these patients, 2.5% (1,077/45,222) were diagnosed with CKD during 280,123 person-years, compared with 0.7% (1,454/202,694) in the matched general population comparators (1,504,765 person-years), resulting in a standardized incidence ratio (SIR) of 4.0. There was a 3.3-7.0-fold risk of patients with CHC requiring hemodialysis. Overall, 17% of patients with CHC receiving hemodialysis were treated for CHC; 24% in the treated cohort died compared with 56% of the untreated cohort (p <0.0001), with antiviral treatment improving survival with an odds ratio of 3.901 (p = 0.001). The results from this nationwide registry study showed that patients with CHC are at a higher risk of developing CKD. Furthermore, hepatitis C treatment seemed to improve survival for patients with CHC on hemodialysis compared with untreated patients. Hepatitis C is an infectious disease that mainly infects the liver, but has also been shown to have negative effects on other organs. This nationwide study demonstrates an increased risk of hepatitis C patients developing reduced kidney function and the need for dialysis. The study also showed improved survival in dialysis patients who received antiviral treatment.


Quantitative RNA-polymerase chain reaction-DNA analysis by capillary electrophoresis and laser-induced fluorescence.
Quantitative RNA-polymerase chain reaction (RNA-PCR) is an extremely powerful analytical tool owing to its specificity and high level of sensitivity. Quantitative RNA-PCR is, however, highly labor intensive. No analytical method currently exists that can accurately and rapidly quantitate the small quantities of DNA in RNA-PCR reaction mixtures. We have developed a method using capillary electrophoresis and laser-induced fluorescence to detect YOYO-1 complexes of DNA produced by PCR. RNA-PCR mixtures can be analyzed either directly (without primer and protein removal) or by electrokinetic injection following desalting. Modified competitive and multiplex competitive RNA-PCR assays for glyceraldehyde-3-phosphate dehydrogenase and P4501A1 were tested in a series of mixtures containing equal concentrations, but different proportions, of RNA from untreated (essentially no P4501A1 mRNA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated (high levels of P4501A1 mRNA) HepG2 cells. Twofold differences in concentrations between two P4501A1 mRNA solutions could be detected by competitive RNA-PCR. Glyceraldehyde-3-phosphate dehydrogenase concentrations were constant throughout. Multiplex competitive PCR produced more variable results due to the presence of contaminating peaks, which hindered accurate area integration. These data demonstrate the potential usefulness of capillary electrophoresis in a variety of quantitative PCR applications.


The price of flexibility - a case study on septanoses as pyranose mimetics.
Seven-membered ring mimetics of mannose were studied as ligands for the mannose-specific bacterial lectin FimH, which plays an essential role in the first step of urinary tract infections (UTI). A competitive binding assay and isothermal titration calorimetry (ITC) experiments indicated an approximately ten-fold lower affinity for the seven-membered ring mannose mimetic 2-O-n-heptyl-1,6-anhydro-d-glycero-d-galactitol (7) compared to n-heptyl α-d-mannopyranoside (2), resulting exclusively from a loss of conformational entropy. Investigations by solution NMR, X-ray crystallography, and molecular modeling revealed that 7 establishes a superimposable H-bond network compared to mannoside 2, but at the price of a high entropic penalty due to the loss of its pronounced conformational flexibility. These results underscore the importance of having access to the complete thermodynamic profile of a molecular interaction to "rescue" ligands from entropic penalties with an otherwise perfect fit to the protein binding site.


Dynamical heterogeneities and mechanical non-linearities: Modeling the onset of plasticity in polymer in the glass transition.
In this paper we focus on the role of dynamical heterogeneities on the non-linear response of polymers in the glass transition domain. We start from a simple coarse-grained model that assumes a random distribution of the initial local relaxation times and that quantitatively describes the linear viscoelasticity of a polymer in the glass transition regime. We extend this model to non-linear mechanics assuming a local Eyring stress dependence of the relaxation times. Implementing the model in a finite element mechanics code, we derive the mechanical properties and the local mechanical fields at the beginning of the non-linear regime. The model predicts a narrowing of distribution of relaxation times and the storage of a part of the mechanical energy --internal stress-- transferred to the material during stretching in this temperature range. We show that the stress field is not spatially correlated under and after loading and follows a Gaussian distribution. In addition the strain field exhibits shear bands, but the strain distribution is narrow. Hence, most of the mechanical quantities can be calculated analytically, in a very good approximation, with the simple assumption that the strain rate is constant.


ANKRD1, the gene encoding cardiac ankyrin repeat protein, is a novel dilated cardiomyopathy gene.
We evaluated ankyrin repeat domain 1 (ANKRD1), the gene encoding cardiac ankyrin repeat protein (CARP), as a novel candidate gene for dilated cardiomyopathy (DCM) through mutation analysis of a cohort of familial or idiopathic DCM patients, based on the hypothesis that inherited dysfunction of mechanical stretch-based signaling is present in a subset of DCM patients. CARP, a transcription coinhibitor, is a member of the titin-N2A mechanosensory complex and translocates to the nucleus in response to stretch. It is up-regulated in cardiac failure and hypertrophy and represses expression of sarcomeric proteins. Its overexpression results in contractile dysfunction. In all, 208 DCM patients were screened for mutations/variants in the coding region of ANKRD1 using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct deoxyribonucleic acid sequencing. In vitro functional analyses of the mutation were performed using yeast 2-hybrid assays and investigating the effect on stretch-mediated gene expression in myoblastoid cell lines using quantitative real-time reverse transcription-polymerase chain reaction. Three missense heterozygous ANKRD1 mutations (P105S, V107L, and M184I) were identified in 4 DCM patients. The M184I mutation results in loss of CARP binding with Talin 1 and FHL2, and the P105S mutation in loss of Talin 1 binding. Intracellular localization of mutant CARP proteins is not altered. The mutations result in differential stretch-induced gene expression compared with wild-type CARP. ANKRD1 is a novel DCM gene, with mutations present in 1.9% of DCM patients. The ANKRD1 mutations may cause DCM as a result of disruption of the normal cardiac stretch-based signaling.


Thoracoscopic ligation versus coil occlusion for patent ductus arteriosus: a matched cohort study of outcomes and cost.
Coil occlusion (CO) and video-assisted thoracoscopic surgery (VATS) have both emerged as minimal access therapies for patent ductus arteriosus (PDA). These techniques have not previously been statistically compared. Twenty-four consecutive children undergoing VATS for PDA were each retrospectively matched by PDA diameter and child weight to two children undergoing CO (total 48) during the same time period. The two modalities were compared with respect to outcome and cost. Statistical analysis was performed using a Student's t-test and Mantel-Haenszel relative risk. Cost analysis from an institutional perspective was used to compare resource consumption. Mean PDA diameter was 3.6 +/- 1.2 mm in both groups. Mean age and weight for VATS and CO children were 2.7 and 2.9 yrs and 13.2 and 13.1 kg, respectively. Mean surgical times were 94 +/- 34 min for VATS and 50 +/- 23 min for CO (p < 0.0001). Mean length of stay was 1.6 +/- 0.2 days for VATS and 0.6 +/- 0.2 days for CO (Mantel-Haenszel RR (95% CI) = 0.15 [0.07, 0.29], p < 0.0001). Mean fluoroscopy time with CO was 13 +/- 7 min. No VATS or CO children required conversion to open surgical ligation. Two children in each arm (8% VATS, 4% CO) required indefinite antibiotic endarteritis prophylaxis for a persistent shunt. The cost per child was C$ 4282.80 (Canadian dollars) for VATS and C$ 3958.08 for CO. VATS is as efficacious for PDA closure as CO but requires longer surgical times and lengths of stay. Costs for each procedure are similar.


Enzymatic activities of the human AGPAT isoform 3 and isoform 5: localization of AGPAT5 to mitochondria.
The enzyme 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT) converts lysophosphatidic acid (LPA) to phosphatidic acid (PA). In this study, we show enzymatic properties, tissue distribution, and subcellular localization of human AGPAT3 and AGPAT5. In cells overexpressing these isoforms, the proteins were detected in the nuclear envelope and the endoplasmic reticulum. AGPAT5-GFP fusion protein was localized in the mitochondria of both Chinese hamster ovary and human epithelial cervical cancer cells. Using lysates of AD293 cells infected with AGPAT3 and AGPAT5 recombinant adenovirus, we show that AGPAT3 and AGPAT5 proteins have AGPAT activity. Both the isoforms have similar apparent V(max) of 6.35 and 2.42 nmol/min/mg protein, respectively, for similar LPA. The difference between the two isoforms is in their use of additional lysophospholipids. AGPAT3 shows significant esterification of lysophosphatidylinositol (LPI) in the presence of C20:4 fatty acid, whereas AGPAT5 demonstrates significant acyltransferase activity toward lysophosphatidylethanolamine (LPE) in the presence of C18:1 fatty acid. The AGPAT3 mRNA is ubiquitously expressed in human tissues with several-fold differences in the expression pattern compared with the closely related AGPAT4. In summary, we show that in the presence of different fatty acids, AGPAT3 and AGPAT5 prefer different lysophospholipids as acyl acceptors. More importantly, localization of overexpressed AGPAT5 (this study) as well as GPAT1 and 2 (previous studies) in mitochondria supports the idea that the mitochondria might be capable of synthesizing some of their own glycerophospholipids.


Quality of care in the intensive care unit from the perspective of patient's relatives: development and psychometric evaluation of the consumer quality index 'R-ICU'.
The quality standards of the Dutch Society of Intensive Care require monitoring of the satisfaction of patient's relatives with respect to care. Currently, no suitable instrument is available in the Netherlands to measure this. This study describes the development and psychometric evaluation of the questionnaire-based Consumer Quality Index 'Relatives in Intensive Care Unit' (CQI 'R-ICU'). The CQI 'R-ICU' measures the perceived quality of care from the perspective of patients' relatives, and identifies aspects of care that need improvement. The CQI 'R-ICU' was developed using a mixed method design. Items were based on quality of care aspects from earlier studies and from focus group interviews with patients' relatives. The time period for the data collection of the psychometric evaluation was from October 2011 until July 2012. Relatives of adult intensive care patients in one university hospital and five general hospitals in the Netherlands were approached to participate. Psychometric evaluation included item analysis, inter-item analysis, and factor analysis. Twelve aspects were noted as being indicators of quality of care, and were subsequently selected for the questionnaire's vocabulary. The response rate of patients' relatives was 81% (n = 455). Quality of care was represented by two clusters, each showing a high reliability: 'Communication' (α = .80) and 'Participation' (α = .84). Relatives ranked the following aspects for quality of care as most important: no conflicting information, information from doctors and nurses is comprehensive, and health professionals take patients' relatives seriously. The least important care aspects were: need for contact with peers, nuisance, and contact with a spiritual counsellor. Aspects that needed the most urgent improvement (highest quality improvement scores) were: information about how relatives can contribute to the care of the patient, information about the use of meal-facilities in the hospital, and involvement in decision-making on the medical treatment of the patient. The CQI 'R-ICU' evaluates quality of care from the perspective of relatives of intensive care patients and provides practical information for quality assurance and improvement programs. The development and psychometric evaluation of the CQI 'R-ICU' led to a draft questionnaire, sufficient to justify further research into the reliability, validity, and the discriminative power of the questionnaire.


Image matching with higher-order geometric features.
We propose a geometric matching technique in which line segments and elliptical arcs are used as edge features. The use of these higher-order features renders feature representation efficient. We derive distance measures to evaluate the similarity between the features of the model and those of the image. The model transformation parameters are found by searching a 3-D transformation space using cell-decomposition. The performance of the proposed method is quite good when tested on a variety of images.


Crystallization of undercooled liquid fenofibrate.
Formulation of hydrophobic drugs as amorphous materials is highly advantageous as this increases their solubility in water and therefore their bioavailability. However, many drugs have a high propensity to crystallize during production and storage, limiting the usefulness of amorphous drugs. We study the crystallization of undercooled liquid fenofibrate, a model hydrophobic drug. Nucleation is the rate-limiting step; once seeded with a fenofibrate crystal, the crystal rapidly grows by consuming the undercooled liquid fenofibrate. Crystal growth is limited by the incorporation of molecules into its surface. As nucleation and growth both entail incorporation of molecules into the surface, this process likely also limits the formation of nuclei and thus the crystallization of undercooled liquid fenofibrate, contributing to the good stability of undercooled liquid fenofibrate against crystallization.


Telemedicine in a pediatric headache clinic: A prospective survey.
The aim of this prospective study was to survey our patients about their experience with our clinic's telemedicine program to better understand telemedicine's utility for families, and to improve patient satisfaction and ultimately patient care. This was a prospective survey study of patients and their families who had a routine telemedicine follow-up visit with the University of California San Francisco Pediatric Headache Program. The survey was administered to patients and a parent(s) following their telemedicine visit. Fifty-one of 69 surveys (74%) were completed. All (51/51) patients and families thought that (1) telemedicine was more convenient compared to a clinic visit, (2) telemedicine caused less disruption of their daily routine, and (3) they would choose to do telemedicine again. The mean round-trip travel time from home to clinic was 6.8 hours (SD ± 8.6 hours). All participants thought telemedicine was more cost-effective than a clinic visit. Parents estimated that participating in a telemedicine visit instead of a clinic appointment saved them on average $486. This prospective, pediatric headache telemedicine study shows that telemedicine is convenient, perceived to be cost-effective, and patient-centered. Providing the option of telemedicine for routine pediatric headache follow-up visits results in high patient and family satisfaction.


CD133+ tumor initiating cells in a syngenic murine model of pancreatic cancer respond to Minnelide.
Pancreatic adenocarcinoma is the fourth leading cause for cancer-related mortality with a survival rate of less than 5%. Late diagnosis and lack of effective chemotherapeutic regimen contribute to these grim survival statistics. Relapse of any tumor is largely attributed to the presence of tumor-initiating cells (TIC) or cancer stem cells (CSC). These cells are considered as hurdles to cancer therapy as no known chemotherapeutic compound is reported to target them. Thus, there is an urgent need to develop a TIC-targeted therapy for pancreatic cancer. We isolated CD133(+) cells from a spontaneous pancreatic ductal adenocarcinoma mouse model and studied both surface expression, molecular markers of pancreatic TICs. We also studied tumor initiation properties by implanting low numbers of CD133(+) cells in immune competent mice. Effect of Minnelide, a drug currently under phase I clinical trial, was studied on the tumors derived from the CD133(+) cells. Our study showed for the first time that CD133(+) population demonstrated all the molecular markers for pancreatic TIC. These cells initiated tumors in immunocompetent mouse models and showed increased expression of prosurvival and proinvasive proteins compared to the CD133(-) non-TIC population. Our study further showed that Minnelide was very efficient in downregulating both CD133(-) and CD133(+) population in the tumors, resulting in a 60% decrease in tumor volume compared with the untreated ones. As Minnelide is currently under phase I clinical trial, its evaluation in reducing tumor burden by decreasing TIC as well as non-TIC population suggests its potential as an effective therapy.


Melanin and fungi.
Production of melanin has been associated with virulence in diverse microorganisms. Melanization of fungi has been noted for many years in predominantly subcutaneous infections such as chromoblastomycosis and more recently most extensively studied in a yeast causing systemic infection, Cryptococcus neoformans. Pigmented fungi are increasingly important human pathogens and currently available antifungals are often sub-optimal for serious infections. This review focuses on recent publications on melanin in fungi with particular reference to the role of melanin in virulence, protection against antifungal drugs, and promoting survival in the environment. Inhibition of melanin production by C. neoformans can prolong survival of lethally infected mice. In contrast, melanin in C. neoformans and Histoplasma capsulatum yeast cells can bind amphotericin B and caspofungin, thereby reducing the fungicidal affects of these drugs. H. capsulatum and Paracoccidioides brasiliensis have only recently been shown to produce melanin in vitro and during infection. Additionally, melanin derived from melanized C. neoformans yeast and Aspergillus niger conidia can activate complement, which may modify immune responses to infection. Studies on C. neoformans laccase have revealed that the enzyme is located on the cell wall, which may allow for interactions with the host. Melanization reduces the susceptibility of C. neoformans to enzymatic degradation and toxicity from a heavy metal, which may afford protection to the fungus against similar insults in the environment. Melanin has been referred to as 'fungal armor' due to the ability of the polymer to protect microorganisms against a broad range of toxic insults. Recent publications continue to reveal important contributions of melanin to survival of fungi in the environment and during infection.


Effect of peripheral IV based blood collection on catheter dwell time, blood collection, and patient response.
To evaluate the effect of daily PIV-based phlebotomy using the PIVO device on PIVC dwell times and replacement rates, as well as the reliability of blood sample collection, and patient response to this method of blood collection. Blood draws which are also known as phlebotomy for laboratory analyses are one of the most common experiences for hospitalized patients. When performed by venipuncture, they are often associated with pain and anxiety for patients. Most hospitals avoid phlebotomy from peripheral IV catheters due to sample hemolysis, sample dilution by fluids in PIVC line or infused medications, PIVC dislodgement or infiltration, and increased rates of phlebitis. A prospective, randomized- controlled study of 160 GI surgery patients was enrolled. Patients were randomized to either control evaluation of PIVC dwell or to receive daily PIVO blood collections in addition to evaluation of PIVC dwell. Daily PIVO blood collections did not negatively affect PIVC dwell or replacement rates. Overall 81% of blood collection attempts were successful and the likelihood of success was strongly associated with PIVC condition. Patients reported 0.7/10 pain for PIVO blood collection on a 0-10 pain scale and a 9.1/10 preference for PIVO on a 0 (strongly prefer needle) to 10 (strongly prefer PIVO) preference scale. Results suggest that use of a PIV based blood collection was a reliable and valid approach and was superior to routine phlebotomy in self-reported responses from patients.


Homeopathy.
Especially in the United States, homeopathy has not become integrated into mainstream medical practice; this is partly because of the historical paucity of quality published research studies or quality educational programs. More recently, there have been better-designed studies in reputable journals, although historically most studies have been inconclusive or of poor methodology. The confusion around homeopathy in the United States exists for several reasons: 1. One of the main reasons for the relative disinterest or opposition to homeopathy is that even well-designed clinical studies on homeopathy leave the reader without any protocol-driven tools to take into daily practice. Individualization of treatment, or, as it is called today, differential therapeutics, is the main requirement of successful homeopathic prescribing. Only well-trained homeopathic practitioners are able to carry out such a task. In many articles that reported positive outcomes for homeopathy, numerous homeopathic remedies had been prescribed for the same diagnostic category. Critics suggest that the pooling of data from trials using different therapeutic agents to assess the overall success of homeopathic prescribing is incorrect. Research protocols that employ combination remedies, in which a medication contains several homeopathic remedies, fall into the same category. 2. Many of the positive and negative studies published are flawed with numerous methodologic problems. One of the most common problems is a lack of objective validated outcome measures. Another common problem is a small sample size. In most positive and negative meta-analyses published to date, research data are pulled together artificially based on either a diagnostic category or a particular remedy. Frequently the concentration of the remedy used and the conditions to which it has been applied are different. Ernst and Pittler published a letter with a critique of the methodology used in one of the meta-analyses of clinical trials of homeopathy. Most importantly, professional homeopaths and conventional scientists criticize the choice of remedy or the condition to which it was applied or both. The design and follow-up in migraine studies has been criticized extensively by one of the world's leading homeopaths, Vithoulkas (personal communication, 1997). Most of the Arnica studies have been designed with either an inappropriate dosing regimen or an inappropriately chosen procedure. In most positive studies on homeopathy, the outcome measures were subjective and poorly quantifiable. 3. Few well-designed studies have been reproduced by independent research teams. This situation exists for two major reasons: lack of sufficient funding and lack of a sufficient number of well-trained homeopaths qualified and interested to participate in research. 4. More rigorous educational programs on homeopathy for professionals need to be encouraged. Most of the existing programs are designed for consumers; academic continuing medical education-quality courses are needed. Meanwhile, while the debate around homeopathy still continues in conventional medical circles, the general public has been using the services of homeopathic practitioners and homeopathic remedies increasingly. In many countries, homeopathy and other complementary modalities have been integrated successfully into a larger armamentarium for the modern physician. According to a study published in 1995 in the Journal of the American Board of Family Practice, 69% of family practice physicians expressed interest in learning more about homeopathy. Increasing public and professional interest calls for attempts to study homeopathy in a more systematic way and to provide quality academic overview for medical practitioners. The growing number of complementary and alternative medicine centers affiliated with major teaching hospitals should provide a solid interface between evidence-based biologic medicine and many emerging complementary and alternative medicine modalities, including homeopathy.


First Report of Tomato yellow leaf curl virus Infecting Common Bean in China.
Common bean (Phaseolus vulgaris) is one of the most economically important vegetable crops in China. In November 2011, symptoms with thickening and crumpling of leaves and stunting were observed on common bean with incidence rate of 50 to 70% in the fields of Huaibei, northern Anhui Province, China. Diseased common bean plants were found to be infested with large population of whiteflies (Bemisia tabaci), which induced leaf crumple symptoms in healthy common beans, suggesting begomovirus etiology. To identify possible begomoviruses, 43 symptomatic leaf samples from nine fields were collected and total DNA of each sample was extracted. PCR was performed using degenerate primers PA and PB to amplify a specific region covering AV2 gene of DNA-A and part of the adjacent intergenic region (2). DNA fragments were successfully amplified from 37 out of 43 samples and PCR amplicons of 31 samples were used for sequencing. Sequence alignments among them showed that the nucleotide sequence identity ranged from 99 to 100%, which implied that only one type of begomovirus might be present. Based on the consensus sequences, a primer pair MB1AbF (ATGTGGGATCCACTTCTAAATGAATTTCC) and MB1AsR (GCGTCGACAGTGCAAGACAAACTACTTGGGGACC) was designed and used to amplify the circular viral DNA genome. The complete genome (Accession No. JQ326957) was 2,781 nucleotides long and had the highest sequence identity (over 99%) with Tomato yellow leaf curl virus (TYLCV; Accession Nos. GQ352537 and GU199587). These samples were also examined by dot immunobinding assay using monoclonal antibody against TYLCV and results confirmed that TYLCV was present in the samples. These results demonstrated that the virus from common bean is an isolate of TYLCV, a different virus from Tomato yellow leaf curl China virus (TYLCCNV). TYLCV is a devastating pathogen causing significant yield losses on tomato in China since 2006 (4). The virus has also been reported from cowpea in China (1) and in common bean in Spain (3). To our knowledge, this is the first report of TYLCV infecting common bean in China. References: (1) F. M. Dai et al. Plant Dis. 95:362, 2011. (2) D. Deng et al. Ann. Appl. Biol. 125:327, 1994. (3) J. Navas-Castillo et al. Plant Dis. 83:29, 1999. (4) J. B. Wu et al. Plant Dis. 90:1359, 2006.


Iohexol degradation in wastewater and urine by UV-based Advanced Oxidation Processes (AOPs): Process modeling and by-products identification.
In this work, an Iodinated Contrast Medium (ICM), Iohexol, was subjected to treatment by 3 Advanced Oxidation Processes (AOPs) (UV, UV/H2O2, UV/H2O2/Fe2+). Water, wastewater and urine were spiked with Iohexol, in order to investigate the treatment efficiency of AOPs. A tri-level approach has been deployed to assess the UV-based AOPs efficacy. The treatment was heavily influenced by the UV transmittance and the organics content of the matrix, as dilution and acidification improved the degradation but iron/H2O2 increase only moderately. Furthermore, optimization of the treatment conditions, as well as modeling of the degradation was performed, by step-wise constructed quadratic or product models, and determination of the optimal operational regions was achieved through desirability functions. Finally, global chemical parameters (COD, TOC and UV-Vis absorbance) were followed in parallel with specific analyses to elucidate the degradation process of Iohexol by UV-based AOPs. Through HPLC/MS analysis the degradation pathway and the effects the operational parameters were monitored, thus attributing the pathways the respective modifications. The addition of iron in the UV/H2O2 process inflicted additional pathways beneficial for both Iohexol and organics removal from the matrix.


Advances in the use of DNA barcodes to build a community phylogeny for tropical trees in a Puerto Rican forest dynamics plot.
Species number, functional traits, and phylogenetic history all contribute to characterizing the biological diversity in plant communities. The phylogenetic component of diversity has been particularly difficult to quantify in species-rich tropical tree assemblages. The compilation of previously published (and often incomplete) data on evolutionary relationships of species into a composite phylogeny of the taxa in a forest, through such programs as Phylomatic, has proven useful in building community phylogenies although often of limited resolution. Recently, DNA barcodes have been used to construct a robust community phylogeny for nearly 300 tree species in a forest dynamics plot in Panama using a supermatrix method. In that study sequence data from three barcode loci were used to generate a well-resolved species-level phylogeny. Here we expand upon this earlier investigation and present results on the use of a phylogenetic constraint tree to generate a community phylogeny for a diverse, tropical forest dynamics plot in Puerto Rico. This enhanced method of phylogenetic reconstruction insures the congruence of the barcode phylogeny with broadly accepted hypotheses on the phylogeny of flowering plants (i.e., APG III) regardless of the number and taxonomic breadth of the taxa sampled. We also compare maximum parsimony versus maximum likelihood estimates of community phylogenetic relationships as well as evaluate the effectiveness of one- versus two- versus three-gene barcodes in resolving community evolutionary history. As first demonstrated in the Panamanian forest dynamics plot, the results for the Puerto Rican plot illustrate that highly resolved phylogenies derived from DNA barcode sequence data combined with a constraint tree based on APG III are particularly useful in comparative analysis of phylogenetic diversity and will enhance research on the interface between community ecology and evolution.


Use of machine learning to shorten observation-based screening and diagnosis of autism.
The Autism Diagnostic Observation Schedule-Generic (ADOS) is one of the most widely used instruments for behavioral evaluation of autism spectrum disorders. It is composed of four modules, each tailored for a specific group of individuals based on their language and developmental level. On average, a module takes between 30 and 60 min to deliver. We used a series of machine-learning algorithms to study the complete set of scores from Module 1 of the ADOS available at the Autism Genetic Resource Exchange (AGRE) for 612 individuals with a classification of autism and 15 non-spectrum individuals from both AGRE and the Boston Autism Consortium (AC). Our analysis indicated that 8 of the 29 items contained in Module 1 of the ADOS were sufficient to classify autism with 100% accuracy. We further validated the accuracy of this eight-item classifier against complete sets of scores from two independent sources, a collection of 110 individuals with autism from AC and a collection of 336 individuals with autism from the Simons Foundation. In both cases, our classifier performed with nearly 100% sensitivity, correctly classifying all but two of the individuals from these two resources with a diagnosis of autism, and with 94% specificity on a collection of observed and simulated non-spectrum controls. The classifier contained several elements found in the ADOS algorithm, demonstrating high test validity, and also resulted in a quantitative score that measures classification confidence and extremeness of the phenotype. With incidence rates rising, the ability to classify autism effectively and quickly requires careful design of assessment and diagnostic tools. Given the brevity, accuracy and quantitative nature of the classifier, results from this study may prove valuable in the development of mobile tools for preliminary evaluation and clinical prioritization-in particular those focused on assessment of short home videos of children--that speed the pace of initial evaluation and broaden the reach to a significantly larger percentage of the population at risk.